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[The below paper is pf-availed.]

Case Studies in Physiology: Maximal Oxygen Consumption and Performance in a Centenarian Cyclist.

Billat VL, Dhonneur G, Mille-Hamard L, Le Moyec L, Momken I, Launay T, Koralsztein JP, Besse S.

J Appl Physiol (1985). 2016 Dec 29:jap.00569.2016. doi: 10.1152/japplphysiol.00569.2016. [Epub ahead of print]

PMID: 28035015


The purpose of this study was to examine the physiological characteristics of an elite centenarian cyclist who, at 101 years old, established the one-hour cycling record for individuals ≥ 100 years old (24.25 km) and to determine the physiological factors associated with his performance improvement two years later at 103 years old (26.92 km; +11%). Before each record, he performed an incremental test on a cycling ergometer. For two years, he trained 5,000 km a year with a polarized training that involved cycling 80% of mileage at "light" RPE ≤ 12 and 20% at "hard" RPE ≥ 15 at a cadence between 50 and 70 rpm.


his bodyweight and lean body mass did not change, while his ⩒O2max increased (31 to 35 ml.kg-1min-1; +13%). Peak power output increased from 90 to 125 W (+39 %), mainly due to increasing the maximal pedaling frequency (69 to 90 rpm; +30%). Maximal heart rate did not change (134 to 137 bpm) in contrast to the maximal ventilation (57 to 70 L.min-1, +23%), increasing with both the respiratory frequency (38 to 41 cycle.min-1; +8%) and the tidal volume (1.5 to 1.7 L; +13%). Respiratory Exchange Ratio increased (1.03 to 1.14) in the same extent as tolerance to ⩒CO2

In conclusion, it is possible to increase performance and ⩒O2max with polarized training focusing on a high pedaling cadence even after turning 100 years old.


aging; cadence of pedaling; centenarian; cycling; ⩒O2max


Table 1: anatomical and physiological variables before and after training.


Before training After training


Weight (Kg) 50.1 48.5

Height (m) 1.52 1.52

Body mass Index 21.7 21.0

Fat body mass (Kg) 13 11

Lean body mass (Kg) 43.6 43.2

Body Surface (m2) 1.45 1.43

Field record power (W) 80 103

Maximal oxygen uptake (mLO2 . min-1) 1553 1698

Maximal carbon dioxide production (mLCO2 . Kg-1. min-1) 31.9 37.1

Maximal respiratory exchange ratio 1.03 1.14

Maximal expiratory minute ventilation (L . min-1) 57 70

Maximal respiratory frequency (cycle . min-1) 38 41

Maximal tidal volume (L/cycle) 1.5 1.7

Maximal oxygen pulse (mL O2 . beat-1) 11.6 13.0

Maximal oxygen pulse (mL O2 . Kg-1 . beat-1) 0.23 0.27

Maximal oxygen cost of pedalling (mL O2 . Kg-1 . W-1 ) 19.4 17.0

Tolerance to CO2 (slope of the regression line between ⩒E and ⩒CO2) 32.9 34.4

Specific power output (W . Kg-1) 1.8 2.5

Power output at ⩒O2max (W) 80 100

Power output at ⩒O2max (W . Kg-1) 1.6 2.0

Power reserve above ⩒O2max (W) 10 25

Heart Rate at rest (beats . min-1) 65 63

Maximal heart rate at ⩒O2max (beats . min-1) 134 137


Human gut microbiota and healthy aging: Recent developments and future prospective.

Kumar M, Babaei P, Ji B, Nielsen J.

Nutr Healthy Aging. 2016 Oct 27;4(1):3-16. doi: 10.3233/NHA-150002. Review.

PMID: 28035338




The human gut microbiota alters with the aging process. In the first 2-3 years of life, the gut microbiota varies extensively in composition and metabolic functions. After this period, the gut microbiota demonstrates adult-like more stable and diverse microbial species. However, at old age, deterioration of physiological functions of the human body enforces the decrement in count of beneficial species (e.g. Bifidobacteria) in the gut microbiota, which promotes various gut-related diseases (e.g. inflammatory bowel disease). Use of plant-based diets and probiotics/prebiotics may elevate the abundance of beneficial species and prevent gut-related diseases. Still, the connections between diet, microbes, and host are only partially known. To this end, genome-scale metabolic modeling can help to explore these connections as well as to expand the understanding of the metabolic capability of each species in the gut microbiota. This systems biology approach can also predict metabolic variations in the gut microbiota during ageing, and hereby help to design more effective probiotics/prebiotics.


Human gut microbiota; aging; diets; genome-scale metabolic modeling; probiotics/prebiotics


[Cancer sores can be a pain. https://en.wikipedia.org/wiki/Carmine#Allergyhappens for https://en.wikipedia.org/wiki/Carmine, another name for cochineal red.]

Is there a role of food additives in recurrent aphthous stomatitis? a prospective study with patch testing.

Gülseren D, Hapa A, Ersoy-Evans S, Elçin G, Karaduman A.

Int J Dermatol. 2016 Dec 30. doi: 10.1111/ijd.13515. [Epub ahead of print]

PMID: 28035659




Recurrent aphthous stomatitis (RAS) is a common disease of the oral mucosa with an unknown etiology. This study aimed to determine if food additives play a role in the etiology of RAS as well as to determine if patch testing can be used to detect which allergens cause RAS.


This prospective study included 24 patients with RAS and 22 healthy controls. All the participants underwent patch testing for 23 food additives.


In total, 21 (87.5%) RAS patients and 3 (13.6%) controls had positive patch test reactions to ≥1 allergens; the difference in the patch test positivity rate between groups was significant (P < 0.05). The most common allergen that elicited positive patch test results in the patient group was cochineal red (n = 15 [62.5%]), followed by azorubine (n = 11 [45.8%]) and amaranth (n = 6 [25%]).


The present findings show that food additives might play a role in the etiology of RAS and that patch testing could be a method for determining the etiology of RAS.

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Changes in leisure time physical activity and subsequent disability retirement: A register-linked cohort study.

Lahti J, Holstila A, Mänty M, Lahelma E, Rahkonen O.

Int J Behav Nutr Phys Act. 2016 Sep 6;13(1):99. doi: 10.1186/s12966-016-0426-2.

PMID: 27599466 Free PMC Article





Disability retirement is an economic, public health and work life issue causing costs for employees, workplaces and society. Adopting physical activity at middle-age has been associated with reduced risk of sickness absence and mortality. The aim of this study was to examine how changes over time in leisure time physical activity are associated with subsequent disability retirement among midlife employees.


The Helsinki Health Study cohort baseline (phase 1) mail questionnaire survey data were collected in 2000, 2001 and 2002 among 40-60-year-old employees of the City of Helsinki, Finland. A phase 2 survey was conducted in 2007 (N = 3943). Respondents were classified into three groups: 1. low-active (<14 MET-hours/week), 2. moderately active (> = 14 MET-hours/week in moderate-intensity physical activity) and 3. vigorously active (> = 14 MET-hours/week including vigorous physical activity) at both phases. This yielded nine groups for describing stability and change of leisure time physical activity. Disability retirement data were derived from the registry of the Finnish Centre for Pensions until the end of 2013. A Cox regression analysis was used to calculate hazard ratios (HR) and their 95 % confidence intervals (CI) adjusting for covariates.


During the follow-up, 264 (6.7 %) participants retired due to disability. Compared with those who were persistently low-active, those who increased their physical activity from low to vigorous had a lower risk of subsequent disability retirement (HR = 0.38, 95 % CI = 0.15-0.97) when adjusting for age, gender, occupational social class, strenuousness of work, smoking and binge drinking. Similarly, compared with those who were persistently moderately active, those increasing from moderate to vigorous (HR = 0.50, 95 % CI = 0.28-0.86) had a reduced risk. In contrast, those decreasing their physical activity from vigorous to low (HR = 2.42, 95 % CI = 1.32-4.41) or moderate (HR = 1.70, 95 % CI = 1.03-2.82) had an increased risk, compared with those who were persistently vigorously active. Adjusting for BMI, limiting longstanding illness and prior sickness absence somewhat attenuated the associations.


Adopting vigorous physical activity was associated with a reduced risk of disability retirement. Promoting vigorous physical activity among midlife employees may help prevent disability retirement.


Exercise; Physical inactivity; Work disability; Working conditions


The descriptive epidemiology of accelerometer-measured physical activity in older adults.

Berkemeyer K, Wijndaele K, White T, Cooper AJ, Luben R, Westgate K, Griffin SJ, Khaw KT, Wareham NJ, Brage S.

Int J Behav Nutr Phys Act. 2016 Jan 7;13:2. doi: 10.1186/s12966-015-0316-z.

PMID: 26739758 Free PMC Article





Objectively measured physical activity between older individuals and between populations has been poorly described. We aimed to describe and compare the variation in accelerometry data in older UK (EPIC-Norfolk) and American (NHANES) adults.


Physical activity was measured by uniaxial accelerometry in 4,052 UK (49-91 years) and 3459 US older adults (49-85 years). We summarized physical activity as volume (average counts/minute), its underlying intensity distribution, and as time spent <100counts/minute, ≥809counts/minute and ≥2020counts/minute both for total activity and that undertaken in ≥10-min bouts.


In EPIC-Norfolk 65% of wear-time was spent at <100 counts/minute and 20% spent in the range 100-500 counts/minute. Only 4.1% of this cohort accumulated more than 30 min/day of activity above 2020 counts/minute in 10-min bouts. If a cut-point of >809 counts/minute is used 18.7% of people reached the 30 min/day threshold. By comparison, 2.5% and 9.5% of American older adults accumulated activity at these levels, respectively.


As assessed by objectively measured physical activity, the majority of older adults in this UK study did not meet current activity guidelines. Older adults in the UK were more active overall, but also spent more time being sedentary than US adults.


Long terms trends of multimorbidity and association with physical activity in older English population.

Dhalwani NN, O'Donovan G, Zaccardi F, Hamer M, Yates T, Davies M, Khunti K.

Int J Behav Nutr Phys Act. 2016 Jan 19;13:8. doi: 10.1186/s12966-016-0330-9.

PMID: 26785753 Free PMC Article





Multimorbidity has become one of the main challenges in the recent years for patients, health care providers and the health care systems globally. However, literature describing the burden of multimorbidity in the elderly population, especially longitudinal trends is very limited. Physical activity is recommended as one of the main lifestyle changes in the prevention and management of multiple chronic diseases worldwide; however, the evidence on its association with multimorbidity remains inconclusive. Therefore, we aimed to assess the longitudinal trends of multimorbidity and the association between multimorbidity and physical activity in a nationally representative cohort of the English population aged ≥50 years between 2002 and 2013.


We used data on 15,688 core participants from six waves of the English Longitudinal Study of Ageing, with complete information on physical activity. Self-reported physical activity was categorised as inactive, mild, moderate and vigorous levels of physical activity. We calculated the number of morbidities and the prevalence of multimorbidity (more than 2 chronic conditions) between 2002 and 2013 overall and by levels of self-reported physical activity. We estimated the odds ratio (OR) and 95% confidence intervals (CI) for multimorbidity by each category of physical activity, adjusting for potential confounders.


There was a progressive decrease over time in the proportion of participants without any chronic conditions (33.9% in 2002/2003 vs. 26.8% in 2012/2013). In contrast, the prevalence of multimorbidity steadily increased over time (31.7% in 2002/2003 vs. 43.1% in 2012/2013). Compared to the physically inactive group, the OR for multimorbidity was 0.84 (95% CI 0.78 to 0.91) in mild, 0.61 (95% CI 0.56 to 0.66) in moderate and 0.45 (95% CI 0.41 to 0.49) in the vigorous physical activity group.


This study demonstrated an inverse dose-response association between levels of physical activity and multimorbidity, however, given the increasing prevalence of multimorbidity over time, there is a need to explore causal associations between physical activity and multimorbidity and its impact as a primary prevention strategy to prevent the occurrence of chronic conditions later in life and reduce the burden of multimorbidity.


Changes in physical activity during transition to retirement: a cohort study.

Stenholm S, Pulakka A, Kawachi I, Oksanen T, Halonen JI, Aalto V, Kivimäki M, Vahtera J.

Int J Behav Nutr Phys Act. 2016 Apr 16;13:51. doi: 10.1186/s12966-016-0375-9.

PMID: 27084334 Free PMC Article





Retirement is a major life transition which may affect lifestyle. The aim of this study is to examine within-individual changes in physical activity during the transition from full-time work to retirement.


The study population consisted of 9,488 Finnish public-sector employees who retired in 2000-2011 and who reported their leisure-time and commuting physical activity before and after retirement. On average, participants provided data at 3.6 (of the four) repeat examinations during 10 years before and 10 years after the retirement. Physical activity was self-reported and was expressed as weekly metabolic equivalent task (MET) hours. Generalized estimating equations were used to examine physical activity trajectories around retirement.


Among participants entering to statutory retirement physical activity first increased by 1.81 MET-hours (95% confidence interval [CI] 1.20 to 2.42) during 4-year retirement transition, but then decreased by -1.80 MET hours (95% CI -2.83 to -0.79) during the subsequent post-retirement period. Older retirement age, higher occupational status and fewer chronic diseases were associated with greater increase in physical activity during transition to statutory retirement.


Statutory retirement appears to be associated with a temporary increase in physical activity. Future research should examine ways to maintain the increased activity level after retirement.


Aging; Cohort Study; Physical activity; Retirement


Retirement-A Transition to a Healthier Lifestyle?: Evidence From a Large Australian Study.

Ding D, Grunseit AC, Chau JY, Vo K, Byles J, Bauman AE.

Am J Prev Med. 2016 Aug;51(2):170-8. doi: 10.1016/j.amepre.2016.01.019.

PMID: 26972491




Population aging is associated with a rising burden of non-communicable disease, profoundly impacting health policy and practice. Adopting and adhering to healthy lifestyles in middle or older age can protect against morbidity and mortality. Retirement brings opportunities to reconfigure habitual lifestyles and establish new routines. This study examines the longitudinal association between retirement and a range of lifestyle risk behaviors among a large population-based sample of Australian adults.


Study sample included working adults aged ≥45 years at baseline (2006-2009, N=23,478-26,895). Lifestyle behaviors, including smoking, alcohol use, physical activity, diet, sedentary behavior, and sleep, were measured at both baseline and follow-up (2010). Logistic regression models estimated the odds of having each risk factor at follow-up and multiple linear regression models calculated the change in the total number of risk factors, adjusted for baseline risk and other covariates. Sociodemographic characteristics and reasons for retirement were tested as potential effect modifiers.


During the 3.3-year follow-up, about 11% of respondents retired. Retirement was associated significantly with reduced odds of smoking (AOR=0.74); physical inactivity (AOR=0.73); excessive sitting (AOR=0.34); and at-risk sleep patterns (AOR=0.82). There was no significant association between retirement and alcohol use or fruit and vegetable consumption. Change in the total number of lifestyle risk factors differed significantly by reason for retirement.


In a large population-based Australian cohort, retirement was associated with positive lifestyle changes. Health professionals and policymakers should consider developing special programs for retirees to capitalize on the healthy transitions through retirement.


Associations between liking for fat, sweet or salt and obesity risk in French adults: a prospective cohort study.

Lampuré A, Castetbon K, Deglaire A, Schlich P, Péneau S, Hercberg S, Méjean C.

Int J Behav Nutr Phys Act. 2016 Jul 4;13:74. doi: 10.1186/s12966-016-0406-6.

PMID: 27378200 Free PMC Article





Individual sensory liking appears to be an important determinant of dietary intake and may consequently influence weight status. Cross-sectional studies have shown positive association between fat liking and weight status and equivocal results regarding salt and sweet liking. Moreover, the contribution of dietary intake to explain this relationship has not been studied yet. We investigated the prospective association between sensory liking for fat, sweet or salt and the onset of obesity over 5 years in adults, and the mediating effect of dietary intake.


We prospectively examine the risk of obesity among 24,776 French adults participating in the NutriNet-Santé cohort study. Liking scores and dietary data were assessed at baseline using a validated web-based questionnaire and 24 h records, respectively. Self-reported anthropometric data were collected using web-based questionnaire, each year during 5 years. Associations between quartiles of liking for fat, sweet or salt and obesity risk, and the mediating effect of diet were assessed by multivariate Cox proportional hazards models stratified by gender, adjusted for sociodemographic and lifestyle factors.


In both genders, sensory liking for fat was associated with an increased risk of obesity (hazard ratios for quartile 4 compared to quartile 1, men: HR(Q4vs.Q1) = 2.39 (95% CI 1.39,4.11) P-trend = 0.0005, women: HR(Q4vs.Q1) = 2.02 (1.51,2.71) P-trend = <0.0001). Dietary intake explained 32% in men and 52% in women of the overall variation of liking for fat in obesity. Sensory liking for sweet was associated with a decreased risk of obesity (men: HR(Q4vs.Q1) = 0.51 (0.31,0.83) P-trend = 0.01, women: HR(Q4vs.Q1) = 0.72 (0.54,0.96) P-trend = 0.035). No significant association between salt liking and the risk of obesity was found.


Unlike sweet and salt liking, higher liking for fat appears to be a major risk factor of obesity, largely explained by dietary intake. Our findings emphasize the need to centrally position sensory liking in obesity prevention.


Dietary intake; Fat sensation; Mediating factor; Obesity; Salty taste; Sensory liking; Sweet taste


Effect of frequent interruptions of prolonged sitting on self-perceived levels of energy, mood, food cravings and cognitive function.

Bergouignan A, Legget KT, De Jong N, Kealey E, Nikolovski J, Groppel JL, Jordan C, O'Day R, Hill JO, Bessesen DH.

Int J Behav Nutr Phys Act. 2016 Nov 3;13(1):113.

PMID: 27809874 Free PMC Article





While physical activity has been shown to improve cognitive performance and well-being, office workers are essentially sedentary. We compared the effects of physical activity performed as (i) one bout in the morning or (ii) as microbouts spread out across the day to (iii) a day spent sitting, on mood and energy levels and cognitive function.


In a randomized crossover trial, 30 sedentary adults completed each of three conditions: 6 h of uninterrupted sitting (SIT), SIT plus 30 min of moderate-intensity treadmill walking in the morning (ONE), and SIT plus six hourly 5-min microbouts of moderate-intensity treadmill walking (MICRO). Self-perceived energy, mood, and appetite were assessed with visual analog scales. Vigor and fatigue were assessed with the Profile of Mood State questionnaire. Cognitive function was measured using a flanker task and the Comprehensive Trail Making Test. Intervention effects were tested using linear mixed models.


Both ONE and MICRO increased self-perceived energy and vigor compared to SIT (p < 0.05 for all). MICRO, but not ONE, improved mood, decreased levels of fatigue and reduced food cravings at the end of the day compared to SIT (p < 0.05 for all). Cognitive function was not significantly affected by condition.


In addition to the beneficial impact of physical activity on levels of energy and vigor, spreading out physical activity throughout the day improved mood, decreased feelings of fatigue and affected appetite. Introducing short bouts of activity during the workday of sedentary office workers is a promising approach to improve overall well-being at work without negatively impacting cognitive performance.


NCT02717377 , registered 22 March 2016.


Appetite; Catecholamines; Exercise; Fatigue; Physical activity; Sedentary behavior; Sitting

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Demographics, Phenotypic Health Characteristics and Genetic Analysis of Centenarians in China.

Zeng Y, Feng Q, Gu D, Vaupel J.

Mech Ageing Dev. 2016 Dec 28. pii: S0047-6374(16)30216-0. doi: 10.1016/j.mad.2016.12.010. [Epub ahead of print] Review.

PMID: 28040447



After a brief introduction to the background, significance and unique features of the centenarian population in China, we describe the Chinese Longitudinal Healthy Longevity Study (CLHLS), which is the world's largest study of centenarians, nonagenarians, octogenarians, and compatible young-old aged 65-79. Based on the CLHLS data and other relevant studies, we summarize demographic and socioeconomic characteristics as well as self-reported and objectively-tested health indicators of centenarians in China, with an emphasis on gender differences and rural/urban disparities. We then compare five-year-age-specific trajectories of physical and cognitive functions, self-reported health, and life satisfactions from ages 65-69 to 100+, concluding that good psychological resilience and optimism are keys to the exceptional longevity enjoyed by centenarians. We discuss recent findings of novel loci and pathways that are significantly associated with longevity based on the genome-wide association study (GWAS) of the CLHLS centenarian sample, which is 2.7 times as large as prior GWAS of longevity. We also highlight colleagues' and our own studies on longevity candidate genes and gene-environment interaction analyses. Finally, we discuss limitations inherent in our studies of centenarians in China and further research perspectives.


Centenarians; China; Genetic variants; GxE interactions; Health phenotypes; Healthy longevity


Effect of inulin-type fructans on blood lipid profile and glucose level: a systematic review and meta-analysis of randomized controlled trials.

Liu F, Prabhakar M, Ju J, Long H, Zhou HW.

Eur J Clin Nutr. 2017 Jan;71(1):9-20. doi: 10.1038/ejcn.2016.156. Review.

PMID: 27623982





This systematic review and meta-analysis was performed to assess the effects of inulin-type fructans (ITF) on human blood lipids and glucose homeostasis associated with metabolic abnormalities, including dyslipidemia, overweight or obesity, and type-2 diabetes mellitus (T2DM).


The MEDLINE, EMBASE and Cochrane Library databases were systematically searched for randomized controlled trials (RCTs) before January 2016. Human trials that investigated the effects of ITF supplementation on the lipid profile, fasting glucose and insulin were included using Review Manager 5.3.


Twenty RCTs with 607 adult participants were included in this systematic review and meta-analysis. In the overall analysis, the supplementation of ITF reduced only the low density lipoprotein-cholesterol (LDL-c) (mean difference (MD): -0.15; 95% confidence interval (CI): -0.29, -0.02; P=0.03) without affecting the other endpoints. Within the T2DM subgroup analysis, ITF supplementation was positively associated with a decreased fasting insulin concentration (MD: -4.01; 95% CI: -5.92, -2.09; P<0.0001) and increased high density lipoprotein-cholesterol (HDL-c) (MD: 0.07; 95% CI: 0, 0.14; P=0.05). Moreover, a reduced fasting glucose tendency was identified only in the T2DM subgroup (MD: -0.42; 95% CI: -0.90, 0.06; P=0.09). There was a potential publication bias, and few trials were available for the T2DM subgroup analysis.


In summary, the use of ITF may have benefits for LDL-c reduction across all study populations, whereas HDL-c improvement and glucose control were demonstrated only in the T2DM subgroup. Thus, additional, well-powered, long-term, randomized clinical trials are required for a definitive conclusion. Overall, ITF supplementation may provide a novel direction for improving the lipid profile and glucose metabolism.


Corn oil intake favorably impacts lipoprotein cholesterol, apolipoprotein and lipoprotein particle levels compared with extra-virgin olive oil.

Maki KC, Lawless AL, Kelley KM, Kaden VN, Geiger CJ, Palacios OM, Dicklin MR.

Eur J Clin Nutr. 2017 Jan;71(1):33-38. doi: 10.1038/ejcn.2016.169.

PMID: 27677368




Corn oil (CO) and extra-virgin olive oil (EVOO) are rich sources of unsaturated fatty acids (UFA), but UFA profiles differ among oils, which may affect lipoprotein levels.


The objective of this study was to assess the effects of CO versus EVOO intake on fasting lipoprotein and subfraction cholesterol levels, apolipoprotein (apo) A1, apo B, and low-density lipoprotein particle concentrations in men and women.


As part of a weight maintenance diet, men and women were provided with food items prepared with 54 g per day of CO or EVOO (21-day treatment, 21-day washout) in a randomized, double-blind, controlled-feeding, crossover trial. Fasting lipoprotein cholesterol and related variables were determined with density gradient ultracentrifugation.


Among the 54 completers, CO reduced total cholesterol, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apo B and LDL particle concentration to a greater extent compared with EVOO intake. Changes in LDL-C and VLDL-C contributed to the larger reduction in non-HDL-C with CO compared with EVOO intake (-0.39 mmol/l vs -0.04 mmol/l; P<0.001). The larger reduction in LDL-C by CO intake was attributable to changes (P<0.05) caused by CO vs EVOO in large LDL1+2-C (-0.22 mmol/l) and intermediate-density lipoprotein cholesterol (-0.12 mmol/l). HDL-C responses did not differ between treatments, but apo A1 increased more with EVOO compared with CO intake (4.6  versus 0.7 mg/dl, respectively, P=0.016).


CO intake reduced atherogenic lipoprotein cholesterol and particle concentrations to a larger extent than did EVOO, which may have implications for cardiovascular disease risk.


This work was funded by ACH Food Companies, Inc. (Oakbrook, IL) and PepsiCo, Inc.

(Purchase, NY). Sponsor role included review and comment on study protocol and



Fruit and vegetable intake and risk of incident of type 2 diabetes: results from the consortium on health and ageing network of cohorts in Europe and the United States (CHANCES).

Mamluk L, O'Doherty MG, Orfanos P, Saitakis G, Woodside JV, Liao LM, Sinha R, Boffetta P, Trichopoulou A, Kee F.

Eur J Clin Nutr. 2017 Jan;71(1):83-91. doi: 10.1038/ejcn.2016.143.

PMID: 27530474




There is limited information to support definitive recommendations concerning the role of diet in the development of type 2 Diabetes mellitus (T2DM). The results of the latest meta-analyses suggest that an increased consumption of green leafy vegetables may reduce the incidence of diabetes, with either no association or weak associations demonstrated for total fruit and vegetable intake. Few studies have, however, focused on older subjects.


The relationship between T2DM and fruit and vegetable intake was investigated using data from the NIH-AARP study and the EPIC Elderly study. All participants below the age of 50 and/or with a history of cancer, diabetes or coronary heart disease were excluded from the analysis. Multivariate logistic regression analysis was used to calculate the odds ratio of T2DM comparing the highest with the lowest estimated portions of fruit, vegetable, green leafy vegetables and cabbage intake.


Comparing people with the highest and lowest estimated portions of fruit, vegetable or green leafy vegetable intake indicated no association with the risk of T2DM. However, although the pooled OR across all studies showed no effect overall, there was significant heterogeneity across cohorts and independent results from the NIH-AARP study showed that fruit and green leafy vegetable intake was associated with a reduced risk of T2DM OR 0.95 (95% CI 0.91,0.99) and OR 0.87 (95% CI 0.87,0.90) respectively.


Fruit and vegetable intake was not shown to be related to incident T2DM in older subjects. Summary analysis also found no associations between green leafy vegetable and cabbage intake and the onset of T2DM. Future dietary pattern studies may shed light on the origin of the heterogeneity across populations.


Plasma 25-hydroxy vitamin D and subsequent prostate cancer risk in a nested Case-Control study in Japan: The JPHC study.

Sawada N, Inoue M, Iwasaki M, Yamaji T, Shimazu T, Sasazuki S, Tsugane S.

Eur J Clin Nutr. 2017 Jan;71(1):132-136. doi: 10.1038/ejcn.2016.184.

PMID: 27759068




Although vitamin D has been experimentally reported to inhibit tumorigenesis, cell growth and prostate cancer invasion, epidemiologic data regarding prostate cancer risk are inconsistent, and some studies have suggested positive but nonsignificant associations. Further, the impact of vitamin D on prostate cancer between Western and Japanese populations may differ due to different plasma vitamin D levels.


We performed a nested case-control study within the Japan Public Health Center-based Prospective (JPHC) Study in 14,203 men (40-69 years) who answered a self-administered questionnaire at baseline (1990-1994) and gave blood samples, and were followed until 2005. We identified 201 prostate cancers which are newly diagnosed during follow-up (mean 12.8 years). We selected two matched controls for each case from the cohort. We used a conditional logistic regression model to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for prostate cancer with respect to levels of 25-hydroxy vitamin D (25(OH)D) in plasma.


We did not observe statistically significant association between 25(OH)D level and total prostate cancer (multivariate OR=1.13 (95%CI=0.66-1.94, Ptrend=0.94) for the highest versus lowest tertile) However, 25(OH) levels were slightly positively associated with advanced cancer. The results remained substantially unchanged after stratification by intake of fish or calcium intake.


25(OH)D level showed no association with overall prostate cancer among Japanese men in this large cohort.


Serum uric acid is an independent predictor for developing prehypertension: a population-based prospective cohort study.

Liu L, Gu Y, Li C, Zhang Q, Meng G, Wu H, Du H, Shi H, Xia Y, Guo X, Liu X, Bao X, Su Q, Fang L, Yu F, Yang H, Yu B, Sun S, Wang X, Zhou M, Jia Q, Guo Q, Song K, Huang G, Wang G, Niu K.

J Hum Hypertens. 2017 Feb;31(2):116-120. doi: 10.1038/jhh.2016.48.

PMID: 27465981



Although the prevalence of prehypertension is rapidly increasing in China, the medical community has paid little attention to its prevention. Prior studies have demonstrated that uric acid directly contributes to vascular remodelling and endothelial dysfunction. However, few prospective studies have assessed the relationship between serum uric acid and prehypertension. We therefore designed a larger-scale cohort study to examine whether uric acid level is a predictive factor for developing prehypertension in adults. Participants were recruited from Tianjin Medical University General Hospital-Health Management Centre. A prospective assessment (n=15 143) was performed. Participants without a history of hypertension or prehypertension were followed up for 2 to 6 years with a median follow-up duration of 2.8 years. Serum uric acid levels and blood pressure were assessed yearly during the follow-up. Adjusted Cox proportional hazards regression models were used to assess relationships between the quintiles of uric acid levels and the incidence of prehypertension. The incidence of prehypertension was 191 per 1000 person-years. In the final multivariate models, the hazard ratios (95% confidence interval) for prehypertension across uric acid quintiles were 1.00 (reference), 0.98 (0.90-1.07), 1.01 (0.93-1.10), 1.09 (1.001-1.20) and 1.17 (1.06-1.29) (P for trend <0.001), respectively. This population-based prospective cohort study has demonstrated that uric acid level is an independent predictor for developing prehypertension.


Dementia risk linked to living close to high-traffic roads

Air pollutants could be a factor, but hypothesis remains unproven

CBC News Posted: Jan 04




Living close to heavy traffic roads, air pollution, and dementia

Lilian Calderón-Garcidueñas, Rodolfo Villarreal-Ríos

Lancet, in press, DOI: http://dx.doi.org/10.1016/S0140-6736(16)32596-X



Increases in chronic non-communicable diseases associated with changes in global economies and population ageing1 can be attributed at least partly to the exposure of urban populations to airborne particulate matter and other pervasive pollutants, poverty, dietary practices, and decreased levels of physical activity. Understanding the importance of particulate matter—a complex mixture of solid and liquid particles suspended in air2—is at the crux of world epidemiological associations with short-term and long-term cardiovascular morbidity and mortality.


Living near major roads and the incidence of dementia, Parkinson's disease, and multiple sclerosis: a population-based cohort study

Hong Chen, Jeffrey C Kwong, Ray Copes, Karen Tu, Paul J Villeneuve, Aaron van Donkelaar, Perry Hystad, Randall V Martin, Brian J Murray, Barry Jessiman, Andrew S Wilton, Alexander Kopp, Richard T Burnett

Lancet, in press, DOI: http://dx.doi.org/10.1016/S0140-6736(16)32399-6




Emerging evidence suggests that living near major roads might adversely affect cognition. However, little is known about its relationship with the incidence of dementia, Parkinson's disease, and multiple sclerosis. We aimed to investigate the association between residential proximity to major roadways and the incidence of these three neurological diseases in Ontario, Canada.


In this population-based cohort study, we assembled two population-based cohorts including all adults aged 20–50 years (about 4·4 million; multiple sclerosis cohort) and all adults aged 55–85 years (about 2·2 million; dementia or Parkinson's disease cohort) who resided in Ontario, Canada on April 1, 2001. Eligible patients were free of these neurological diseases, Ontario residents for 5 years or longer, and Canadian-born. We ascertained the individual's proximity to major roadways based on their residential postal-code address in 1996, 5 years before cohort inception. Incident diagnoses of dementia, Parkinson's disease, and multiple sclerosis were ascertained from provincial health administrative databases with validated algorithms. We assessed the associations between traffic proximity and incident dementia, Parkinson's disease, and multiple sclerosis using Cox proportional hazards models, adjusting for individual and contextual factors such as diabetes, brain injury, and neighbourhood income. We did various sensitivity analyses, such as adjusting for access to neurologists and exposure to selected air pollutants, and restricting to never movers and urban dwellers.


Between 2001, and 2012, we identified 243 611 incident cases of dementia, 31 577 cases of Parkinson's disease, and 9247 cases of multiple sclerosis. The adjusted hazard ratio (HR) of incident dementia was 1·07 for people living less than 50 m from a major traffic road (95% CI 1·06–1·08), 1·04 (1·02–1·05) for 50–100 m, 1·02 (1·01–1·03) for 101–200 m, and 1·00 (0·99–1·01) for 201–300 m versus further than 300 m (p for trend=0·0349). The associations were robust to sensitivity analyses and seemed stronger among urban residents, especially those who lived in major cities (HR 1·12, 95% CI 1·10–1·14 for people living <50 m from a major traffic road), and who never moved (1·12, 1·10–1·14 for people living <50 m from a major traffic road). No association was found with Parkinson's disease or multiple sclerosis.


In this large population-based cohort, living close to heavy traffic was associated with a higher incidence of dementia, but not with Parkinson's disease or multiple sclerosis.


Correlation between visit-to-visit and short-term blood pressure variability calculated using different methods and glomerular filtration rate.

Wang J, Jiang B, Song L, Yang C, Wu Y, Chen S, Li C, Zhao H, Wang F, Wu S.

J Hum Hypertens. 2017 Feb;31(2):132-137. doi: 10.1038/jhh.2016.51.

PMID: 27488611



The aim of this study was to explore the correlation between visit-to-visit and short-term blood pressure variability (BPV), including systolic BPV (SBPV) and diastolic BPV (DBPV), calculated using different methods, and the glomerular filtration rate (GFR) in a late, middle-aged population. Using cluster sampling, we randomly selected retired employees of the Kailuan Group who were ⩾60 years and participated in a third health examination for 24-h ambulatory blood pressure monitoring and inspection. Among the 3064 randomly selected observation subjects, 2464 were included based on the criteria. BPV was calculated using s.d., coefficient of variation (CV, s.d./Mean), variability independent of mean (VIM, s.d./Meanx) and BPV ratio (BPVR, s.d. (SBPV)/s.d. (DBPV)). Multivariate linear regression was used to analyse the correlation between estimated GFR (eGFR) and BPV calculated using different methods. The mean age of 2464 subjects was 67.4±6.1 years, with 1667 male subjects (67.7%). A total of 2104 cases were included in the visit-to-visit BPV group, and 1382 in the short-term BPV group. SBPV calculated using different methods showed statistically significant increasing trends for the SBP versus all s.d. and short-term BPVR. There was a significant, positive correlation between the visit-to-visit and short-term BPV calculated using different methods, which were all negatively correlated with eGFR (P<0.05). Multivariate linear regression analysis showed that, with correction for possible confounding factors, SBPV (24-h s.d., CV and VIM, and daytime CV and night time CV) and all DBPV demonstrated negative linear relationships with eGFR (P<0.05).


Relationship Between Ties With Adult Children and Life Satisfaction Among the Middle-Aged, the Young-Old, and the Oldest-Old Korean Adults.

Chai HW, Jun HJ.

Int J Aging Hum Dev. 2016 Jan 1:91415016685834. doi: 10.1177/0091415016685834. [Epub ahead of print]

PMID: 28042718


One of the important determinants of well-being among aging parents is their relationship with adult children. Using the two waves of the Korean Longitudinal Study of Ageing, this study examined how different types of ties with adult children affect the life satisfaction of the Korean middle-aged, the young-old, and the oldest-old adults. Multigroup analysis was used to see if the effects of ties with adult children differ by the three age-groups. The results showed that frequency of contact had positive effect on life satisfaction for all of the age-groups. However, coresidence with children had a negative effect for the middle-aged, but a positive effect for the oldest-old. Finally, exchanges of support with adult children had significant effects only for the young-old. These results show that the importance of different types of ties with children change according to aging parents' life stages.


intergenerational relationships; life satisfaction; multigroup analysis; the middle-aged; the oldest-old; the young-old


[Offspriing of centenarians may have been better subjects to chose to study.]

The gut microbiota of centenarians: Signatures of longevity in the gut microbiota profile.

Elena B, Rampelli S, Turroni S, Quercia S, Marco C, Patrizia B.

Mech Ageing Dev. 2016 Dec 31. pii: S0047-6374(16)30171-3. doi: 10.1016/j.mad.2016.12.013. [Epub ahead of print] Review.

PMID: 28049008



The changing physiology and lifestyle of elderly people affect the gut microbiota composition, the changes of which can, in turn, affect the health maintenance of the ageing host. In a co-evolutionary vision of the relationship between gut microbiota and ageing as an adaptive process of the human superorganism, long-living individuals who get to "successfully" age might be the ones whose microbiota manages to continuously re-establish a mutualistic relationship with the host, adapting to the progressive endogenous and environmental changes. The study of the gut microbiota of long-living people might provide insights on whether and how the gut microbiota can contribute to health maintenance and survival. Here, we provide the state of the art on the study of the gut microbiota in ageing and longevity, with particular attention to the perspective and direction this peculiar field of the microbiota research should take, in order to be a starting point for future mechanistic, pharmacological and clinical studies in ageing research. In particular, longevous people having different genetic, environmental, and cultural background must be analyzed and compared in the attempt to describe "universal" longevity dynamics, useful to unravel how the gut microbial ecosystem can help in expanding human healthspan.


Centenarians; Gut microbiota; Longevity

"According to this study, the

centenarian gut microbiome shows a proteolytic propensity, being enriched in genes involved in the

metabolism of aromatic amino acids (eg. tryptophan and phenylalanine), tyrosine, valine and lysine,

while correspondingly depleted in functions involved in carbohydrate metabolism."

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Bending the blood pressure curve down: are we succeeding?

Published Online

November 15, 2016



See Articles page 37

www.thelancet.com Vol 389 January 7, 2017 3-4



Refers To

NCD Risk Factor Collaboration (NCD-RisC)

Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19·1 million participants

The Lancet, Volume 389, Issue 10064, 7–13 January 2017, Pages 37-55




Raised blood pressure is an important risk factor for cardiovascular diseases and chronic kidney disease. We estimated worldwide trends in mean systolic and mean diastolic blood pressure, and the prevalence of, and number of people with, raised blood pressure, defined as systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher.


For this analysis, we pooled national, subnational, or community population-based studies that had measured blood pressure in adults aged 18 years and older. We used a Bayesian hierarchical model to estimate trends from 1975 to 2015 in mean systolic and mean diastolic blood pressure, and the prevalence of raised blood pressure for 200 countries. We calculated the contributions of changes in prevalence versus population growth and ageing to the increase in the number of adults with raised blood pressure.


We pooled 1479 studies that had measured the blood pressures of 19·1 million adults. Global age-standardised mean systolic blood pressure in 2015 was 127·0 mm Hg (95% credible interval 125·7–128·3) in men and 122·3 mm Hg (121·0–123·6) in women; age-standardised mean diastolic blood pressure was 78·7 mm Hg (77·9–79·5) for men and 76·7 mm Hg (75·9–77·6) for women. Global age-standardised prevalence of raised blood pressure was 24·1% (21·4–27·1) in men and 20·1% (17·8–22·5) in women in 2015. Mean systolic and mean diastolic blood pressure decreased substantially from 1975 to 2015 in high-income western and Asia Pacific countries, moving these countries from having some of the highest worldwide blood pressure in 1975 to the lowest in 2015. Mean blood pressure also decreased in women in central and eastern Europe, Latin America and the Caribbean, and, more recently, central Asia, Middle East, and north Africa, but the estimated trends in these super-regions had larger uncertainty than in high-income super-regions. By contrast, mean blood pressure might have increased in east and southeast Asia, south Asia, Oceania, and sub-Saharan Africa. In 2015, central and eastern Europe, sub-Saharan Africa, and south Asia had the highest blood pressure levels. Prevalence of raised blood pressure decreased in high-income and some middle-income countries; it remained unchanged elsewhere. The number of adults with raised blood pressure increased from 594 million in 1975 to 1·13 billion in 2015, with the increase largely in low-income and middle-income countries. The global increase in the number of adults with raised blood pressure is a net effect of increase due to population growth and ageing, and decrease due to declining age-specific prevalence.


During the past four decades, the highest worldwide blood pressure levels have shifted from high-income countries to low-income countries in south Asia and sub-Saharan Africa due to opposite trends, while blood pressure has been persistently high in central and eastern Europe.


Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity.

Wahl S, Drong A, Lehne B, Loh M, Scott WR, Kunze S, Tsai PC, Ried JS, Zhang W, Yang Y, Tan S, Fiorito G, Franke L, Guarrera S, Kasela S, Kriebel J, Richmond RC, Adamo M, Afzal U, Ala-Korpela M, Albetti B, Ammerpohl O, Apperley JF, Beekman M, Bertazzi PA, Black SL, Blancher C, Bonder MJ, Brosch M, Carstensen-Kirberg M, de Craen AJ, de Lusignan S, Dehghan A, Elkalaawy M, Fischer K, Franco OH, Gaunt TR, Hampe J, Hashemi M, Isaacs A, Jenkinson A, Jha S, Kato N, Krogh V, Laffan M, Meisinger C, Meitinger T, Mok ZY, Motta V, Ng HK, Nikolakopoulou Z, Nteliopoulos G, Panico S, Pervjakova N, Prokisch H, Rathmann W, Roden M, Rota F, Rozario MA, Sandling JK, Schafmayer C, Schramm K, Siebert R, Slagboom PE, Soininen P, Stolk L, Strauch K, Tai ES, Tarantini L, Thorand B, Tigchelaar EF, Tumino R, Uitterlinden AG, van Duijn C, van Meurs JB, Vineis P, Wickremasinghe AR, Wijmenga C, Yang TP, Yuan W, Zhernakova A, Batterham RL, Smith GD, Deloukas P, Heijmans BT, Herder C, Hofman A, Lindgren CM, Milani L, van der Harst P, Peters A, Illig T, Relton CL, Waldenberger M, Järvelin MR, Bollati V, Soong R, Spector TD, Scott J, McCarthy MI, Elliott P, Bell JT, Matullo G, Gieger C, Kooner JS, Grallert H, Chambers JC.

Nature. 2017 Jan 5;541(7635):81-86. doi: 10.1038/nature20784.

PMID: 28002404



Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances. Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation, a key regulator of gene expression and molecular phenotype. Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 × 10-7, range P = 9.2 × 10-8 to 6.0 × 10-46; n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 × 10-6, range P = 5.5 × 10-6 to 6.1 × 10-35, n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07-2.56); P = 1.1 × 10-54). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity.


Nutrition Across the Lifespan for Healthy Aging: Proceedings of a Workshop—in Brief.

National Academies of Sciences, Engineering, and Medicine, Health and Medicine Division, Food and Nutrition Board, Food Forum.

Washington (DC): National Academies Press (US); 2016 Dec 29.

PMID: 28055151 Free Books & Documents



On September 13-14, 2016, the National Academies of Sciences, Engineering, and Medicine's Food Forum convened a workshop in Washington, DC, to (1) examine trends and patterns in aging and factors related to healthy aging in the United States with a focus on nutrition; (2) examine how nutrition can sustain and promote healthy aging, not only in late adulthood, but beginning in pregnancy and early childhood and extending throughout the lifespan; (3) highlight the role of nutrition in the aging process at various stages in life; (4) discuss changes in organ systems over the lifespan, including the skeletal, muscular, and cardiovascular systems, and changes that occur with age related to cognitive, brain, and mental health; diet-related sensory preferences; oral health; and the microbiome; and (5) explore opportunities to move forward in promoting healthy aging in the United States. This Proceedings of a Workshop-in Brief summarizes key points of the workshop presentations and discussions. A comprehensive summary of the workshop will be publicly available in a forthcoming full-length Proceedings of a Workshop.

"Gordon Jensen, University of Vermont College of Medicine, emphasized the existence of a large body of literature that obesity is a much stronger predictor of all-cause mortality at younger ages (in children and young adults) than at older ages. He also provided an overview of the growing body of data supporting the so-called obesity paradox, beginning with a 2013 review paper by epidemiologist Katherine Flegal and colleagues showing that, compared to a “desirable” body mass index (BMI) (i.e., normal weight), class II and III obesity were associated with significantly greater all-cause mortality, while in contrast, class I obesity was not associated with higher mortality, and overweight was associated with significantly lower mortality.3 Flegal's work, Jensen said, started a “raging controversy,” a key issue being how to interpret its findings for health professionals and the public. In Jensen's opinion, the obesity paradox may be explained, at least in part, by body composition and a subset of what he described as “pretty robust healthy overweight and mildly obese older people”—as recent work from his research group has shown that overweight in older adults is protective only in patients with high muscle mass. He concluded by noting that it is safe to say that obesity does not generally confer mortality or health benefits, as such, rather than changing BMI guidelines for older persons, it is the use of the current guidelines that warrants re-evaluation."


Dietary total flavonoids intake and risk of mortality from all causes and cardiovascular disease in the general population: a systematic review and meta-analysis of cohort studies.

Liu XM, Liu YJ, Huang Y, Yu HJ, Yuan S, Tang BW, Wang PG, He QQ.

Mol Nutr Food Res. 2017 Jan 5. doi: 10.1002/mnfr.201601003. [Epub ahead of print] Review.

PMID: 28054441




Epidemiologic studies assessing the association between dietary total flavonoids intake and the risk of mortality from cardiovascular disease (CVD) and all causes have yielded inconsistent results. Therefore, we conducted a dose-response meta-analysis to investigate this association.


We searched PubMed and Embase databases from January 1966 through May 2016 and examined the references of retrieved articles to identify relevant prospective cohort studies. The random-effect model was used to calculate the summary risk estimates and dose-response analysis was performed.


Ten studies were included in the present meta-analysis. The relative risk (RR) of all-cause mortality for the highest versus lowest category of total flavonoids intake was 0.82 (95% confidence interval (CI): 0.72-0.92). Dose-response analysis showed that those consuming 200mg/d of total flavonoids had the lowest risk of all-cause mortality. Furthermore, a marginally significant association was found between dietary total flavonoids consumption and risk of death from CVD (summary RR: 0.85; 95% CI: 0.70-1.03; P = 0.099) and coronary heart diseases (CHD) (summary RR: 0.74; 95% CI: 0.54-1.02; P = 0.069), respectively.


The meta-analysis provides strong evidence for the recommendation of consuming flavonoids-rich food to reduce risks of mortality from all causes as part of a healthy diet among general adults.


CVD; flavonoids; meta-analysis; mortality; prospective cohort study


A 3-Arm Randomized Trial for Achilles Tendinopathy: Eccentric Training, Eccentric Training Plus a Dietary Supplement Containing Mucopolysaccharides, or Passive Stretching Plus a Dietary Supplement Containing Mucopolysaccharides.

Balius R, Álvarez G, Baró F, Jiménez F, Pedret C, Costa E, Martínez-Puig D.

Curr Ther Res Clin Exp. 2016 Nov 18;78:1-7. doi: 10.1016/j.curtheres.2016.11.001.

PMID: 28053674





Tendinopathy is an overuse tendon injury that occurs in loaded tendons and results in pain and functional impairment. Although many treatments for painful tendons are described, the scientific evidence for most of the conservative and surgical treatments is not always conclusive.


This study was designed to evaluate the efficacy of 3 different interventions in patients with Achilles tendinopathy. The interventions include the combination of 2 physical therapy programs (eccentric training [EC] or passive stretching [PS]) with a supplement containing mucopolisaccharides. The efficacy of the interventions was evaluated depending on the stage of the disease.


Fifty-nine patients were randomly assigned to 1 of 3 treatment groups, and classified according to the disease stage: reactive versus degenerative tendinopathy. Treatment groups were EC; EC + a dietary supplement containing mucopolisaccharides, type I collagen, and vitamin C (MCVC); and a passive stretching program + MCVC. Patients were evaluated at baseline, 6 weeks, and 12 weeks with the Victorian Institute of Sports Assessment-Achilles questionnaire for function, a visual analog scale for pain, and ultrasound characterization for the evolution of tendon structure.


A significant improvement in Victorian Institute of Sports Assessment-Achilles questionnaire score, pain at rest, and pain during activity were detected in all 3 treatment groups at 6 and 12 weeks' follow-up when compared with baseline. In patients with reactive tendinopathy, the reduction in pain at rest was greater in the groups who took the supplemental MCVC than in the EC alone group (P < 0.05).


MCVC seems to be therapeutically useful for management of tendinopathies, providing some additional benefit to physical therapy. This is especially evident in early stages of the disease, when the tendon does not present severe matrix and vascular changes.


eccentric training; food supplement; passive stretching; tendinopathy


Grilled, Barbecued, and Smoked Meat Intake and Survival Following Breast Cancer.

Parada H Jr, Steck SE, Bradshaw PT, Engel LS, Conway K, Teitelbaum SL, Neugut AI, Santella RM, Gammon MD.

J Natl Cancer Inst. 2017 Jan 4. pii: djw299. doi: 10.1093/jnci/djw299. [Epub ahead of print]

PMID: 28052933




Grilled, barbecued, and smoked meat intake, a prevalent dietary source of polycyclic aromatic hydrocarbon (PAH) carcinogens, may increase the risk of incident breast cancer. However, no studies have examined whether intake of this PAH source influences survival after breast cancer.


We interviewed a population-based cohort of 1508 women diagnosed with first primary invasive or in situ breast cancer in 1996 and 1997 at baseline and again approximately five years later to assess grilled/barbecued and smoked meat intake. After a median of 17.6 years of follow-up, 597 deaths, of which 237 were breast cancer related, were identified. Multivariable Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality as related to prediagnosis intake, comparing high (above the median) to low intake, as well as postdiagnosis changes in intake, comparing every combination of pre-/postdiagnosis intake to low pre-/postdiagnosis intake. All statistical tests were two-sided.


High prediagnosis grilled/barbecued and smoked meat intake was associated with increased risk of all-cause mortality (HR = 1.23, 95% CI = 1.03 to 1.46). Other associations were noted, but estimates were not statistically significant. These include high prediagnosis smoked beef/lamb/pork intake and increased all-cause (HR = 1.17, 95% CI = 0.99 to 1.38, Ptrend = .10) and breast cancer-specific (HR = 1.23, 95% CI = 0.95 to 1.60, Ptrend = .09) mortality. Also, among women with continued high grilled/barbecued and smoked meat intake after diagnosis, all-cause mortality risk was elevated 31% (HR = 1.31, 95% CI = 0.96 to 1.78). Further, breast cancer-specific mortality was decreased among women with any pre- and postdiagnosis intake of smoked poultry/fish (HR = 0.55, 95% CI = 0.31 to 0.97).


High intake of grilled/barbecued and smoked meat may increase mortality after breast cancer.


Association of TSH Elevation with All-Cause Mortality in Elderly Patients with Chronic Kidney Disease.

Chuang MH, Liao KM, Hung YM, Chou YC, Chou P.

PLoS One. 2017 Jan 3;12(1):e0168611. doi: 10.1371/journal.pone.0168611.

PMID: 28045962




Chronic kidney disease (CKD) is a widespread condition in the global population and is more common in the elderly. Thyroid-stimulating hormone (TSH) level increases with aging, and hypothyroidism is highly prevalent in CKD patients. However, the relationship between low thyroid function and mortality in CKD patients is unclear. Therefore, we conducted a retrospective cohort study to examine the relationship between TSH elevation and all-cause mortality in elderly patients with CKD. This retrospective cohort study included individuals ≥65 years old with CKD (n = 23,786) in Taipei City. Health examination data from 2005 to 2010 were provided by the Taipei Databank for Public Health Analysis. Subjects were categorized according to thyroid-stimulating hormone (TSH) level as follows: low normal (0.34<TSH<1.074 mIU/L), middle normal (1.074≤TSH≤2.46 mIU/L), high normal (2.46<TSH<5.2 mIU/L), elevated I (5.2≤TSH<10 mIU/L), and elevated II (TSH≥10 mIU/L). Risk of mortality was evaluated using a Cox proportional hazard regression model adjusted for sex, age, hypertension, diabetes mellitus, CKD stage, serum albumin, high-density lipoprotein cholesterol, uric acid, hemoglobin, body mass index, glutamic-pyruvic transaminase, smoking, alcohol consumption, and history of cardiovascular disease (coronary artery disease, congestive heart failure, cerebral vascular disease), history of cancer, and history of chronic obstructive pulmonary disease. Our results showed that compared to the reference group (middle normal TSH), the risk of all-cause mortality was increased in the elevated I group (hazard ratio {HR}, 1.21; 95% confidence interval [CI], 1.02-1.45) and elevated II group (HR, 1.30; 95% CI, 1.00-1.69). We found a significant association between TSH elevation and all-cause mortality in this cohort of elderly persons with CKD. However, determining the benefit of treatment for moderately elevated TSH level (5.2-10 mIU/L) in elderly patients with CKD will require a well-designed randomized controlled trial.


Subclinical Thyroid Disease and Mortality in the Elderly: A Retrospective Cohort Study.

Grossman A, Weiss A, Koren-Morag N, Shimon I, Beloosesky Y, Meyerovitch J.

Am J Med. 2016 Apr;129(4):423-30. doi: 10.1016/j.amjmed.2015.11.027.

PMID: 26714213





The association between subclinical hypothyroidism and hyperthyroidism and mortality in the elderly is poorly defined. This study was designed to evaluate the association between subclinical hypothyroidism and subclinical hyperthyroidism and mortality in the elderly and to define the thyroid-stimulating hormone values associated with excess mortality in the elderly.


We performed a retrospective cohort study with a review of a computerized database of a large health care organization. Patients aged more than 65 years evaluated in the years 2002 to 2012 with documented normal free T4 values were included in the analysis. All cases of known thyroid disease or cases in which thyroid medications were dispensed were excluded. Analysis was performed only on individuals who were not treated for hyperthyroidism or hypothyroidism during the follow-up period. Subjects were divided into 3 groups based on thyroid-stimulating hormone values: normal (normal thyroid-stimulating hormone), subclinical hypothyroidism (thyroid-stimulating hormone >4.2 mIU/L), and subclinical hyperthyroidism (thyroid-stimulating hormone <0.35 mIU/L). All-cause mortality hazard ratio (HR) was compared among the 3 groups, and a subanalysis according to thyroid-stimulating hormone values was performed in those with subclinical hypothyroidism and subclinical hyperthyroidism.


A final analysis was performed on 17,440 individuals with subclinical thyroid disease (538 with subclinical hyperthyroidism [3.1%], 1956 with subclinical hypothyroidism [11.2%], 14,946 normal cases [85.7%], average age of 83 years, 10,289 were women) who were followed up for 10 years. Both subclinical hypothyroidism (HR, 1.75; confidence interval [CI], 1.63-1.88) and subclinical hyperthyroidism (HR, 2.33; CI, 2.08-2.63) were associated with significantly increased mortality, and this association persisted on multivariate analysis (subclinical hypothyroidism HR, 1.68; CI, 1.56-1.8, subclinical hyperthyroidism HR, 1.93; CI, 1.7-2.17). Crude mortality was elevated at 1, 2, and 5 years, but this association seemed to decrease as time from initial analysis increased (most significant association at 1 year). Thyroid-stimulating hormone values greater than 6.38 mIU/L were associated with the highest mortality in those with subclinical hypothyroidism after multivariate adjustment (HR, 1.708; CI, 1.38-2.12), whereas in subclinical hyperthyroidism, no threshold for increased mortality was identified. Mortality was higher.


Both subclinical hypothyroidism and subclinical hyperthyroidism are associated with increased mortality in the elderly. A threshold thyroid-stimulating hormone value (>6.35 mIU/L) exists for increased mortality in subclinical hypothyroidism, but not in subclinical hyperthyroidism.


Elderly; Mortality; Subclinical hyperthyroidism; Subclinical hypothyroidism


Subclinical hypothyroidism and the risk of coronary heart disease and mortality.

Rodondi N, den Elzen WP, Bauer DC, Cappola AR, Razvi S, Walsh JP, Asvold BO, Iervasi G, Imaizumi M, Collet TH, Bremner A, Maisonneuve P, Sgarbi JA, Khaw KT, Vanderpump MP, Newman AB, Cornuz J, Franklyn JA, Westendorp RG, Vittinghoff E, Gussekloo J; Thyroid Studies Collaboration..

JAMA. 2010 Sep 22;304(12):1365-74. doi: 10.1001/jama.2010.1361.

PMID: 20858880 Free PMC Article





Data regarding the association between subclinical hypothyroidism and cardiovascular disease outcomes are conflicting among large prospective cohort studies. This might reflect differences in participants' age, sex, thyroid-stimulating hormone (TSH) levels, or preexisting cardiovascular disease.


To assess the risks of coronary heart disease (CHD) and total mortality for adults with subclinical hypothyroidism.


The databases of MEDLINE and EMBASE (1950 to May 31, 2010) were searched without language restrictions for prospective cohort studies with baseline thyroid function and subsequent CHD events, CHD mortality, and total mortality. The reference lists of retrieved articles also were searched.


Individual data on 55,287 participants with 542,494 person-years of follow-up between 1972 and 2007 were supplied from 11 prospective cohorts in the United States, Europe, Australia, Brazil, and Japan. The risk of CHD events was examined in 25,977 participants from 7 cohorts with available data. Euthyroidism was defined as a TSH level of 0.50 to 4.49 mIU/L. Subclinical hypothyroidism was defined as a TSH level of 4.5 to 19.9 mIU/L with normal thyroxine concentrations.


Among 55,287 adults, 3450 had subclinical hypothyroidism (6.2%) and 51,837 had euthyroidism. During follow-up, 9664 participants died (2168 of CHD), and 4470 participants had CHD events (among 7 studies). The risk of CHD events and CHD mortality increased with higher TSH concentrations. In age- and sex-adjusted analyses, the hazard ratio (HR) for CHD events was 1.00 (95% confidence interval [CI], 0.86-1.18) for a TSH level of 4.5 to 6.9 mIU/L (20.3 vs 20.3/1000 person-years for participants with euthyroidism), 1.17 (95% CI, 0.96-1.43) for a TSH level of 7.0 to 9.9 mIU/L (23.8/1000 person-years), and 1.89 (95% CI, 1.28-2.80) for a TSH level of 10 to 19.9 mIU/L (n = 70 events/235; 38.4/1000 person-years; P <.001 for trend). The corresponding HRs for CHD mortality were 1.09 (95% CI, 0.91-1.30; 5.3 vs 4.9/1000 person-years for participants with euthyroidism), 1.42 (95% CI, 1.03-1.95; 6.9/1000 person-years), and 1.58 (95% CI, 1.10-2.27, n = 28 deaths/333; 7.7/1000 person-years; P = .005 for trend). Total mortality was not increased among participants with subclinical hypothyroidism. Results were similar after further adjustment for traditional cardiovascular risk factors. Risks did not significantly differ by age, sex, or preexisting cardiovascular disease.


Subclinical hypothyroidism is associated with an increased risk of CHD events and CHD mortality in those with higher TSH levels, particularly in those with a TSH concentration of 10 mIU/L or greater.


Abnormal Thyroid-Stimulating Hormone and Chronic Kidney Disease in Elderly Adults in Taipei City.

Chuang MH, Liao KM, Hung YM, Wang PY, Chou YC, Chou P.

J Am Geriatr Soc. 2016 Jun;64(6):1267-73. doi: 10.1111/jgs.14102.

PMID: 27321605





To examine whether older people with abnormal thyroid function are more likely to develop chronic kidney disease (CKD) over a 5-year follow-up period.


Retrospective cohort study.


Health examination data from the Taipei Databank for Public Health Analysis.


Individuals aged 65 and older (N = 41,454).


Thyroid-stimulating hormone (TSH) levels were repeatedly measured, and subjects were categorized into four thyroid function groups (hyperthyroid, euthyroid, subclinical hypothyroid, overt hypothyroid). The risk of incident CKD was evaluated using a stepwise Cox proportional hazards regression model adjusted for sex, baseline age, hypertension, diabetes mellitus (DM), dyslipidemia, hyperuricemia, anemia, obesity, liver function, smoking, and alcohol.


Higher TSH levels were associated with greater risk of subsequent CKD. Individuals with subclinical hypothyroidism (hazard ratio (HR) = 1.15, 95% confidence interval (CI) = 1.05-1.26) and those with overt hypothyroidism (HR = 1.27, 95% CI = 1.04-1.55) were more likely than those who were euthyroid to have CKD. Women were more likely to have CKD than men (HR = 1.11, 95% CI = 1.06-1.16). When stratified by gender, subclinical hypothyroidism in women was associated with an increased risk of developing CKD (HR = 1.22; 95% CI = 1.08-1.39). When stratified by DM, subclinical hypothyroidism and overt hypothyroidism were associated with an increased risk of developing CKD in nondiabetics (HR = 1.19; 95% CI = 1.07-1.31; and HR = 1.34; 95% CI = 1.08-1.65, respectively).


This cohort study of elderly persons in Taipei City found a significant association between hypothyroidism and development of CKD in women and individuals without DM.


chronic kidney disease; glomerular filtration rate; hypothyroidism; proteinuria; thyroid-stimulating hormone


Vegetarian diet and all-cause mortality: Evidence from a large population-based Australian cohort - the 45 and Up Study.

Mihrshahi S, Ding D, Gale J, Allman-Farinelli M, Banks E, Bauman AE.

Prev Med. 2016 Dec 28. pii: S0091-7435(16)30447-9. doi: 10.1016/j.ypmed.2016.12.044. [Epub ahead of print]

PMID: 28040519



The vegetarian diet is thought to have health benefits including reductions in type 2 diabetes, hypertension, and obesity. Evidence to date suggests that vegetarians tend to have lower mortality rates when compared with non-vegetarians, but most studies are not population-based and other healthy lifestyle factors may have confounded apparent protective effects. The aim of this study was to evaluate the association between categories of vegetarian diet (including complete, semi and pesco-vegetarian) and all-cause mortality in a large population-based Australian cohort. The 45 and Up Study is a cohort study of 267,180 men and women aged ≥45years in New South Wales (NSW), Australia. Vegetarian diet status was assessed by baseline questionnaire and participants were categorized into complete vegetarians, semi-vegetarians (eat meat≤once/week), pesco-vegetarians and regular meat eaters. All-cause mortality was determined by linked registry data to mid-2014. Cox proportional hazards models quantified the association between vegetarian diet and all-cause mortality adjusting for a range of potential confounding factors. Among 243,096 participants (mean age: 62.3years, 46.7% men) there were 16,836 deaths over a mean 6.1years of follow-up. Following extensive adjustment for potential confounding factors there was no significant difference in all-cause mortality for vegetarians versus non-vegetarians [hr hr=1.16 (95% CI 0.93-1.45)]. There was also no significant difference in mortality risk between pesco-vegetarians [hr hr=0.79 (95% CI 0.59-1.06)] or semi-vegetarians [hr hr=1.12 (95% CI 0.96-1.31)] versus regular meat eaters. We found no evidence that following a vegetarian diet, semi-vegetarian diet or a pesco-vegetarian diet has an independent protective effect on all-cause mortality.


Diet; Mortality; Non-vegetarian; Pesco-vegetarian; Semi-vegetarian; Vegetarian


The Impact of Gastric Atrophy on the Incidence of Diabetes.

Yu TY, Wei JN, Kuo CH, Liou JM, Lin MS, Shih SR, Hua CH, Hsein YC, Hsu YW, Chuang LM, Lee MK, Hsiao CH, Wu MS, Li HY.

Sci Rep. 2017 Jan 3;7:39777. doi: 10.1038/srep39777.

PMID: 28045079




Gastric atrophy results in lower plasma ghrelin, higher gastrin secretion, a change in gut microbiota, and altered dietary nutrient absorption, which may be associated with the incidence of diabetes. Helicobacter pylori (H. pylori) infection is a major cause of gastric atrophy and is associated with diabetes in some reports. Since there is no study which investigates the impact of gastric atrophy on diabetes, we conduct a prospective cohort study to examine the relationship between H. pylori infection, gastric atrophy, and incident diabetes. In this study, subjects with gastric atrophy had a lower risk of incident diabetes, compared to those without gastric atrophy. The extent of gastric atrophy, measured by serum pepsinogen (PG) I/II ratio, was correlated with age, H. pylori IgG titer, HOMA2-IR, and HOMA2%B. When gastric atrophy is more extensive, presented as a lower serum PG I/II ratio, the risk of incident diabetes is lower. On the other hand, there was no significant association between H. pylori infection and the incidence of diabetes. In conclusion, the presence and the extent of gastric atrophy, but not H. pylori infection, are associated with incident diabetes. Further studies are needed to investigate the detailed mechanisms and the potential applications of the findings to guide diabetes screening and treatment strategies.


Optimism and Cause-Specific Mortality: A Prospective Cohort Study.

Kim ES, Hagan KA, Grodstein F, DeMeo DL, De Vivo I, Kubzansky LD.

Am J Epidemiol. 2016 Dec 7. [Epub ahead of print]

PMID: 27927621



Growing evidence has linked positive psychological attributes like optimism to a lower risk of poor health outcomes, especially cardiovascular disease. It has been demonstrated in randomized trials that optimism can be learned. If associations between optimism and broader health outcomes are established, it may lead to novel interventions that improve public health and longevity. In the present study, we evaluated the association between optimism and cause-specific mortality in women after considering the role of potential confounding (sociodemographic characteristics, depression) and intermediary (health behaviors, health conditions) variables. We used prospective data from the Nurses' Health Study (n = 70,021). Dispositional optimism was measured in 2004; all-cause and cause-specific mortality rates were assessed from 2006 to 2012. Using Cox proportional hazard models, we found that a higher degree of optimism was associated with a lower mortality risk. After adjustment for sociodemographic confounders, compared with women in the lowest quartile of optimism, women in the highest quartile had a hazard ratio of 0.71 (95% confidence interval: 0.66, 0.76) for all-cause mortality. Adding health behaviors, health conditions, and depression attenuated but did not eliminate the associations (hazard ratio = 0.91, 95% confidence interval: 0.85, 0.97). Associations were maintained for various causes of death, including cancer, heart disease, stroke, respiratory disease, and infection. Given that optimism was associated with numerous causes of mortality, it may provide a valuable target for new research on strategies to improve health.


health psychology; optimism; psychological well-being; resilience


Ambient Fine Particulate Matter, Outdoor Temperature, and Risk of Metabolic Syndrome.

Wallwork RS, Colicino E, Zhong J, Kloog I, Coull BA, Vokonas P, Schwartz JD, Baccarelli AA.

Am J Epidemiol. 2016 Dec 7. [Epub ahead of print]

PMID: 27927620



Ambient air pollution and temperature have been linked with cardiovascular morbidity and mortality. Metabolic syndrome and its components-abdominal obesity, elevated fasting blood glucose concentration, low high-density lipoprotein cholesterol concentration, hypertension, and hypertriglyceridemia-predict cardiovascular disease, but the environmental causes are understudied. In this study, we prospectively examined the long-term associations of air pollution, defined as particulate matter with an aerodynamic diameter less than or equal to 2.5 µm (PM2.5), and temperature with the development of metabolic syndrome and its components. Using covariate-adjustment Cox proportional hazards models, we estimated associations of mean annual PM2.5 concentration and temperature with risk of incident metabolic dysfunctions between 1993 and 2011 in 587 elderly (mean = 70 (standard deviation, 7) years of age) male participants in the Normative Aging Study. A 1-μg/m3 increase in mean annual PM2.5 concentration was associated with a higher risk of developing metabolic syndrome (hazard ratio (HR) = 1.27, 95% confidence interval (CI): 1.06, 1.52), an elevated fasting blood glucose level (HR = 1.20, 95% CI: 1.03, 1.39), and hypertriglyceridemia (HR = 1.14, 95% CI: 1.00, 1.30). Our findings for metabolic syndrome and high fasting blood glucose remained significant for PM2.5 levels below the Environmental Protection Agency's health-safety limit (12 μg/m3). A 1°C increase in mean annual temperature was associated with a higher risk of developing elevated fasting blood glucose (HR = 1.33, 95% CI: 1.14, 1.56). Men living in neighborhoods with worse air quality-with higher PM2.5 levels and/or temperatures than average-showed increased risk of developing metabolic dysfunctions.


air pollution; blood glucose; high-density lipoprotein cholesterol; hypertension; metabolic syndrome; obesity; temperature; triglycerides


Dissociation of muscle insulin sensitivity from exercise endurance in mice by HDAC3 depletion.

Hong S, Zhou W, Fang B, Lu W, Loro E, Damle M, Ding G, Jager J, Zhang S, Zhang Y, Feng D, Chu Q, Dill BD, Molina H, Khurana TS, Rabinowitz JD, Lazar MA, Sun Z.

Nat Med. 2016 Dec 19. doi: 10.1038/nm.4245. [Epub ahead of print]

PMID: 27991918



Type 2 diabetes and insulin resistance are associated with reduced glucose utilization in the muscle and poor exercise performance. Here we find that depletion of the epigenome modifier histone deacetylase 3 (HDAC3) specifically in skeletal muscle causes severe systemic insulin resistance in mice but markedly enhances endurance and resistance to muscle fatigue, despite reducing muscle force. This seemingly paradoxical phenotype is due to lower glucose utilization and greater lipid oxidation in HDAC3-depleted muscles, a fuel switch caused by the activation of anaplerotic reactions driven by AMP deaminase 3 (Ampd3) and catabolism of branched-chain amino acids. These findings highlight the pivotal role of amino acid catabolism in muscle fatigue and type 2 diabetes pathogenesis. Further, as genome occupancy of HDAC3 in skeletal muscle is controlled by the circadian clock, these results delineate an epigenomic regulatory mechanism through which the circadian clock governs skeletal muscle bioenergetics. These findings suggest that physical exercise at certain times of the day or pharmacological targeting of HDAC3 could potentially be harnessed to alter systemic fuel metabolism and exercise performance.


Increased intermediate M1-M2 macrophage polarization and improved cognition in mild cognitive impairment patients on ω-3 supplementation.

Famenini S, Rigali EA, Olivera-Perez HM, Dang J, Chang MT, Halder R, Rao RV, Pellegrini M, Porter V, Bredesen D, Fiala M.

FASEB J. 2017 Jan;31(1):148-160. doi: 10.1096/fj.201600677RR.

PMID: 27677546 Free PMC Article



Monocyte/macrophages of patients with mild cognitive impairment (MCI) and Alzheimer disease (AD) are defective in phagocytosis and degradation amyloid β1-42 (Aβ1-42), but are improved by ω-3 fatty acids (ω-3s). The hypothesis of this study was that active Aβ1-42 phagocytosis by macrophages prevents brain amyloidosis and thus maintains cognition. We studied the effects of self-supplementation with a drink with ω-3s, antioxidants, and resveratrol on Mini-Mental State Examination (MMSE) scores, macrophage M1M2 phenotype [the ratio of inflammatory cluster of differentiation (CD)54+CD80 and proresolution markers CD163+CD206], and Aβ1-42 phagocytosis in patients initially diagnosed as having MCI or subjective cognitive impairment (SCI). At baseline, the median MMSE score in patients in both the apolipoprotein E (ApoE) ε3/ε3 and ApoE ε3/ε4 groups was 26.0 and macrophage Aβ1-42 phagocytosis was defective. The MMSE rate of change increased in the ApoE ε3/ε3 group a median 2.2 points per year (P = 0.015 compared to 0) but did not change in the ApoE ε3/ε4 group (P = 0.014 between groups). In the ApoE ε3/ε3 group, all patients remained cognitively stable or improved; in the ApoE ε3/ε4 group, 1 recovered from dementia, but 3 lapsed into dementia. The macrophage phenotype polarized in patients bearing ApoE ε3/ε3 to an intermediate (green zone) M1-M2 type at the rate of 0.226 U/yr, whereas in patients bearing ApoE ε3/ε4, polarization was negative (P = 0.08 between groups). The baseline M1M2 type in the extreme M1 (red zone) or M2 (white zone) was unfavorable for cognitive outcome. Aβ1-42 phagocytosis increased in both ApoE groups (P = 0.03 in each groups). In vitro, the lipidic mediator resolvin D1 (RvD1) down regulated the M1 type in patients with ApoE ε3/ε3 but in some patients with ε3/ε4, paradoxically up-regulated the M1 type. Antioxidant/ω-3/resveratrol supplementation was associated with favorable immune and cognitive responses in ApoE ε3/ε3 and individual patients bearing ApoE ε3/ε4, and brings into personalized clinical practice the immune benefits expected from ω-3 mediators called resolvins. The validity of this study is limited by its small size and uncontrolled design.


[The first report below is just an abstract for a poster.]

On-Treatment Blood Pressure and Cardiovascular Outcomes in Older Adults With Isolated Systolic Hypertension.

Yano Y, Rakugi H, Bakris GL, Lloyd-Jones DM, Oparil S, Saruta T, Shimada K, Matsuoka H, Imai Y, Ogihara T.

Hypertension. 2017 Jan 3. pii: HYPERTENSIONAHA.116.08600. doi: 10.1161/HYPERTENSIONAHA.116.08600. [Epub ahead of print]

PMID: 28049699


Our aim was to assess optimal on-treatment blood pressure (BP) at which cardiovascular disease (CVD) and all-cause mortality risks are minimized in Japanese older adults with isolated systolic hypertension. We used data from the VALISH study (Valsartan in Elderly Isolated Systolic Hypertension) that recruited older adults (n=3035; mean age, 76 years) with systolic BP (SBP) of ≥160 mm Hg and diastolic BP of <90 mm Hg. Patients were treated by valsartan. Patients were also categorized into 3 groups based on achieved on-treatment SBP of <130 mm Hg (n=317), 130 to <145 mm Hg (n=2025), or ≥145 mm Hg (n=693). The primary outcome was composite CVD (coronary heart disease, stroke, heart failure, cardiovascular deaths, other vascular diseases, and kidney diseases) with secondary outcome being all-cause mortality. Cox proportional hazards models were used to assess the CVD risk for each group. Over a median 3-year follow-up (8022 person-years), 93 CVD events and 52 deaths occurred. Using the on-treatment SBP of 130 to <145 mm Hg as reference stratum, the multivariable-adjusted hazard ratios and 95% confidence intervals of CVD and all-cause mortality risks for those with SBP<130 mm Hg were 2.08 (1.12-3.83) and 2.09 (0.93-4.71) and for those with SBP≥145 mm Hg were 2.29 (1.44-3.62) and 2.51 (1.35-4.66), respectively. On-treatment diastolic BP yielded no relationships with CVD or all-cause mortality risk. In conclusion, among Japanese older adults with isolated systolic hypertension, SBP in the range between 130 and 144 mm Hg was associated with minimal adverse outcomes and a reduction in CVD and all-cause mortality. The BP range will need to be confirmed in randomized controlled trials.


U-shaped relationship; blood pressure; cardiovascular diseases; elderly; hypertension; mortality


Isolated systolic hypertension in young and middle-aged adults and 31-year risk for cardiovascular mortality: the Chicago Heart Association Detection Project in Industry study.

Yano Y, Stamler J, Garside DB, Daviglus ML, Franklin SS, Carnethon MR, Liu K, Greenland P, Lloyd-Jones DM.

J Am Coll Cardiol. 2015 Feb 3;65(4):327-35. doi: 10.1016/j.jacc.2014.10.060.

PMID: 25634830 Free PMC Article





Isolated systolic hypertension (ISH), defined as systolic blood pressure (SBP) ≥140 mm Hg and diastolic blood pressure (DBP) <90 mm Hg, in younger and middle-aged adults is increasing in prevalence.


The aim of this study was to assess the risk for cardiovascular disease (CVD) with ISH in younger and middle-aged adults.


CVD risks were explored in 15,868 men and 11,213 women 18 to 49 years of age (mean age 34 years) at baseline, 85% non-Hispanic white, free of coronary heart disease (CHD) and antihypertensive therapy, from the Chicago Heart Association Detection Project in Industry study. Participant classifications were as follows: 1) optimal-normal blood pressure (BP) (SBP <130 mm Hg and DBP <85 mm Hg); 2) high-normal BP (130 to 139/85 to 89 mm Hg); 3) ISH; 4) isolated diastolic hypertension (SBP <140 mm Hg and DBP ≥90 mm Hg); and 5) systolic diastolic hypertension (SBP ≥140 mm Hg and DBP ≥90 mm Hg).


During a 31-year average follow-up period (842,600 person-years), there were 1,728 deaths from CVD, 1,168 from CHD, and 223 from stroke. Cox proportional hazards models were adjusted for age, race, education, body mass index, current smoking, total cholesterol, and diabetes. In men, with optimal-normal BP as the reference stratum, hazard ratios for CVD and CHD mortality risk for those with ISH were 1.23 (95% confidence interval [CI]: 1.03 to 1.46) and 1.28 (95% CI: 1.04 to 1.58), respectively. ISH risks were similar to those with high-normal BP and less than those associated with isolated diastolic hypertension and systolic diastolic hypertension. In women with ISH, hazard ratios for CVD and CHD mortality risk were 1.55 (95% CI: 1.18 to 2.05) and 2.12 (95% CI: 1.49 to 3.01), respectively. ISH risks were higher than in those with high-normal BP or isolated diastolic hypertension and less than those associated with systolic diastolic hypertension.


Over long-term follow-up, younger and middle-aged adults with ISH had higher relative risk for CVD and CHD mortality than those with optimal-normal BP.


cardiovascular risk; long-term follow-up; younger adults


Association of regular physical activity with total and cause-specific mortality among middle-aged and older Chinese: a prospective cohort study.

Zhou Y, Zhang R, Liu Y, Guo Y, Wang D, He M, Yuan J, Liang Y, Zhang X, Wang Y, Guo H, Wei S, Miao X, Yao P, Wu T, Chen W.

Sci Rep. 2017 Jan 4;7:39939. doi: 10.1038/srep39939.

PMID: 28051177




Association between physical activity and mortality has rarely been investigated among the Chinese population. Furthermore, the most appropriate amount of physical activity for longevity benefits remains unclear. We used data from the Dongfeng-Tongji cohort, including 24,606 middle-aged and older retired adults in 2008 and followed to 2013, to quantify linear and non-linear dose-response relationships between regular physical activity and mortality risks by Cox proportional hazards model. Compared with participants who did not engage in regular physical activity, those performing regular physical activity had significantly 46%, 56%, and 49% decreased risks of mortality from all causes, circulatory, and respiratory diseases, respectively. Each one-SD increase in regular physical activity was associated with 32% decrease of respiratory disease mortality. There were significant nonlinear dose-response associations between regular physical activity and mortality from all causes and circulatory diseases. Mortality risks decreased monotonically with increased regular physical activity amount, and appeared to reach a threshold at around 100 MET-hours/week. More mortality benefits were found among non-smokers than that among current and former smokers. Our results suggest that middle-aged and older Chinese adults can achieve mortality benefits from regular physical activity at the WHO recommended minimum, and the benefit threshold appears at approximately 100 MET hours/week.


Black tea consumption improves postprandial glycemic control in normal and pre-diabetic subjects: a randomized, double-blind, placebo-controlled crossover study.

Butacnum A, Chongsuwat R, Bumrungpert A.

Asia Pac J Clin Nutr. 2017 Jan;26(1):59-64. doi: 10.6133/apjcn.112015.08.

PMID: 28049262




Postprandial glycemic control is important for prevention of diabetes. Black tea consumption may improve postprandial glycemic control. The major bioactive compounds are polyphenols, black tea polymerized polyphenol (BTPP).This study examined the effect of black tea consumption on postprandial blood glucose and insulin response following sucrose loading in normal and pre-diabetes subjects.


This study was a randomized, double-blind, placebo-controlled crossover study. Twenty-four subjects, male and female aged 20-60 years, normal and pre-diabetic, randomly ingested a sucrose solution with a low dose (110 mg BTPP), a high dose (220 mg BTPP) of black tea drink or a placebo drink (0 mg BTPP). Blood samples were collected at 0, 30, 60, 90, and 120 min from commencement of drink ingestion to measure blood glucose and insulin levels.


The drink containing low dose and high dose BTPP significantly decreased incremental blood glucose area under the curve (AUC) after sucrose intake compared with placebo in the normal (T0-60 min 3,232±356 vs 3,295±312 vs 3,652±454 mg.min/dL; p=0.016) and pre-diabetic subjects (T0-60 min 2,554±395 vs 2,472±280 vs 2,888±502 mg.min/dL; p=0.048). There was no statistically significant difference of changes in insulin levels between the placebo and black tea groups (p>0.05). No significant differences in adverse effects were observed with the placebo, low dose and high dose of BTPP groups.


Black tea consumption can decrease postprandial blood glucose after sucrose intake.

Edited by AlPater

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Zinc Supplementation in Children with Asthma Exacerbation.

Rerksuppaphol S, Rerksuppaphol L.

Pediatr Rep. 2016 Dec 9;8(4):6685. doi: 10.4081/pr.2016.6685.

PMID: 28058103



Zinc deficiency has demonstrated an association with the risk of asthma. This study aimed to evaluate the efficacy of zinc supplementation in reducing the severity of childhood asthma exacerbation. A number of 42 children with asthma exacerbation admitted to the hospital were randomized to receive either zinc bis-glycinate (30 mg elemental zinc/day) or a placebo in adjuvant to the standard treatment. The pediatric respiratory assessment measure (PRAM) was used to measure the asthma severity. The primary outcome was a change in asthma severity from the baseline to the end of study. The study found that PRAM score in the zinc group showed a more rapid decrease compared to the control group at the 24-hour (2.2±1.3 vs. 1.2±1.3; P = 0.015) and 48-hour (3.4±2.0 vs. 2.2±1.8; P = 0.042) intervals. At admission, overall mean serum zinc level was 63.8 mg/dL and 57.1% of children had zinc deficiency with no difference in prevalence between groups. PRAM scores did not differ between children with low and normal zinc status. In conclusion, zinc supplementation as the adjuvant therapy to the standard treatment during asthma exacerbation resulted in rapid lessening of severity.


Asthma; Child; Dietary supplement; Zinc


[The below paper is pdf-availed.]

Relationship between tongue strength and 1-year life expectancy in elderly people needing nursing care.

Yajima Y, Kikutani T, Tamura F, Yoshida M.

Odontology. 2017 Jan 5. doi: 10.1007/s10266-016-0289-7. [Epub ahead of print]

PMID: 28058515


Tongue strength is a useful indicator of oral function and has been found to decrease with aging and reduced physical functioning. The present study aimed to assess the relationships of tongue strength with physical function, mental function, and nutritional status, and also between these factors and 1-year outcomes, to determine whether tongue strength is related to life expectancy in elderly people needing nursing care. The subjects were 140 elderly individuals requiring needing nursing care (49 men and 91 women; ≥65 years). The investigated items included sex, age, activities of daily living (ADL), comorbidity, cognitive function, nutritional status, eating function, occlusal support, and tongue strength. Furthermore, a follow-up study was conducted 1 year later, and factors related to death were identified. The mean tongue strength of the total 140 subjects was 20.3 ± 8.6 kPa. Tongue strength was assessed relative to each of the investigated items, using the t test and one-way analysis of variance. Tongue strength was significantly related to ADL, comorbidity, cognitive function, calf circumference, food intake, and occlusal support. Fifteen subjects were found to have died at the 1-year follow-up study. We assessed the relationships of 1-year outcomes with each of the factors examined, and 1-year outcomes were found to be significantly related to ADL and tongue strength.


Elderly; Life expectancy; Tongue strength


Table 2

Relationships between death at 1 year and each of the investigated items

Death (N) Survive (N) p value









Age (years)











Barthel index





















Very mild dementia






CC (cm)









Normal nutritional status




At risk of malnutrition






Eating function

Wet hoarseness








Prolonged feeding time








Decreased food intake








Occlusal support

Eichner A




Eichner B



Eichner C



Tongue strength (kPa)









CCI Charlson comorbidity index, CDR Washington University Clinical Dementia Rating, CC Calf circumference, MNA-SF mini nutritional assessment-short form


Coffee consumption in aged mice increases energy production and decreased hepatic mTOR levels

Keita Takahashi, Shuichi Yanai, Kentaro Shimokado, Akihito Ishigami

Nutrition Articles in Press DOI: http://dx.doi.org/10.1016/j.nut.2016.12.021

Publication stage: In Press Accepted Manuscript

Published online: January 6, 2017



●We investigated the locomotor activity, energy metabolism, and lipid metabolism of aged mice fed coffee.

●Aged mice that consumed either caffeine-containing regular or decaffeinated coffee had decreased plasma-free fatty acids and increased ATP and total phosphorylated mTOR, which is closely associated with aging, in the liver.

●Consumption of regular coffee increased the food and water intake, locomotor activity, volume of oxygen consumption (VCO2), and respiration exchange ratio (RER) of aged mice.

●Coffee, one of the world’s most consumed beverages, has potential anti-aging effects.



Coffee, one of the world’s most consumed beverages, has many benefits. Some studies have reported the effects of coffee on aging. In this study, we investigated the locomotor activity, energy metabolism, and lipid metabolism of aged (20-month-old) mice given coffee.


Aged C57BL/6NCr mice were divided into three groups that were given no coffee (controls, n = 9), 0.1% regular (caffeinated) coffee (n = 9), or 0.1% decaffeinated coffee (n = 9). This regimen continued for 17 weeks until mice reached the age of 24 months.


Regular and decaffeinated coffee consumption decreased plasma-free fatty acid levels, increased hepatic ATP content, and decreased total mammalian target of rapamycin (mTOR) and phosphorylated mTOR (p-mTOR) protein content in the liver. However, no differences were found in the protein or activity levels of Akt, AMP-activated protein kinase (AMPK), p70 S6 kinase (S6K), or sterol regulatory element binding protein 1 (SREBP-1), proteins that are upstream or downstream of the mTOR complex 1 (mTORC1)-related pathways. Regular coffee consumption increased food and water intake, locomotor activity, the volume of carbon dioxide (VCO2) production, and the respiration exchange ratio (RER).


Regular and decaffeinated coffee consumption decreased hepatic total mTOR and p-mTOR levels independently of Akt and AMPK pathways in aged mice. Since decreased mTORC1 activity is known to have anti-aging effects, coffee consumption during old age may retard aging. Moreover, coffee consumption by the aged population had a positive effect on behavioral energy and lipid metabolism.

Key words:

aging, coffee, decaffeinated coffee, energy metabolism, lipid metabolism, mTOR


No modifying effect of education level on the association between lifestyle behaviors and cardiovascular mortality: the Japan Collaborative Cohort Study.

Eguchi E, Iso H, Honjo K, Yatsuya H, Tamakoshi A.

Sci Rep. 2017 Jan 6;7:39820. doi: 10.1038/srep39820.

PMID: 28057921



We examined the effect of education level on the association between healthy lifestyle behaviors and cardiovascular mortality in the Japanese population. A total of 42,647 community-based men and women aged 40-79 years were enrolled at baseline (1988-1990), followed through 2009. The components of the healthy lifestyle score included the intake of fruits, fish, and milk; body mass index; exercise; avoidance of smoking; moderate alcohol intake; and moderate sleep duration. During the 19.3 years of follow-up, 8,314 all-cause and 2,377 total cardiovascular mortality cases were noted. Inverse associations were observed between healthy lifestyle scores and total cardiovascular disease (CVD) for both the lower and higher education level groups. Multivariable hazard ratios (95% confidence interval) for CVD mortality from the highest to the lowest healthy lifestyle scores, and the population attributable fraction (95% CIs) without healthy lifestyle scores of 7-8 were 0.51 (0.33-0.52) and 42% (24-58%), and 0.38 (0.27-0.47) and 55% (36-69%) for the higher and lower education levels, respectively. Our findings suggest that the association between higher CVD mortality and lower education level can be explained by the individuals' lower adherence to a healthy lifestyle; hence, lifestyle modification would be beneficial for the prevention of cardiovascular mortality, irrespective of the education level.


Effects of Long-Term Vitamin D Supplementation on Regression and Metabolic Status of Cervical Intraepithelial Neoplasia: a Randomized, Double-Blind, Placebo-Controlled Trial.

Vahedpoor Z, Jamilian M, Bahmani F, Aghadavod E, Karamali M, Kashanian M, Asemi Z.

Horm Cancer. 2017 Jan 3. doi: 10.1007/s12672-016-0278-x. [Epub ahead of print]

PMID: 28050798



We are not aware of any study examining the effects of long term vitamin D administration on regression and metabolic status of patients with cervical intraepithelial neoplasia grade 1 (CIN1). This study was performed to evaluate the effects of long-term vitamin D administration on regression and metabolic status of patients with CIN1. This randomized, double-blind, placebo-controlled trial was performed among 58 women diagnosed with CIN1. CIN1 diagnosis was performed based on specific diagnostic procedures of biopsy, pathological diagnosis, and colposcopy. Patients were randomly allocated into two groups to take 50,000 IU vitamin D3 supplements (n = 29) or placebo (n = 29) every 2 weeks for 6 months. Fasting blood samples were taken at the beginning of the study and end-of-trial to measure related markers. After 6 months of vitamin D administration, greater percentage of women in the vitamin D group had regressed CIN1 (84.6 vs. 53.8%, P = 0.01) than those in the placebo group. Long-term vitamin D supplementation increased serum-25(OH) vitamin D levels in the intervention group compared to the placebo group (+12.3 ± 11.4 vs. -0.1 ± 3.7 ng/mL, P < 0.001). In addition, vitamin D intake led to significant decreases in serum insulin levels (-5.3 ± 7.3 vs. +2.4 ± 5.9 μIU/mL, P < 0.001), homeostasis model of assessment-insulin resistance (-1.2 ± 1.6 vs. +0.5 ± 1.2, P < 0.001), homeostatic model assessment-Beta cell function (P = 0.005) and a significant elevation in quantitative insulin sensitivity check index (+0.03 ± 0.04 vs. -0.007 ± 0.02, P < 0.001) compared with the placebo group. Additionally, significant increases in plasma nitric oxide (NO) (+15.5 ± 10.3 vs. +4.0 ± 13.4 μmol/L, P = 0.001), total antioxidant capacity (TAC) (P = 0.04), total glutathione (GSH) (+11.8 ± 153.5 vs. -294.2 ± 595.1 μmol/L, P = 0.01) and a significant reduction in plasma malondialdehyde (MDA) levels (-0.8 ± 1.0 vs. -0.03 ± 1.4 μmol/L, P = 0.03) were observed following the administration of vitamin D supplements compared with the placebo group. In conclusion, vitamin D3 administration for 6 months among women with CIN1 resulted in its regression and had beneficial effects on markers of insulin metabolism, plasma NO, TAC, GSH and MDA levels.


CIN1; Metabolic profiles; Regression; Supplementation; Vitamin D


People aged 85 and over experience more joint pain than previously recognised.

[No authors listed]

Nurs Stand. 2011 Oct 26;26(8):17. doi: 10.7748/ns.26.8.17.s24.

PMID: 28044692



The prevalence of arthritis and joint pain among the 'oldest old' may have been underestimated. Researchers in the UK also found that the condition is both more common and more painful in women than men.

Arthritis is associated strongly with age, yet few studies have investigated how the condition affects the oldest old – people aged 85 years and older – who will number 3.3 million in the UK by 2033.

A new observational cohort study by researchers at Newcastle University found that the lifetime prevalence of arthritis in 85 year olds was 65.4 per cent – higher than suggested by previous studies. A total of 1,049 people aged 85 years participated in the study. Researchers examined general practice records, and drew on health assessments conducted by nurses in the participants’ own home or care home.


Arthritis is more common and more painful in women than men

Picture credit: Getty

Knee osteoarthritis and cervical spondylosis were the most common diagnoses. In the 11 joint areas studied, pain occurred more frequently in women in all areas. Women also reported a higher total number of painful joints than men. Many participants identified the knee as the most painful joint, although the foot, ankle and lower back received the highest pain scores.

Almost two thirds of the study population reported joint pain in the last month of the study, with 71.7 per cent reporting pain occurring on most days of the month.

The authors conclude: ‘The economic burden of musculoskeletal disease in the oldest old is potentially huge and its management presents a major challenge.’


Prevalence of arthritis and joint pain in the oldest old: findings from the Newcastle 85+ study.

Duncan R, Francis RM, Collerton J, Davies K, Jagger C, Kingston A, Kirkwood T, Robinson L, Birrell F.

Age Ageing. 2011 Nov;40(6):752-5. doi: 10.1093/ageing/afr105. No abstract available.

PMID: 21937515 Free Article




Monti D, Ostan R, Borelli V, Castellani G, Franceschi C.

Mech Ageing Dev. 2016 Dec 27. pii: S0047-6374(16)30261-5. doi: 10.1016/j.mad.2016.12.008. [Epub ahead of print] Review.

PMID: 28038993



Inflammaging is a recent theory of aging originally proposed in 2000 where data and conceptualizations regarding the aging of the immune system (immunosenescence) and the evolution of immune responses from invertebrates to mammals converged. This theory has received an increasing number of citations and experimental confirmations. Here we present an updated version of inflammaging focused on omic data - particularly on glycomics - collected on centenarians, supercentenarians and their offspring. Accordingly, we arrived to the following conclusions: i) inflammaging has a structure where specific combinations of pro- and anti-inflammatory mediators are involved; ii) inflammaging is systemic and more complex than we previously thought, as many organs, tissues and cell types participate in producing pro- and anti-inflammatory stimuli conceptualized as "molecular garbage"; iii) inflammaging is dynamic, can be propagated locally to neighboring cells and systemically from organ to organ by circulating products and microvesicles, and amplified by chronic age-related diseases constituting a "local fire" which in turn produces additional inflammatory stimuli and molecular garbage; iv) an integrated Systems Medicine approach is urgently needed to let emerge a robust and highly informative set/combination of omic markers able to better grasp the complex molecular core of inflammaging in elderly and centenarians.


Inflammaging; N-glycans; Systems Medicine; aging; centenarians


Outcomes of Treated Hypertension at Age 80 and Older: Cohort Analysis of 79,376 Individuals.

Delgado J, Masoli JA, Bowman K, Strain WD, Kuchel GA, Walters K, Lafortune L, Brayne C, Melzer D, Ble A; As part of the Ageing Well Programme of the NIHR School for Public Health Research, England..

J Am Geriatr Soc. 2016 Dec 30. doi: 10.1111/jgs.14712. [Epub ahead of print]

PMID: 28039870




To estimate outcomes according to attained blood pressure (BP) in the oldest adults treated for hypertension in routine family practice.


Cohort analysis of primary care inpatient and death certificate data for individuals with hypertension.


Primary care practices in England (Clinical Practice Research Datalink).


Individuals aged 80 and older taking antihypertensive medication and free of dementia, cancer, coronary heart disease, stroke, heart failure, and end-stage renal failure at baseline.


Outcomes were mortality, cardiovascular events, and fragility fractures. Systolic BP (SBP) was grouped in 10-mmHg increments from less than 125 to 185 mmHg or more (reference 145-154 mmHg).


Myocardial infarction hazards increased linearly with increasing SBP, and stroke hazards increased for SBP of 145 mmHg or greater, although lowest mortality was in individuals with SBP of 135 to 154 mmHg. Mortality of the 13.1% of patients with SBP less than 135 mmHg was higher than that of the reference group (Cox hazard ratio=1.25, 95% confidence interval=1.19-1.31; equating to one extra death per 12.6 participants). This difference in mortality was consistent over short- and long-term follow-up; adjusting for diastolic BP did not change the risk. Incident heart failure rates were higher in those with SBP less than 125 mmHg than in the reference group.


In routine primary care, SBP less than 135 mmHg was associated with greater mortality in the oldest adults with hypertension and free of selected potentially confounding comorbidities. Although important confounders were accounted for, observational studies cannot exclude residual confounding. More work is needed to establish whether unplanned SBPs less than 135 mmHg in older adults with hypertension may be a useful clinical sign of poor prognosis, perhaps requiring clinical review of overall care.


hypertension; mortality; oldest old; outcomes; primary care

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Effect of Resting Heart Rate on All-Cause Mortality and Cardiovascular Events According to Age.

Li K, Yao C, Yang X, Dong L.

J Am Geriatr Soc. 2016 Dec 30. doi: 10.1111/jgs.14714. [Epub ahead of print]

PMID: 28039873





To examine whether the association between resting heart rate (RHR) and all-cause mortality and cardiovascular events differs according to age.


Prospective cohort.


Community in Beijing, China.


Individuals aged 40 and older without cardiovascular disease at baseline (N = 6,209).


Trained investigators interviewed participants using a standard questionnaire to obtain information on demographic characteristics, medical history and lifestyle risk factors in 1991. RHR was evaluated according to quartiles (<72, 72-76, 76-84, ≥84 beats/min). Cox regression models were used to assess the associations between RHR and all-cause mortality and cardiovascular events.


During a mean follow-up of 8.3 years, 840 subjects died, and 676 experienced a cardiovascular event. Higher RHR was significantly associated with all-cause mortality (P trend < .001) and cardiovascular events (P trend = .002) in older (≥60) but not younger (<60) participants (both P trend > .05). There were significant modifying effects of age on the association between RHR and all-cause mortality (P interaction < .001) and cardiovascular events (P interaction =.002). Similar results were observed after exclusion of individuals who died (n = 100) or had a cardiovascular event (n = 45) during the first 2 years of follow-up.


High RHR appears to be an independent determinant of all-cause mortality and cardiovascular events in older but not younger individuals.


cardiovascular disease; cohort study; death; epidemiology; resting heart rate


Statins for Primary PreventionThe Debate Is Intense, but the Data Are Weak

Rita F. Redberg, MD, MSc; Mitchell H. Katz, MD

JAMA Intern Med. 2017;177(1):21-23. doi:10.1001/jamainternmed.2016.7585


Journal preamble:

A recent issue of JAMA contains the latest US Preventive Services Task Force (USPSTF) recommendation statement on statins for prevention of cardiovascular disease in adults,1 along with the accompanying evidence report and systematic review2 on which the recommendations are based. The evidence report summarized data from 19 trials including a total of 71 344 patients and concluded that statin therapy was associated with reduced risk of all-cause and cardiovascular mortality and cardiovascular disease (CVD) events. Thus, the task force recommended “initiating use of low- to moderate-dose statins in adults aged 40 to 75 years without a history of CVD who have 1 or more CVD risk factors and a calculated 10-year CVD event risk of 10% or greater (B recommendation)” or “7.5% to 10% (C recommendation).”1 Although the task force did their usual careful job of reviewing the evidence, the evidence for treating asymptomatic persons with statins does not appear to merit a grade B or even a grade C recommendation.


Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: US Preventive Services Task Force Recommendation Statement.

US Preventive Services Task Force., Bibbins-Domingo K, Grossman DC, Curry SJ, Davidson KW, Epling JW Jr, García FA, Gillman MW, Kemper AR, Krist AH, Kurth AE, Landefeld CS, LeFevre ML, Mangione CM, Phillips WR, Owens DK, Phipps MG, Pignone MP.

JAMA. 2016 Nov 15;316(19):1997-2007. doi: 10.1001/jama.2016.15450.

PMID: 27838723




Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States, accounting for 1 of every 3 deaths among adults.


To update the 2008 US Preventive Services Task Force (USPSTF) recommendation on screening for lipid disorders in adults.


The USPSTF reviewed the evidence on the benefits and harms of screening for and treatment of dyslipidemia in adults 21 years and older; the benefits and harms of statin use in reducing CVD events and mortality in adults without a history of CVD events; whether the benefits of statin use vary by subgroup, clinical characteristics, or dosage; and the benefits of various treatment strategies in adults 40 years and older without a history of CVD events.


The USPSTF recommends initiating use of low- to moderate-dose statins in adults aged 40 to 75 years without a history of CVD who have 1 or more CVD risk factors (dyslipidemia, diabetes, hypertension, or smoking) and a calculated 10-year CVD event risk of 10% or greater (B recommendation). The USPSTF recommends that clinicians selectively offer low- to moderate-dose statins to adults aged 40 to 75 years without a history of CVD who have 1 or more CVD risk factors and a calculated 10-year CVD event risk of 7.5% to 10% (C recommendation). The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of initiating statin use in adults 76 years and older (I statement).


Interpretation and Use of Another Statin Guideline.

Greenland P, Bonow RO.

JAMA. 2016 Nov 15;316(19):1977-1979. doi: 10.1001/jama.2016.15087. No abstract available.

PMID: 27838703



Parental Obesity and Early Childhood Development.

Edwina H. Yeung, Rajeshwari Sundaram, Akhgar Ghassabian, Yunlong Xie, Germaine Buck Louis

Pediatrics Jan 2017, e20161459; DOI: 10.1542/peds.2016-1459

PMID: 28044047




BACKGROUND: Previous studies identified associations between maternal obesity and childhood neurodevelopment, but few examined paternal obesity despite potentially distinct genetic/epigenetic effects related to developmental programming.

METHODS: Upstate KIDS (2008–2010) recruited mothers from New York State (excluding New York City) at ∼4 months postpartum. Parents completed the Ages and Stages Questionnaire (ASQ) when their children were 4, 8, 12, 18, 24, 30, and 36 months of age corrected for gestation. The ASQ is validated to screen for delays in 5 developmental domains (ie, fine motor, gross motor, communication, personal-social functioning, and problem-solving ability). Analyses included 3759 singletons and 1062 nonrelated twins with ≥1 ASQs returned. Adjusted odds ratios (aORs) and 95% confidence intervals were estimated by using generalized linear mixed models accounting for maternal covariates (ie, age, race, education, insurance, marital status, parity, and pregnancy smoking).

RESULTS: Compared with normal/underweight mothers (BMI <25), children of obese mothers (26% with BMI ≥30) had increased odds of failing the fine motor domain (aOR 1.67; confidence interval 1.12–2.47). The association remained after additional adjustment for paternal BMI (1.67; 1.11–2.52). Paternal obesity (29%) was associated with increased risk of failing the personal-social domain (1.75; 1.13–2.71), albeit attenuated after adjustment for maternal obesity (aOR 1.71; 1.08–2.70). Children whose parents both had BMI ≥35 were likely to additionally fail the problem-solving domain (2.93; 1.09–7.85).

CONCLUSIONS: Findings suggest that maternal and paternal obesity are each associated with specific delays in early childhood development, emphasizing the importance of family information when screening child development.


A Comparison of the Prevalence of Dementia in the United States in 2000 and 2012.

Langa KM, Larson EB, Crimmins EM, Faul JD, Levine DA, Kabeto MU, Weir DR.

JAMA Intern Med. 2017 Jan 1;177(1):51-58. doi: 10.1001/jamainternmed.2016.6807.

PMID: 27893041


Preamble: This population-based study uses data from the Health and Retirement Study to compare the prevalence of dementia in the United States in 2000 and 2012.

Key Points

Question Has the prevalence of dementia among older adults in the United States changed between 2000 and 2012?

Findings In this observational cohort study of more than 21 000 US adults 65 years or older from the nationally representative Health and Retirement Study, dementia prevalence declined significantly, from 11.6% in 2000 to 8.8% in 2012.

Meaning Population brain health seemed to improve between 2000 and 2012; increasing educational attainment and better control of cardiovascular risk factors may have contributed to the improvement, but the full set of social, behavioral, and medical factors contributing to the improvement is still uncertain.



The aging of the US population is expected to lead to a large increase in the number of adults with dementia, but some recent studies in the United States and other high-income countries suggest that the age-specific risk of dementia may have declined over the past 25 years. Clarifying current and future population trends in dementia prevalence and risk has important implications for patients, families, and government programs.


To compare the prevalence of dementia in the United States in 2000 and 2012.


We used data from the Health and Retirement Study (HRS), a nationally representative, population-based longitudinal survey of individuals in the United States 65 years or older from the 2000 (n = 10 546) and 2012 (n = 10 511) waves of the HRS.


Dementia was identified in each year using HRS cognitive measures and validated methods for classifying self-respondents, as well as those represented by a proxy. Logistic regression was used to identify socioeconomic and health variables associated with change in dementia prevalence between 2000 and 2012.


The study cohorts had an average age of 75.0 years (95% CI, 74.8-75.2 years) in 2000 and 74.8 years (95% CI, 74.5-75.1 years) in 2012 (P = .24); 58.4% (95% CI, 57.3%-59.4%) of the 2000 cohort was female compared with 56.3% (95% CI, 55.5%-57.0%) of the 2012 cohort (P < .001). Dementia prevalence among those 65 years or older decreased from 11.6% (95% CI, 10.7%-12.7%) in 2000 to 8.8% (95% CI, 8.2%-9.4%) (8.6% with age- and sex-standardization) in 2012 (P < .001). More years of education was associated with a lower risk for dementia, and average years of education increased significantly (from 11.8 years [95% CI, 11.6-11.9 years] to 12.7 years [95% CI, 12.6-12.9 years]; P < .001) between 2000 and 2012. The decline in dementia prevalence occurred even though there was a significant age- and sex-adjusted increase between years in the cardiovascular risk profile (eg, prevalence of hypertension, diabetes, and obesity) among older US adults.


The prevalence of dementia in the United States declined significantly between 2000 and 2012. An increase in educational attainment was associated with some of the decline in dementia prevalence, but the full set of social, behavioral, and medical factors contributing to the decline is still uncertain. Continued monitoring of trends in dementia incidence and prevalence will be important for better gauging the full future societal impact of dementia as the number of older adults increases in the decades ahead.


Dementia Trends in the United States: Read Up and Weigh In.

Okonkwo OC, Asthana S.

JAMA Intern Med. 2017 Jan 1;177(1):58-60. doi: 10.1001/jamainternmed.2016.7073. No abstract available.

PMID: 27893015


Nonfasting for Routine Lipid Testing: From Evidence to Action.

Mora S.

JAMA Intern Med. 2016 Jul 1;176(7):1005-6. doi: 10.1001/jamainternmed.2016.1979. No abstract available.

PMID: 27119719



Robust evidence supports the use of nonfasting blood draws for routine

clinical practice, as this would be highly effective, practical and

offer many advantages for cardiovascular risk screening and treatment

inmost people compared with amandate to fast. The time has

come to move this strong evidence into action."

4. JAMA. 2009 Nov 11;302(18):1993-2000. doi: 10.1001/jama.2009.1619.

Major lipids, apolipoproteins, and risk of vascular disease.

Emerging Risk Factors Collaboration, Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A, Wood AM, Lewington S, Sattar N, Packard CJ, Collins R, Thompson SG, Danesh J.

PMID: 1990392





Associations of major lipids and apolipoproteins with the risk of vascular disease have not been reliably quantified.


To assess major lipids and apolipoproteins in vascular risk.


Individual records were supplied on 302,430 people without initial vascular disease from 68 long-term prospective studies, mostly in Europe and North America. During 2.79 million person-years of follow-up, there were 8857 nonfatal myocardial infarctions, 3928 coronary heart disease [CHD] deaths, 2534 ischemic strokes, 513 hemorrhagic strokes, and 2536 unclassified strokes.


Hazard ratios (HRs), adjusted for several conventional factors, were calculated for 1-SD higher values: 0.52 log(e) triglyceride, 15 mg/dL high-density lipoprotein cholesterol (HDL-C), 43 mg/dL non-HDL-C, 29 mg/dL apolipoprotein AI, 29 mg/dL apolipoprotein B, and 33 mg/dL directly measured low-density lipoprotein cholesterol (LDL-C). Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis.


The rates of CHD per 1000 person-years in the bottom and top thirds of baseline lipid distributions, respectively, were 2.6 and 6.2 with triglyceride, 6.4 and 2.4 with HDL-C, and 2.3 and 6.7 with non-HDL-C. Adjusted HRs for CHD were 0.99 (95% CI, 0.94-1.05) with triglyceride, 0.78 (95% CI, 0.74-0.82) with HDL-C, and 1.50 (95% CI, 1.39-1.61) with non-HDL-C. Hazard ratios were at least as strong in participants who did not fast as in those who did. The HR for CHD was 0.35 (95% CI, 0.30-0.42) with a combination of 80 mg/dL lower non-HDL-C and 15 mg/dL higher HDL-C. For the subset with apolipoproteins or directly measured LDL-C, HRs were 1.50 (95% CI, 1.38-1.62) with the ratio non-HDL-C/HDL-C, 1.49 (95% CI, 1.39-1.60) with the ratio apo B/apo AI, 1.42 (95% CI, 1.06-1.91) with non-HDL-C, and 1.38 (95% CI, 1.09-1.73) with directly measured LDL-C. Hazard ratios for ischemic stroke were 1.02 (95% CI, 0.94-1.11) with triglyceride, 0.93 (95% CI, 0.84-1.02) with HDL-C, and 1.12 (95% CI, 1.04-1.20) with non-HDL-C.


Lipid assessment in vascular disease can be simplified by measurement of either total and HDL cholesterol levels or apolipoproteins without the need to fast and without regard to triglyceride.


Effectiveness of Screening Colonoscopy to Prevent Colorectal Cancer Among Medicare Beneficiaries Aged 70 to 79 Years: A Prospective Observational Study

Xabier García-Albéniz, MD, PhD; John Hsu, MD, MBA, MSCE; Michael Bretthauer, MD, PhD; Miguel A. Hernán

Ann Intern Med. 2017;166(1):18-26. DOI: 10.7326/M16-0758




No randomized, controlled trials of screening colonoscopy have been completed, and ongoing trials exclude persons aged 75 years or older. The Medicare program, however, reimburses screening colonoscopy without an upper age limit.


To evaluate the effectiveness and safety of screening colonoscopy to prevent colorectal cancer (CRC) in persons aged 70 to 74 and those aged 75 to 79 years.


Large-scale, population-based, prospective study. The observational data were used to emulate a target trial with 2 groups: colonoscopy screening and no screening.


United States.


1 355 692 Medicare beneficiaries (2004 to 2012) aged 70 to 79 years at average risk for CRC who used Medicare preventive services and had no previous diagnostic or surveillance colonoscopies in the past 5 years.


8-year risk for CRC and 30-day risk for adverse events.


In beneficiaries aged 70 to 74 years, the 8-year risk for CRC was 2.19% (95% CI, 2.00% to 2.37%) in the screening colonoscopy group and 2.62% (CI, 2.56% to 2.67%) in the no-screening group (absolute risk difference, −0.42% [CI, −0.24% to −0.63%]). Among those aged 75 to 79 years, the 8-year risk for CRC was 2.84% (CI, 2.54% to 3.13%) in the screening colonoscopy group and 2.97% (CI, 2.92% to 3.03%) in the no-screening group (risk difference, −0.14% [CI, −0.41 to 0.16]). The excess 30-day risk for any adverse event in the colonoscopy group was 5.6 events per 1000 individuals (CI, 4.4 to 6.8) in the 70- to 74-year age group and 10.3 per 1000 (CI, 8.6 to 11.1) in the 75- to 79-year age group.


CRC-specific mortality was not available, but CRC incidence and stage were studied at diagnosis.


Screening colonoscopy may have had a modest benefit in preventing CRC in beneficiaries aged 70 to 74 years and a smaller benefit in older beneficiaries. The risk for adverse events was low but greater among older persons.


Effects of free sugars on blood pressure and lipids: a systematic review and meta-analysis of nutritional isoenergetic intervention trials.

Fattore E, Botta F, Agostoni C, Bosetti C.

Am J Clin Nutr. 2016 Dec 21. pii: ajcn139253. doi: 10.3945/ajcn.116.139253. [Epub ahead of print]

PMID: 28003201




Sugar has been suggested as a central risk factor in the development of noncommunicable diseases.


We assessed the evidence of the effects of free sugars compared with complex carbohydrates on selected cardiovascular disease risk factors.


We conducted a systematic review and meta-analysis of intervention trials to compare diets that provide a given amount of energy from free sugars with a control diet that provides the same amount of energy from complex carbohydrates. The primary outcomes were: blood pressure, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triacylglycerols, apolipoproteins A-I and B, or very low-density lipoprotein cholesterol. Body weight was also recorded but was not a primary outcome of the studies.


In all, 28 studies involving 510 volunteers were included. When free sugars were substituted for complex carbohydrates, no significant increases were detected in systolic or diastolic blood pressure, and no heterogeneity was observed. There were significant increases in HDL cholesterol, LDL cholesterol, and triacylglycerols, although for LDL cholesterol and triacylglycerols there was significant heterogeneity between studies and evidence of publication bias. After adjustment for missing studies, these increases lost significance. Subgroup analyses showed that diets providing the largest total energy intake and energy exchange enhanced the effect of free sugars on total and LDL cholesterol and triacylglycerols. The increase of triacylglycerols was no longer significant when studies with the highest risk of bias were excluded or when only randomized trials were considered. Free sugars had no effect on body weight.


In short- or moderate-term isoenergetic intervention trials, the substitution of free sugars for complex carbohydrates had no effect on blood pressure or body weight and an unclear effect on blood lipid profile. Further independent trials are required to assess whether the reduction of free sugars improves cardiovascular disease risk factors. This review was registered at http://www.crd.york.ac.uk/prosperoas CRD42016042930.


blood pressure; body weight; cholesterol; complex carbohydrates; free sugars; intervention trials; meta-analysis; triacylglycerols


Sex differences in the effect of fish-oil supplementation on the adaptive response to resistance exercise training in older people: a randomized controlled trial.

Da Boit M, Sibson R, Sivasubramaniam S, Meakin JR, Greig CA, Aspden RM, Thies F, Jeromson S, Hamilton DL, Speakman JR, Hambly C, Mangoni AA, Preston T, Gray SR.

Am J Clin Nutr. 2017 Jan;105(1):151-158. doi: 10.3945/ajcn.116.140780.

PMID: 27852617 Free Article





Resistance exercise increases muscle mass and function in older adults, but responses are attenuated compared with younger people. Data suggest that long-chain n-3 polyunsaturated fatty acids (PUFAs) may enhance adaptations to resistance exercise in older women. To our knowledge, this possibility has not been investigated in men.


We sought to determine the effects of long-chain n-3 PUFA supplementation on resistance exercise training-induced increases in muscle mass and function and whether these effects differ between older men and women.


Fifty men and women [men: n = 27, mean ± SD age: 70.6 ± 4.5 y, mean ± SD body mass index (BMI; in kg/m2): 25.6 ± 4.2; women: n = 23, mean ± SD age: 70.7 ± 3.3 y, mean ± SD BMI: 25.3 ± 4.7] were randomly assigned to either long-chain n-3 PUFA (n = 23; 3 g fish oil/d) or placebo (n = 27; 3 g safflower oil/d) and participated in lower-limb resistance exercise training twice weekly for 18 wk. Muscle size, strength, and quality (strength per unit muscle area), functional abilities, and circulating metabolic and inflammatory markers were measured before and after the intervention.


Maximal isometric torque increased after exercise training to a greater (P < 0.05) extent in the long-chain n-3 PUFA group than in the placebo group in women, with no differences (P > 0.05) between groups in men. In both sexes, the effect of exercise training on maximal isokinetic torque at 30, 90, and 240° s-1, 4-m walk time, chair-rise time, muscle anatomic cross-sectional area, and muscle fat did not differ (P > 0.05) between groups. There was a greater (P < 0.05) increase in muscle quality in women after exercise training in the long-chain n-3 PUFA group than in the placebo group, with no such differences in men (P > 0.05). Long-chain n-3 PUFAs resulted in a greater decrease (P < 0.05) than the placebo in plasma triglyceride concentrations in both sexes, with no differences (P > 0.05) in glucose, insulin, or inflammatory markers.


Long-chain n-3 PUFA supplementation augments increases in muscle function and quality in older women but not in older men after resistance exercise training.


aging; exercise; fatty acids; muscle; sarcopenia


A prospective study of water intake and subsequent risk of all-cause mortality in a national cohort.

Kant AK, Graubard BI.

Am J Clin Nutr. 2017 Jan;105(1):212-220. doi: 10.3945/ajcn.116.143826.


PMID: 27903521



Water, an essential nutrient, is believed to be related to a variety of health outcomes. Published studies have examined the association of fluid or beverage intake with risk of mortality from coronary diseases, diabetes, or cancer, but few studies have examined the association of total water intake with all-cause mortality.


We examined prospective risk of mortality from all causes in relation to intakes of total water and each of the 3 water sources.


We used public-domain, mortality-linked water intake data from the NHANES conducted in 1988-1994 and 1999-2004 for this prospective cohort study (n = 12,660 women and 12,050 men; aged ≥25 y). Mortality follow-up was completed through 31 December 2011. We used sex-specific Cox proportional hazards regression methods that were appropriate for complex surveys to examine the independent associations of plain water, beverage water, water in foods, and total water with multiple covariate-adjusted risk of mortality from all causes.


Over a median of 11.4 y of follow-up, 3504 men and 3032 women died of any cause in this cohort. In men, neither total water intake nor each of the individual water source variables (plain water, water in beverages, and water in foods) was independently related with risk of all-cause mortality. In women, risk of mortality increased slightly in the highest quartile of total or plain water intake but did not approach the Bonferroni-corrected level of significance of P < 0.002.


There was no survival advantage in association with higher total or plain water intake in men or women in this national cohort. The slight increase in risk of mortality noted in women with higher total and plain water intakes may be spurious and requires further investigation.


NHANES; all-cause mortality; beverages; fluid; food moisture; plain water; prospective cohort; water intake


Higher serum phenylalanine concentration is associated with more rapid telomere shortening in men.

Eriksson JG, Guzzardi MA, Iozzo P, Kajantie E, Kautiainen H, Salonen MK.

Am J Clin Nutr. 2017 Jan;105(1):144-150. doi: 10.3945/ajcn.116.130468.

PMID: 27881392




Telomere length and telomere shortening are associated with age-related health outcomes. Only a few studies have been able to longitudinally report on factors that are associated with changes in telomere length in an aging population.


We studied the longitudinal relation between telomere length, the change in telomere length, and circulating amino acids.


A total of 812 subjects from the Helsinki Birth Cohort Study (born from 1934 to 1944), who underwent 3 clinical visits during a 10-y interval that included measurements of cardiometabolic risk factors, were included in the study. Leukocyte telomere length (LTL) was measured with the use of quantitative real-time polymerase chain reaction. Circulating branched-chain and aromatic amino acids (alanine, glycine, histidine, phenylalanine, leucine, isoleucine, valine, and tyrosine) were assessed with the use of high-throughput nuclear magnetic resonance spectroscopy.


The relative ± SD LTL at a mean age of 71 y was 0.79 ± 0.27 in men and 0.89 ± 0.35 in women (P < 0.001). Of the studied amino acids, the strongest inverse association was observed between the phenylalanine concentration that was measured 5 y earlier and the LTL. This finding was significant in men (P = 0.021) and remained significant after adjustment for multiple comparisons, but it was not significant in women (P = 0.39). Longitudinally, the change in LTL over 10 y was inversely associated with the phenylalanine concentration in men (P = 0.007) but not in women (P = 0.58) after adjustment for baseline LTL, age, smoking, and percentage of body fat.


The serum phenylalanine concentration is associated with telomere length and, therefore, potentially with the aging process. Because the associations reported are observational, no conclusions can be made regarding causality. Our findings support the hypothesis that cellular pathways that regulate aging are sex specific.

© 2017 American Society for Nutrition.


aging; amino acids; longitudinal study; phenylalanine; telomere shortening; telomeres


Total red meat intake of ≥0.5 servings/d does not negatively influence cardiovascular disease risk factors: a systemically searched meta-analysis of randomized controlled trials.

O'Connor LE, Kim JE, Campbell WW.

Am J Clin Nutr. 2017 Jan;105(1):57-69. doi: 10.3945/ajcn.116.142521.

PMID: 27881394




Observational associations between red meat intake and cardiovascular disease (CVD) are inconsistent. There are limited comprehensive analyses of randomized controlled trials (RCTs) that investigate the effects of red meat consumption on CVD risk factors.


The purpose of this systematically searched meta-analysis was to assess the effects of consuming ≥0.5 or <0.5 servings of total red meat/d on CVD risk factors [blood total cholesterol (TC), LDL cholesterol, HDL cholesterol, triglycerides, ratio of TC to HDL cholesterol (TC:HDL), and systolic and diastolic blood pressures (SBP and DBP, respectively)]. We hypothesized that the consumption of ≥0.5 servings of total red meat/d would have a negative effect on these CVD risk factors.


Two researchers independently screened 945 studies from PubMed, Cochrane Library, and Scopus databases and extracted data from 24 qualified RCTs. Inclusion criteria were 1) RCT, 2) subjects aged ≥19 y, 3) consumption of ≥0.5 or <0.5 total red meat servings/d [35 g (1.25 ounces)], and 4) reporting ≥1 CVD risk factor. We performed an adjusted 2-factor nested ANOVA mixed-effects model procedure on the postintervention values of TC, LDL cholesterol, HDL cholesterol, TC:HDL cholesterol, triglycerides, SBP, and DBP; calculated overall effect sizes of change values; and used a repeated-measures ANOVA to assess pre- to postintervention changes.


Red meat intake did not affect lipid-lipoprotein profiles or blood pressure values postintervention (P > 0.05) or changes over time [weighted mean difference (95% CI): -0.01 mmol/L (-0.08, 0.06 mmol/L), 0.02 mmol/L (-0.05, 0.08 mmol/L), 0.03 mmol/L (-0.01, 0.07 mmol/L), and 0.04 mmol/L (-0.02, 0.10 mmol/L); -0.08 mm Hg (-0.26, 0.11 mm Hg); and -1.0 mm Hg (-2.4, 0.78 mm Hg) and 0.1 mm Hg (-1.2, 1.5 mm Hg) for TC, LDL cholesterol, HDL cholesterol, triglycerides, TC:HDL cholesterol, SBP, and DBP, respectively]. Among all subjects, TC, LDL cholesterol, HDL cholesterol, TC:HDL cholesterol, triglycerides, and DBP, but not SBP, decreased over time (P < 0.05).


The results from this systematically searched meta-analysis of RCTs support the idea that the consumption of ≥0.5 servings of total red meat/d does not influence blood lipids and lipoproteins or blood pressures.


animal flesh; blood lipids; blood lipoproteins; blood pressure; diet; dietary guidance; meat; meat products

"During the time this manuscript was

being developed and written, WWC received research support from American

Egg Board–Egg Nutrition Center, Beef Checkoff, Coca-Cola Foundation,

National Dairy Council, National Institutes of Health, Pork Checkoff,

and USDA and had a consulting arrangement with Coca-Cola Company.

None of these organizations provided support to conduct this meta-analysis.

WWC also served on the 2015 Dietary Guidelines Advisory Committee and

was a member of the Advisory Council on Nutrition and Healthy Food

Choices, Foundation for Food and Agriculture Research. JEK received support

from the American Egg Board–Egg Nutrition Center. "


[The first below paper is not pdf-availed.]

Breaking down, starting up: can a vitamin C-enriched gelatin supplement before exercise increase collagen synthesis?

Levine M, Violet PC.

Am J Clin Nutr. 2016 Dec 21. pii: ajcn148312. doi: 10.3945/ajcn.116.148312. [Epub ahead of print] No abstract available.

PMID: 28003207

Vitamin C-enriched gelatin supplementation before intermittent activity augments collagen synthesis.

Shaw G, Lee-Barthel A, Ross ML, Wang B, Baar K.

Am J Clin Nutr. 2016 Nov 16. pii: ajcn138594. [Epub ahead of print]

PMID: 27852613




Musculoskeletal injuries are the most common complaint in active populations. More than 50% of all injuries in sports can be classified as sprains, strains, ruptures, or breaks of musculoskeletal tissues. Nutritional and/or exercise interventions that increase collagen synthesis and strengthen these tissues could have an important effect on injury rates.


This study was designed to determine whether gelatin supplementation could increase collagen synthesis.


Eight healthy male subjects completed a randomized, double-blinded, crossover-design study in which they consumed either 5 or 15 g of vitamin C-enriched gelatin or a placebo control. After the initial drink, blood was taken every 30 min to determine amino acid content in the blood. A larger blood sample was taken before and 1 h after consumption of gelatin for treatment of engineered ligaments. One hour after the initial supplement, the subjects completed 6 min of rope-skipping to stimulate collagen synthesis. This pattern of supplementation was repeated 3 times/d with ≥6 h between exercise bouts for 3 d. Blood was drawn before and 4, 24, 48, and 72 h after the first exercise bout for determination of amino-terminal propeptide of collagen I content.


Supplementation with increasing amounts of gelatin increased circulating glycine, proline, hydroxyproline, and hydroxylysine, peaking 1 h after the supplement was given. Engineered ligaments treated for 6 d with serum from samples collected before or 1 h after subjects consumed a placebo or 5 or 15 g gelatin showed increased collagen content and improved mechanics. Subjects who took 15 g gelatin 1 h before exercise showed double the amino-terminal propeptide of collagen I in their blood, indicating increased collagen synthesis.


These data suggest that adding gelatin to an intermittent exercise program improves collagen synthesis and could play a beneficial role in injury prevention and tissue repair. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12616001092482.


bone; exercise; inury prevention; ligament; return to play; tendon

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A randomized controlled trial to study the effects of breakfast on energy intake, physical activity, and body fat in women who are nonhabitual breakfast eaters.

LeCheminant GM, LeCheminant JD, Tucker LA, Bailey BW.

Appetite. 2017 Jan 4. pii: S0195-6663(16)31031-5. doi: 10.1016/j.appet.2016.12.041. [Epub ahead of print]

PMID: 28063876




The purpose of this study was to determine the effects of eating breakfast on energy intake, physical activity, body weight, and body fat in women who are nonhabitual breakfast eaters over a four-week period.


Forty-nine women who were nonhabitual breakfast-eaters were randomized to one of two conditions: breakfast or no breakfast. Breakfast eaters were required to eat at least 15% of their daily energy requirement before 8:30 a.m. Non-breakfast eaters did not consume any energy until after 11:30 a.m. Weight and body fat were assessed at baseline and after four weeks of intervention. Body fat was measured by dual energy x-ray absorptiometry (DXA). Participants completed seven 24-hour recalls to assess dietary intake during the intervention. Physical activity was measured by accelerometry for 32 consecutive days.


On average, the participants randomized to eat breakfast consumed 266 ± 496 (F = 12.81; P < 0.01) more calories per day over the course of the study and weighed 0.7 ± 0.8 kg (F = 7.81; p < 0.01) more at the end of the intervention. There was no observed caloric compensation at subsequent meals and no change in self-reported hunger or satiety. There was also no physical activity compensation with the addition of breakfast.


The findings of our study showed that requiring non-breakfast eaters to eat breakfast resulted in higher caloric intake and weight gain. Future research should evaluate this relationship for a longer period of time to see if adding breakfast to the diet of women who generally do not eat breakfast results in adaptive behavior change over time.


Body composition; Body fat; Breakfast; Daily energy intake; List of tables; Morning meal; Physical activity


Season of birth and the risk of type 2 diabetes in adulthood: a prospective cohort study of 0.5 million Chinese adults.

Si J, Yu C, Guo Y, Bian Z, Li X, Yang L, Chen Y, Sun H, Yu B, Chen J, Chen Z, Lv J, Li L; China Kadoorie Biobank Collaborative Group..

Diabetologia. 2017 Jan 7. doi: 10.1007/s00125-016-4200-4. [Epub ahead of print]

PMID: 28064359




Season of birth as a surrogate for potential environmental exposure during fetal development and early postnatal life has shown an inconsistent association with adult type 2 diabetes in white populations living in high-latitude regions. The present study aimed to examine the association between birth seasonality and risk of adult type 2 diabetes in Chinese individuals living across wide regions of low latitude and lower to middle latitude.


Participants from the China Kadoorie Biobank were enrolled during 2004-2008 and followed up until 31 December 2013. After excluding participants with cancer, heart disease, stroke and diabetes at baseline, the present study included 189,153 men and 272,058 women aged 30-79 years. We used multivariable Cox proportional hazards model to estimate the HR and 95% CI.


During a median follow-up of 7.2 years (3.3 million person-years), we documented 8784 incident cases of type 2 diabetes. In the whole cohort, compared with summer-born participants, the adjusted HRs (95% CIs) were 1.09 (1.02, 1.16), 1.08 (1.02, 1.15) and 1.09 (1.02, 1.15) for those who were born in Spring, Autumn and Winter, respectively. The association was consistent in both men and women and across subgroups defined by residence and lifestyle factors later in life.


In this large prospective study, participants born in summer had a lower risk of adult type 2 diabetes compared with other seasons of birth, suggesting exposures in early life with some degree of seasonal variation might influence the risk of adult diabetes.


Fetal development; Seasons; Type 2 diabetes


Dietary fibre for the prevention of recurrent colorectal adenomas and carcinomas.

Yao Y, Suo T, Andersson R, Cao Y, Wang C, Lu J, Chui E.

Cochrane Database Syst Rev. 2017 Jan 8;1:CD003430. doi: 10.1002/14651858.CD003430.pub2. [Epub ahead of print] Review.

PMID: 28064440




This is an update of the Cochrane review published in 2002.Colorectal cancer (CRC) is a major cause of morbidity and mortality in industrialised countries. Experimental evidence has supported the hypothesis that dietary fibre may protect against the development of CRC, although epidemiologic data have been inconclusive.


To assess the effect of dietary fibre on the recurrence of colorectal adenomatous polyps in people with a known history of adenomatous polyps and on the incidence of CRC compared to placebo. Further, to identify the reported incidence of adverse effects, such as abdominal pain or diarrhoea, that resulted from the fibre intervention.


We identified randomised controlled trials (RCTs) from Cochrane Colorectal Cancer's Specialised Register, CENTRAL, MEDLINE and Embase (search date, 4 April 2016). We also searched ClinicalTrials.gov and WHO International Trials Registry Platform on October 2016.


We included RCTs or quasi-RCTs. The population were those having a history of adenomatous polyps, but no previous history of CRC, and repeated visualisation of the colon/rectum after at least two-years' follow-up. Dietary fibre was the intervention. The primary outcomes were the number of participants with: 1. at least one adenoma, 2. more than one adenoma, 3. at least one adenoma greater than or equal to 1 cm, or 4. a new diagnosis of CRC. The secondary outcome was the number of adverse events.


Two reviewers independently extracted data, assessed trial quality and resolved discrepancies by consensus. We used risk ratios (RR) and risk difference (RD) with 95% confidence intervals (CI) to measure the effect. If statistical significance was reached, we reported the number needed to treat for an additional beneficial outcome (NNTB) or harmful outcome (NNTH). We combined the study data using the fixed-effect model if it was clinically, methodologically, and statistically reasonable.


We included seven studies, of which five studies with 4798 participants provided data for analyses in this review. The mean ages of the participants ranged from 56 to 66 years. All participants had a history of adenomas, which had been removed to achieve a polyp-free colon at baseline. The interventions were wheat bran fibre, ispaghula husk, or a comprehensive dietary intervention with high fibre whole food sources alone or in combination. The comparators were low-fibre (2 to 3 g per day), placebo, or a regular diet. The combined data showed no statistically significant difference between the intervention and control groups for the number of participants with at least one adenoma (5 RCTs, n = 3641, RR 1.04, 95% CI 0.95 to 1.13, low-quality evidence), more than one adenoma (2 RCTs, n = 2542, RR 1.06, 95% CI 0.94 to 1.20, low-quality evidence), or at least one adenoma 1 cm or greater (4 RCTs, n = 3224, RR 0.99, 95% CI 0.82 to 1.20, low-quality evidence) at three to four years. The results on the number of participants diagnosed with colorectal cancer favoured the control group over the dietary fibre group (2 RCTS, n = 2794, RR 2.70, 95% CI 1.07 to 6.85, low-quality evidence). After 8 years of comprehensive dietary intervention, no statistically significant difference was found in the number of participants with at least one recurrent adenoma (1 RCT, n = 1905, RR 0.97, 95% CI 0.78 to 1.20), or with more than one adenoma (1 RCT, n = 1905, RR 0.89, 95% CI 0.64 to 1.24). More participants given ispaghula [https://en.wikipedia.org/wiki/Psyllium]husk group had at least one recurrent adenoma than the control group (1 RCT, n = 376, RR 1.45, 95% CI 1.01 to 2.08). Other analyses by types of fibre intervention were not statistically significant. The overall dropout rate was over 16% in these trials with no reasons given for these losses. Sensitivity analysis incorporating these missing data shows that none of the results can be considered as robust; when the large numbers of participants lost to follow-up were assumed to have had an event or not, the results changed sufficiently to alter the conclusions that we would draw. Therefore, the reliability of the findings may have been compromised by these missing data (attrition bias) and should be interpreted with caution.


There is a lack of evidence from existing RCTs to suggest that increased dietary fibre intake will reduce the recurrence of adenomatous polyps in those with a history of adenomatous polyps within a two to eight year period. However, these results may be unreliable and should be interpreted cautiously, not only because of the high rate of loss to follow-up, but also because adenomatous polyp is a surrogate outcome for the unobserved true endpoint CRC. Longer-term trials with higher dietary fibre levels are needed to enable confident conclusion.


Whole-Body Docosahexaenoic Acid Synthesis-Secretion Rates in Rats Are Constant across a Large Range of Dietary α-Linolenic Acid Intakes.

Domenichiello AF, Kitson AP, Metherel AH, Chen CT, Hopperton KE, Stavro PM, Bazinet RP.

J Nutr. 2017 Jan;147(1):37-44. doi: 10.3945/jn.116.232074.

PMID: 27852871




Docosahexaenoic acid (DHA) is an ω-3 (n-3) polyunsaturated fatty acid (PUFA) thought to be important for brain function. Although the main dietary source of DHA is fish, DHA can also be synthesized from α-linolenic acid (ALA), which is derived from plants. Enzymes involved in DHA synthesis are also active toward ω-6 (n-6) PUFAs to synthesize docosapentaenoic acid n-6 (DPAn-6). It is unclear whether DHA synthesis from ALA is sufficient to maintain brain DHA.


The objective of this study was to determine how different amounts of dietary ALA would affect whole-body DHA and DPAn-6 synthesis rates.


Male Long-Evans rats were fed an ALA-deficient diet (ALA-D), an ALA-adequate (ALA-A) diet, or a high-ALA (ALA-H) diet for 8 wk from weaning. Dietary ALA concentrations were 0.07%, 3%, and 10% of the fatty acids, and ALA was the only dietary PUFA that differed between the diets. After 8 wk, steady-state stable isotope infusion of labeled ALA and linoleic acid (LA) was performed to determine the in vivo synthesis-secretion rates of DHA and DPAn-6.


Rats fed the ALA-A diet had an ∼2-fold greater capacity to synthesize DHA than did rats fed the ALA-H and ALA-D diets, and a DHA synthesis rate that was similar to that of rats fed the ALA-H diet. However, rats fed the ALA-D diet had a 750% lower DHA synthesis rate than rats fed the ALA-A and ALA-H diets. Despite enrichment into arachidonic acid, we did not detect any labeled LA appearing as DPAn-6.


Increasing dietary ALA from 3% to 10% of fatty acids did not increase DHA synthesis rates, because of a decreased capacity to synthesize DHA in rats fed the ALA-H diet. Tissue concentrations of DPAn-6 may be explained at least in part by longer plasma half-lives.


docosahexaenoic acid; kinetics; synthesis; α-linolenic acid; ω-3 PUFA


Dietary Leucine Supplementation Decreases Whole-Body Protein Turnover before, but Not during, Immune System Stimulation in Pigs.

Rudar M, Zhu CL, de Lange CF.

J Nutr. 2017 Jan;147(1):45-51. doi: 10.3945/jn.116.236893.

PMID: 27798336





Immune system stimulation (ISS) adversely affects protein metabolism and reduces pig productivity. Leu has a regulatory role in skeletal muscle and whole-body protein turnover, which may be affected by ISS.


We sought to determine the effect of supplemental Leu intake on whole-body protein turnover in pigs before and during ISS.


Pigs [mean ± SD initial body weight (BW): 10.6 ± 1.1 kg] were surgically fitted with jugular vein catheters and assigned to 1 of 3 treatments: 1.36% standardized ileal-digestible (SID) Leu (CON; n = 13); 2.04% SID Leu (LEU-M; n = 8); and 2.72% SID Leu (LEU-H; n = 7). Pigs were infused continuously with 0.66 ± 0.05 mmol 15N ⋅ kg BW-1 ⋅ d-1 to determine whole-body protein kinetics. The study consisted of a 72-h prechallenge period followed by a 36-h challenge period. At the start of the challenge period, ISS was induced in all LEU-M and LEU-H pigs and half of the CON pigs with LPS (ISS+); the remaining CON pigs were administered saline (ISS-).


Whole-body protein synthesis (309, 273, and 260 ± 14 mmol N ⋅ kg BW-1 ⋅ d-1 for CON, LEU-M, and LEU-H pigs, respectively) and protein degradation (233, 203, and 185 ± 14 mmol N ⋅ kg BW-1 ⋅ d-1 for CON, LEU-M, and LEU-H pigs, respectively) were reduced with increasing Leu intake during the prechallenge period (P < 0.05). ISS reduced whole-body protein synthesis (203 compared with 169 ± 12 mmol N ⋅ kg BW-1 ⋅ d-1 for ISS- and ISS+ pigs fed CON, respectively; P < 0.05) and protein deposition (PD) (64.9 compared with 45.0 ± 2.9 mmol N ⋅ kg BW-1 ⋅ d-1 for ISS- and ISS+ pigs fed CON, respectively; P < 0.01), whereas ISS did not affect whole-body protein degradation. Leu intake did not affect whole-body protein synthesis or degradation in ISS+ pigs.


Our results indicate that supplemental Leu intake improves the efficiency of PD rather than PD directly in healthy pigs but did not affect whole-body protein turnover during ISS.


immune system stimulation; leucine; pigs; protein deposition; whole-body protein turnover


Maternal Circadian Eating Time and Frequency Are Associated with Blood Glucose Concentrations during Pregnancy.

Loy SL, Chan JK, Wee PH, Colega MT, Cheung YB, Godfrey KM, Kwek K, Saw SM, Chong YS, Natarajan P, Müller-Riemenschneider F, Lek N, Chong MF, Yap F.

J Nutr. 2017 Jan;147(1):70-77. doi: 10.3945/jn.116.239392.

PMID: 27798346




Synchronizing eating schedules to daily circadian rhythms may improve metabolic health, but its association with gestational glycemia is unknown.


This study examined the association of maternal night-fasting intervals and eating episodes with blood glucose concentrations during pregnancy.


This was a cross-sectional study within a prospective cohort in Singapore. Maternal 24-h dietary recalls, fasting glucose, and 2-h glucose concentrations were ascertained at 26-28 wk gestation for 1061 women (aged 30.7 ± 5.1 y). Night-fasting intervals were based on the longest fasting duration during the night (1900-0659). Eating episodes were defined as events that provided >50 kcal, with a time interval between eating episodes of ≥15 min. Multiple linear regressions with adjustment for confounders were conducted.


Mean ± SD night-fasting intervals and eating episodes per day were 9.9 ± 1.6 h and 4.2 ± 1.3 times/d, respectively; fasting and 2-h glucose concentrations were 4.4 ± 0.5 and 6.6 ± 1.5 mmol/L, respectively. In adjusted models, each hourly increase in night-fasting intervals was associated with a 0.03 mmol/L decrease in fasting glucose (95% CI: -0.06, -0.01 mmol/L), whereas each additional daily eating episode was associated with a 0.15 mmol/L increase in 2-h glucose (95% CI: 0.03, 0.28 mmol/L). Conversely, night-fasting intervals and daily eating episodes were not associated with 2-h and fasting glucose, respectively.


Increased maternal night-fasting intervals and reduced eating episodes per day were associated with decreased fasting glucose and 2-h glucose, respectively, in the late-second trimester of pregnancy. This points to potential alternative strategies to improve glycemic control in pregnant women.


food timing; gestational diabetes; hyperglycemia; meal frequency; pregnancy diet


'Greed, competing interests and poor information' drive over- and underuse of medicine worldwide, expert says

Thomson Reuters Posted: Jan 09, 2017


Inappropriate antibiotic prescribing can cause avoidable harms at the same time as wasting resources better spent on much-needed services.

(Sherry Vivian/CBC)

Up to 70 per cent of hysterectomies in the United States, a quarter of knee replacements in Spain and more than half the antibiotics prescribed in China are inappropriate, overused healthcare, researchers said on Monday.

Experts who carried out a series of studies across the world found that medicine and healthcare are routinely both over- and underused, causing avoidable harm and suffering and wasting precious resources.

The studies, commissioned by The Lancet journal and conducted by 27 international specialists, also found rates of Caesarian section deliveries are soaring — often in women who do not need them — while the simple use of steroids to prevent premature births has lagged for 40 years.

"A common tragedy in both wealthy and poor countries is the use of expensive and sometimes ineffective technology while low-cost effective interventions are neglected," the experts wrote in a statement about their findings.

Antibiotic resistance poses threat to routine surgery, doctors warn

The World Health Organization estimates that 6.2 million excess C-sections are performed each year — 50 per cent of them in Brazil and China alone.

Vikas Saini, one of the lead authors of the study series and president of the U.S. Lown Institute in Boston, said factors driving the global failure to the right level of care include "greed, competing interests and poor information," which he said combine to create "an ecosystem of poor healthcare delivery."

Co-lead researcher Shannon Brownlee added: "Patients and citizens need to understand what's at stake here if their health systems fail to address these twin problems. In the U.S., we are wasting billions of dollars that should be devoted to improving the nation's health."

The study series analysed the scope, causes and consequences of underuse and overuse of healthcare around the world. It found that both can occur in the same country, the same organization or health facility, and even afflict the same patient.

The researchers noted that a study in China found 57 per cent of patients received inappropriate antibiotics; that inappropriate hysterectomies in the United States range from 16 to 70 per cent; and inappropriate total knee replacement rates were 26 per cent in Spain and 34 per cent in the United States.

Rates of inappropriate hysterectomies were 20 per cent in Taiwan and 13 per cent in Switzerland, they found.

Underuse leaves patients "vulnerable to avoidable disease and suffering" the researchers said, while overuse causes avoidable harms from tests or treatments at the same time as wasting resources better spent on much-needed services.


Drivers of poor medical care

Vikas Saini, Sandra Garcia-Armesto, David Klemperer, Valerie Paris, Adam G Elshaug, Shannon Brownlee, John P A Ioannidis, Elliott S Fisher

Lancet, in press, JANUARY 9, 2017 DOI: http://dx.doi.org/10.1016/S0140-6736(16)30947-3 |


The global ubiquity of overuse and underuse of health-care resources and the gravity of resulting harms necessitate an investigation of drivers to inform potential solutions. We describe the network of influences that contribute to poor care and suggest that it is driven by factors that fall into three domains: money and finance; knowledge, bias, and uncertainty; and power and human relationships. In each domain the drivers operate at the global, national, regional, and individual level, and are modulated by the specific contexts within which they act. We discuss in detail drivers of poor care in each domain.


Lancer in press JANUARY 9, 2017

JANUARY 8, 2017



Evidence for overuse of medical services around the world

Shannon Brownlee, Kalipso Chalkidou, Jenny Doust, Adam G Elshaug, Paul Glasziou, Iona Heath, Somil Nagpal, Vikas Saini, Divya Srivastava, Kelsey Chalmers, Deborah Korenstein


Avoiding overuse—the next quality frontier

Donald M Berwick



Vikas Saini: leading activist in the Right Care Alliance

Richard Lane


From universal health coverage to right care for health

Sabine Kleinert, Richard Horton


Levers for addressing medical underuse and overuse: achieving high-value health care

Adam G Elshaug, Meredith B Rosenthal, John N Lavis, Shannon Brownlee, Harald Schmidt, Somil Nagpal, Peter Littlejohns, Divya Srivastava, Sean Tunis, Vikas Saini



Addressing overuse and underuse around the world

Vikas Saini, Shannon Brownlee, Adam G Elshaug, Paul Glasziou, Iona Heath


Evidence for underuse of effective medical services around the world

Paul Glasziou, Sharon Straus, Shannon Brownlee, Lyndal Trevena, Leonila Dans, Gordon Guyatt, Adam G Elshaug, Robert Janett, Vikas Saini


Plasma Inflammation Markers of the Tumor Necrosis Factor Pathway but Not C-Reactive Protein Are Associated with Processed Meat and Unprocessed Red Meat Consumption in Bavarian Adults.

Schwedhelm C, Pischon T, Rohrmann S, Himmerich H, Linseisen J, Nimptsch K.

J Nutr. 2017 Jan;147(1):78-85. doi: 10.3945/jn.116.237180.

PMID: 27798340




High consumption of red and processed meats has been linked to higher chronic disease risk. It has been hypothesized that inflammation markers may mediate part of this association. Most previous studies on the association of red meat intake with circulating inflammation markers used C-reactive protein (CRP) but rarely other markers, and not all differentiated between processed meat and unprocessed red meat.


We investigated the cross-sectional association of processed meat and unprocessed red meat consumption with plasma concentrations of CRP, interleukin 6 (IL-6), tumor necrosis factor (TNF)-α, soluble TNF receptor (sTNF-R) 1, and sTNF-R2 in German adults.


Inflammation markers were quantified in the plasma of 553 adults (233 men and 320 women) aged 18-80 y within the cross-sectional Bavarian Food Consumption Survey II. Dietary intake was estimated from three 24-h dietary recalls. The association between red meat consumption and inflammation markers was analyzed with the use of multivariable-adjusted linear regression.


Processed meat consumption was borderline significantly associated with higher IL-6 [relative difference per 50-g increment: 5% (95% CI: -1%, 10%)] but not with CRP (2%; 95% CI: -6%, 10%), and it was inversely associated with total TNF-α (-3%; 95% CI: -6%, -1%), sTNF-R1 (-3%; 95% CI: -4%, -1%), and sTNF-R2 (-2%; 95% CI: -4%, 0%) concentrations. Unprocessed red meat consumption was not associated with CRP (-5%; 95% CI: -15%, 5%) or IL-6 (-1%; 95% CI: -9%, 7%) but was inversely associated with sTNF-R1 (-3%; 95% CI: -5%, -1%) and sTNF-R2 (-4%; 95% CI: -7%, -2%).


Our results suggest an inverse association between both processed meat and unprocessed red meat with inflammation markers of the TNF pathway in Bavarian adults but no association with CRP. Further research on the role of TNF pathway markers in chronic inflammation is warranted.


C-reactive protein; IL-6; TNF-α; inflammation; processed meat; soluble TNF receptor; unprocessed red meat


A Carbohydrate-Rich Beverage Prior to Surgery Prevents Surgery-Induced Immunodepression: A Randomized, Controlled, Clinical Trial.

Melis GC, van Leeuwen PA, von Blomberg-van der Flier BM, Goedhart-Hiddinga AC, Uitdehaag BM, van Schijndel RJ, Wuisman PI, van Bokhorst-de van der Schueren MA.

JPEN J Parenter Enteral Nutr. 2006;30(1):21-26. doi: 10.1177/014860710603000121.

PMID: 28059013





Fasting before surgery is still common care in a lot of western hospitals. Overnight fasting can induce postoperative insulin resistance. Insulin resistance has been shown to be related to infectious morbidity. It was shown that postoperative insulin resistance can be attenuated by preoperative intake of a clear carbohydrate-rich beverage. The aim of this study was to investigate whether preoperative intake of carbohydrate-rich beverages could postoperatively influence the immune system.


In this randomized, controlled study, we investigated the effect of surgery on the postoperative immune response in 10 preoperatively fasted patients (control) and 2 groups of 10 patients receiving 2 different carbohydrate-rich beverages preoperatively, by measuring human leukocyte antigen (HLA)-DR expression on monocytes on the day before and on the day after surgery. Furthermore, we studied perioperative fluid homeostasis and preoperative well-being of the patients.


HLA-DR expression decreased significantly after surgery in the control group. Patients receiving any of the 2 carbohydrate-rich beverages did not show this postoperative decrease. Fluid homeostasis was not affected in any of the groups, and well-being tended to be better in patients receiving carbohydrate-rich beverages compared with controls.


This study suggests that preoperative intake of a carbohydrate-rich beverage can prevent surgery-induced immunodepression and thus might reduce the risk of infectious complications.


Short-term high-fat diet compromises myocardial function: a radial strain rate imaging study.

Ternacle J, Wan F, Sawaki D, Surenaud M, Pini M, Mercedes R, Ernande L, Audureau E, Dubois-Rande JL, Adnot S, Hue S, Czibik G, Derumeaux G.

Eur Heart J Cardiovasc Imaging. 2017 Jan 6. pii: jew316. doi: 10.1093/ehjci/jew316. [Epub ahead of print]

PMID: 28062567




Long-term high-fat diet (HFD) induces both cardiac remodelling and myocardial dysfunction in murine models. The aim was to assess the time course and mechanisms of metabolic and cardiac modifications induced by short-term HFD in wild-type (WT) mice.


Thirty-three WT mice were subjected to HFD (60% fat, n = 16) and chow diet (CD, 13% fat, n = 17). Metabolic and echocardiographic data were collected at baseline and every 5 weeks for 20 weeks. Invasive haemodynamic data and myocardial samples were collected at 5 and 20 weeks. Echocardiographic data included left ventricular (LV) diameters and thickness, and systolic function using radial strain rate (SR). Histological assessment of cardiomyocyte and adipocyte sizes, interstitial fibrosis, and apoptosis index were performed. During follow-up, body weight, and glycaemia levels were higher in HFD than in CD mice, in association with an early adipose tissue remodelling. Despite no difference between both groups in blood pressure and LV mass at 5 weeks, an early LV dysfunction was observed in HFD mice as assessed by radial SR (21 ± 0.8 vs. 27 ± 0.8 unit/s, P < 0.001) and haemodynamic assessment. During follow-up, both groups demonstrated a progressive systolic and diastolic LV dysfunction and remodelling including dilatation and hypertrophy, which were more severe in HFD mice. Compared with CD mice, the early LV impairment in HFD mice was coupled with a higher cardiomyocyte apoptosis level (0.95 vs. 0.02%, P < 0.05) associated with an interstitial fibrosis process (2.3 vs. 0.2%, P < 0.05), which worsen during follow-up.


The HFD promoted early metabolic and cardiac dysfunctions, and adipose and myocardial tissues remodelling.


cardiomyopathy; high-fat diet; obesity; strain rate imaging


Diabetes, plasma glucose and incidence of pancreatic cancer: A prospective study of 0.5 million Chinese adults and a meta-analysis of 22 cohort studies.

Pang Y, Kartsonaki C, Guo Y, Bragg F, Yang L, Bian Z, Chen Y, Iona A, Millwood IY, Lv J, Yu C, Chen J, Li L, Holmes MV, Chen Z.

Int J Cancer. 2017 Jan 7. doi: 10.1002/ijc.30599. [Epub ahead of print]

PMID: 28063165



Diabetes is associated with an increased risk of pancreatic cancer (PC) in Western populations. Uncertainty remains, however, about the relevance of plasma glucose for PC among people without diabetes and about the associations of diabetes and high blood glucose with PC in China where the increase in diabetes prevalence has been very recent. The prospective China Kadoorie Biobank (CKB) study recruited 512,000 adults aged 30-79 years from 10 diverse areas of China during 2004-08, recording 595 PC cases during 8 years of follow-up. Cox regression yielded adjusted hazard ratios (HRs) for PC associated with diabetes (previously diagnosed or screen-detected) and, among those without previously diagnosed diabetes, with levels of random plasma glucose (RPG). These were further meta-analysed with 22 published prospective studies. Overall 5.8% of CKB participants had diabetes at baseline. Diabetes was associated with almost two-fold increased risk of PC (adjusted HR=1.87, 95% CI 1.48-2.37), with excess risk higher in those with longer duration since diagnosis (p for trend=0.01). Among those without previously diagnosed diabetes, each 1 mmol/L higher usual RPG was associated with a HR of 1.12 (1.04-1.21). In meta-analysis of CKB and 22 other studies, previously diagnosed diabetes was associated with a 52% excess risk (1.52, 1.43-1.63). Among those without diabetes, each 1 mmol/L higher blood glucose was associated with a 15% (1.15, 1.09-1.21) excess risk. In Chinese and non-Chinese populations, diabetes and higher blood glucose levels among those without diabetes are associated with an increased risk of PC. This article is protected by copyright.


Chinese; Diabetes; pancreatic cancer; plasma glucose

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Sodium and Its Role in Cardiovascular Disease - The Debate Continues.

Kong YW, Baqar S, Jerums G, Ekinci EI.

Front Endocrinol (Lausanne). 2016 Dec 23;7:164. doi: 10.3389/fendo.2016.00164. Review.

PMID: 28066329



Guidelines have recommended significant reductions in dietary sodium intake to improve cardiovascular health. However, these dietary sodium intake recommendations have been questioned as emerging evidence has shown that there is a higher risk of cardiovascular disease with a low sodium diet, including in individuals with type 2 diabetes. This may be related to the other pleotropic effects of dietary sodium intake. Therefore, despite recent review of dietary sodium intake guidelines by multiple organizations, including the dietary guidelines for Americans, American Diabetes Association, and American Heart Association, concerns about the impact of the degree of sodium restriction on cardiovascular health continue to be raised. This literature review examines the effects of dietary sodium intake on factors contributing to cardiovascular health, including left ventricular hypertrophy, heart rate, albuminuria, rennin-angiotensin-aldosterone system activation, serum lipids, insulin sensitivity, sympathetic nervous system activation, endothelial function, and immune function. In the last part of this review, the association between dietary sodium intake and cardiovascular outcomes, especially in individuals with diabetes, is explored. Given the increased risk of cardiovascular disease in individuals with diabetes and the increasing incidence of diabetes worldwide, this review is important in summarizing the recent evidence regarding the effects of dietary sodium intake on cardiovascular health, especially in this population.


cardiovascular death; cardiovascular disease; chronic kidney disease; diabetes mellitus; dietary sodium intake; morbidity and mortality; salt intake; sodium intake


Association between consumption of soy and risk of cardiovascular disease: A meta-analysis of observational studies.

Yan Z, Zhang X, Li C, Jiao S, Dong W.

Eur J Prev Cardiol. 2017 Jan 1:2047487316686441. doi: 10.1177/2047487316686441. [Epub ahead of print]

PMID: 28067550




Background The relationships between dietary intake of soy foods and risk of cardiovascular disease are uncertain. The aims of this study were to evaluate and summarize the evidence on the association between consumption of soy and risk of cardiovascular disease (including stroke and coronary heart disease). Methods We systematically searched the MEDLINE and EMBASE databases from their inception up to 22 February 2016. We included only observational studies, and used random-effects models to calculate summary relative risks (SRRs) and 95% confidence intervals (CIs). Results A total of 10 prospective cohort and seven case-control studies met the inclusion criteria. There were a total of 17,269 cardiovascular disease events, including 6265 stroke events, 10,806 coronary heart disease events, and 198 other cardiovascular disease events. A significant negative association was shown between soy intake and risk of cardiovascular disease (SRR = 0.84 95% CI: 0.75-0.94; pheterogeneity<0.001, I2 = 71.4%). Subgroup meta-analyses indicated that a statistically significant protective effect was primarily observed in case-control studies and in Asian populations. There was a borderline significant association between intake of tofu and the risk of cardiovascular disease (SRR = 0.80, 95% CI: 0.64-1.00). A significant negative association was shown for the association between soy intake and risk of stroke (SRR = 0.82, 95% CI: 0.68-0.99) and coronary heart disease (SRR = 0.83, 95% CI: 0.72-0.95). There were no associations between soy isoflavones consumption and risk of cardiovascular disease, stroke, and coronary heart disease. Conclusion Overall evidence indicated that consumption of soy was negatively associated with the risk of cardiovascular disease, stroke, and coronary heart disease risk.


Cardiovascular disease; coronary heart disease; soy consumption; soy isoflavones; stroke


Health Benefits of Fiber Fermentation.

Dahl WJ, Agro NC, Eliasson ÅM, Mialki KL, Olivera JD, Rusch CT, Young CN.

J Am Coll Nutr. 2017 Jan 9:1-10. doi: 10.1080/07315724.2016.1188737. [Epub ahead of print]

PMID: 28067588



Although fiber is well recognized for its effect on laxation, increasing evidence supports the role of fiber in the prevention and treatment of chronic disease. The aim of this review is to provide an overview of the health benefits of fiber and its fermentation, and describe how the products of fermentation may influence disease risk and treatment. Higher fiber intakes are associated with decreased risk of cardiovascular disease, type 2 diabetes, and some forms of cancer. Fiber may also have a role in lowering blood pressure and in preventing obesity by limiting weight gain. Fiber is effective in managing blood glucose in type 2 diabetes, useful for weight loss, and may provide therapeutic adjunctive roles in kidney and liver disease. In addition, higher fiber diets are not contraindicated in inflammatory bowel disease or irritable bowel syndrome and may provide some benefit. Common to the associations with disease reduction is fermentation of fiber and its potential to modulate microbiota and its activities and inflammation, specifically the production of anti-inflammatory short chain fatty acids, primarily from saccharolytic fermentation, versus the deleterious products of proteolytic activity. Because fiber intake is inversely associated with all-cause mortality, mechanisms by which fiber may reduce chronic disease risk and provide therapeutic benefit to those with chronic disease need further elucidation and large, randomized controlled trials are needed to confirm causality.Teaching Points• Strong evidence supports the association between higher fiber diets and reduced risk of cardiovascular disease, type 2 diabetes, and some forms of cancer.• Higher fiber intakes are associated with lower body weight and body mass index, and some types of fiber may facilitate weight loss.• Fiber is recommended as an adjunctive medical nutritional therapy for type 2 diabetes, chronic kidney disease, and certain liver diseases.• Fermentation and the resulting shifts in microbiota composition and its activity may be a common means by which fiber impacts disease risk and management.


chronic disease prevention; fermentation; fiber; microbiota; nutrition therapy; short chain fatty acids


[The cohort studies were not impressive.]

Dietary Patterns and Pancreatic Cancer Risk: A Meta-Analysis.

Lu PY, Shu L, Shen SS, Chen XJ, Zhang XY.

Nutrients. 2017 Jan 5;9(1). pii: E38. doi: 10.3390/nu9010038. Review.

PMID: 28067765



A number of studies have examined the associations between dietary patterns and pancreatic cancer risk, but the findings have been inconclusive. Herein, we conducted this meta-analysis to assess the associations between dietary patterns and the risk of pancreatic cancer. MEDLINE (provided by the National Library of Medicine) and EBSCO (Elton B. Stephens Company) databases were searched for relevant articles published up to May 2016 that identified common dietary patterns. Thirty-two studies met the inclusion criteria and were finally included in this meta-analysis. A reduced risk of pancreatic cancer was shown for the highest compared with the lowest categories of healthy patterns (odds ratio, OR = 0.86; 95% confidence interval, CI: 0.77-0.95; p = 0.004) and light-moderate drinking patterns (OR = 0.90; 95% CI: 0.83-0.98; p = 0.02). There was evidence of an increased risk for pancreatic cancer in the highest compared with the lowest categories of western-type pattern (OR = 1.24; 95% CI: 1.06-1.45; p = 0.008) and heavy drinking pattern (OR = 1.29; 95% CI: 1.10-1.48; p = 0.002). The results of this meta-analysis demonstrate that healthy and light-moderate drinking patterns may decrease the risk of pancreatic cancer, whereas western-type and heavy drinking patterns may increase the risk of pancreatic cancer. Additional prospective studies are needed to confirm these findings.


alcohol consumption; dietary patterns; meta-analysis; pancreatic cancer


[i guess not liking the result does not mean I should ignore it.]

Effect of a Long-Term Intensive Lifestyle Intervention on Cognitive Function: Action for Health in Diabetes Study.

Rapp SR, Luchsinger JA, Baker LD, Blackburn GL, Hazuda HP, Demos-McDermott KE, Jeffery RW, Keller JN, McCaffery JM, Pajewski NM, Evans M, Wadden TA, Arnold SE, Espeland MA; Look AHEAD Research Group..

J Am Geriatr Soc. 2017 Jan 9. doi: 10.1111/jgs.14692. [Epub ahead of print]

PMID: 28067945




To assess whether randomization to 10 years of lifestyle intervention to induce and maintain weight loss improves cognitive function.


Randomized controlled clinical trial.


Data obtained as part of the Action for Health in Diabetes (Look AHEAD) trial (NCT00017953) and Look AHEAD Continuation study (U01 DK057136-15).


Overweight and obese individuals with type 2 diabetes mellitus aged 45 to 76 (N = 3,751).


Intensive lifestyle intervention (ILI) for weight loss through reduced caloric intake and increased physical activity compared with a control condition of diabetes support and education (DSE).


Certified examiners who were masked to intervention assignment administered a standard battery of cognitive function tests (Modified Mini-Mental State Examination, Rey Auditory Verbal Learning Test, Digit Symbol Coding, Trail-Making Test, Modified Stroop Color-Word Test) to participants 10 to 13 years after enrollment.


Assignment to lifestyle intervention was not associated with significantly different overall (P = .10) or domain-specific (all P > .10) cognitive function than assignment to diabetes support and education. Results were fairly consistent across prespecified groups, but there was some evidence of trends for differential intervention effects showing modest harm in ILI in participants with greater body mass index and in individuals with a history of cardiovascular disease. Cognitive function was not associated with changes in weight or fitness (all P > .05).


A long-term behavioral weight loss intervention for overweight and obese adults with diabetes mellitus was not associated with cognitive benefit.


cognition; diabetes mellitus; intervention; obesity; weight loss


Long-term impact of behavioral weight loss intervention on cognitive function.

Espeland MA, Rapp SR, Bray GA, Houston DK, Johnson KC, Kitabchi AE, Hergenroeder AL, Williamson J, Jakicic JM, van Dorsten B, Kritchevsky SB; Action for Health In Diabetes (Look AHEAD) Movement and Memory Subgroup.; Look AHEAD Research Group..

J Gerontol A Biol Sci Med Sci. 2014 Sep;69(9):1101-8. doi: 10.1093/gerona/glu031.

PMID: 24619151 Free PMC Article





It is unknown whether intentional weight loss provides long-term benefits for cognitive function.


An ancillary study to a randomized controlled clinical trial was conducted in overweight and obese individuals (N = 978), aged 45-76 years at enrollment, with type 2 diabetes. An intensive behavioral intervention designed to promote and maintain weight loss through caloric restriction and increased physical activity was compared with diabetes support and education. Standardized assessments of cognitive function were collected an average of 8.1 years after trial enrollment.


Participants assigned to intensive lifestyle intervention lost a mean (SE) 11.1% (0.4%) and 7.2% (0.5%) of weight at Years 1 and 8, respectively, compared with 1.0% (0.2%) and 3.3% (0.5%) in the control group (p < .001). Covariate-adjusted mean composite cognitive function test scores were similar for the two groups (p = .69), and no significant differences were found for any individual cognitive test. There was some evidence of a differential effect (nominal interaction p = .008) for a prespecified comparison: Intensive lifestyle intervention was associated with a relative mean benefit for composite cognitive function of 0.276 (95% confidence interval: 0.033, 0.520) SDs among individuals with body mass index less than 30 kg/m(2) at baseline compared with a relative mean deficit of 0.086 (-0.021, 0.194) SDs among individuals with body mass more than or equal to 30 kg/m(2).


Eight years of intensive lifestyle intervention did not alter cognitive function in obese adults with type 2 diabetes; however, there was evidence for benefit among overweight but not obese individuals. Changes in cognition were not assessed in this cross-sectional study.


Clinical trials.; Cognition; Diabetes; Obesity


[i would have liked to see analysis including energy intake, acid reflux, ulcers, etcetera in the adjustments meade.]

The Association of Hot Red Chili Pepper Consumption and Mortality: A Large Population-Based Cohort Study.

Chopan M, Littenberg B.

PLoS One. 2017 Jan 9;12(1):e0169876. doi: 10.1371/journal.pone.0169876.

PMID: 28068423




The evidence base for the health effects of spice consumption is insufficient, with only one large population-based study and no reports from Europe or North America. Our objective was to analyze the association between consumption of hot red chili peppers and mortality, using a population-based prospective cohort from the National Health and Nutritional Examination Survey (NHANES) III, a representative sample of US noninstitutionalized adults, in which participants were surveyed from 1988 to 1994. The frequency of hot red chili pepper consumption was measured in 16,179 participants at least 18 years of age. Total and cause-specific mortality were the main outcome measures. During 273,877 person-years of follow-up (median 18.9 years), a total of 4,946 deaths were observed. Total mortality for participants who consumed hot red chili peppers was 21.6% compared to 33.6% for those who did not (absolute risk reduction of 12%; relative risk of 0.64). Adjusted for demographic, lifestyle, and clinical characteristics, the hazard ratio was 0.87 (P = 0.01; 95% Confidence Interval 0.77, 0.97). Consumption of hot red chili peppers was associated with a 13% reduction in the instantaneous hazard of death. Similar, but statistically nonsignificant trends were seen for deaths from vascular disease, but not from other causes. In this large population-based prospective study, the consumption of hot red chili pepper was associated with reduced mortality. Hot red chili peppers may be a beneficial component of the diet.


[ https://en.wikipedia.org/wiki/Diverticulosis#Epidemiology ]

Western Dietary Pattern Increases, Whereas Prudent Dietary Pattern Decreases, Risk of Incident Diverticulitis in a Prospective Cohort Study.

Strate LL, Keeley BR, Cao Y, Wu K, Giovannucci EL, Chan AT.

Gastroenterology. 2017 Jan 5. pii: S0016-5085(17)30006-9. doi: 10.1053/j.gastro.2016.12.038. [Epub ahead of print]

PMID: 28065788




Dietary fiber is implicated as a risk factor for diverticulitis. Analyses of dietary patterns may provide information on risk beyond those of individual foods or nutrients. We examined whether major dietary patterns are associated with risk of incident diverticulitis.


We performed a prospective cohort study of 46,295 men who were free of diverticulitis and known diverticulosis in 1986 (baseline) using data from the Health Professionals Follow-up Study. Each study participant completed a detailed medical and dietary questionnaire at baseline. We sent supplemental questionnaires to men reporting incident diverticulitis on biennial follow-up questionnaires. We assessed diet every 4 years using a validated food frequency questionnaire. Western (high in red meat, refined grains, and high-fat dairy) and prudent (high in fruits, vegetables, and whole grains) dietary patterns were identified using principal component analysis. Follow-up time accrued from the date of return of the baseline questionnaire in 1986 until a diagnosis of diverticulitis, diverticulosis or diverticular bleeding; death; or December 31, 2012. The primary endpoint was incident diverticulitis.


During 894,468 person years of follow-up, we identified 1063 incident cases of diverticulitis. After adjustment for other risk factors, men in the highest quintile of western dietary pattern score had a multivariate hazard ratio (HR) of 1.55 (95% CI, 1.20-1.99) for diverticulitis compared to men in the lowest quintile. High vs low prudent scores were associated with decreased risk of diverticulitis (multivariate HR 0.74; 95% CI, 0.60-0.91). The association between dietary patterns and diverticulitis was predominantly attributable to intake of fiber and red meat.


In a prospective cohort study of 46,295 men, a western dietary pattern was associated with increased risk of diverticulitis, whereas a prudent pattern was associated with decreased risk. These data may guide dietary interventions for the prevention of diverticulitis.


HPFS; PCA; alternative healthy eating index; diverticular disease

Edited by AlPater

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Anxiety symptoms and risk of dementia and mild cognitive impairment in the oldest old women.

Kassem AM, Ganguli M, Yaffe K, Hanlon JT, Lopez OL, Wilson JW, Ensrud K, Cauley JA; Study of Osteoporotic Fractures (SOF) Research Group..

Aging Ment Health. 2017 Jan 10:1-9. doi: 10.1080/13607863.2016.1274370. [Epub ahead of print]

PMID: 28071922




Research is limited and findings conflict regarding anxiety as a predictor of future cognitive decline in the oldest old persons. We examined the relationship between levels of and changes in anxiety symptoms, and subsequent dementia and mild cognitive impairment (MCI) in the oldest old women.


We conducted secondary analyses of data collected from 1425 community-dwelling women (mean age = 82.8, SD ±3.1 years) followed on average for five years. The Goldberg Anxiety Scale was used to assess anxiety symptoms at baseline, and an expert clinical panel adjudicated dementia and MCI at follow-up. Participants with probable cognitive impairment at baseline were excluded.


At baseline, 190 (13%) women had moderate/severe anxiety symptoms and 403 (28%) had mild anxiety symptoms. Compared with those with no anxiety symptoms at baseline, women with mild anxiety symptoms were more likely to develop dementia at follow-up (multivariable-adjusted odds ratio = 1.66, 95% confidence interval 1.12-2.45). No significant association was observed between anxiety symptoms and MCI.


In the oldest old women, our findings suggest that mild anxiety symptoms may predict future risk of dementia, but not MCI. Future studies should explore potential biological mechanisms underlying associations of anxiety with cognitive impairment.


Aging; community sample; epidemiology


The effect of modifiable healthy practices on higher-level functional capacity decline among Japanese community dwellers.

Otsuka R, Nishita Y, Tange C, Tomida M, Kato Y, Nakamoto M, Ando F, Shimokata H, Suzuki T.

Prev Med Rep. 2016 Dec 28;5:205-209. doi: 10.1016/j.pmedr.2016.12.022.

PMID: 28070478




This study aimed to clarify the effects of the accumulation of 8 modifiable practices related to health, including smoking, alcohol drinking, physical activity, sleeping hours, body mass index, dietary diversity, ikigai (life worth living), and health checkup status, on higher-level functional capacity decline among Japanese community dwellers. Data were derived from the National Institute for Longevity Sciences - Longitudinal Study of Aging. Subjects comprised 1269 men and women aged 40 to 79 years at baseline (1997-2000) who participated in a follow-up postal survey (2013). Higher-level functional capacity was measured using the Tokyo Metropolitan Institute of Gerontology Index of Competence (total score and 3 subscales: instrumental self-maintenance, intellectual activity, and social role). The odds ratio (OR) and 95% confidence interval (CI) for a decline in higher-level functional capacity in the follow-up study according to the total number of healthy practices were analyzed using the lowest category as a reference. Multivariate adjusted ORs (95% CIs) for the total score of higher-level functional capacity, which declined according to the total number of healthy practices (0-4, 5-6, 7-8 groups) were 1.00 (reference), 0.63 (0.44-0.92), and 0.54 (0.31-0.94). For the score of social role decline, multivariate adjusted ORs (95% CIs) were 1.00 (reference), 0.62 (0.40-0.97), and 0.46 (0.23-0.90), respectively (P for trend = 0.04). Having more modifiable healthy practices, especially in social roles, may protect against a decline in higher-level functional capacity among middle-aged and elderly community dwellers in Japan.


BMI, body mass index; CI, confidence interval; Community dwellers; Healthy practices; Higher-level functional capacity; Japan; NILS-LSA, National Institute for Longevity Sciences - Longitudinal Study of Aging; OR, odds ratio; QUANTIDD, Quantitative Index for Dietary Diversity; Social role; TMIG-IC, Tokyo Metropolitan Institute of Gerontology Index of Competence


Caloric Intake in Medical ICU Patients: Consistency of Care With Guidelines and Relationship to Clinical Outcomes.

Krishnan JA, Parce PB, Martinez A.

Nutr Clin Pract. 2004 Dec;19(6):645-646. doi: 10.1177/0115426504019006645.

PMID: 28064571




To assess the consistency of caloric intake with American College of Chest Physicians (ACCP) recommendations for critically ill patients and to evaluate the relationship of caloric intake with clinical outcomes.


Prospective cohort study.


Adult intensive care units (ICUs) at 2 teaching hospitals.


Patients with an ICU length of stay of at least 96 hours.


On ICU admission, severity of illness (ie, simplified acute physiology score II) and markers of nutritional status (ie, serum albumin level and body mass index) were recorded. The route of feeding (ie, enteral or parenteral), actual caloric intake (ie, percentage of ACCP recommendations: 0% to 32% [tertile I]; 33% to 65% [tertile II]; ≥66% [tertile III]), and evidence of GI intolerance (ie, gastric aspirate levels, ≥100 mL) were recorded daily. The following outcomes were assessed: status on hospital discharge (alive vs dead); spontaneous ventilation before ICU discharge (yes vs no); and ICU discharge without developing nosocomial sepsis (yes vs no). The average caloric intake among 187 participants was 50.6% of the ACCP targets and was similar in both hospitals. Caloric intake was inversely related to the mean number of gastric aspirates≥ 100 mL/d (Spearman ρ =-.04; p = .06), but not to severity of illness, nutritional status, or route of feeding. After accounting for the number of gastric aspirates ≥100 mL, severity of illness, nutritional status, and route of feeding, tertile II of caloric intake ( vs tertile I) was associated with a significantly greater likelihood of achieving spontaneous ventilation before ICU discharge. Tertile III of caloric intake ( vs tertile I) was associated with a significantly lower likelihood of both hospital discharge alive and spontaneous ventilation before ICU discharge.


Study participants were underfed relative to ACCP targets. These targets, however, may overestimate needs because moderate caloric intake (ie, 33% to 65% of ACCP targets; approximately 9 to 18 kcal/kg per day) was associated with better outcomes than higher levels of caloric intake.


Lifestyle behaviours associated with 5-year weight gain in a prospective cohort of Australian adults aged 26-36 years at baseline.

Smith KJ, Gall SL, McNaughton SA, Cleland VJ, Otahal P, Dwyer T, Venn AJ.

BMC Public Health. 2017 Jan 10;17(1):54. doi: 10.1186/s12889-016-3931-y.

PMID: 28068968





Whether not meeting common guidelines for lifestyle behaviours is associated with weight gain is uncertain. This study examined whether 5-year weight gain was predicted by not meeting guidelines for: breakfast consumption (eating between 6 and 9 am), takeaway food consumption (<2 times/week), television viewing (<2 h/day) and daily steps (≥10,000 steps/day).


One thousand one hundred and fifty-five Australian participants (43% men, 26-36 years) completed questionnaires and wore a pedometer at baseline (2004-06) and follow-up (2009-11). Weight was measured or self-reported, with a correction factor applied. For each behaviour, participants were classified according to whether they met the guideline: consistently met at baseline and follow-up (reference group); not met at baseline but met at follow-up; met at baseline but not met at follow-up; consistently not met at baseline and follow-up. For each behaviour, weight gain was calculated using linear regression. Weight gain by number of guidelines met was also examined.


Mean 5-year weight gain was 2.0 kg (SD:6.3). Compared to the reference group, additional weight (mean, 95% CI) was gained among those who did not meet the guideline at follow-up, or consistently did not meet the guideline, for breakfast (1.8 kg, 0.7-2.9; 1.5 kg, 0.1-2.8); takeaway food (2.2 kg, 0.7-3.6; 1.9 kg, 0.7-3.1); watching television (1.9 kg, 0.9-2.9; 1.4 kg, 0.4-2.3); and daily steps (2.6 kg, 1.1-4.04; 1.6 kg, 0.5-2.7). Those who met ≤1 guideline at follow-up gained 3.8 kg (95% CI 2.3-5.3) more than those meeting all guidelines.


Individuals who adopted healthier behaviours between baseline and follow-up had similar weight gain to those who met the guidelines at both time points. Encouraging young adults to meet these simple guidelines may reduce weight gain.


Fast food; Guidelines; Physical activity; Sedentary behaviour; Skipping breakfast; Steps; Takeaway food; Television; Weight gain; Young adults


Multiple lifestyle behaviours and mortality, findings from a large population-based Norwegian cohort study - The HUNT Study.

Krokstad S, Ding D, Grunseit AC, Sund ER, Holmen TL, Rangul V, Bauman A.

BMC Public Health. 2017 Jan 10;17(1):58. doi: 10.1186/s12889-016-3993-x.

PMID: 28068991





Lifestyle risk behaviours are responsible for a large proportion of disease burden and premature mortality worldwide. Risk behaviours tend to cluster in populations. We developed a new lifestyle risk index by including emerging risk factors (sleep, sitting time, and social participation) and examine unique risk combinations and their associations with all-cause and cardio-metabolic mortality.


Data are from a large population-based cohort study in a Norway, the Nord-Trøndelag Health Study (HUNT), with an average follow-up time of 14.1 years. Baseline data from 1995-97 were linked to the Norwegian Causes of Death Registry. The analytic sample comprised 36 911 adults aged 20-69 years. Cox regression models were first fitted for seven risk factors (poor diet, excessive alcohol consumption, current smoking, physical inactivity, excessive sitting, too much/too little sleep, and poor social participation) separately and then adjusted for socio-demographic covariates. Based on these results, a lifestyle risk index was developed. Finally, we explored common combinations of the risk factors in relation to all-cause and cardio-metabolic mortality outcomes.


All single risk factors, except for diet, were significantly associated with both mortality outcomes, and were therefore selected to form a lifestyle risk index. Risk of mortality increased as the index score increased. The hazard ratio for all-cause mortality increased from 1.37 (1.15-1.62) to 6.15 (3.56-10.63) as the number of index risk factors increased from one to six respectively. Among the most common risk factor combinations the association with mortality was particularly strong when smoking and/or social participation were included.


This study adds to previous research on multiple risk behaviours by incorporating emerging risk factors. Findings regarding social participation and prolonged sitting suggest new components of healthy lifestyles and potential new directions for population health interventions.


All-cause mortality; Cardiovascular disease; Cohort study; Lifestyle behaviour; Metabolic disease; Risk factors


Meat intake and risk of diverticulitis among men.

Cao Y, Strate LL, Keeley BR, Tam I, Wu K, Giovannucci EL, Chan AT.

Gut. 2017 Jan 9. pii: gutjnl-2016-313082. doi: 10.1136/gutjnl-2016-313082. [Epub ahead of print]

PMID: 28069830





Diverticulitis is a common disease with a substantial clinical and economic burden. Besides dietary fibre, the role of other foods in the prevention of diverticulitis is underexplored.


We prospectively examined the association between consumption of meat (total red meat, red unprocessed meat, red processed meat, poultry and fish) with risk of incident diverticulitis among 46 461 men enrolled in the Health Professionals Follow-Up Study (1986-2012). Cox proportional hazards models were used to compute relative risks (RRs) and 95% CIs.


During 651 970 person-years of follow-up, we documented 764 cases of incident diverticulitis. Compared with men in the lowest quintile (Q1) of total red meat consumption, men in the highest quintile (Q5) had a multivariable RR of 1.58 (95% CI 1.19 to 2.11; p for trend=0.01). The increase in risk was non-linear, plateauing after six servings per week (p for non-linearity=0.002). The association was stronger for unprocessed red meat (RR for Q5 vs Q1: 1.51; 95% CI 1.12 to 2.03; p for trend=0.03) than for processed red meat (RR for Q5 vs Q1: 1.03; 95% CI 0.78 to 1.35; p for trend=0.26). Higher consumption of poultry or fish was not associated with risk of diverticulitis. However, the substitution of poultry or fish for one serving of unprocessed red meat per day was associated with a decrease in risk of diverticulitis (multivariable RR 0.80; 95% CI 0.63 to 0.99).


Red meat intake, particularly unprocessed red meat, was associated with an increased risk of diverticulitis. The findings provide practical dietary guidance for patients at risk of diverticulitis.




Advances in IBS 2016: A Review of Current and Emerging Data.

Schoenfeld PS.

Gastroenterol Hepatol (N Y). 2016 Aug;12(8 Suppl 3):1-11.

PMID: 28070176




Irritable bowel syndrome (IBS) is characterized by chronic intermittent abdominal pain and associated diarrhea (IBS-D), constipation (IBS-C), or both. IBS can significantly impact patient function and quality of life. The diagnosis of IBS is based on the presence of characteristic symptoms, the exclusion of concerning features, and selected tests to exclude organic diseases that can mimic IBS. The pathophysiology of IBS remains incompletely understood, and new contributing factors have been identified over the past decade. Altered gut immune activation, intestinal permeability, and the intestinal and colonic microbiome may be important factors. Poorly absorbed carbohydrates have been implicated in triggering IBS symptoms. Increasing evidence supports the benefit of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). Although there are several randomized controlled trials of probiotics in IBS, they are typically poorly designed and have not consistently demonstrated efficacy. Until recently, there were few effective treatments for IBS-D. Data from recent clinical trials support the use of rifaximin, eluxadoline, and peppermint oil. Options for the treatment of IBS-C include lubiprostone and linaclotide.

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The metabolic syndrome and 10-year cognitive and functional decline in very old men. A population-based study.

Viscogliosi G, Donfrancesco C, Palmieri L, Giampaoli S.

Arch Gerontol Geriatr. 2017 Jan 3;70:62-66. doi: 10.1016/j.archger.2016.12.008. [Epub ahead of print]

PMID: 28076836



To describe longitudinal relationships of metabolic syndrome (MetS) to cognitive decline and functional disability in a sample of older non-institutionalized men.


data from 1991 to 2000 of the Italian cohorts of the Finland, Italy, the Netherlands, Elderly (FINE) study, were used. Global cognitive function and functional disability, defined as limitations in mobility, basic (ADLs) and instrumental activities of daily living (IADLs) were screened in 1991 and 2000. MetS was defined according to the NCEP ATP-III criteria.


The study sample consisted of 195 men, baseline age 76.1±3.1years. Baseline MetS was prospectively associated with greater 10-year cognitive and functional decline in ADLs and IADLs. After multiple adjustment including age, education, marital status, ApoE ε4 allele, cerebrovascular disease and initial cognitive and depressive status, MetS predicted cognitive decline (B=-1.684, 95%CI=-2.202 to -1.167, p<0.001) and risk of IADLs (OR=1.09, 95% CI=1.01-1.20, p=0.048) and ADLs disability (OR=1.35, 95%CI=1.12-1.62, p<0.001). Interestingly, such associations were not attributable to individual altered components of MetS nor to their sum. Incident disability in ADLs and IADLs were not explained by parallel decline in cognitive function.


MetS as an entity was associated with accelerated cognitive and functional decline in a population-based sample of very old men.


Cognitive decline; Functional disability; Incidence; Metabolic syndrome


How the stressed brain boosts heart attack risk

Talking, exercising, mindfulness suggested as stress busters

CBC News Posted: Jan 11, 2017



Lancet in press JANUARY 11, 2017


Stressed brain, stressed heart?

Ilze Bot, Johan Kuiper



Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study

Ahmed Tawakol, Amorina Ishai, Richard AP Takx, Amparo L Figueroa, Abdelrahman Ali, Yannick Kaiser, Quynh A Truong, Chloe JE Solomon, Claudia Calcagno, Venkatesh Mani, Cheuk Y Tang, Willem JM Mulder, James W Murrough, Udo Hoffmann, Matthias Nahrendorf, Lisa M Shin, Zahi A Fayad, Roger K Pitman

DOI: http://dx.doi.org/10.1016/S0140-6736(16)31714-7 |




Emotional stress is associated with increased risk of cardiovascular disease. We imaged the amygdala, a brain region involved in stress, to determine whether its resting metabolic activity predicts risk of subsequent cardiovascular events.


Individuals aged 30 years or older without known cardiovascular disease or active cancer disorders, who underwent 18F-fluorodexoyglucose PET/CT at Massachusetts General Hospital (Boston, MA, USA) between Jan 1, 2005, and Dec 31, 2008, were studied longitudinally. Amygdalar activity, bone-marrow activity, and arterial inflammation were assessed with validated methods. In a separate cross-sectional study we analysed the relation between perceived stress, amygdalar activity, arterial inflammation, and C-reactive protein. Image analyses and cardiovascular disease event adjudication were done by mutually blinded researchers. Relations between amygdalar activity and cardiovascular disease events were assessed with Cox models, log-rank tests, and mediation (path) analyses.


293 patients (median age 55 years [iQR 45·0–65·5]) were included in the longitudinal study, 22 of whom had a cardiovascular disease event during median follow-up of 3·7 years (IQR 2·7–4·8). Amygdalar activity was associated with increased bone-marrow activity (r=0·47; p<0·0001), arterial inflammation (r=0·49; p<0·0001), and risk of cardiovascular disease events (standardised hazard ratio 1·59, 95% CI 1·27–1·98; p<0·0001), a finding that remained significant after multivariate adjustments. The association between amygdalar activity and cardiovascular disease events seemed to be mediated by increased bone-marrow activity and arterial inflammation in series. In the separate cross-sectional study of patients who underwent psychometric analysis (n=13), amygdalar activity was significantly associated with arterial inflammation (r=0·70; p=0·0083). Perceived stress was associated with amygdalar activity (r=0·56; p=0·0485), arterial inflammation (r=0·59; p=0·0345), and C-reactive protein (r=0·83; p=0·0210).


In this first study to link regional brain activity to subsequent cardiovascular disease, amygdalar activity independently and robustly predicted cardiovascular disease events. Amygdalar activity is involved partly via a path that includes increased bone-marrow activity and arterial inflammation. These findings provide novel insights into the mechanism through which emotional stressors can lead to cardiovascular disease in human beings.


Enhancing Cardiac Rehabilitation With Stress Management Training: A Randomized, Clinical Efficacy Trial.

Blumenthal JA, Sherwood A, Smith PJ, Watkins L, Mabe S, Kraus WE, Ingle K, Miller P, Hinderliter A.

Circulation. 2016 Apr 5;133(14):1341-50. doi: 10.1161/CIRCULATIONAHA.115.018926.


PMID: 27045127



Cardiac rehabilitation (CR) is the standard of care for patients with coronary heart disease. Despite considerable epidemiological evidence that high stress is associated with worse health outcomes, stress management training (SMT) is not included routinely as a component of CR.


One hundred fifty-one outpatients with coronary heart disease who were 36 to 84 years of age were randomized to 12 weeks of comprehensive CR or comprehensive CR combined with SMT (CR+SMT), with assessments of stress and coronary heart disease biomarkers obtained before and after treatment. A matched sample of CR-eligible patients who did not receive CR made up the no-CR comparison group. All participants were followed up for up to 5.3 years (median, 3.2 years) for clinical events. Patients randomized to CR+SMT exhibited greater reductions in composite stress levels compared with those randomized to CR alone (P=0.022), an effect that was driven primarily by improvements in anxiety, distress, and perceived stress. Both CR groups achieved significant, and comparable, improvements in coronary heart disease biomarkers. Participants in the CR+SMT group exhibited lower rates of clinical events compared with those in the CR-alone group (18% versus 33%; hazard ratio=0.49; 95% confidence interval, 0.25-0.95; P=0.035), and both CR groups had lower event rates compared with the no-CR group (47%; hazard ratio=0.44; 95% confidence interval, 0.27-0.71; P<0.001).


CR enhanced by SMT produced significant reductions in stress and greater improvements in medical outcomes compared with standard CR. Our findings indicate that SMT may provide incremental benefit when combined with comprehensive CR and suggest that SMT should be incorporated routinely into CR.


coronary disease; epidemiology; exercise; rehabilitation; stress, psychological



Added sugar found in two-thirds of packaged foods in Canada: study

Photo: Mother Sarah Nowak looks at baby food

Researchers who examined more than 40,000 packaged foods and beverages in Canada found 66 per cent of them have added sugars, including some infant formulas, baby foods and breakfast cereals.


Added sugar in the packaged foods and beverages available at a major Canadian retailer in 2015: a descriptive analysis

Rachel B. Acton, BSc, Lana Vanderlee, PhD, Erin P. Hobin, PhD, David Hammond

10.9778/cmajo.20160076 cmajo January 12, 2017 vol. 5 no. 1 E1-E6




Background: Excess consumption of added sugars has been associated with a variety of health problems, but there is little information available characterizing added sugar in the Canadian food supply. This study examined the presence and types of added sugars in the packaged food and beverage products available at a major Canadian grocery retailer.

Methods: We searched the ingredients lists of over 40 000 packaged food products available for sale in March 2015 for a variety of added sugar terms. Proportions of food products containing added sugar were identified overall and within food product categories. Differences in total sugar content were identified between food products with and without added sugar.

Results: Overall, 66% of the packaged food products analyzed contained at least 1 added sugar. The added sugar term "sugar" (and its variations) appeared the most frequently, followed by "dextrose." Added sugar presence and total sugar content varied within many product categories but were consistently higher in expected categories such as "beverages." Mean total sugar content was significantly higher in products with added sugar than in those without, both overall (p < 0.001) and within most product subcategories (p < 0.02).

Interpretation: About two-thirds of the packaged foods and beverages available at a major Canadian grocery retailer contain added sugar, similar to recent patterns estimated for the US food supply. The results provide an estimation of the baseline characterization of added sugar in the Canadian food supply, which can be used to assess outcomes of future changes to sugar labelling policies in Canada.


Stress and multiple sclerosis: A systematic review considering potential moderating and mediating factors and methods of assessing stress.

Briones-Buixassa L, Milà R, Mª Aragonès J, Bufill E, Olaya B, Arrufat FX.

Health Psychol Open. 2015 Nov 4;2(2):2055102915612271. doi: 10.1177/2055102915612271. Review.

PMID: 28070374




Research about the effects of stress on multiple sclerosis has yielded contradictory results. This study aims to systematically review the evidence focusing on two possible causes: the role of stress assessment and potential moderating and mediating factors. The Web of Knowledge (MEDLINE and Web of Science), Scopus, and PsycINFO databases were searched for relevant articles published from 1900 through December 2014 using the terms "stress*" AND "multiple sclerosis." Twenty-three articles were included. Studies focused on the effect of stress on multiple sclerosis onset (n = 9) were mostly retrospective, and semi-structured interviews and scales yielded the most consistent associations. Studies focused on multiple sclerosis progression (n = 14) were mostly prospective, and self-reported diaries yielded the most consistent results. The most important modifying factors were stressor duration, severity, and frequency; cardiovascular reactivity and heart rate; and social support and escitalopram intake. Future studies should consider the use of prospective design with self-reported evaluations and the study of moderators and mediators related to amount of stress and autonomic nervous system reactivity to determine the effects of stress on multiple sclerosis.


moderating and mediating factors; multiple sclerosis; stress; stress evaluation


The n-3 Polyunsaturated Fatty Acids Supplementation Improved the Cognitive Function in the Chinese Elderly with Mild Cognitive Impairment: A Double-Blind Randomized Controlled Trial.

Bo Y, Zhang X, Wang Y, You J, Cui H, Zhu Y, Pang W, Liu W, Jiang Y, Lu Q.

Nutrients. 2017 Jan 10;9(1). pii: E54. doi: 10.3390/nu9010054.

PMID: 28075381




Intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) may protect against mild cognitive impairment (MCI). However, there is still a lack of the n-3 PUFAs intervention in the elderly with MCI in China. The aim of the present study was to investigate the effect of n-3 PUFA supplementation on cognitive function in the Chinese elderly with MCI.


Eighty six MCI individuals aged 60 years or older were randomly assigned to receive either n-3 PUFAs (480 mg DHA and 720 mg EPA per day, n = 44) or placebo (olive oil, n = 42) capsules. The changes of cognitive functions were assessed using Basic Cognitive Aptitude Tests (BCAT).


The mean age of participants was 71 years old, and 59% of the participants were men. n-3 PUFA supplementation was associated with improved total BCAT scores, perceptual speed, space imagery efficiency, and working memory (p < 0.01), but not with mental arithmetic efficiency or recognition memory (p > 0.05). Subgroup analysis by sex showed that n-3 PUFAs significantly improved perceptual speed (p = 0.001), space imagery efficiency (p = 0.013), working memory (p = 0.018), and total BCAT scores (p = 0.000) in males. However, in females, the significant beneficial effects can only be observed in perceptual speed (p = 0.027), space imagery efficiency (p = 0.006), and total BCAT scores (p = 0.015)-not working memory (p = 0.113).


n-3 PUFAs can improve cognitive function in people with MCI. Further studies with different fish oil dosages, longer intervention periods, and larger sample sizes should be investigated before definite recommendations can be made.


basic cognitive aptitude tests; cognition; elderly; mild cognitive impairment; n-3 polyunsaturated fatty acids

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Legume consumption and CVD risk: a systematic review and meta-analysis.

Marventano S, Izquierdo Pulido M, Sánchez-González C, Godos J, Speciani A, Galvano F, Grosso G.

Public Health Nutr. 2017 Feb;20(2):245-254. doi: 10.1017/S1368980016002299.

PMID: 28077199




The aim of the present study was to systematically review and perform a meta-analysis of prospective cohort studies exploring the association between dietary legume consumption and CVD risk, including CHD and stroke.


The PubMed and EMBASE databases were searched up to December 2015. A meta-analysis of the highest v. lowest (reference) category of dietary legume consumption was performed through random-effects models.


Fourteen studies conducted on eleven cohorts and accounting for a total of 367 000 individuals and 18 475 cases of CVD (7451 CHD and 6336 stroke cases) were considered for the analyses. Compared with lower legume consumption, the highest category of exposure was associated with a decreased risk of 10 % in both CVD and CHD (relative risk=0·90; 95 % CI 0·84, 0·97) with no or little evidence of heterogeneity and no publication bias. Null results were found regarding legume consumption and stroke risk. No substantial confounding factors were evident in stratified analyses.


Legume consumption was associated with lower risk of CVD. Legumes' intrinsic characteristics, because they are often part of an overall healthy diet, or because they are a substitute for unhealthy sources of protein may potentially explain the current findings.


CVD; Fibre; Legumes; Meta-analysis; Mortality


Nut consumption and lung cancer risk: Results from two large observational studies.

Lee JT, Lai GY, Liao LM, Subar AF, Bertazzi PA, Pesatori AC, Freedman ND, Landi MT, Lam TK.

Cancer Epidemiol Biomarkers Prev. 2017 Jan 11. pii: cebp.0806.2016. doi: 10.1158/1055-9965.EPI-16-0806. [Epub ahead of print]

PMID: 28077426




Epidemiological evidence on the association between nut consumption and lung cancer risk is limited.


We investigated this relationship in the Environment And Genetics in Lung cancer Etiology (EAGLE) study, a population-based case-control study, and the National Institutes of Health (NIH) American Association of Retired Persons (AARP) Diet and Health Study, a prospective cohort. We identified 2098 lung cases for EAGLE and 18,533 incident cases in AARP. Diet was assessed by food frequency questionnaire for both studies. Multivariable odds ratios (ORs) and hazards ratio (HRs) and respective 95% confidence intervals (CIs) were calculated using unconditional logistic regression and Cox proportional hazards regression for EAGLE and AARP, respectively.


Higher frequency of intake of nut consumption was inversely associated with overall lung cancer risk (highest-versus-lowest quintile, OREAGLE=0.74, 95% CI=0.57-0.95; HRAARP=0.86, 95% CI=0.81-0.91), regardless of smoking status. Results from the prospective cohort showed similar associations across histological subtypes, and a more pronounced benefits from nut consumption for those who smoked 1-20 cigarettes/day (OREAGLE=0.61, 95% CI=0.39-0.95; HRAARP=0.83, 95% CI=0.74-0.94).


Nut consumption was inversely associated with lung cancer in two large population-based studies, and associations were independent of cigarette smoking and other known risk factors.


To our knowledge, this is the first study that examined the association between nut consumption and lung cancer risk by histologic subtypes and smoking intensity.


Tea consumption and risk of ischaemic heart disease.

Li X, Yu C, Guo Y, Bian Z, Si J, Yang L, Chen Y, Ren X, Jiang G, Chen J, Chen Z, Lv J, Li L; China Kadoorie Biobank Collaborative Group..

Heart. 2017 Jan 11. pii: heartjnl-2016-310462. doi: 10.1136/heartjnl-2016-310462. [Epub ahead of print]

PMID: 28077466





To prospectively examine the association between tea consumption and the risk of ischaemic heart disease (IHD).


Prospective study using the China Kadoorie Biobank; participants from 10 areas across China were enrolled during 2004-2008 and followed up until 31 December 2013. After excluding participants with cancer, heart disease and stroke at baseline, the present study included 199 293 men and 288 082 women aged 30-79 years at baseline. Information on IHD incidence was collected through disease registries and the new national health insurance databases.


During a median follow-up of 7.2 years, we documented 24 665 (7.19 cases/1000 person-years) incident IHD cases and 3959 (1.13 cases/1000 person-years) major coronary events (MCEs). Tea consumption was associated with reduced risk of IHD and MCE. In the whole cohort, compared with participants who never consumed tea during the past 12 months, the multivariable-adjusted HRs and 95% CIs for less than daily and daily tea consumers were 0.97 (0.94 to 1.00) and 0.92 (0.88 to 0.95) for IHD, 0.92 (0.85 to 1.00) and 0.90 (0.82 to 0.99) for MCE. No linear trends in the HRs across the amount of tea were observed in daily consumers for IHD and MCE (PLinear >0.05). The inverse association between tea consumption and IHD was stronger in rural (PInteraction 0.006 for IHD, <0.001 for MCE), non-obese (PInteraction 0.012 for MCE) and non-diabetes participants (PInteraction 0.004 for IHD).


In this large prospective study, daily tea consumption was associated with a reduced risk of IHD.


Benefits of whole-body vibration training on arterial function and muscle strength in young overweight/obese women.

Alvarez-Alvarado S, Jaime SJ, Ormsbee MJ, Campbell JC, Post J, Pacilio J, Figueroa A.

Hypertens Res. 2017 Jan 12. doi: 10.1038/hr.2016.178. [Epub ahead of print]

PMID: 28077859




The early arterial dysfunction linked with obesity and a sedentary lifestyle heightens the likelihood of suffering from future cardiovascular events. Whole-body vibration training (WBVT) may improve systemic arterial stiffness (brachial-ankle pulse wave velocity (baPWV)) and muscle strength in pre- and post-menopausal women. However, the effectiveness of WBVT to impact the arterial segments included in baPWV is unknown. The aim of this study was to investigate the effects of WBVT on aortic and leg arterial stiffness in young sedentary overweight/obese women. Thirty-eight young (21 years) overweight/obese women were randomized to WBVT (n=25) or a nonexercising control (CON, n=13) groups for 6 weeks. PWV, brachial and aortic blood pressures (BP), wave reflection (augmentation index (AIx)) and leg muscle strength measurements were acquired before and after 6 weeks. WBVT significantly reduced carotid-femoral PWV (aortic stiffness, P<0.05), femoral-ankle (leg arterial stiffness, P<0.01) and baPWV (systemic arterial stiffness, P<0.01) compared with CON. The reduction in brachial systolic BP (SBP), heart rate, aortic SBP, aortic diastolic BP, AIx normalized to a heart rate of 75 beats per min (AIx@75; P<0.01) and AIx (P<0.05) following WBVT was significant compared with CON (P<0.05). WBVT increased leg muscle strength compared with CON (P<0.001). There was a significant negative correlation between changes in relative muscle strength and aortic stiffness (r=-0.41, P<0.05). WBVT led to reductions in arterial stiffness, central BP and wave reflection in young obese women. WBVT may be an effective intervention toward vascular health promotion and prevention in young overweight/obese women.


Association between sauna bathing and fatal cardiovascular and all-cause mortality events.

Laukkanen T, Khan H, Zaccardi F, Laukkanen JA.

JAMA Intern Med. 2015 Apr;175(4):542-8. doi: 10.1001/jamainternmed.2014.8187.

PMID: 25705824




Sauna bathing is a health habit associated with better hemodynamic function; however, the association of sauna bathing with cardiovascular and all-cause mortality is not known.


To investigate the association of frequency and duration of sauna bathing with the risk of sudden cardiac death (SCD), fatal coronary heart disease (CHD), fatal cardiovascular disease (CVD), and all-cause mortality.


We performed a prospective cohort study (Finnish Kuopio Ischemic Heart Disease Risk Factor Study) of a population-based sample of 2315 middle-aged (age range, 42-60 years) men from Eastern Finland. Baseline examinations were conducted from March 1, 1984, through December 31, 1989.


Frequency and duration of sauna bathing assessed at baseline.


During a median follow-up of 20.7 years (interquartile range, 18.1-22.6 years), 190 SCDs, 281 fatal CHDs, 407 fatal CVDs, and 929 all-cause mortality events occurred. A total of 601, 1513, and 201 participants reported having a sauna bathing session 1 time per week, 2 to 3 times per week, and 4 to 7 times per week, respectively. The numbers (percentages) of SCDs were 61 (10.1%), 119 (7.8%), and 10 (5.0%) in the 3 groups of the frequency of sauna bathing. The respective numbers were 89 (14.9%), 175 (11.5%), and 17 (8.5%) for fatal CHDs; 134 (22.3%), 249 (16.4%), and 24 (12.0%) for fatal CVDs; and 295 (49.1%), 572 (37.8%), and 62 (30.8%) for all-cause mortality events. After adjustment for CVD risk factors, compared with men with 1 sauna bathing session per week, the hazard ratio of SCD was 0.78 (95% CI, 0.57-1.07) for 2 to 3 sauna bathing sessions per week and 0.37 (95% CI, 0.18-0.75) for 4 to 7 sauna bathing sessions per week (P for trend = .005). Similar associations were found with CHD, CVD, and all-cause mortality (P for trend ≤.005). Compared with men having a sauna bathing session of less than 11 minutes, the adjusted hazard ratio for SCD was 0.93 (95% CI, 0.67-1.28) for sauna bathing sessions of 11 to 19 minutes and 0.48 (95% CI, 0.31-0.75) for sessions lasting more than 19 minutes (P for trend = .002); significant inverse associations were also observed for fatal CHDs and fatal CVDs (P for trend ≤.03) but not for all-cause mortality events.


Increased frequency of sauna bathing is associated with a reduced risk of SCD, CHD, CVD, and all-cause mortality. Further studies are warranted to establish the potential mechanism that links sauna bathing and cardiovascular health.


JAMA Intern Med. 2015 Apr;175(4):548. doi: 10.1001/jamainternmed.2014.8206.

Health benefits of sauna bathing.

Redberg RF.

Comment on

Association between sauna bathing and fatal cardiovascular and all-cause mortality events. [JAMA Intern Med. 2015]

PMID: 25706401 DOI: 10.1001/jamainternmed.2014.8206


Often I have advised a patient who was considering an unnecessary test, such as a coronary artery calcium test or carotid ultrasonography from a mobile van, to forgo that test and instead spend the money on something that he or she would actually enjoy, such as a massage or spa treatment. In this issue, Laukkanen et al1 present data indicating that my advice would not only help my patients feel good but would also, if they chose to regularly use a sauna bath, help them live longer. Analyzing data from the Finnish Kuopio Ischemic Heart Disease Study, the authors found that men who took more frequent saunas (4-7 times per week) actually live longer than once-per-week users. Although we do not know why the men who took saunas more frequently had greater longevity (whether it is the time spent in the hot room, the relaxation time, the leisure of a life that allows for more relaxation time, or the camaraderie of the sauna), clearly time spent in the sauna is time well spent.


B-Vitamin Intake and Biomarker Status in Relation to Cognitive Decline in Healthy Older Adults in a 4-Year Follow-Up Study.

Hughes CF, Ward M, Tracey F, Hoey L, Molloy AM, Pentieva K, McNulty H.

Nutrients. 2017 Jan 10;9(1). pii: E53. doi: 10.3390/nu9010053.

PMID: 28075382




Advancing age can be associated with an increase in cognitive dysfunction, a spectrum of disability that ranges in severity from mild cognitive impairment to dementia. Folate and the other B-vitamins involved in one-carbon metabolism are associated with cognition in ageing but the evidence is not entirely clear. The hypothesis addressed in this study was that lower dietary intake or biomarker status of folate and/or the metabolically related B-vitamins would be associated with a greater than expected rate of cognitive decline over a 4-year follow-up period in healthy older adults. Participants (aged 60-88 years; n = 155) who had been previously screened for cognitive function were reassessed four years after initial investigation using the Mini-Mental State Examination (MMSE). At the 4-year follow-up assessment when participants were aged 73.4 ± 7.1 years, mean cognitive MMSE scores had declined from 29.1 ± 1.3 at baseline to 27.5 ± 2.4 (p < 0.001), but some 27% of participants showed a greater than expected rate of cognitive decline (i.e., decrease in MMSE > 0.56 points per year). Lower vitamin B6 status, as measured using pyridoxal-5-phosphate (PLP; <43 nmol/L) was associated with a 3.5 times higher risk of accelerated cognitive decline, after adjustment for age and baseline MMSE score (OR, 3.48; 95% CI, 1.58 to 7.63; p < 0.05). Correspondingly, lower dietary intake (0.9-1.4 mg/day) of vitamin B6 was also associated with a greater rate of cognitive decline (OR, 4.22; 95% CI, 1.28-13.90; p < 0.05). No significant relationships of dietary intake or biomarker status with cognitive decline were observed for the other B-vitamins. In conclusion, lower dietary and biomarker status of vitamin B6 at baseline predicted a greater than expected rate of cognitive decline over a 4-year period in healthy older adults. Vitamin B6 may be an important protective factor in helping maintain cognitive health in ageing.


B-vitamin biomarkers; ageing; cognition; dietary intakes; one-carbon metabolism; pyridoxal-5-phosphate (PLP); vitamin B6


Soluble transferrin receptor and risk of type 2 diabetes in the obese and non-obese.

Fernández-Cao JC, Arija V, Aranda N, Basora J, Diez-Espino J, Estruch R, Fitó M, Pharm DC, Salas-Salvadó J.

Eur J Clin Invest. 2017 Jan 11. doi: 10.1111/eci.12725. [Epub ahead of print]

PMID: 28075490




Studies evaluating the relationship between soluble transferrin receptor (sTfR), a biomarker inversely related to body iron stores, and risk of type 2 diabetes mellitus (T2DM) are scarce and inconclusive. Furthermore, sTfR concentrations have been observed to be significantly higher in obese than in non-obese individuals. Therefore, the aim of the present study was to assess the relationship between sTfR and the risk of T2DM in obese and non-obese subjects.


A nested case-control study of 153 cases of newly diagnosed diabetic subjects, 73 obese and 80 non-obese, and 306 individually matched-controls, 138 obese and 166 non-obese, who did not develop T2DM for a median 6-year follow-up (interquartile range: 3.9-6.5) was conducted using data from the PREDIMED (PREvention with MEDiterranean Diet) cohort (http://www.controlled-trials.com/ISRCTN35739639). Cases and controls were matched for age (≤67 vs. >67years), gender, dietary intervention group, and BMI (≤27 vs. >27kg/m2 ).


Waist circumference is the main determinant of sTfR concentrations in the whole sample (β=0.476, P<0.001), in the obese (β=0.802, P<0.001) and the non-obese (β=0.455, P=0.003). Furthermore, sTfR is directly associated with the risk of T2DM in obese individuals (OR=2.79; 95% CI:1.35-5.77, P=0.005) and inversely associated in non-obese individuals (OR=0.40; 95% CI:0.20-0.79, P=0.015).


The association between sTfR levels and risk of T2DM in a population at high cardiovascular risk depend on the presence or absence of obesity. While in non-obese subjects elevated sTfR levels are associated with a decreased risk of developing T2DM, in obese subjects the risk increases. This suggests that obesity alters the relationship between sTfR and T2DM incidence.


PREDIMED ; Soluble transferrin receptor; body iron stores; nested case-control; obesity; type 2 diabetes mellitus


[The below paper is pdf-availed.]

Protein intake and risk of hip fractures in postmenopausal women and men age 50 and older.

Fung TT, Meyer HE, Willett WC, Feskanich D.

Osteoporos Int. 2017 Jan 10. doi: 10.1007/s00198-016-3898-7. [Epub ahead of print]

PMID: 28074249


In this study, we followed postmenopausal women and men aged 50 and above for up to 32 years and found no evidence that higher protein intake increased the risk of hip fracture. Protein intake from specific sources was inversely associated with risk, but these associations appeared to differ by gender.


We examined the association between intakes of total and specific sources of protein and hip fracture risk in postmenopausal women and men over 50 years of age. Our hypothesis was that a higher protein intake would not be associated with a higher risk of hip fractures.


In this analysis, we followed 74,443 women in the Nurses' Health Study between 1980 and 2012 and 35,439 men from the Health Professionals Follow-up Study between 1986 and 2012. Health and lifestyle information and hip fractures were self-reported on biennial questionnaires. Protein was assessed approximately every 4 years with a food frequency questionnaire. Relative risks (RR) were computed for hip fracture by quintiles of total, animal, dairy, and plant protein intakes using Cox proportional hazard models, adjusting for potential confounders.


During follow-up, we ascertained 2156 incident hip fractures in women and 595 fractures in men. Among men, we observed significant inverse associations for each 10 g increase of total protein (RR = 0.92, 95% CI = 0.85-0.99) and animal protein (RR = 0.91, 95% CI = 0.85-0.98) intakes. Total and animal proteins were not significantly associated with hip fractures in women. Both plant (RR = 0.88, 95% CI 0.79-0.99 per 10 g) and dairy protein (RR = 0.92, 95% CI 0.86-0.97) were associated with significantly lower risks of hip fracture when results for men and women were combined. None of these associations were modified by BMI, smoking, physical activity, age, or calcium intake.


We found no evidence that higher protein intake increases risk of hip fracture in these Caucasian men and women. Protein intake from specific sources was inversely associated with risk, but these associations appeared to differ by gender.


Diet; Fractures; Hip; Nutrition; Protein

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GnIH Control of Feeding and Reproductive Behaviors.

Tsutsui K, Ubuka T.

Front Endocrinol (Lausanne). 2016 Dec 27;7:170. doi: 10.3389/fendo.2016.00170. Review.

PMID: 28082949



In 2000, Tsutsui and colleagues discovered a neuropeptide gonadotropin-inhibitory hormone (GnIH) that inhibits gonadotropin release in birds. Subsequently, extensive studies during the last 15 years have demonstrated that GnIH is a key neurohormone that regulates reproduction in vertebrates, acting in the brain and on the pituitary to modulate reproduction and reproductive behavior. On the other hand, deprivation of food and other metabolic challenges inhibit the reproductive axis as well as sexual motivation. Interestingly, recent studies have further indicated that GnIH controls feeding behavior in vertebrates, such as in birds and mammals. This review summarizes the discovery of GnIH and its conservation in vertebrates and the neuroendocrine control of feeding behavior and reproductive behavior by GnIH.


feeding behavior; gonadotropin-inhibitory hormone; gonadotropin-releasing hormone; gonadotropins; reproduction; reproductive behavior


The influence of genes on the Lifespan of Long- and Short-Lived Families.

Kolovou V, Fragopoulou E, Antonopoulou S, Kolovou G.

Hellenic J Cardiol. 2017 Jan 7. pii: S1109-9666(16)30134-8. doi: 10.1016/j.hjc.2017.01.002. [Epub ahead of print] No abstract available.

PMID: 28081978



[The Dutch Eating Behavior Questionnaire Restraint Scale (DEBQ-R) seemed like the most important variable affecting choice of high versus low calorie food.]

The influence of calorie and physical activity labelling on snack and beverage choices.

Masic U, Christiansen P, Boyland EJ.

Appetite. 2017 Jan 9. pii: S0195-6663(17)30028-4. doi: 10.1016/j.appet.2017.01.007. [Epub ahead of print]

PMID: 28082195




Much research suggests nutrition labelling does not influence lower energy food choice. This study aimed to assess the impact of physical activity based and kilocalorie (Kcal) based labels on the energy content of snack food and beverage choices made.


An independent-groups design, utilizing an online questionnaire platform tested 458 UK adults (87 men), aged 18-64 years (mean: 30 years) whose BMI ranged from 16 to 41 kg/m2 (mean: 24 kg/m2). Participants were randomized to one of four label information conditions (no label, Kcal label, physical activity label [duration of walking required to burn the Kcal in the product], Kcal and physical activity label) and were asked to choose from higher and lower energy options for a series of items.


Label condition significantly affected low vs. high-energy product selection of snack foods (p < 0.001) and beverages (p < 0.001). The physical activity label condition resulted in significantly lower energy snack and beverage choices than the Kcal label condition (p < 0.001). This effect was found across the full sample and persisted even when participants' dietary restraint, BMI, gender, socioeconomic status, habitual physical activity, calorie and numerical literacy were controlled.


The provision of physical activity information appeared most effective in influencing the selection of lower Kcal snack food and beverage items, when compared with no information or Kcal information. These findings could inform the debate around potential legislative policies to facilitate healthier nutritional choices at a population level.


Beverage choice; Energy intake; Exercise; Food choice; Nutrition labelling; Snack choice


The effect of menu labeling with calories and exercise equivalents on food selection and consumption.

Platkin C, Yeh MC, Hirsch K, Wiewel EW, Lin CY, Tung HJ, Castellanos VH.

BMC Obes. 2014 Sep 24;1:21. doi: 10.1186/s40608-014-0021-5.

PMID: 26217508 Free PMC Article





Better techniques are needed to help consumers make lower calorie food choices. This pilot study examined the effect of menu labeling with caloric information and exercise equivalents (EE) on food selection. Participants, 62 females, ages 18-34, recruited for this study, ordered a fast food meal with menus that contained the names of the food (Lunch 1 (L1), control meal). One week later (Lunch 2 (L2), experiment meal), participants ordered a meal from one of three menus with the same items as the previous week: no calorie information, calorie information only, or calorie information and EE.


There were no absolute differences between groups in calories ordered from L1 to L2. However, it is noteworthy that calorie only and calorie plus exercise equivalents ordered about 16% (206 kcal) and 14% (162 kcal) fewer calories from Lunch 1 to Lunch 2, respectively; whereas, the no information group ordered only 2% (25 kcal) fewer.


Menu labeling alone may be insufficient to reduce calories; however, further research is needed in finding the most effective ways of presenting the menu labels for general public.


Exercise equivalents; Fast food; Menu labeling; Nutrition labeling; Obesity; Point-of-purchase


International Variation in Outcomes Among People with Cardiovascular Disease or Cardiovascular Risk Factors and Impaired Glucose Tolerance: Insights from the NAVIGATOR Trial

Marilia Harumi Higuchi dos Santos, Abhinav Sharma, Jie‐Lena Sun, Karen Pieper, John J.V. McMurray, Rury R. Holman, Renato D. Lopes


Journal of the American Heart Association. 2017;6:e003892

Originally published January 13, 2017




Regional differences in risk of diabetes mellitus and cardiovascular outcomes in people with impaired glucose tolerance are poorly characterized. Our objective was to evaluate regional variation in risk of new‐onset diabetes mellitus, cardiovascular outcomes, and treatment effects in participants from the NAVIGATOR (Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research) trial.

Methods and Results

NAVIGATOR randomized people with impaired glucose tolerance and cardiovascular risk factors or with established cardiovascular disease to valsartan (or placebo) and to nateglinide (or placebo) with a median 5‐year follow‐up. Data from the 9306 participants were categorized by 5 regions: Asia (n=552); Europe (n=4909); Latin America (n=1406); North America (n=2146); and Australia, New Zealand, and South Africa (n=293). Analyzed outcomes included new‐onset diabetes mellitus; cardiovascular death; a composite cardiovascular outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke; and treatment effects of valsartan and nateglinide. Respective unadjusted 5‐year risks for new‐onset diabetes mellitus, cardiovascular death, and the composite cardiovascular outcome were 33%, 0.4%, and 4% for Asia; 34%, 2%, and 6% for Europe; 37%, 4%, and 8% for Latin America; 38%, 2%, and 6% for North America; and 32%, 4%, and 8% for Australia, New Zealand, and South Africa. After adjustment, compared with North America, European participants had a lower risk of new‐onset diabetes mellitus (hazard ratio 0.86, 95% CI 0.78–0.94; P=0.001), whereas Latin American participants had a higher risk of cardiovascular death (hazard ratio 2.68, 95% CI 1.82–3.96; P<0.0001) and the composite cardiovascular outcome (hazard ratio 1.48, 95% CI 1.15–1.92; P=0.003). No differential interactions between treatment and geographic location were identified.


Major regional differences regarding the risk of new‐onset diabetes mellitus and cardiovascular outcomes in NAVIGATOR participants were identified. These differences should be taken into account when planning global trials.


cardiovascular diseasediabetes mellitusrisk factor


The Longer, the Better? An Empirical Study of the Extent and Mechanisms of Attenuating Biomarker Associations in Cardiovascular Patient Cohorts.

Breitling LP, Mons U, Hahmann H, Koenig W, Rothenbacher D, Brenner H.

Clin Chem. 2017 Jan 10. pii: clinchem.2016.263202. doi: 10.1373/clinchem.2016.263202. [Epub ahead of print]

PMID: 28073900




Identifying novel risk markers in cardiovascular patients remains a research priority. Longer follow-up generally is considered favorable in such studies, but associations of interest may become attenuated with increasing follow-up. This issue has not been adequately addressed in the context of patient cohorts. The current study analyzed the extent and mechanisms of attenuating associations in a cardiovascular patient cohort.


The associations of numerous biomarkers with all-cause mortality were estimated by multiple Cox regression in the Langzeiterfolge der KARdiOLogischen Anschlussheilbehandlung (KAROLA) prospective cohort study of 1204 patients who had participated in an inpatient rehabilitation program after an acute coronary syndrome (ACS) or coronary bypass operation. Hazard ratios were estimated based on the entire follow-up period (13 years), and after truncation at previous follow-up times (3, 4.5, 6, 8, 10 years).


For the majority of markers, a clear and sometimes very pronounced attenuation of the hazard ratios could be observed with increasing follow-up duration. Differential attrition generally was not a sufficient explanation for this phenomenon, whereas further analyses suggested a role for reverse causality for some of the markers. Power analyses showed that the relationship of follow-up duration and statistical power can be counterintuitive in the presence of realistic amounts of attenuation.


The attenuation of estimates of association in patient cohorts is a much more substantial and complex issue than currently appreciated. This has important implications for the design and interpretation of prognostic, as well as etiologic, studies which may be particularly relevant in the case of patient cohorts defined by an initial acute event.


Visit-to-Visit Blood Pressure Variability and Mortality and Cardiovascular Outcomes Among Older Adults: The Health, Aging, and Body Composition Study.

Wu C, Shlipak MG, Stawski RS, Peralta CA, Psaty BM, Harris TB, Satterfield S, Shiroma EJ, Newman AB, Odden MC; Health ABC Study..

Am J Hypertens. 2016 Sep 6. pii: hpw106. [Epub ahead of print]

PMID: 27600581




Level of blood pressure (BP) is strongly associated with cardiovascular (CV) events and mortality. However, it is questionable whether mean BP can fully capture BP-related vascular risk. Increasing attention has been given to the value of visit-to-visit BP variability.


We examined the association of visit-to-visit BP variability with mortality, incident myocardial infarction (MI), and incident stroke among 1,877 well-functioning elders in the Health, Aging, and Body Composition Study. We defined visit-to-visit diastolic BP (DBP) and systolic BP (SBP) variability as the root-mean-square error of person-specific linear regression of BP as a function of time. Alternatively, we counted the number of considerable BP increases and decreases (separately; 10mm Hg for DBP and 20mm Hg for SBP) between consecutive visits for each individual.


Over an average follow-up of 8.5 years, 623 deaths (207 from CV disease), 153 MIs, and 156 strokes occurred. The median visit-to-visit DBP and SBP variability was 4.96 mmHg and 8.53 mmHg, respectively. After multivariable adjustment, visit-to-visit DBP variability was related to higher all-cause (hazard ratio (HR) = 1.18 per 1 SD, 95% confidence interval (CI) = 1.01-1.37) and CV mortality (HR = 1.35, 95% CI = 1.05-1.73). Additionally, individuals having more considerable decreases of DBP (≥10mm Hg between 2 consecutive visits) had higher risk of all-cause (HR = 1.13, 95% CI = 0.99-1.28) and CV mortality (HR = 1.30, 95% CI = 1.05-1.61); considerable increases of SBP (≥20mm Hg) were associated with higher risk of all-cause (HR = 1.18, 95% CI = 1.03-1.36) and CV mortality (HR = 1.37, 95% CI = 1.08-1.74).


Visit-to-visit DBP variability and considerable changes in DBP and SBP were risk factors for mortality in the elderly.


aged.; blood pressure; blood pressure variability; hypertension; mortality; myocardial infarction; stroke


Orthostatic Hypotension in Middle-Age and Risk of Falls.

Juraschek SP, Daya N, Appel LJ, Miller ER 3rd, Windham BG, Pompeii L, Griswold ME, Kucharska-Newton A, Selvin E.

Am J Hypertens. 2016 Sep 16. pii: hpw108. [Epub ahead of print]

PMID: 27638848




One-third of older adults fall each year. Orthostatic hypotension (OH) has been hypothesized as an important risk factor for falls, but findings from prior studies have been inconsistent.


We conducted a prospective study of the association between baseline OH (1987-1989) and risk of falls in the Atherosclerosis Risk in Communities (ARIC) Study. Falls were ascertained during follow-up via ICD-9 hospital discharge codes or Centers for Medicare & Medicaid Services claims data. OH was defined as a drop in systolic blood pressure (SBP) ≥20mm Hg or diastolic blood pressure (DBP) ≥10mm Hg within 2 minutes of moving from the supine to standing position. Changes in SBP or DBP during OH assessments were also examined as continuous variables.


During a median follow-up of 23 years, there were 2,384 falls among 12,661 participants (mean age 54 years, 55% women, 26% black). OH was associated with risk of falls even after adjustment for demographic characteristics and other risk factors (hazard ratio (HR): 1.30; 95% confidence interval (CI): 1.10, 1.54; P = 0.002). Postural change in DBP was more significantly associated with risk of falls (HR 1.09 per -5mm Hg change in DBP; 95% CI: 1.05, 1.13; P < 0.001) than postural change in SBP (HR 1.03 per -5mm Hg change in SBP; 95% CI: 1.01, 1.05; P = 0.002).


In a community-based, middle-aged population, OH, and in particular, postural change in DBP, were independent risk factors for falls over 2 decades of follow-up. Future studies are needed to examine OH thresholds associated with increased risk of falls.


ARIC; blood pressure; epidemiology; fall; hypertension; orthostatic hypotension; prospective cohort.

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Effect of Vitamin D on Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Trial

Lea Borgi Ciaran McMullan Ann Wohlhueter Gary C. Curhan Naomi D. Fisher John P. Forman

Am J Hypertens (2016) 30 (2): 124-129. DOI: https://doi.org/10.1093/ajh/hpw135

Published: 15 November 2016 Article history





In nonhypertensive individuals, lower levels of 25-hydroxyvitamin D (25[OH]D) have been associated with an increased risk of hypertension, and vitamin D deficiency has been associated with endothelial dysfunction in such individuals. However, the effect of vitamin D supplementation on endothelial dysfunction in nonhypertensive individuals has not been examined in a rigorous fashion.


In this randomized, double-blind, placebo-controlled trial of nonhypertensive, nondiabetic overweight, or obese individuals with vitamin D deficiency (body mass index ≥25 and 25[OH]D ≤ 20 ng/ml), we assigned subjects to receive either ergocalciferol (50,000 units) or matching placebo, once a week for 8 weeks. Our primary outcome was endothelial-dependent vasodilation (EDV) measured by brachial artery ultrasound at baseline and 8 weeks postrandomization.


By the end of the trial, 46 and 47 participants were allocated to receive ergocalciferol and placebo, respectively. Mean 25(OH)D levels increased from 14.9 to 30.3 in the vitamin D group and 14.4 to 17.4 in the placebo. EDV did not change significantly with either vitamin D repletion (from 6.3 ± 3.6% at baseline to 6.1 ± 4.6% at 8 weeks; P value = 0.78) or placebo (7.9 ± 4.7% to 6.8 ± 4.7%; P = 0.17). The treatment effect P value (comparing the 8-week change with ergocalciferol to the change with placebo) was 0.35.


In this randomized, double-blind, placebo-controlled trial, there was no improvement in endothelial function (measured as EDV) after repletion of vitamin D in overweight/obese nonhypertensive individuals.

blood pressure, endothelial function, hypertension, randomized controlled trial, vitamin D deficiency


Association between reductions in low-density lipoprotein cholesterol with statin therapy and the risk of new-onset diabetes: a meta-analysis.

Wang S, Cai R, Yuan Y, Varghese Z, Moorhead J, Ruan XZ.

Sci Rep. 2017 Jan 10;7:39982. doi: 10.1038/srep39982.

PMID: 28071756



A recent meta-analysis demonstrated that statin therapy was associated with a risk of diabetes. The present study investigated whether the relative reduction in low-density lipoprotein cholesterol (LDL-c) was a good indicator of the risk of new-onset diabetes. We searched the PubMed, Embase, Cochrane Central Register, Lilacs, Food and Drug Administration, and European Medicines Agency databases for randomized controlled trials of statins. Fourteen trials were included in the study. Eight trials with target LDL-c levels ≤100 mg/dL (2.6 mmol/L) or LDL-c reductions of at least 30% were extracted separately. The results showed that the overall risk of incident diabetes increased by 11% (OR = 1.11; 95% CI 1.03-1.20). The group with intensive LDL-c-lowering statin had an 18% increase in the likelihood of developing diabetes (OR = 1.18; 95% CI, 1.10-1.28). Furthermore, the risks of incident diabetes were 13% (OR = 1.13; 95% CI 1.01-1.26) and 29% (OR = 1.29; 95% CI 1.13-1.47) in the subgroups with 30-40% and 40-50% reductions in LDL-c, respectively, suggesting that LDL-c reduction may provide a dynamic risk assessment parameter for new-onset diabetes. In conclusion, LDL-c reduction is positively related to the risk of new-onset diabetes. When LDL-c is reduced by more than 30% during lipid-lowering therapy, blood glucose monitoring is suggested to detect incident diabetes in high-risk populations.


Relationship Between Marital Transitions, Health Behaviors, and Health Indicators of Postmenopausal Women: Results from the Women's Health Initiative.

Kutob RM, Yuan NP, Wertheim BC, Sbarra DA, Loucks EB, Nassir R, Bareh G, Kim MM, Snetselaar LG, Thomson CA.

J Womens Health (Larchmt). 2017 Jan 10. doi: 10.1089/jwh.2016.5925. [Epub ahead of print]

PMID: 28072926





Historically, marital status has been associated with lower mortality and transitions into marriage were generally accompanied by improved health status. Conversely, divorce has been associated with increased mortality, possibly mediated by changes in health behaviors.


This study uses data from a prospective cohort of 79,094 postmenopausal women participating in the Women's Health Initiative Observational Study (WHI-OS) to examine the relationship between marital transition and health indicators (blood pressure, waist circumference, body mass index [bMI]) as well as health behaviors (diet pattern, alcohol use, physical activity, and smoking) in a sample of relatively healthy and employed women. Linear and logistic regression modeling were used to test associations, controlling for confounding factors.


Women's transitions into marriage/marriage-like relationship after menopause were associated with greater increase in BMI (β = 0.22; confidence interval (95% CI), 0.11-0.33) and alcohol intake (β = 0.08; 95% CI, 0.04-0.11) relative to remaining unmarried. Divorce/separation was associated with a reduction in BMI and waist circumference, changes that were accompanied by improvements in diet quality (β = 0.78, 95% CI, 0.10-1.47) and physical activity (β = 0.98, 95% CI, 0.12-1.85), relative to women who remained married.


Contrary to earlier literature, these findings among well-educated, predominantly non-Hispanic white women suggest that marital transitions after menopause are accompanied by modifiable health outcomes/behaviors that are more favorable for women experiencing divorce/separation than those entering a new marriage.


body mass index; divorce; health behaviors; marriage; menopausal; obesity; smoking


Sex differences in the association of obesity and colorectal cancer risk.

Kim H, Giovannucci EL.

Cancer Causes Control. 2017 Jan;28(1):1-4. doi: 10.1007/s10552-016-0831-5.

PMID: 27878394



Epidemiological research has convincingly shown that obesity increases colorectal cancer (CRC) risk, with generally stronger associations observed in men than in women. Evidence from the past several years has demonstrated a divergent pattern between men and women regarding the weight changes throughout life or timing of obesity for CRC risk. For men, weight gain later in life appears to be an important risk factor for CRC that mostly accounts for their generally strong association between adult body mass index and CRC risk. For women, however, early life obesity seems to be more important than adult weight gain in determining CRC risk. A knowledge of these sex patterns may have implications on better understanding colorectal carcinogenesis and may further improve prevention efforts for CRC.


Body mass index; Colorectal cancer; Female; Male; Obesity


7. Long-term status and change of body fat distribution, and risk of colorectal cancer: a prospective cohort study.

Song M, Hu FB, Spiegelman D, Chan AT, Wu K, Ogino S, Fuchs CS, Willett WC, Giovannucci EL.

Int J Epidemiol. 2016 Jun;45(3):871-83. doi: 10.1093/ije/dyv177.

PMID: 26403814




Although obesity has been linked to an increased risk of colorectal cancer (CRC), the risk associated with long-term status or change of body fat distribution has not been fully elucidated.


Using repeated anthropometric assessments in the Nurses' Health Study and Health Professionals Follow-up Study, we prospectively investigated cumulative average waist circumference, hip circumference and waist-to-hip ratio, as well as their 10-year changes over adulthood, in relation to CRC risk over 23-24 years of follow-up. Cox proportional hazards models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI).


High waist circumference, hip circumference and waist-to-hip ratio were all associated with a higher CRC risk in men, even after adjusting for body mass index. The association was attenuated to null in women after adjusting for body mass index. Ten-year gain of waist circumference was positively associated with CRC risk in men (P for trend = 0.03), but not in women (P for trend = 0.34).Compared with men maintaining their waist circumference, those gaining waist circumference by ≥ 10 cm were at a higher risk of CRC, with a multivariable-adjusted HR of 1.59 (95% CI, 1.01-2.49). This association appeared to be independent of weight change.


Abdominal adiposity, independent of overall obesity, is associated with an increased CRC risk in men but not in women. Our findings also provide the first prospective evidence that waist circumference gain during adulthood may be associated with higher CRC risk in men, thus highlighting the importance of maintaining a healthy waist for CRC prevention.


Body fat distribution; postmenopausal hormone therapy; sex difference


Adult weight change and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition.

Aleksandrova K, Pischon T, Buijsse B, May AM, Peeters PH, Bueno-de-Mesquita HB, Jenab M, Fedirko V, Dahm CC, Siersema PD, Freisling H, Ferrari P, Overvad K, Tjønneland A, Trichopoulou A, Lagiou P, Naska A, Pala V, Mattiello A, Ohlsson B, Jirström K, Key TJ, Khaw KT, Riboli E, Boeing H.

Eur J Cancer. 2013 Nov;49(16):3526-36. doi: 10.1016/j.ejca.2013.06.021.

PMID: 23867126




Weight change during adult life may reflect metabolic changes and influence colorectal cancer (CRC) development, but such role is not well established. We aimed to explore the association between adult weight change (from age 20 to 50) and CRC risk. In particular, we investigated differences according to colon and rectal cancer, sex and measures of attained adiposity.


We included 201,696 participants from six participating countries in the European Prospective Investigation into Cancer and Nutrition (1992-2010). During a mean follow-up of 11.2 years 2384 (1194 in men and 1190 in women) incident CRC cases occurred. Cox proportional hazard models adjusted for body mass index at age 20 and lifestyle factors at study recruitment were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).


After multivariable adjustment, each kg of weight gained annually from age 20 to 50 was associated with a 60% higher risk of colon cancer (95% CI 1.20-2.09), but not rectal cancer (HR 1.13, 95% CI 0.79-1.62, P(interaction)=0.04). The higher risk of colon cancer was restricted to people with high attained waist circumference at age 50 (HR 1.82, 95%CI 1.14-2.91, P(interaction)=0.02). Results were not different in men and women (P(interaction)=0.81).


Adult weight gain, as reflected by attained abdominal obesity at age 50, increases colon cancer risk in both men and women. These data underline the importance of weight management and metabolic health maintenance in early adult life years for colon cancer prevention.


Abdominal obesity; Body weight change; Cancer prevention; Colorectal neoplasms


Dietary Protein Sources and Risk for Incident Chronic Kidney Disease: Results From the Atherosclerosis Risk in Communities (ARIC) Study.

Haring B, Selvin E, Liang M, Coresh J, Grams ME, Petruski-Ivleva N, Steffen LM, Rebholz CM.

J Ren Nutr. 2017 Jan 5. pii: S1051-2276(16)30179-0. doi: 10.1053/j.jrn.2016.11.004. [Epub ahead of print]

PMID: 28065493




Dietary protein restriction is recommended for patients with moderate to severe renal insufficiency. Long-term data on the relationship between dietary protein sources and risk for incident kidney disease in individuals with normal kidney function are largely missing. This study aimed to assess the association between dietary protein sources and incident chronic kidney disease (CKD).


Prospective cohort.


Atherosclerosis Risk in Communities study participants from 4 US communities.


A total of 11,952 adults aged 44-66 years in 1987-1989 who were free of diabetes mellitus, cardiovascular disease, and had an estimated glomerular filtration rate (eGFR) ≥ 60 mL/minute/1.73 m2.


A 66-item food frequency questionnaire was used to assess food intake. CKD stage 3 was defined as a decrease in eGFR of ≥25% from baseline resulting in an eGFR of less than 60 mL/minute/1.73 m2; CKD-related hospitalization; CKD-related death; or end-stage renal disease. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression.


During a median follow-up of 23 years, there were 2,632 incident CKD cases. Red and processed meat consumption was associated with increased CKD risk (HRQ5 vs. Q1: 1.23, 95% CI: 1.06-1.42, ptrend = 0.01). In contrast, higher dietary intake of nuts, legumes, and low-fat dairy products was associated with lower CKD risk (nuts: HRQ5 vs. Q1: 0.81, 95% CI: 0.72-0.92, ptrend <0.001; low-fat dairy products: HRQ5 vs. Q1: 0.75, 95% CI: 0.65-0.85, ptrend <0.001; legumes: HRQ5 vs. Q1: 0.83, 95% CI: 0.72-0.95, ptrend = 0.03).


There were varied associations of specific dietary protein sources with risk of incident CKD; with red and processed meat being adversely associated with CKD risk; and nuts, low-fat dairy products, and legumes being protective against the development of CKD.


Table 3. Association of Food Sources of Protein With Incident Chronic Kidney Disease, ARIC, 1987-2012


Protein Sources===Quintiles of Protein Consumption*=== -

... ===Quintile 1 Quintile 2 Quintile 3 Quintile 4 Quintile 5===P Value for Linear Trend


Red meat

Person-years 51,458 50,381 46,369 50,169 47,151

Events 524 520 515 528 545

Median, svg/d 0.17 0.35 0.57 0.78 1.15

HR (95% CI)† 1 (ref) 1.05 (0.93-1.19) 1.12 (0.99-1.27) 1.12 (0.98-1.27) 1.27 (1.11-1.46) ,.001

HR (95% CI)‡ 1 (ref) 1.01 (0.89-1.14) 1.07 (0.94-1.21) 1.06 (0.93-1.21) 1.19 (1.03-1.36) .02

Processed meat

Person-years 56,652 48,075 47,322 47,079 46,399

Events 554 482 505 514 577

Median, svg/d 0.03 0.14 0.29 0.53 1.00

HR (95% CI)† 1 (ref) 1.03 (0.91-1.16) 1.07 (0.95-1.21) 1.09 (0.96-1.24) 1.25 (1.09-1.43) .002

HR (95% CI)‡ 1 (ref) 0.98 (0.87-1.11) 1.00 (0.88-1.13) 0.99 (0.87-1.13) 1.12 (0.98-1.29) .16

Red and processed meat

Person-years 50,795 50,096 49,163 48,670 46,803

Events 495 510 521 540 566

Median, svg/d 0.30 0.62 0.92 1.28 1.93

HR (95% CI)† 1 (ref) 1.09 (0.96-1.24) 1.13 (0.99-1.28) 1.22 (1.07-1.39) 1.36 (1.18-1.56) ,.001

HR (95% CI)‡ 1 (ref) 1.03 (0.91-1.17) 1.05 (0.93-1.20) 1.11 (0.97-1.27) 1.23 (1.06-1.42) .01


Person-years 60,072 57,204 59,868 18,964 49,418

Events 699 606 624 179 524

Median, svg/d 0.13 0.28 0.43 0.50 0.71

HR (95% CI)† 1 (ref) 0.88 (0.79-0.99) 0.88 (0.79-0.98) 0.83 (0.71-0.98) 0.93 (0.83-1.05) .12

HR (95% CI)‡ 1 (ref) 0.92 (0.82-1.02) 0.90 (0.80-1.00) 0.85 (0.72-1.01) 0.94 (0.84-1.06) .26

Fish and seafood

Person-years 51,557 48,650 46,426 49,625 49,267

Events 570 546 501 502 513

Median, svg/d 0.07 0.14 0.23 0.35 0.64

HR (95% CI)† 1 (ref) 1.01 (0.89-1.13) 0.96 (0.85-1.08) 0.86 (0.76-0.97) 0.89 (0.78-1.01) .003

HR (95% CI)‡ 1 (ref) 0.98 (0.87-1.10) 0.97 (0.86-1.09) 0.85 (0.75-0.97) 0.89 (0.78-1.01) .01


Person-years 65,463 37,876 49,151 58,751 34,261

Events 692 400 520 635 384

Median, svg/d 0.03 0.10 0.14 0.43 0.72

HR (95% CI)† 1 (ref) 0.93 (0.82-1.05) 0.97 (0.86-1.08) 0.98 (0.88-1.09) 0.94 (0.83-1.08) .76

HR (95% CI)‡ 1 (ref) 0.93 (0.82-1.05) 0.94 (0.84-1.06) 0.96 (0.86-1.07) 0.92 (0.81, 1.06) .33

High-fat dairy

Person-years 48,866 52,059 47,937 50,524 46,064

Events 513 536 501 561 521

Median, svg/d 0.13 0.35 0.57 0.90 1.61

HR (95% CI)† 1 (ref) 0.95 (0.84-1.08) 0.91 (0.80-1.03) 0.95 (0.84-1.07) 0.90 (0.79-1.03) .24

HR (95% CI)‡ 1 (ref) 0.96 (0.85-1.08) 0.93 (0.82-1.06) 0.96 (0.84-1.08) 0.93 (0.81-1.06) .32

Low-fat dairy

Person-years 48,236 47,894 42,299 50,024 50,048

Events 603 532 531 493 473

Median, svg/d 0.00 0.22 0.60 1.07 2.04

HR (95% CI)† 1 (ref) 0.87 (0.77-0.98) 0.81 (0.71-0.91) 0.72 (0.64-0.82) 0.72 (0.63-0.82) ,.001

HR (95% CI)‡ 1 (ref) 0.88 (0.78-0.99) 0.81 (0.72-0.91) 0.74 (0.65-0.84) 0.75 (0.65-0.85) ,.001


Person-years 59,643 39,092 48,463 48,763 49,541

Events 708 415 523 484 502

Median, svg/d 0.03 0.10 0.21 0.43 0.86

HR (95% CI)† 1 (ref) 0.88 (0.78-0.99) 0.87 (0.78-0.98) 0.78 (0.70-0.88) 0.77 (0.68-0.87) ,.001

HR (95% CI)‡ 1 (ref) 0.89 (0.78-1.00) 0.88 (0.79-0.99) 0.82 (0.73-0.92) 0.81 (0.72-0.92) ,.001


Person-years 56,812 42,547 49,648 53,035 43,485

Events 582 442 556 605 447

Median, svg/d 0.07 0.14 0.21 0.36 0.68

HR (95% CI)† 1 (ref) 0.94 (0.83-1.06) 0.99 (0.88-1.12) 0.96 (0.85-1.08) 0.82 (0.72-0.94) .02

HR (95% CI)‡ 1 (ref) 0.95 (0.83-1.07) 0.97 (0.86-1.10) 0.96 (0.85-1.08) 0.83 (0.72-0.95) .03


ARIC, Atherosclerosis Risk in Communities Study; CI, confidence interval; HR, hazard ratio; and svg/d, servings/day.

*Protein consumption was estimated using cumulative average intake. For those who developed kidney disease or were censored from the analysis before visit 3, food frequency questionnaire data from visit 1 were used. Otherwise, for those who developed kidney disease or were censored from the analysis after study visit 3, the average of food frequency questionnaire data from visits 1 and 3 was used.

†Model 1: Adjusted for age, race center, sex, education level, and total caloric intake.

‡Model 2: Adjusted for variables in Model 1 1 high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, total cholesterol, lipid-lowering medication use, systolic blood pressure, antihypertensive medication use, alcohol intake, current smoker, physical activity index, leisure-related physical activity, total carbohydrate intake, body mass index, and waist-to-hip ratio.


Vascular risk factors in INPH: A prospective case-control study (the INPH-CRasH study).

Israelsson H, Carlberg B, Wikkelsö C, Laurell K, Kahlon B, Leijon G, Eklund A, Malm J.

Neurology. 2017 Jan 6. pii: 10.1212/WNL.0000000000003583. doi: 10.1212/WNL.0000000000003583. [Epub ahead of print]

PMID: 28062721




To assess the complete vascular risk factor (VRF) profile of idiopathic normal pressure hydrocephalus (INPH) using a large sample of representative patients with INPH and population-based controls to determine the extent to which vascular disease influences INPH pathophysiology.


All patients with INPH who underwent shunting in Sweden in 2008-2010 were compared to age- and sex-matched population-based controls. Inclusion criteria were age 60-85 years and no dementia. The 10 most important VRFs and cerebrovascular and peripheral vascular disease were prospectively assessed using blood samples, clinical examinations, and standardized questionnaires. Assessed VRFs were hypertension, hyperlipidemia, diabetes, obesity, psychosocial factors, smoking habits, diet, alcohol intake, cardiac disease, and physical activity.


In total, 176 patients with INPH and 368 controls participated. Multivariable logistic regression analysis indicated that hyperlipidemia (odds ratio [OR] 2.380; 95% confidence interval [CI] 1.434-3.950), diabetes (OR 2.169; 95% CI 1.195-3.938), obesity (OR 5.428; 95% CI 2.502-11.772), and psychosocial factors (OR 5.343; 95% CI 3.219-8.868) were independently associated with INPH. Hypertension, physical inactivity, and cerebrovascular and peripheral vascular disease were also overrepresented in INPH. Moderate alcohol intake and physical activity were overrepresented among the controls. The population-attributable risk percentage was 24%.


Our findings confirm that patients with INPH have more VRFs and lack the protective factors present in the general population. Almost 25% of cases of INPH may be explained by VRFs. This suggests that INPH may be a subtype of vascular dementia. Targeted interventions against modifiable VRFs are likely to have beneficial effects on INPH.


Omega-3 Fatty Acid Therapy: The Tide Turns for a Fish Story.

O'Keefe JH, Jacob D, Lavie CJ.

Mayo Clin Proc. 2017 Jan;92(1):1-3. doi: 10.1016/j.mayocp.2016.11.008. No abstract available.

PMID: 28062059




A Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies of Eicosapentaenoic and Docosahexaenoic Long-Chain Omega-3 Fatty Acids and Coronary Heart Disease Risk.

Alexander DD, Miller PE, Van Elswyk ME, Kuratko CN, Bylsma LC.

Mayo Clin Proc. 2017 Jan;92(1):15-29. doi: 10.1016/j.mayocp.2016.10.018.

PMID: 28062061






To conduct meta-analyses of randomized controlled trials (RCTs) to estimate the effect of eicosapentaenoic and docosahexaenoic acid (EPA+DHA) on coronary heart disease (CHD), and to conduct meta-analyses of prospective cohort studies to estimate the association between EPA+DHA intake and CHD risk.


A systematic literature search of Ovid/Medline, PubMed, Embase, and the Cochrane Library from January 1, 1947, to November 2, 2015, was conducted; 18 RCTs and 16 prospective cohort studies examining EPA+DHA from foods or supplements and CHD, including myocardial infarction, sudden cardiac death, coronary death, and angina, were identified. Random-effects meta-analysis models were used to generate summary relative risk estimates (SRREs) and 95% CIs. Heterogeneity was examined in subgroup and sensitivity analyses and by meta-regression. Dose-response was evaluated in stratified dose or intake analyses. Publication bias assessments were performed.


Among RCTs, there was a nonstatistically significant reduction in CHD risk with EPA+DHA provision (SRRE=0.94; 95% CI, 0.85-1.05). Subgroup analyses of data from RCTs indicated a statistically significant CHD risk reduction with EPA+DHA provision among higher-risk populations, including participants with elevated triglyceride levels (SRRE=0.84; 95% CI, 0.72-0.98) and elevated low-density lipoprotein cholesterol (SRRE=0.86; 95% CI, 0.76-0.98). Meta-analysis of data from prospective cohort studies resulted in a statistically significant SRRE of 0.82 (95% CI, 0.74-0.92) for higher intakes of EPA+DHA and risk of any CHD event.


Results indicate that EPA+DHA may be associated with reducing CHD risk, with a greater benefit observed among higher-risk populations in RCTs.



January 10, 2017

Global Burden of Raised Blood Pressure -- Coming Into Focus

Mark D. Huffman, MD, MPH1,2; Donald M. Lloyd-Jones

JAMA. 2017;317(2):142-143. doi:10.1001/jama.2016.19685



1. Forouzanfar MH, Liu P, Roth GA, et al.

Global burden of hypertension and systolic blood pressure of at least 110 to 115 mm Hg, 1990-2015.

JAMA. doi:10.1001/jama.2016.19043



This population epidemiology study uses pooled global health evaluation surveys data to estimate trends in the association between elevated stystolic blood pressure and death and disability between 1990 and 2015.

Key Points

Question What is the worldwide association between elevated blood pressure and the burden of disease?

Findings In studies from 154 countries that included 8.69 million participants, it is estimated that between 1990 and 2015 the rate of systolic blood pressure (SBP) of at least 110 to 115 mm Hg increased from 73 119 to 81 373 per 100 000 persons, and SBP of 140 mm Hg or higher increased from 17 307 to 20 526 per 100 000 persons. The estimated rate of annual deaths associated with SBP of of at least 110 to 115 mm Hg increased from 135.6 to 145.2 per 100 000 persons, and for SBP of 140 mm Hg or higher increased from 97.9 to 106.3 per 100 000 persons.

Meaning Over the past 25 years, the number of individuals with worldwide SBP levels of at least 110 to 115 mm Hg and of 140 mm Hg or higher and the estimated associated deaths have increased substantially.


Importance Elevated systolic blood (SBP) pressure is a leading global health risk. Quantifying the levels of SBP is important to guide prevention policies and interventions.

Objective To estimate the association between SBP of at least 110 to 115 mm Hg and SBP of 140 mm Hg or higher and the burden of different causes of death and disability by age and sex for 195 countries and territories, 1990-2015.

Design A comparative risk assessment of health loss related to SBP. Estimated distribution of SBP was based on 844 studies from 154 countries (published 1980-2015) of 8.69 million participants. Spatiotemporal Gaussian process regression was used to generate estimates of mean SBP and adjusted variance for each age, sex, country, and year. Diseases with sufficient evidence for a causal relationship with high SBP (eg, ischemic heart disease, ischemic stroke, and hemorrhagic stroke) were included in the primary analysis.

Main Outcomes and Measures Mean SBP level, cause-specific deaths, and health burden related to SBP (≥110-115 mm Hg and also ≥140 mm Hg) by age, sex, country, and year.

Results Between 1990-2015, the rate of SBP of at least 110 to 115 mm Hg increased from 73 119 (95% uncertainty interval [uI], 67 949-78 241) to 81 373 (95% UI, 76 814-85 770) per 100 000, and SBP of 140 mm Hg or higher increased from 17 307 (95% UI, 17 117-17 492) to 20 526 (95% UI, 20 283-20 746) per 100 000. The estimated annual death rate per 100 000 associated with SBP of at least 110 to 115 mm Hg increased from 135.6 (95% UI, 122.4-148.1) to 145.2 (95% UI 130.3-159.9) and the rate for SBP of 140 mm Hg or higher increased from 97.9 (95% UI, 87.5-108.1) to 106.3 (95% UI, 94.6-118.1). Loss of disability-adjusted life-years (DALYs) associated with SBP of at least 110 to 115 mm Hg increased from 148 million (95% UI, 134-162 million) to 211 million (95% UI, 193-231 million), and for SBP of 140 mm Hg or higher, the loss increased from 5.2 million (95% UI, 4.6-5.7 million) to 7.8 million (95% UI, 7.0-8.7 million). The largest numbers of SBP-related deaths were caused by ischemic heart disease (4.9 million [95% UI, 4.0-5.7 million]; 54.5%), hemorrhagic stroke (2.0 million [95% UI, 1.6-2.3 million]; 58.3%), and ischemic stroke (1.5 million [95% UI, 1.2-1.8 million]; 50.0%). In 2015, China, India, Russia, Indonesia, and the United States accounted for more than half of the global DALYs related to SBP of at least 110 to 115 mm Hg.

Conclusions and Relevance In international surveys, although there is uncertainty in some estimates, the rate of elevated SBP (≥110-115 and ≥140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased. Projections based on this sample suggest that in 2015, an estimated 3.5 billion adults had SBP of at least 110 to 115 mm Hg and 874 million adults had SBP of 140 mm Hg or higher.


Patient-Reported Outcomes Following LASIK -- Quality of Life in the PROWL Studies

Alan Sugar, MD1; Christopher T. Hood, MD1; Shahzad I. Mian

JAMA. 2017;317(2):204-205. doi:10.1001/jama.2016.19323

JAMA Ophthalmology



Symptoms and Satisfaction of Patients in the Patient-Reported Outcomes With Laser In Situ Keratomileusis (PROWL) Studies

Malvina Eydelman, MD; Gene Hilmantel, OD, MS; Michelle E. Tarver, MD, PhD; Elizabeth M. Hofmeister, MD; Jeanine May, PhD; Keri Hammel, MS; Ron D. Hays, PhD; Frederick Ferris III, MD

JAMA Ophthalmol. Published online November 23, 2016. doi:10.1001/jamaophthalmol.2016.4587




Patient-reported outcomes should be collected using validated questionnaires prior to and following laser in situ keratomileusis (LASIK) surgery.


To report the frequency of patient-reported visual symptoms, dry eye symptoms, satisfaction with vision, and satisfaction with LASIK surgery in the Patient-Reported Outcomes With LASIK (PROWL) studies.

Design, Setting, and Participants

The PROWL-1 and PROWL-2 studies were prospective, observational studies conducted from September 13, 2011, to June 27, 2014. The PROWL-1 study was a single–military center study of 262 active-duty Navy personnel 21 to 52 years of age. The PROWL-2 study was a study of 312 civilians 21 to 57 years of age conducted at 5 private practice and academic centers. The LASIK surgery and the postoperative care were performed based on the usual practice and clinical judgment at the site. Participants completed a self-administered, web-based questionnaire, preoperatively and postoperatively at 1 and 3 months (the PROWL-1 and -2 studies) and at 6 months (the PROWL-2 study).


Participants underwent LASIK surgery for myopia, hyperopia, and/or astigmatism.

Main Outcomes and Measures

Visual symptoms (double images, glare, halos, and/or starbursts), dry eye symptoms, participant satisfaction (with vision and LASIK surgery), and clinical measures (visual acuity, refractive error, and slitlamp and posterior segment eye examination findings) were assessed preoperatively and at 1, 3, and 6 months postoperatively.


A total of 262 participants were enrolled in the PROWL-1 study (mean [sD] age, 29.1 [6.1] years), and a total of 312 participants were enrolled in the PROWL-2 study (mean [sD] age, 31.5 [7.3] years). Visual symptoms and dissatisfaction with vision were common preoperatively. Overall, the prevalence of visual symptoms and dry eye symptoms decreased, although a substantial percentage of participants reported new visual symptoms after surgery (43% [95% CI, 31%-55%] from the PROWL-1 study and 46% [95% CI, 33%-58%] from the PROWL-2 study at 3 months). The percentages of participants in the PROWL-1 study with normal Ocular Surface Disease Index scores were 55% (95% CI, 48%-61%) at baseline, 66% (95% CI, 59%-72%) at 3 months, and 73% (95% CI, 67%-79%) at 6 months. The percentages of participants in the PROWL-2 study with normal Ocular Surface Disease Index scores were 44% (95% CI, 38%-50%) at baseline and 65% (95% CI, 59%-71%) at 3 months. Of those participants who had normal scores at baseline in both the PROWL-1 and -2 studies, about 28% (95% CI, 19%-37%) had mild, moderate, or severe dry eye symptoms at 3 months. While most participants were satisfied, the rates of dissatisfaction with vision ranged from 1% (95% CI, 0%-4%) to 4% (95% CI, 2%-7%), and the rates of dissatisfaction with surgery ranged from 1% (95% CI, 0%-4%) to 2% (95% CI, 1%-5%).

Conclusions and Relevance

The systematic administration of a questionnaire to patients who have undergone LASIK surgery is a new approach to assess symptoms and satisfaction. Our findings support the need for adequate counseling about the possibility of developing new symptoms after LASIK surgery.


News From the Centers for Disease Control and Prevention January 10, 2017 Drop in Preventable Cancer Deaths

JAMA. 2017;317(2):128. doi:10.1001/jama.2016.19514

Section Editor: Rebecca Voelker


Better disease detection and treatment as well as lower smoking rates have helped cut potentially preventable cancer deaths, a recent study reported. However, the data also showed that prescription and illicit drug overdoses and falls among elderly adults fueled an increase in avoidable unintentional injury deaths.

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The Association of Reproductive Hormone Levels and All-Cause, Cancer, and Cardiovascular Disease Mortality in Men.

Holmboe SA, Vradi E, Jensen TK, Linneberg A, Husemoen LL, Scheike T, Skakkebæk NE, Juul A, Andersson AM.

J Clin Endocrinol Metab. 2015 Dec;100(12):4472-80. doi: 10.1210/jc.2015-2460.

PMID: 26488309





Testosterone (T) levels have been associated with mortality, but controversy exists.


Our objective was to investigate associations between serum levels of total T, SHBG, free T, estradiol, LH and FSH, and subsequent mortality with up to 30 years of follow-up.


This was a prospective cohort study consisting of men participating in four independent population-based surveys (MONICA I-III and Inter99) from 1982 to 2001 and followed until December 2012 with complete registry follow-up.


A total of 5350 randomly selected men from the general population aged 30, 40, 50, 60, or 70 years at baseline participated.


All-cause mortality, cardiovascular disease (CVD) mortality, and cancer mortality were the main outcomes.


A total of 1533 men died during the follow-up period; 428 from CVD and 480 from cancer. Cox proportional hazard models revealed that men in highest LH quartile had an increased all-cause mortality compared to lowest quartile (hazard ratio {HR}, 1.32; 95% confidence interval [CI], 1.14-1.53). Likewise, increased quartiles of LH/T and estradiol increased the risk of all-cause mortality (HR, 1.23; 95% CI, 1.06-1.43; HR, 1.23; 95% CI 1.06-1.43). No association to T levels was found. Higher LH levels were associated with increased cancer mortality (HR, 1.42; 95% CI, 1.10-1.84) independently of smoking status. Lower CVD mortality was seen for men with T in the highest quartile compared to lowest (HR, 0.72; 95% CI, 0.53-0.98). Furthermore, negative trends were seen for SHBG and free T in relation to CVD mortality, however insignificant.


The observed positive association of LH and LH/T, but not T, with all-cause mortality suggests that a compensated impaired Leydig cell function may be a risk factor for death by all causes in men. Our findings underpin the clinical importance of including LH measurement in the diagnostic work-up of male patients seeking help for possible androgen insufficiency.


A lifestyle intervention among elderly men on active surveillance for non-aggressive prostate cancer: a randomised feasibility study with whole-grain rye and exercise.

Eriksen AK, Hansen RD, Borre M, Larsen RG, Jensen JM, Overgaard K, Borre M, Kyrø C, Landberg R, Olsen A, Tjønneland A.

Trials. 2017 Jan 13;18(1):20. doi: 10.1186/s13063-016-1734-1.

PMID: 28086943




The prognosis for men with non-aggressive prostate cancer is good, and several studies have investigated the impact of lifestyle changes including physical activity and diet on the prognosis. Despite positive results in animal studies and a few human interventions with whole-grain rye on markers of prostate cancer progression, the feasibility of trials investigating such dietary changes in combination with physical activity remains largely unstudied. The primary aim was to investigate the feasibility of an intervention with high whole-grain rye intake and vigorous physical activity for 6 months in men diagnosed with prostate cancer.


In total, 26 men (53-72 years) recently diagnosed with non-aggressive prostate cancer and on active surveillance, were enrolled in 2011-2012 and randomly assigned to an intervention or a control group. The intervention included 170 g/day of whole-grain rye and 3 × 45 minutes/week of vigorous physical activity. The duration of the intervention was 6 months and end of follow-up 12 months after baseline. Clinic visits were scheduled at baseline and 3, 6 and 12 months after baseline. Compliance with the intervention was evaluated by diaries, food frequency questionnaires, biomarkers, and heart rate monitor data. The effect of the intervention was evaluated by linear multiple regression analysis.


In the intervention group, the mean daily intake of whole-grain rye measured from diaries was 146 g (SD: 19) for the first 3 months and 125 g (SD: 40) for the last 3 months of the intervention. The median level (5th and 95th percentiles) of vigorous physical activity was 91 (17, 193) min/week for the first 3 months and 66 (13, 259) min/week for the last 3 months. No recordings of physical activity were done for the control group. Aerobic fitness (VO2 peak) increased in the intervention group compared to the control group after the intervention. No effects were found on other cardio-metabolic outcomes or prostate cancer progression.


The lifestyle intervention appeared feasible for 6 months among Danish men and the results are encouraging for conducting full-scale studies, where the impact of whole-grain rye and vigorous physical activity on prostate cancer progression and metabolic parameters can be evaluated.


Feasibility; Intervention; Physical activity; Prostate cancer; Whole-grain rye


Substitution of sugar-sweetened beverages with other beverage alternatives: a review of long-term health outcomes.

Zheng M, Allman-Farinelli M, Heitmann BL, Rangan A.

J Acad Nutr Diet. 2015 May;115(5):767-79. doi: 10.1016/j.jand.2015.01.006. Review.

PMID: 25746935




Excessive consumption of sugar-sweetened beverages (SSBs) has become an intractable public health concern worldwide, making investigation of healthy beverage alternatives for SSBs imperative.


To summarize the available evidence on the effects of replacing SSBs with beverage alternatives on long-term health outcomes.


We systematically retrieved studies from six electronic databases from inception to November 2013. Prospective cohort studies and randomized controlled trials (RCTs) examining the effects of substituting beverage alternatives for SSBs on long-term health outcomes in both children and adults were included. The quality of included studies was assessed using the Scottish Intercollegiate Guidelines Network 50 methodology checklists.


Six cohort studies and four RCTs were included in the systematic review with the quality rating ranging from acceptable to high. Evidence from both cohort studies and RCTs showed substitution of SSBs by various beverage alternatives was associated with long-term lower energy intake and lower weight gain. However, evidence was insufficient to draw conclusions regarding the effect of beverage substitution on other health outcomes, and which beverage alternative is the best choice.


Although studies on this topic are sparse, the available evidence suggests a potential beneficial effect on body weight outcomes when SSBs are replaced by water or low-calorie beverages. Further studies in this area are warranted to fully understand the long-term health implications of beverage substitutions.


Health outcomes; Long term; Substitution; Sugar-sweetened beverages; Systematic review

Edited by AlPater

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Will Trump promote vaccine refusal?

By Dr. Brian Goldman

White Coat Black Art


00:00 09:02

This week Donald Trump will be sworn in as the 45th President of the United States. He's promised to cancel Obamacare, but some are also wondering how a Trump presidency might affect U.S. vaccine policy.

On Tuesday last week, President-elect Trump met with Robert Kennedy Junior at Trump Tower in New York. Kennedy is son of the late Senator and 1968 Presidential candidate Robert Kennedy. He is also a well-known critic of vaccines. Kennedy came away from the meeting with Trump announcing that the President-elect had asked him to lead a panel on vaccine safety. This has not been confirmed by Trump or his spokespeople. Later in the week, a presidential transition national spokeswoman has said that the president-elect would like to a form a commission on autism, but no final decision has been made.

USA-TRUMP/Kennedy Jr.

Robert F. Kennedy Jr. gestures while entering the lobby of Trump Tower in Manhattan, N.Y. (Shannon Stapleton/Reuters)

Critics are concerned that the main purpose of the panel would be to raise once again the fraudulent allegation that that measles, mumps and rubella or MMR vaccine causes autism.

In 2005, Kennedy wrote an article published simultaneously in Salon and Rolling Stone in which he stated that thimerosal, a mercury-based preservative once commonly found in MMR vaccine but largely removed from all childhood vaccines, is dangerous to kids. The article alleged that public health authorities knowingly let the profit-driven pharmaceutical industry expose millions of American children to harm, and then engaged in a cover up about it.

In an article late last week in Scientific American, Seth Mnookin pointed out that Kennedy ignored a mountain of scientific evidence - nine studies by the U.S. Centers for Disease Control (CDC) and an immunization safety review by the Institute of Medicine -that thimerosal does not cause harm.

Because of his rambling and sometimes disjointed way of answering questions, it's often difficult to know Trump's views on vaccine safety precisely.

During a 2015 Republican primary debate, Trump linked what he referred to as an "epidemic" of autism to vaccines. In September, 2015, Trump said, "We had so many instances, people that work for me, just the other day, 2 years old, a beautiful child, went to have the vaccine and came back and a week later got a tremendous fever, got very, very sick. Now is autistic."

Before he ran for President, Trump accused doctors of lying about vaccines. Here is a tweet he sent on September 3, 2014, which has been posted in the Washington Post: "I am being proven right about massive vaccinations. The doctors lied. Save our children & their future."

We also know that Trump has aligned himself with conservatives like Dr. Ben Carson, the paediatric neurosurgeon who is Trump's nominee as Secretary of Housing and Urban Development. As Lawrence Solomon pointed out last week in the National Post, Carson has said that vaccines that prevent death or crippling are important, but that there are a multitude of other vaccines that are pushed by big government that don't fit in that category.

There are clues as to how the incoming President might change current vaccine policy. Trump has consistently blamed autism on "massive combined inoculations to small children." In one of his tweets, Trump called for a return to single vaccinations spread out over time. Breaking up the MMR vaccine into single vaccines for measles, mumps and rubella sounds like a policy. Another possibility is for Trump and fellow Republicans to make it easier for parents to pick and choose vaccines and to boost the right of parents to object to specific vaccines.

The sleeper issue concerns Trump's views on the CDC. Currently, the CDC has responsibility both for vaccine safety and promotion, which some say is a conflict of interest. Vaccine critics want Congress to take vaccine safety away from the CDC and hand it to an independent agency. I could see Trump doing that, and in the process trying to discredit the CDC by claiming the agency is in the pockets of drug companies.

These aren't idle musings. There's plenty at stake here. Increasing vaccine refusal lowers herd immunity, and contributes to outbreaks of communicable diseases. A 2016 study published in the Journal of the American Medical Association looked at more than 1400 cases of measles between 2000 and 2015. Of those, nearly 60 percent had no history of measles vaccination, which was refused for religious or philosophical reasons. Of roughly 10000 cases of pertussis or whooping cough, between 24 and 45 percent of those affected missed shots. Keep in mind that young infants who are too young to get the whooping cough vaccine are at greater risk of dying from pertussis. A 2010 study in Pediatrics calculated the cost of treating an outbreak of measles at between $10,000 and $15,000 per child infected. If Trump makes vaccine refusal acceptable, they'll be paying costs like that for years to come.


Friday January 13, 2017

Is sugar killing us? Author Gary Taubes makes his case

Science writer Gary Taubes argues sugar is responsible for more premature deaths than cigarettes. (Gunilla G/flickr cc)

Listen 19:51


A new Ontario study that looked at more than 40,000 products on Canadian supermarket shelves found more than two-thirds of them contained added sugar — including baby foods and products marketed as healthy choices.

From glucose and fructose to fruit juice concentrate — however manufacturers name it on the label, science writer and author of The Case Against Sugar Gary Taubes says we need to dramatically change our relationship to sugar because it's killing us.

"It's a very distinctive crime — these obesity and diabetes sugar — is always at the scene of the crime," Taubes tells The Current's Anna Maria Tremonti.

He argues that obesity and diabetes is not caused by overeating and sedentary lives as suggested by public health officials and health advocates.

"It's a biological issue, not a physics issue — it's not an accounting issue," Taubes says.

Author Gary Taubes says the argument obesity or diabetes is caused by overeating and sedentary lives is wrong.

(Uwe Hermann/flickr cc)

"Like everything else in your body the amount of fat on your body is exceedingly well regulated … we didn't just evolve to be able to spill excess calories into our fat tissue."

Taubes explains how hormones regulate fat accumulation and foods affect hormonal status.

"When you eat carbohydrates and you eat sugar that raises this hormone insulin which works to make you store calories as fat."

He goes on to say that sugar — in particular fructose — metabolizes in the liver and points to evidence that a condition called insulin resistance begins in the liver and insulin resistance is the fundamental defect in the common form of diabetes known as Type 2.

In a recent New York Times article, Taubes argues sugar has prematurely killed more people than tobacco.

He tells Tremonti that in the late 19th century the innovation of flue-curing tobacco would increase the sugar content of tobacco leaves from about two per cent to 20 per cent.

In 1913, when the first American blended cigarette came on the market it included the flue-curing tobacco and chewing tobacco that was marinated with a sugar sauce that also had a high sugar content and high nicotine content.

"So the lung cancer epidemic that followed the explosion of success of American blended cigarettes was in part largely due to the sugar content of the leaves of the tobacco."

"So that's not a sugar industry issue — that's a tobacco issue."

"The point is we wouldn't have nearly the deaths from lung cancer and heart disease that tobacco has caused if it wasn't for sugar."


Aging and SKN-1-dependent Loss of 20S Proteasome Adaptation to Oxidative Stress in C. elegans.

Raynes R, Juarez C, Pomatto LC, Sieburth D, Davies KJ.

J Gerontol A Biol Sci Med Sci. 2017 Feb;72(2):143-151. doi: 10.1093/gerona/glw093.

PMID: 27341854




Aging is marked by a collapse of protein homeostasis and deterioration of adaptive stress responses that often lead to disease. During aging, the induction of stress responses decline along with protein quality control. Here, we have shown that the ability to mount an adaptive response by pretreatment with minor oxidative stress is abrogated in aged Caenorhabditis elegans We have identified a defect in SKN-1 signaling sensitivity during aging and have also found an aging-related increase in basal proteasome expression and in vitro activity, however, adaptation of the 20S proteasome in response to stress is lost in old animals. Interestingly, increased activation of SKN-1 promotes stress resistance, but is unable to rescue declining adaptation during aging. Our data demonstrate that the aging-dependent decline in SKN-1 signaling negatively impacts adaptation of the 20S proteasome in response to acute oxidative stress.


Adaptive homeostasis; Hydrogen peroxide; Nrf2; Protein oxidation; Proteolysis


Obesity in Older People With and Without Conditions Associated With Weight Loss: Follow-up of 955,000 Primary Care Patients.

Bowman K, Delgado J, Henley WE, Masoli JA, Kos K, Brayne C, Thokala P, Lafortune L, Kuchel GA, Ble A, Melzer D; as part of the Ageing Well Programme of the NIHR School for Public Health Research, England..

J Gerontol A Biol Sci Med Sci. 2017 Feb;72(2):203-209. doi: 10.1093/gerona/glw147.

PMID: 27492450





Moderate obesity in later life may improve survival, prompting calls to revise obesity control policies. However, this obesity paradox may be due to confounding from smoking, diseases causing weight-loss, plus varying follow-up periods. We aimed to estimate body mass index (BMI) associations with mortality, incident type 2 diabetes, and coronary heart disease in older people with and without the above confounders.


Cohort analysis in Clinical Practice Research Datalink primary care, hospital and death certificate electronic medical records in England for ages 60 to more than 85 years. Models were adjusted for age, gender, alcohol use, smoking, calendar year, and socioeconomic status.


Overall, BMI 30-34.9 (obesity class 1) was associated with lower overall death rates in all age groups. However, after excluding the specific confounders and follow-up less than 4 years, BMI mortality risk curves at age 65-69 were U-shaped, with raised risks at lower BMIs, a nadir between 23 and 26.9 and steeply rising risks above. In older age groups, mortality nadirs were at modestly higher BMIs (all <30) and risk slopes at higher BMIs were less marked, becoming nonsignificant at age 85 and older. Incidence of diabetes was raised for obesity-1 at all ages and for coronary heart disease to age 84.


Obesity is associated with shorter survival plus higher incidence of coronary heart disease and type 2 diabetes in older populations after accounting for the studied confounders, at least to age 84. These results cast doubt on calls to revise obesity control policies based on the claimed risk paradox at older ages.


BMI; Mortality; Overweight; Paradox


Midlife Risk Factors for Impaired Physical and Cognitive Functioning at Older Ages: A Cohort Study.

Brunner EJ, Welch CA, Shipley MJ, Ahmadi-Abhari S, Singh-Manoux A, Kivimäki M.

J Gerontol A Biol Sci Med Sci. 2017 Feb;72(2):237-242. doi: 10.1093/gerona/glw092.

PMID: 27271050




Previous studies examined midlife risk factors separately for old-age impaired physical and cognitive functioning. We determined the overlap of risk factors for both domains of functioning within the same setting.


Biological and behavioral risk factors at age 50 years and cognitive and physical functioning were assessed 18 (SD = 5) years later in the Whitehall II study (N = 6,316). Impaired physical functioning was defined as ≥1 limitation on the activities of daily living scale. Impaired cognitive functioning was defined as Mini-Mental State Examination score <27. Two statistical analyses were employed: minimally adjusted analysis (for age, sex, and ethnicity) and mutually adjusted analysis (including all risk factors). Missing data on risk factors were imputed.


After confounder adjustment, impaired physical and cognitive functioning at older ages were predicted by hypertension (odds ratios [ORs] 1.80 95% confidence interval [CI] 1.39-2.33 and 1.57 95% CI 1.07-2.31, respectively), poor lung function (1.51 95% CI 1.28-1.78 and 1.31 95% CI 1.08-1.59), and physical inactivity, marginally in the case of cognitive function (1.50 95% CI 1.19-1.90 and 1.27 95% CI 0.99-1.62) at age 50 years. Impaired physical functioning but not cognitive functioning was additionally predicted by depression and higher body mass index (1.72 95% CI 1.46-2.03 and 1.29 95% CI 1.16-1.44, respectively).


Several midlife risk factors are associated with impaired physical and cognitive functioning in old age, supporting a unified prevention policy. Analysis of 12 risk factors at age 50 suggests that strategies targeting physical inactivity, hypertension, and poor lung function will reduce impairments in both cognitive and physical functioning in old age.


Aging; Cognitive functioning; Life course; Physical functioning


Safety and Effectiveness of Statins for Prevention of Recurrent Myocardial Infarction in 12 156 Typical Older Patients: A Quasi-Experimental Study.

Ble A, Hughes PM, Delgado J, Masoli JA, Bowman K, Zirk-Sadowski J, Mujica Mota RE, Henley WE, Melzer D.

J Gerontol A Biol Sci Med Sci. 2017 Feb;72(2):243-250. doi: 10.1093/gerona/glw082.

PMID: 27146371





There is limited evidence on statin risk and effectiveness for patients aged 80+. We estimated risk of recurrent myocardial infarction, muscle-related and other adverse events, and statin-related incremental costs in "real-world" older patients treated with statins versus no statins.


We used primary care electronic medical records from the UK Clinical Practice Research Datalink. Subhazard ratios (competing risk of death) for myocardial infarction recurrence (primary end point), falls, fractures, ischemic stroke, and dementia, and hazard ratios (Cox) for all-cause mortality were used to compare older (60+) statin users and 1:1 propensity-score-matched controls (n = 12,156). Participants were followed-up for 10 years.


Mean age was 76.5±9.2 years; 45.5% were women. Statins were associated with near significant reduction in myocardial infarction recurrence (subhazard ratio = 0.84, 0.69-1.02, p = .073), with protective effect in the 60-79 age group (0.73, 0.57-0.94) but a nonsignificant result in the 80+ group (1.06, 0.78-1.44; age interaction p = .094). No significant associations were found for stroke or dementia. Data suggest an increased risk of falls (1.36, 1.17-1.60) and fractures (1.33, 1.04-1.69) in the first 2 years of treatment, particularly in the 80+ group. Treatment was associated with lower all-cause mortality. Statin use was associated with health care cost savings in the 60-79 group but higher costs in the 80+ group.


Estimates of statin effectiveness for the prevention of recurrent myocardial infarction in patients aged 60-79 years were similar to trial results, but more evidence is needed in the older group. There may be an excess of falls and fractures in very old patients, which deserves further investigation.


Falls; Fractures; Myocardial infarction; Older; Statins


Risk Factors Associated With Cognitive, Functional, and Behavioral Trajectories of Newly Diagnosed Dementia Patients.

Jutkowitz E, MacLehose RF, Gaugler JE, Dowd B, Kuntz KM, Kane RL.

J Gerontol A Biol Sci Med Sci. 2017 Feb;72(2):251-258. doi: 10.1093/gerona/glw079.

PMID: 27129917




Dementia results in changes in cognition, function, and behavior. We examine the effect of sociodemographic and clinical risk factors on cognitive, functional, and behavioral declines in incident dementia patients.


We used longitudinal data from the National Alzheimer's Coordinating Center to evaluate cognitive (Mini-Mental State Exam [MMSE]), functional (Functional Activities Questionnaire [FAQ]), and behavioral (Neuropsychiatric Inventory Questionnaire [NPI-Q] severity score) trajectories for incident dementia patients over an 8-year period. We evaluated trajectories of 457 patients with mixed effects linear regression models.


In the first year, cognition worsened by -1.518 (95% confidence interval [CI] -1.745, -1.291) MMSE points (0-30 scale). Education, race, and region of residence predicted cognition at diagnosis. Age of onset, geographic region of residence, and history of hypertension and congestive heart failure predicted cognitive changes. Function worsened by 3.464 (95% CI 3.131, 3.798) FAQ points in the first year (0-30 scale). Cognition, gender, race, region of residence and place of residence, and a history of stroke and hypercholesterolemia predicted function at diagnosis. Place of residence and a history of diabetes predicted functional changes. Behavioral symptoms worsened by 0.354 (95% CI 0.123, 0.585) NPI-Q points in the first year (0-36 scale). Age of onset, region of residence, and history of hypertension and psychiatric problems predicted behaviors at diagnosis. Cognition explained changes in behavior.


Sociodemographic characteristics and clinical comorbidities predict cognitive and functional changes. Only cognitive status explains behavioral decline. Results provide an understanding of the characteristics that impact cognitive, functional, and behavioral decline.


Alzheimer’s; Dementia; Health services; Public health


Associations of Guideline Recommended Medications for Acute Coronary Syndromes With Fall-Related Hospitalizations and Cardiovascular Events in Older Women With Ischemic Heart Disease.

Peeters G, Tett SE, Hollingworth SA, Gnjidic D, Hilmer SN, Dobson AJ, Hubbard RE.

J Gerontol A Biol Sci Med Sci. 2017 Feb;72(2):259-265. doi: 10.1093/gerona/glw111.

PMID: 27384327




Guidelines for acute coronary syndrome recommend statins, β-blockers, angiotensin-converting-enzyme inhibitors or renin-angiotensin system blockers, and antiplatelet agents for the secondary prevention of cardiovascular events. The aim was to examine associations between guideline recommended medications and fall-related hospitalizations and cardiovascular events in robust and frail older women.


2002-2011 surveys from the Australian Longitudinal Study on Women's Health linked with administrative hospital, pharmaceutical and death registry data (2003-mid-2011) were used. Eight hundred eighty-five women (82.7±2.7 years, range 76-90) had prior admission for ischemic heart disease and ≥1 claims for any of the four medication classes. Four hundred thirteen (46.7%) were robust and 472 (53.3%) were frail. Fall-related admissions; cardiovascular event-related admissions or death; and cardiovascular death were recorded. Associations between each of the exposures and outcomes were analyzed using survival analyses with noncardiovascular death as a competing risk.


There were 192 fall-related admissions and 314 cardiovascular events including 82 deaths. Using four recommended classes (compared to using one) was associated with increased risks of fall-related admissions (hazard ratio {HR} = 2.57, 95% confidence interval [CI] = 1.24-5.33), but not with cardiovascular events (HR = 1.41, CI = 0.97-2.05) or cardiovascular death (HR = 0.68, CI = 0.35-1.34). Associations for fall-related admissions were stronger in frail participants (HR = 5.46, CI = 1.34-22.30) than robust (HR = 1.37, CI = 0.48-3.95).


In older women with ischemic heart disease, the combination of the four recommended medication classes was associated with increased risk of falls, particularly among frail women, with no statistically significant gain in cardiovascular health. The risks of falls and consequential morbidity in women over 75 needs consideration when prescribing medications after myocardial infarction.


accidental falls; beta-blocker; ischemic heart disease; mortality.; pharmaceutical therapy; statin


Walking Pace and the Risk of Cognitive Decline and Dementia in Elderly Populations: A Meta-analysis of Prospective Cohort Studies.

Quan M, Xun P, Chen C, Wen J, Wang Y, Wang R, Chen P, He K.

J Gerontol A Biol Sci Med Sci. 2017 Feb;72(2):266-270. doi: 10.1093/gerona/glw121.

PMID: 27927757




Data on the longitudinal association of walking pace with the risk of cognitive decline and dementia are inconsistent and inconclusive. Therefore, researchers conducted a meta-analysis of prospective cohort studies to quantitatively assess the association of walking pace with the risk of cognitive decline and dementia among elderly populations.


Eligible studies were searched in PubMed and EMBASE through April 22, 2016. Additional information was retrieved through Google Scholar or hand review of the reference lists from the relevant studies. Prospective cohort studies were included if they reported relative risk (RR) and the corresponding 95% confidence interval (CI) of cognitive decline or dementia in relation to walking pace.


Seventeen studies were identified, including 10 studies reporting the RR of cognitive decline (9,949 participants and 2,547 events) and 10 presenting the RR of dementia (14,140 participants and 1,903 events). Comparing the lowest to the highest category of walking pace, the pooled RR was 1.89 (95% CI = 1.54-2.31) for cognitive decline and 1.66 (95% CI = 1.43-1.92) for dementia. With every 1 dm/s (360 m/h) decrement in walking pace, the risk of dementia was increased by 13% (RR = 1.13; 95% CI = 1.08-1.18).


This meta-analysis provides accumulated evidence supporting that slow or decreased walking pace is significantly associated with elevated risk of cognitive decline and dementia in elderly populations.


Cognitive decline; Dementia; Walking pace; “Meta-analysis”


Association of Muscle Endurance, Fatigability, and Strength With Functional Limitation and Mortality in the Health Aging and Body Composition Study.

Roshanravan B, Patel KV, Fried LF, Robinson-Cohen C, de Boer IH, Harris T, Murphy RA, Satterfield S, Goodpaster BH, Shlipak M, Newman AB, Kestenbaum B; Health ABC study..

J Gerontol A Biol Sci Med Sci. 2017 Feb;72(2):284-291. doi: 10.1093/gerona/glw210.

PMID: 27907890




Mobility limitation is highly prevalent among older adults and is central to the loss of functional independence. Dynamic isokinetic muscle fatigue testing may reveal increased vulnerability to disability and mortality beyond strength testing.


We studied community-dwelling older adults enrolled in the Health Aging and Body Composition study (age range: 71-82) free of mobility disability and who underwent isokinetic muscle fatigue testing in 1999-2000 (n = 1,963). Isokinetic quadriceps work and fatigue index was determined over 30 repetitions and compared with isometric quadriceps maximum torque. Work was normalized to leg lean mass accounting for gender-specific differences (specific work). The primary outcome was incident persistent severe lower extremity limitation (PSLL), defined as two consecutive reports of either having a lot of difficulty or being unable to walk 1/4 mile or climb 10 steps without resting. The secondary outcome was all-cause mortality.


There were 608 (31%) occurrences of incident PSLL and 488 (25%) deaths during median follow-up of 9.3 years. After adjustment, lower isokinetic work was associated with significantly greater risks of PSLL and mortality across the full measured range. Hazard ratios per standard deviation lower specific isokinetic work were 1.22 (95% CI 1.12, 1.33) for PSLL and 1.21 (95% CI 1.13, 1.30) for mortality, respectively. Lower isometric strength was associated with PSLL, but not mortality. Fatigue index was not associated with PSLL or mortality.


Muscle endurance, estimated by isokinetic work, is an indicator of muscle health associated with mobility limitation and mortality providing important insight beyond strength testing.

© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.


Fatigue; Mobility; Muscle; Sarcopenia; Strength

Edited by AlPater

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Nutritional Considerations for Healthy Aging and Reduction in Age-Related Chronic Disease

Julie Shlisky, David E Bloom, Amy R Beaudreault, Katherine L Tucker, Heather H Keller, Yvonne Freund-Levi, Roger A Fielding, Feon W Cheng, Gordon L Jensen, Dayong Wu, and Simin N Meydani

Adv Nutr 2017; 8:17-26 doi:10.3945/an.116.013474



A projected doubling in the global population of people aged ≥60 y by the year 2050 has major health and economic implications, especially in developing regions. Burdens of unhealthy aging associated with chronic noncommunicable and other age-related diseases may be largely preventable with lifestyle modification, including diet. However, as adults age they become at risk of “nutritional frailty,” which can compromise their ability to meet nutritional requirements at a time when specific nutrient needs may be high. This review highlights the role of nutrition science in promoting healthy aging and in improving the prognosis in cases of age-related diseases. It serves to identify key knowledge gaps and implementation challenges to support adequate nutrition for healthy aging, including applicability of metrics used in body-composition and diet adequacy for older adults and mechanisms to reduce nutritional frailty and to promote diet resilience. This review also discusses management recommendations for several leading chronic conditions common in aging populations, including cognitive decline and dementia, sarcopenia, and compromised immunity to infectious disease. The role of health systems in incorporating nutrition care routinely for those aged ≥60 y and living independently and current actions to address nutritional status before hospitalization and the development of disease are discussed.

Keywords: nutrition aging chronic disease cognitive decline health care risk factors sarcopenia age-related disease


Formation of Fructose-Mediated Advanced Glycation End Products and Their Roles in Metabolic and Inflammatory Diseases

Alejandro Gugliucci

Adv Nutr 2017; 8:54-62 doi:10.3945/an.116.013912



Fructose is associated with the biochemical alterations that promote the development of metabolic syndrome (MetS), nonalcoholic fatty liver disease, and type 2 diabetes. Its consumption has increased in parallel with MetS. It is metabolized by the liver, where it stimulates de novo lipogenesis. The triglycerides synthesized lead to hepatic insulin resistance and dyslipidemia. Fructose-derived advanced glycation end products (AGEs) may be involved via the Maillard reaction. Fructose has not been a main focus of glycation research because of the difficulty in measuring its adducts, and, more importantly, because although it is 10 times more reactive than glucose, its plasma concentration is only 1% of that of glucose. In this focused review, I summarize exogenous and endogenous fructose metabolism, fructose glycation, and in vitro, animal, and human data. Fructose is elevated in several tissues of diabetic patients where the polyol pathway is active, reaching the same order of magnitude as glucose. It is plausible that the high reactivity of fructose, directly or via its metabolites, may contribute to the formation of intracellular AGEs and to vascular complications. The evidence, however, is still unconvincing. Two areas that have been overlooked so far and should be actively explored include the following: 1) enteral formation of fructose AGEs, generating an inflammatory response to the receptor for AGEs (which may explain the strong association between fructose consumption and asthma, chronic bronchitis, and arthritis); and 2) inactivation of hepatic AMP-activated protein kinase by a fructose-mediated increase in methylglyoxal flux (perpetuating lipogenesis, fatty liver, and insulin resistance). If proven correct, these mechanisms would put the fructose-mediated Maillard reaction in the limelight again as a contributing factor in chronic inflammatory diseases and MetS.


fructose Maillard reaction advanced glycation metabolic syndrome AMPK inflammation RAGE asthma arthritis diabetes


Dietary Supplements and Risk of Cause-Specific Death, Cardiovascular Disease, and Cancer: A Systematic Review and Meta-Analysis of Primary Prevention Trials

Lukas Schwingshackl, Heiner Boeing, Marta Stelmach-Mardas, Marion Gottschald, Stefan Dietrich, Georg Hoffmann, and Anna Chaimani

Adv Nutr 2017; 8:27-39 doi:10.3945/an.116.013516 OPEN ACCESS ARTICLE




Our aim was to assess the efficacy of dietary supplements in the primary prevention of cause-specific death, cardiovascular disease (CVD), and cancer by using meta-analytical approaches. Electronic and hand searches were performed until August 2016. Inclusion criteria were as follows: 1) minimum intervention period of 12 mo; 2) primary prevention trials; 3) mean age ≥18 y; 4) interventions included vitamins, fatty acids, minerals, supplements containing combinations of vitamins and minerals, protein, fiber, prebiotics, and probiotics; and 5) primary outcome of all-cause mortality and secondary outcomes of mortality or incidence from CVD or cancer. Pooled effects across studies were estimated by using random-effects meta-analysis. Overall, 49 trials (69 reports) including 287,304 participants met the inclusion criteria. Thirty-two trials were judged as low risk–, 15 trials as moderate risk–, and 2 trials as high risk–of-bias studies. Supplements containing vitamin E (RR: 0.88; 95% CI: 0.80, 0.96) significantly reduced cardiovascular mortality risk, whereas supplements with folic acid reduced the risk of CVD (RR: 0.81; 95% CI: 0.70, 0.94). Vitamins D, C, and K; selenium; zinc; magnesium; and eicosapentaenoic acid showed no significant risk reduction for any of the outcomes. On the contrary, vitamin A was linked to an increased cancer risk (RR: 1.16; 95% CI: 1.00, 1.35). Supplements with β-carotene showed no significant effect; however, in the subgroup with β-carotene given singly, an increased risk of all-cause mortality by 6% (RR: 1.06; 95% CI: 1.02, 1.10) was observed. Taken together, we found insufficient evidence to support the use of dietary supplements in the primary prevention of cause-specific death, incidence of CVD, and incidence of cancer. The application of some supplements generated small beneficial effects; however, the heterogeneous types and doses of supplements limit the generalizability to the overall population.

Keywords: dietary supplements meta-analysis systematic review mortality cardiovascular disease cancer


Tasting profile affects adoption of caloric beverage reduction in a randomized weight loss intervention.

Turner-McGrievy G, Wang X, Popkin B, Tate DF.

Obes Sci Pract. 2016 Dec;2(4):392-398. doi: 10.1002/osp4.64.

PMID: 28090344





The aim of this study was to examine differences in rates of non-caloric beverage adoption by participants classified as sweet likers (SLs) or sweet dislikers (measured using a behavioural tasting task).


Data are a sub-study from a 6-month, three-group, randomized weight loss trial (CHOICE) (body mass index 36.3 ± 5.8 kg m-2, 84% female, aged 42.2 ± 10.9 years, 53% African-American) comparing the replacement of caloric beverages with either non-caloric sweetened beverages (diet) or water (water) compared with a control group. This sub-study, which included participants within the water (n = 106) and diet (n = 103) groups only, examined whether SLs (n = 33 water; n = 37 diet) varied in their adherence to caloric beverage recommendations compared with sweet dislikers (n = 73 water; n = 76 diet) over the 6-month study.


Diet intake and sweet-liking data collected on 190 (3 months) and 169 participants (6 months) were used for analysis. The interaction between SL status and beverage group (diet vs. water) approached significance (P = 0.06) at 3 months but not 6 months. Caloric beverage intake (% energy) at 3 months was significantly higher in SLs within the water group (9.7 ± 1.4%) compared with SLs in the diet group (5.4 ± 1.0%, P = 0.03).


Results suggest that SL status may affect the rate in reduction of caloric beverages when water is the recommended substitution. Future studies should explore tailoring beverage recommendations to tasting profile.


Beverages; dietary adherence; tasting preference; water

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Does selection for short sleep duration explain human vulnerability to Alzheimer's disease?

Nesse RM, Finch CE, Nunn CL.

Evol Med Public Health. 2017 Jan 16. pii: eow035. doi: 10.1093/emph/eow035. [Epub ahead of print]

PMID: 28096295



Compared with other primates, humans sleep less and have a much higher prevalence of Alzheimer 's disease (AD) pathology. This article reviews evidence relevant to the hypothesis that natural selection for shorter sleep time in humans has compromised the efficacy of physiological mechanisms that protect against AD during sleep. In particular, the glymphatic system drains interstitial fluid from the brain, removing extra-cellular amyloid beta (eAβ) twice as fast during sleep. In addition, melatonin - a peptide hormone that increases markedly during sleep - is an effective antioxidant that inhibits the polymerization of soluble eAβ into insoluble amyloid fibrils that are associated with AD. Sleep deprivation increases plaque formation and AD, which itself disrupts sleep, potentially creating a positive feedback cycle. These and other physiological benefits of sleep may be compromised by short sleep durations. Our hypothesis highlights possible long-term side effects of medications that reduce sleep, and may lead to potential new strategies for preventing and treating AD.


Physical inactivity is a strong risk factor for stroke in the oldest old: Findings from a multi-ethnic population (the Northern Manhattan Study).

Willey JZ, Moon YP, Sacco RL, Greenlee H, Diaz KM, Wright CB, Elkind MS, Cheung YK.

Int J Stroke. 2016 Jan 1:1747493016676614. doi: 10.1177/1747493016676614. [Epub ahead of print]

PMID: 28093966




Background The fastest growing segment of the population is those age ≥80 who have the highest stroke incidence. Risk factor management is complicated by polypharmacy-related adverse events. Aims To characterize the impact of physical inactivity for stroke by age in a multi-ethnic prospective cohort study (NOMAS, n = 3298). Methods Leisure time physical activity was assessed by a validated questionnaire and our primary exposure was physical inactivity (PI). Participants were followed annually for incident stroke. We fit Cox-proportional hazard models to calculate hazard ratios and 95% confidence intervals (HR 95% CI) for the association of PI and other risk factors with risk of stroke including two-way interaction terms between the primary exposures and age (<80 vs. ≥80). Results The mean age was 69 ± 10.3 years and 562 (17%) were ≥80 at enrolment. PI was common in the cohort (40.8%). Over a median of 14 years, we found 391 strokes. We found a significant interaction of age ≥80 on the risk of stroke with PI ( p = 0.03). In stratified models, PI versus any activity (adjusted HR 1.60, 95%CI 1.05-2.42) was associated with an increased risk of stroke among those ≥80. Conclusion Physical inactivity is a treatable risk factor for stroke among those older than age 80. Improving activity may reduce the risk of stroke in this segment of the population.


Stroke; aging; epidemiology; exercise; mortality; physical inactivity


Alcohol consumption and dementia risk: a dose-response meta-analysis of prospective studies.

Xu W, Wang H, Wan Y, Tan C, Li J, Tan L, Yu JT.

Eur J Epidemiol. 2017 Jan 17. doi: 10.1007/s10654-017-0225-3. [Epub ahead of print]

PMID: 28097521


It is widely believed that light-to-moderate alcohol intake may protect against dementia while excessive drinking may instead increase the risk. Nonetheless, these findings need cautious interpretations due to varying methodologies and lack of standard definition, which hindered our transferring into preventative practice. The objective of this study is to investigate the potential dose-response association between alcohol consumption and risk of dementia. A systematic search was conducted in electronic databases to identify relevant studies. Risk estimates were combined using a random-effect model. Eleven studies with 73,330 participants and 4586 cases for all-cause dementia (ACD), five studies with 52,715 participants and 1267 cases for Alzheimer's dementia (AD) and four studies with 49,535 participants and 542 cases for vascular dementia were included. We observed a nonlinear association between alcohol consumption and ACD risk (p nonlinearity < 0.05). The alcohol dose associated with lower risk of dementia was confined to at most 12.5 g/day, with the risk hitting bottom (RR ≈ 0.9) at roughly 6 g/day. Of note, the ACD risk seemed to be elevated (≈10%) when the dose surpasses certain levels: 23 drinks/week or 38 g/day. For the alcohol type, recommendation for wine is prioritized. The subgroup analysis further indicated that the effect of alcohol may be greater in younger adults (<60 years old) with regard to fighting against dementia. Modest alcohol consumption (≤12.5 g/day) is associated with a reduced risk of dementia with 6 g/day of alcohol conferring a lower risk than other levels while excessive drinking (≥38 g/day) may instead elevate the risk.


Alcohol; Dementia; Dose–response; Meta-analysis


Qualitative analysis

In qualitative analysis, we observed a trend indicating a U-shaped relationship between alcohol consumption and dementia (Fig. 2): An inverse association of ACD with light, light-to-moderate or moderate drinking was revealed while the summary RR for heavier dose marched upwards despite with no statistical significance (Fig. 2a) Similar results were also indicated for AD (Fig. 2b). However, we did not identify significant association for VD despite with a nonlinear shape (Fig. 2c). Egger’s regression test provided no evidence of substantial publication bias.


Further, we conducted the qualitative analysis for ACD according to the alcohol type (wine [1, 2, 6, 26–28], beer [2, 6, 26–28] and liquor [1, 2, 26–28]) (Table 2). The exposure can be categorized into “current versus never drinker”, “light-to-moderate drinker versus none”, and “highest versus lowest”. It seemed that the protective effects from alcohol only existed for wine (alcoholic beverage made from grapes or other fruits/vegetables) consumption: current drinker (RR 0.67; 95% CI 0.48–0.94) or light-to-moderate drinker (RR 0.58; 95% CI 0.39–0.87). Further, we observed an elevated risk for highest versus lowest consumption of beer (RR 1.84; 95% CI 1.01–3.34). We cannot explore the quantitative relationship for alcohol type or the qualitative association between alcohol type and other dementia types because of the constrained data.

Also, we explored whether the association between alcohol intake and ACD was influenced by APOE4 status (Table 3). A total of three studies [2, 3, 29] reported the effect size stratified by APOE4 status, among which the case number in study by Kivipelto et al. [29] was too small and thus excluded. We found a roughly 40% reduction of dementia risk for light drinking or light-to-moderate drinking for APOE4 carriers. Otherwise, the non-significant association for APOE4 non-carriers should be interpreted with caution due to a massive heterogeneity.

Dose–response analysis

Among the 10 prospective studies included in the dose–response analysis for ACD, 6 studies [2–4, 28, 30, 31] used drinks/week, 3 studies used times/week [5, 7, 32] and only one study [1] used g/day as alcohol unit. Consistent with the qualitative analysis, we uncovered a significantly nonlinear association between alcohol consumption and ACD risk (Fig. 3) (pfornon-linearity < 0.05). Several cutoffs were of great value especially in defining the alcohol dose associated with the dementia’s risk. Specifically, we found the alcohol dose associated with lower risk was roughly situated between 0 and 7.5 drinks/week (Fig. 3a) or 12.5 g/day (Fig. 3b) or 2 times/week (Fig. 3c) with the lowest risk (RR ≈ 0.9) corresponding to roughly 4 drinks/week (Fig. 3a), 6 g/day (Fig. 3b), and 1 times/week (Fig. 3c). On the other hand, the ACD risk was significantly elevated when the alcohol consumed surpasses certain cutoff: 23 drinks/week (Fig. 3a) or 38 g/day (Fig. 3b). The subgroup analysis further indicated that it might be favorable for adults aged <60 years old to drink less than 6 drinks/week (Fig. 4a) while for those aged >60 years old, the safe drinking frequency for dementia prevention was ≤2 times/week (pfor nonlinearity < 0.05).

Among the four studies eligible for dose–response analysis for AD, two studies [2, 3] reported drinks/week while another two studies [5, 7] reported times/week. We thus cannot conduct the quantitative analysis because number of eligible studies is small. The quantitative analysis for VD was hindered for similar reason. In spite of this, some clues can still be implied: Mukamal et al. [2] reported elders aged >65 years old who consumed alcohol ≤6 drinks/week would have magnificent lower risk of AD. This amount is similar to that concluded by the present analysis for ACD, which is reasonable because AD is the most common type of ACD. Otherwise, Ruitenberg et al. [3] proposed one to three drinks per day as the optimal dose against VD. Zhou et al. [7] found that daily drinking (frequency) can markedly increase the risk of AD or VD.

The influence of “optimal” dose range for dementia on the overall health

As mentioned above, alcohol consumption was also associated with risk of diseases other than dementia. From the perspective of overall health, assessing whether the optimal dose range (≤12.5 g/day) for dementia is still protective for other diseases is pretty necessary. Thus, we searched the PubMed database using the keywords “dose–response” AND “meta-analysis” AND “alcohol”, and found eleven studies exploring dose–response relationship with other diseases, including heart disease, DM-2, cancer, stroke, and hypertension. By comparison, we identified drinking ≤12.5 g/day was still protective for all diseases above except some cancers, which is also the major source of dispute concerning whether alcohol consumption should be regarded as a safe approach to preventing dementia. (Supplementary Table 3).


Prolonged job strain and subsequent risk of cancer in women - a longitudinal study, based on the Danish Nurse Cohort.

Vesterlund GK, Høeg BL, Johansen C, Heitmann BL, E Bidstrup P.

Acta Oncol. 2017 Jan 17:1-6. doi: 10.1080/0284186X.2016.1267399. [Epub ahead of print]

PMID: 28093051




The role of psychological stress in cancer risk is continuously debated. Stress at work is the most common form of stress and previous studies have shown inconsistent results regarding cancer risk. In this longitudinal study, we examined the association between prolonged job strain across six years and subsequent cancer risk.


We used data from 6571 cancer-free women from the Danish Nurse Cohort aged 45-70 years at inclusion, and self-reported questionnaires on job strain at baseline in 1993 and again in 1999. Prolonged job strain was defined as high job busyness and speed, and low control in both 1993 and 1999. Information on cancer diagnosis was obtained from the Danish Cancer Registry. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for overall cancer as well as subgroups of virus immune-related, hormone-related, digestive and lung cancers according to level of prolonged job strain. The women were followed from 1 January 2000 until cancer diagnosis, emigration, death or 31 December 2013 (mean follow-up 13 years) and models were adjusted for potential confounders. Effect modification was examined according to working nightshifts and full time.


No significant differences in the risk of overall cancer or any of the cancer subgroups were identified in relation to prolonged busyness, speed, influence, or overall job strain. Effect modification by working full time was observed when examining job influence in relation to overall cancer risk, and by working nightshifts when examining job influence in relation to hormone related cancer risk. However, none of the associations were significant in stratified analyses.


We found no evidence of an increased risk of any cancer among women with prolonged job strain. Since a large proportion of cancer patients perceive psychological stress as a possible cause of their cancer disease, it is of importance to communicate these findings to the public.


Association between midlife health behaviours and transitions out of employment from midlife to early old age: Whitehall II cohort study.

Hagger-Johnson G, Carr E, Murray E, Stansfeld S, Shelton N, Stafford M, Head J.

BMC Public Health. 2017 Jan 17;17(1):82. doi: 10.1186/s12889-016-3970-4.

PMID: 28095887




It is important to determine whether unhealthy behaviours might influence transitions out of employment from midlife to old age, given the anticipated need for adults to work for longer. Our aim was to determine the association between repeated assessments of cigarette smoking, heavy/problem alcohol drinking, low physical activity and poor diet at midlife, in relation to work exit from midlife to old age.


Data from 7704 participants (5392 men) from the Whitehall II cohort study in employment at midlife were used to evaluate the association between unhealthy behaviours and a subsequent transition out of work during 22 years follow-up, using logistic regression models.


Men who smoked cigarettes, consistently drank alcohol heavily, or reported problem drinking, were more likely to leave employment over follow-up. Women with a consistently poor diet were more likely to leave employment. Associations were stronger when the reason for leaving was health grounds, and stronger among those with persistently unhealthy behaviours over follow-up. The size of the effects were broadly equivalent to one advancing year of age on employment. Physical health functioning over follow-up only partly accounted for the associations with work exit, whereas physical and mental functioning accounted for most of the associations with work exit on health grounds.


Unhealthy behaviours in midlife are associated with transitions out of employment into old age. Promoting healthy behaviours at midlife might support current policy initiatives aimed at extending working life. Future research should consider possible mechanisms that link behaviours to transitions out of employment, and consider sex differences in larger cohorts.


Alcohol drinking; Cigarette smoking; Employment; Health behaviour; Retirement


[i was able only to find the first author's thesis as a pdf.]

How expensive is a cardioprotective diet? Analysis from the CRESSIDA study.

Reidlinger DP, Sanders TA, Goff LM.

Public Health Nutr. 2017 Jan 18:1-8. doi: 10.1017/S1368980016003529. [Epub ahead of print]

PMID: 28095936




To determine whether a cardioprotective dietary intervention based on UK dietary guidelines was more expensive than a conventional UK diet.


Cost analysis of food records collected at baseline and after a 12-week dietary intervention of a cardioprotective diet v. conventional UK diet.


A randomized controlled dietary intervention study (CRESSIDA; ISRCTN 92382106) investigating the impact of following a diet consistent with UK dietary guidelines on CVD risk.


Participants were healthy UK residents aged 40-70 years. A sub-sample of participants was randomly selected from those who completed the cardioprotective dietary intervention (n 20) or the conventional UK dietary intervention (n 20).


Baseline diet costs did not differ between groups; mean daily food cost for all participants was £6·12 (sd £1·83). The intervention diets were not more expensive: at end point the mean daily cost of the cardioprotective diet was £6·43 (sd £2·05) v. the control diet which was £6·53 (sd £1·53; P=0·86).


There was no evidence that consumption of a cardioprotective diet was more expensive than a conventional dietary pattern. Despite the perception that healthier foods are less affordable, these results suggest that cost may not be a barrier when modifying habitual intake and under tightly controlled trial conditions. The identification of specific food groups that may be a cost concern for individuals may be useful for tailoring interventions for CVD prevention for individuals and populations.


CVD; Diet; Dietary guidelines; Food costs; Monetary costs


Protein Intake and Breast Cancer Survival in the Nurses' Health Study.

Holmes MD, Wang J, Hankinson SE, Tamimi RM, Chen WE.

J Clin Oncol. 2017 Jan 20;35(3):325-333. doi: 10.1200/JCO.2016.68.3292.

PMID: 28095274





Greater protein intake has been associated with better breast cancer survival in several prospective studies, including among 1,982 women in the Nurses' Health Study. We proposed to extend this previous finding. We hypothesized that protein, essential amino acid, branched-chain amino acid, and leucine intakes are associated with improved survival and that these associations are stronger in tumors expressing insulin receptor (IR). Patients and Methods We included 6,348 women diagnosed with stage I to III breast cancer between 1976 and 2004. There were 1,046 distant recurrences. Relative risks (RRs) and 95% CIs were calculated according to quintiles of updated postdiagnostic diet using adjusted Cox proportional hazards models based on follow-up until 2010. Results There was an inverse association between energy-adjusted protein intake and recurrence. Multivariable RRs for increasing quintiles of intake compared with the lowest were 0.95 (95% CI, 0.79 to 1.15), 0.92 (95% CI, 0.76 to 1.11), 0.75 (95% CI, 0.61 to 0.91), and 0.84 (95% CI, 0.69 to 1.03; trend P = .02). For animal protein intake, the RRs were 0.88 (95% CI, 0.73 to 1.06), 0.85 (95% CI, 0.70 to 1.02), 0.75 (95% CI, 0.62 to 0.92), and 0.78 (95% CI, 0.63 to 0.95; trend P = .003). Neither essential amino acids, branched-chain amino acids, nor any individual amino acid stood out as being the source of the association. The association also did not differ by IR status. There was no clear association with any protein-containing foods. Conclusion We found a modest survival advantage with higher intake of protein, regardless of IR status. There was no clear mechanism for this association, although it is consistent with prior studies. Our data suggest that there is likely no advantage for women with a history of breast cancer in restricting protein intake or protein-containing foods.



January 17, 2017

Osteoporosis and Fracture Risk Evaluation and Management

Shared Decision Making in Clinical Practice

Nelson B. Watts, MD1; JoAnn E. Manson, MD, DrPH2,3

JAMA. 2017;317(3):253-254. doi:10.1001/jama.2016.19087


Fractures due to osteoporosis represent a serious and costly public health problem, leading to disability and increased mortality risk.1 For postmenopausal women, osteoporotic fractures are more common than stroke, myocardial infarction, and breast cancer combined.2 A fracture can be a life-changing event and may represent a significant threat to personal independence. Although osteoporosis is commonly defined as “a skeletal disorder characterized by decreased bone strength predisposing to an increased risk of fracture,” it is fracture that is the important end result. A more pragmatic definition is “high risk of fracture, due at least in part to increased skeletal fragility.” Primary care clinicians should be comfortable evaluating, preventing, and treating osteoporosis and related risks (Box).

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TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons.

Gao Y, Yao T, Deng Z, Sohn JW, Sun J, Huang Y, Kong X, Yu KJ, Wang RT, Chen H, Guo H, Yan J, Cunningham KA, Chang Y, Liu T, Williams KW.

Cell Rep. 2017 Jan 17;18(3):583-592. doi: 10.1016/j.celrep.2016.12.072.

PMID: 28099839




The molecular mechanisms underlying acute leptin and serotonin 2C receptor-induced hypophagia remain unclear. Here, we show that neuronal and pro-opiomelanocortin (Pomc)-specific loss of transient receptor potential cation 5 (TrpC5) subunits is sufficient to decrease energy expenditure and increase food intake resulting in elevated body weight. Deficiency of Trpc5 subunits in Pomc neurons is also sufficient to block the anorexigenic effects of leptin and serotonin 2C receptor (Ht2Cr) agonists. The loss of acute anorexigenic effects of these receptors is concomitant with a blunted electrophysiological response to both leptin and Ht2Cr agonists in arcuate Pomc neurons. We also demonstrate that the Ht2Cr agonist lorcaserin-induced improvements in glucose and insulin tolerance are blocked by TrpC5 deficiency in Pomc neurons. Together, our results link TrpC5 subunits in the brain with leptin- and serotonin 2C receptor-dependent changes in neuronal activity, as well as energy balance, feeding behavior, and glucose metabolism.


diabetes; electrophysiology; glycemia; leptin; lorcaserin; melanocortin; obesity; patch-clamp; serotonin; thermogenesis; transient receptor potential cation channels


[The below paper is not pdf-avialed.]

The effects of flavanone-rich citrus juice on cognitive function and cerebral blood flow: an acute, randomised, placebo-controlled cross-over trial in healthy, young adults.

Lamport DJ, Pal D, Macready AL, Barbosa-Boucas S, Fletcher JM, Williams CM, Spencer JP, Butler LT.

Br J Nutr. 2016 Dec;116(12):2160-2168. doi: 10.1017/S000711451600430X.

PMID: 28091350


A plausible mechanism underlying flavonoid-associated cognitive effects is increased cerebral blood flow (CBF). However, behavioural and CBF effects following flavanone-rich juice consumption have not been explored. The aim of this study was to investigate whether consumption of flavanone-rich juice is associated with acute cognitive benefits and increased regional CBF in healthy, young adults. An acute, single-blind, randomised, cross-over design was applied with two 500-ml drink conditions - high-flavanone (HF; 70·5 mg) drink and an energy-, and vitamin C- matched, zero-flavanone control. A total of twenty-four healthy young adults aged 18-30 years underwent cognitive testing at baseline and 2-h after drink consumption. A further sixteen, healthy, young adults were recruited for functional MRI assessment, whereby CBF was measured with arterial spin labelling during conscious resting state at baseline as well as 2 and 5 h after drink consumption. The HF drink was associated with significantly increased regional perfusion in the inferior and middle right frontal gyrus at 2 h relative to baseline and the control drink. In addition, the HF drink was associated with significantly improved performance on the Digit Symbol Substitution Test at 2 h relative to baseline and the control drink, but no effects were observed on any other behavioural cognitive tests. These results demonstrate that consumption of flavanone-rich citrus juice in quantities commonly consumed can acutely enhance blood flow to the brain in healthy, young adults. However, further studies are required to establish a direct causal link between increased CBF and enhanced behavioural outcomes following citrus juice ingestion.


CBF cerebral blood flow; CT control; DSST Digit Symbol Substitution Test; HF high flavanone; fMRI functional MRI; Cerebral blood flow; Cognition; Cognitive function; Flavonoids; Functional MRI; Juices


Flavanone-rich citrus beverages counteract the transient decline in postprandial endothelial function in humans: a randomised, controlled, double-masked, cross-over intervention study.

Rendeiro C, Dong H, Saunders C, Harkness L, Blaze M, Hou Y, Belanger RL, Corona G, Lovegrove JA, Spencer JP.

Br J Nutr. 2016 Dec;116(12):1999-2010. doi: 10.1017/S0007114516004219.

PMID: 28065188



Specific flavonoid-rich foods/beverages are reported to exert positive effects on vascular function; however, data relating to effects in the postprandial state are limited. The present study investigated the postprandial, time-dependent (0-7 h) impact of citrus flavanone intake on vascular function. An acute, randomised, controlled, double-masked, cross-over intervention study was conducted by including middle-aged healthy men (30-65 years, n 28) to assess the impact of flavanone intake (orange juice: 128·9 mg; flavanone-rich orange juice: 272·1 mg; homogenised whole orange: 452·8 mg; isoenergetic control: 0 mg flavanones) on postprandial (double meal delivering a total of 81 g of fat) endothelial function. Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery at 0, 2, 5 and 7 h. Plasma levels of naringenin/hesperetin metabolites (sulphates and glucuronides) and nitric oxide species were also measured. All flavanone interventions were effective at attenuating transient impairments in FMD induced by the double meal (7 h post intake; P<0·05), but no dose-response effects were observed. The effects on FMD coincided with the peak of naringenin/hesperetin metabolites in circulation (7 h) and sustained levels of plasma nitrite. In summary, citrus flavanones are effective at counteracting the negative impact of a sequential double meal on human vascular function, potentially through the actions of flavanone metabolites on nitric oxide.


FMD flow-mediated dilation; FROJ flavanone-rich orange juice; NO nitric oxide; OJ orange juice beverage; RXNO nitroso species including nitrosothiols; WO whole orange beverage; iron-nitrosylhaemoglobin and nitrosohaemoglobin; nitrosamines; Citrus flavanones; Endothelial function; High-fat meals; Nitric oxide; Postprandial state

"This work was supported by PepsiCo Inc."


Phenotypic factors influencing the variation in response of circulating cholesterol level to personalised dietary advice in the Food4Me study.

Kirwan L, Walsh MC, Celis-Morales C, Marsaux CF, Livingstone KM, Navas-Carretero S, Fallaize R, O'Donovan CB, Woolhead C, Forster H, Kolossa S, Daniel H, Moschonis G, Manios Y, Surwillo A, Godlewska M, Traczyk I, Drevon CA, Gibney MJ, Lovegrove JA, Martinez JA, Saris WH, Mathers JC, Gibney ER, Brennan L.

Br J Nutr. 2016 Dec;116(12):2011-2019. doi: 10.1017/S0007114516004256.

PMID: 28065180



Individual response to dietary interventions can be highly variable. The phenotypic characteristics of those who will respond positively to personalised dietary advice are largely unknown. The objective of this study was to compare the phenotypic profiles of differential responders to personalised dietary intervention, with a focus on total circulating cholesterol. Subjects from the Food4Me multi-centre study were classified as responders or non-responders to dietary advice on the basis of the change in cholesterol level from baseline to month 6, with lower and upper quartiles defined as responder and non-responder groups, respectively. There were no significant differences between demographic and anthropometric profiles of the groups. Furthermore, with the exception of alcohol, there was no significant difference in reported dietary intake, at baseline. However, there were marked differences in baseline fatty acid profiles. The responder group had significantly higher levels of stearic acid (18 : 0, P=0·034) and lower levels of palmitic acid (16 : 0, P=0·009). Total MUFA (P=0·016) and total PUFA (P=0·008) also differed between the groups. In a step-wise logistic regression model, age, baseline total cholesterol, glucose, five fatty acids and alcohol intakes were selected as factors that successfully discriminated responders from non-responders, with sensitivity of 82 % and specificity of 83 %. The successful delivery of personalised dietary advice may depend on our ability to identify phenotypes that are responsive. The results demonstrate the potential use of metabolic profiles in identifying response to an intervention and could play an important role in the development of precision nutrition.


FA fatty acid; Cholesterol; Fatty acid profiles; Personalised nutrition; Phenotypes; Responders


Diets high in resistant starch increase plasma levels of trimethylamine-N-oxide, a gut microbiome metabolite associated with CVD risk.

Bergeron N, Williams PT, Lamendella R, Faghihnia N, Grube A, Li X, Wang Z, Knight R, Jansson JK, Hazen SL, Krauss RM.

Br J Nutr. 2016 Dec;116(12):2020-2029. doi: 10.1017/S0007114516004165.

PMID: 27993177



Production of trimethylamine-N-oxide (TMAO), a biomarker of CVD risk, is dependent on intestinal microbiota, but little is known of dietary conditions promoting changes in gut microbial communities. Resistant starches (RS) alter the human microbiota. We sought to determine whether diets varying in RS and carbohydrate (CHO) content affect plasma TMAO levels. We also assessed postprandial glucose and insulin responses and plasma lipid changes to diets high and low in RS. In a cross-over trial, fifty-two men and women consumed a 2-week baseline diet (41 percentage of energy (%E) CHO, 40 % fat, 19 % protein), followed by 2-week high- and low-RS diets separated by 2-week washouts. RS diets were assigned at random within the context of higher (51-53 %E) v. lower CHO (39-40 %E) intake. Measurements were obtained in the fasting state and, for glucose and insulin, during a meal test matching the composition of the assigned diet. With lower CHO intake, plasma TMAO, carnitine, betaine and γ-butyrobetaine concentrations were higher after the high- v. low-RS diet (P<0·01 each). These metabolites were not differentially affected by high v. low RS when CHO intake was high. Although the high-RS meal reduced postprandial insulin and glucose responses when CHO intake was low (P<0·01 each), RS did not affect fasting lipids, lipoproteins, glucose or insulin irrespective of dietary CHO content. In conclusion, a lower-CHO diet high in RS was associated with higher plasma TMAO levels. These findings, together with the absence of change in fasting lipids, suggest that short-term high-RS diets do not improve markers of cardiometabolic health.


HOMA-IR homoeostatic model assessment of insulin resistance; RS resistant starches; TMAO trimethylamine-N-oxide; CVD; Carbohydrate; Glucose; Insulin; Lipids; Resistant starch; Trimethylamine-N-oxide


[it seems that at least not in all cases is alpha-linolenic acid intake good.]

Intake of n-3 fatty acids and long-term outcome in renal transplant recipients: a post hoc analysis of a prospective cohort study.

Pranger IG, Gruppen EG, van den Berg E, Soedamah-Muthu SS, Navis G, Gans RO, Muskiet FA, Kema IP, Joosten MM, Bakker SJ.

Br J Nutr. 2016 Dec;116(12):2066-2073. doi: 10.1017/S0007114516004207.

PMID: 27993180



Supplementation with n-3 fatty acids may improve long-term outcomes of renal transplant recipients (RTR). Recent evidence suggests that EPA and DHA have different outcomes compared with α-linolenic acid (ALA). We examined the prospective associations of EPA-DHA and ALA intakes with graft failure and all-cause mortality in 637 RTR. During 3·1 years (interquartile range 2·7, 3·8) of follow-up, forty-one developed graft failure and sixty-seven died. In age- and sex-adjusted analyses, EPA-DHA and ALA intakes were not associated with graft failure. EPA-DHA intake was not significantly associated with mortality (hazard ratio (HR) 0·79; 95% CI 0·54, 1·15 per 0·1 energy% difference). ALA intake was significantly associated with mortality (HR 1·17; 95% CI 1·04, 1·31 per 0·1 energy% difference). This association remained following adjustments for BMI, proteinuria and intakes of fat, carbohydrate and protein. RTR in the highest tertile of ALA intake exhibited about 2-fold higher mortality risk (HR 2·21; 95% CI 1·23, 3·97) compared with the lowest tertile. In conclusion, ALA intake may be associated with increased mortality in RTR. Future RCT are needed to confirm these results.


n-3 Fatty acids; ALA α-linolenic acid; En% energy percentage; HR hazard ratio; IQR interquartile range; RTR renal transplant recipients; Graft failure; Mortality; Renal transplant recipients


[The below paper is not pdf-availed.]

Maternal fish oil supplementation during lactation is associated with reduced height at 13 years of age and higher blood pressure in boys only.

Lauritzen L, Eriksen SE, Hjorth MF, Nielsen MS, Olsen SF, Stark KD, Michaelsen KF, Damsgaard CT.

Br J Nutr. 2016 Dec;116(12):2082-2090. doi: 10.1017/S0007114516004293.

PMID: 28065179


Dietary long-chain n-3 PUFA (n-3 LCPUFA) in infancy may have long-term effects on lifestyle disease risk. The present follow-up study investigated whether maternal fish oil (FO) supplementation during lactation affected growth and blood pressure in adolescents and whether the effects differed between boys and girls. Mother-infant pairs (n 103) completed a randomised controlled trial with FO (1·5 g/d n-3 LCPUFA) or olive oil (OO) supplements during the first 4 months of lactation; forty-seven mother-infant pairs with high fish intake were followed-up for 4 months as the reference group. We also followed-up 100 children with assessment of growth, blood pressure, diet by FFQ and physical activity by 7-d accelerometry at 13·5 (sd 0·4) years of age. Dried whole-blood fatty acid composition was analysed in a subgroup (n 49). At 13 years of age, whole-blood n-3 LCPUFA, diet, physical activity and body composition did not differ between the three groups. The children from the FO group were 3·4 (95 % CI 0·2, 6·6) cm shorter (P=0·035) than those from the OO group, and tended to have less advanced puberty (P=0·068), which explained the difference in height. There was a sex-specific effect on diastolic blood pressure (P sex×group=0·020), which was driven by a 3·9 (95 % CI 0·2, 7·5) mmHg higher diastolic blood pressure in the FO compared with the OO group among boys only (P=0·041). Our results indicate that early n-3 LCPUFA intake may reduce height in early adolescence due to a delay in pubertal maturation and increase blood pressure specifically in boys, thereby tending to counteract existing sex differences.


n-3 Long-chain PUFA; n-3 LCPUFA long-chain n-3 PUFA; DBP diastolic blood pressure; FO fish oil; MAP mean arterial blood pressure; OO olive oil; Growth; Health; Programming; Puberty


[The below paper is not pdf-availed.]

Dietary calcium impairs tomato lycopene bioavailability in healthy humans.

Borel P, Desmarchelier C, Dumont U, Halimi C, Lairon D, Page D, Sébédio JL, Buisson C, Buffière C, Rémond D.

Br J Nutr. 2016 Dec;116(12):2091-2096. doi: 10.1017/S0007114516004335.

PMID: 28069089


Lycopene (LYC) bioavailability is relatively low and highly variable, because of the influence of several factors. Recent in vitro data have suggested that dietary Ca can impair LYC micellarisation, but there is no evidence whether this can lead to decreased LYC absorption efficiency in humans. Our objective was to assess whether a nutritional dose of Ca impairs dietary LYC bioavailability and to study the mechanism(s) involved. First, in a randomised, two-way cross-over study, ten healthy adults consumed either a test meal that provided 19-mg (all-E)-LYC from tomato paste or the same meal plus 500-mg calcium carbonate as a supplement. Plasma LYC concentration was measured at regular time intervals over 7 h postprandially. In a second approach, an in vitro digestion model was used to assess the effect of increasing Ca doses on LYC micellarisation and on the size and zeta potential of the mixed micelles produced during digestion of a complex food matrix. LYC bioavailability was diminished by 83 % following the addition of Ca in the test meal. In vitro, Ca affected neither LYC micellarisation nor mixed micelle size but it decreased the absolute value of their charge by 39 %. In conclusion, a nutritional dose of Ca can impair dietary LYC bioavailability in healthy humans. This inhibition could be due to the fact that Ca diminishes the electrical charge of micelles. These results call for a thorough assessment of the effects of Ca, or other divalent minerals, on the bioavailability of other carotenoids and lipophilic micronutrients.


LYC lycopene; SR-BI scavenger receptor class B type I; Bioaccessibility; Carotenoid micellarisation; Carotenoids; Lycopene Absorption; Micelles; Zeta potential


[The below paper is not pdf-availed.]

Association between carbohydrate nutrition and prevalence of depressive symptoms in older adults.

Gopinath B, Flood VM, Burlutksy G, Louie JC, Mitchell P.

Br J Nutr. 2016 Dec;116(12):2109-2114. doi: 10.1017/S0007114516004311.

PMID: 28065177


We aimed to examine the relationship between dietary glycaemic index (GI) and glycaemic load of foods consumed, intakes of carbohydrates, sugars and fibre, and the prevalence of depressive symptoms in older adults. Data collected from 2334 participants aged 55+ years and 1952 participants aged 60+ years were analysed. Dietary information was collected using a semi-quantitative FFQ. Depressive symptoms were based on antidepressant use or either the 36-Item Short-Form Survey, which included the Mental Health Index (MHI), or the Center for Epidemiologic Studies Depression-10 Scale. Participants in the highest v. lowest tertile of dietary GI intake had increased odds of depressive symptoms (assessed by the MHI scale), multivariable-adjusted OR 1·55 (95 % CI 1·12, 2·14). Participants in the highest compared with lowest tertile of fruit consumption had reduced odds of prevalent depressive symptoms, multivariable-adjusted OR 0·66 (95 % CI 0·46, 0·95). Total fibre, vegetable fibre and breads/cereal fibre intakes were all inversely associated with the prevalence of depressive symptoms, with global P values of 0·03, 0·01 and 0·03, respectively. Participants in the second v. first tertile of vegetable consumption had 41 % reduced odds of prevalent depressive symptoms, multivariable-adjusted OR 0·59 (95 % CI 0·40, 0·88). We show that dietary GI and fibre intakes as well as consumption of fruits and vegetables are associated with the prevalence of depressive symptoms.


BMES Blue Mountains Eye Study; CES-D Center for Epidemiologic Studies Depression; GI glycaemic index; GL glycaemic load; MHI Mental Health Index; Blue Mountains Eye Study; Carbohydrates; Depressive symptoms; Fibres; Fruits; Glycaemic index; Vegetables


Cheese Consumption and Risk of All-Cause Mortality: A Meta-Analysis of Prospective Studies.

Tong X, Chen GC, Zhang Z, Wei YL, Xu JY, Qin LQ.

Nutrients. 2017 Jan 13;9(1). pii: E63. doi: 10.3390/nu9010063.

PMID: 28098767



The association between cheese consumption and risk for major health endpoints has been investigated in many epidemiologic studies, but findings are inconsistent. As all-cause mortality can be viewed as the final net health effect of dietary intakes, we conducted a meta-analysis to examine the long-term association of cheese consumption with all-cause mortality. Relevant studies were identified by a search of the PubMed database through May 2016. Reference lists from retrieved articles were also reviewed. Summary relative risks (RR) and 95% confidence intervals (CI) were calculated using a random-effects model. Pre-specified stratified and dose-response analyses were also performed. The final analysis included nine prospective cohort studies involving 21,365 deaths. The summary RR of all-cause mortality for the highest compared with the lowest cheese consumption was 1.02 (95% CI: 0.97, 1.06), and little evidence of heterogeneity was observed. The association between cheese consumption and risk of all-cause mortality did not significantly differ by study location, sex, age, number of events, study quality score or baseline diseases excluded. There was no dose-response relationship between cheese consumption and risk of all-cause mortality (RR per 43 g/day = 1.03, 95% CI: 0.99-1.07). No significant publication bias was observed. Our findings suggest that long-term cheese consumption was not associated with an increased risk of all-cause mortality.


cheese; dairy; fermented food; meta-analysis; mortality



Tumours slowed by diet tweak

Nature 541, 263 (19 January 2017) doi:10.1038/541263e

Published online 18 January 2017


Subject terms: Cancer Metabolism

A high-fat diet speeds tumour growth in mice, but this can be counteracted by drugs that lower levels of a metabolite in the blood.

Diet can influence cancer survival, but the molecular reasons are largely unknown. Jing Chen at Emory University in Atlanta, Georgia, and his colleagues searched for clues in mice with tumours that carried the BRAF V600E mutation, which occurs in some human cancers. They found that high-fat, low-carbohydrate diets boosted concentrations of acetoacetate — which is made when the liver breaks down fat — in the animals' blood, and that this spurred tumour growth. Treatment with cholesterol-lowering agents slowed tumour growth by reducing acetoacetate levels. Moreover, an acetate inhibitor reversed the effects of a fatty diet on tumours.

The results suggest that physicians could one day tailor diets to slow cancer progression.


Prevention of Dietary-Fat-Fueled Ketogenesis Attenuates BRAF V600E Tumor Growth.

Xia S, Lin R, Jin L, Zhao L, Kang HB, Pan Y, Liu S, Qian G, Qian Z, Konstantakou E, Zhang B, Dong JT, Chung YR, Abdel-Wahab O, Merghoub T, Zhou L, Kudchadkar RR, Lawson DH, Khoury HJ, Khuri FR, Boise LH, Lonial S, Lee BH, Pollack BP, Arbiser JL, Fan J, Lei QY, Chen J.

Cell Metab. 2017 Jan 9. pii: S1550-4131(16)30643-X. doi: 10.1016/j.cmet.2016.12.010. [Epub ahead of print]

PMID: 28089569



Lifestyle factors, including diet, play an important role in the survival of cancer patients. However, the molecular mechanisms underlying pathogenic links between diet and particular oncogenic mutations in human cancers remain unclear. We recently reported that the ketone body acetoacetate selectively enhances BRAF V600E mutant-dependent MEK1 activation in human cancers. Here we show that a high-fat ketogenic diet increased serum levels of acetoacetate, leading to enhanced tumor growth potential of BRAF V600E-expressing human melanoma cells in xenograft mice. Treatment with hypolipidemic agents to lower circulating acetoacetate levels or an inhibitory homolog of acetoacetate, dehydroacetic acid, to antagonize acetoacetate-BRAF V600E binding attenuated BRAF V600E tumor growth. These findings reveal a signaling basis underlying a pathogenic role of dietary fat in BRAF V600E-expressing melanoma, providing insights into the design of conceptualized "precision diets" that may prevent or delay tumor progression based on an individual's specific oncogenic mutation profile.


BRAF V600E; acetoacetate; cancer metabolism; cancer prevention; cancer risk; cancer therapy; dehydroacetic acid; dietary fat; ketogenesis; precision diet

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Handgrip Strength in Old and Very Old Adults: Mood, Cognition, Function, and Mortality.

Stessman J, Rottenberg Y, Fischer M, Hammerman-Rozenberg A, Jacobs JM.

J Am Geriatr Soc. 2017 Jan 19. doi: 10.1111/jgs.14509. [Epub ahead of print]

PMID: 28102890



To determine the trajectory of handgrip strength (HGS) from age 70 to 90 and its association with mood, cognition, functional status, and mortality.


Prospective follow-up of an age-homogenous representative community-dwelling cohort (born 1920-21) in the Jerusalem Longitudinal Cohort Study (1990-2015).


Home-based assessment.


Subjects aged 70 (n = 327), 78 (n = 384), 85 (n = 1187), and 90 (n = 406), examined in 1990, 1998, 2005, and 2010, respectively.


Handgrip strength (kg) (dynamometer), low HGS defined as sex-specific lowest quartile grip; geriatric assessment; all-cause mortality (1990-2015).


Mean HGS declined between age 70 and 90 from 21.3 ± 7.2 to 11.5 ± 5.6 kg in women and from 35.3 ± 8.4 to 19.5 ± 8.2 kg in men. Cross-sectional associations were observed between low HGS and poor functional measures (age 70-90), lower educational and financial status, smoking, and diabetes mellitus (ages 78-90). After adjustment for baseline education, self-rated health, physical activity, diabetes mellitus, depression, and cognition, low HGS predicted subsequent activity of daily living dependence from age 78 to 85 (odds ratio (OR) = 2.68, 95% confidence interval (CI) = 1.04-6.89) and 85 to 90 (OR = 2.31, 95% CI = 1.01-5.30), whereas the adjusted ORs for activities of daily living difficulty and depression failed to achieve significance. HGS did not predict subsequent cognitive decline. Survival rates were significantly lower in participants with low HGS (Quartile 1) than in those with normal HGS (Quartiles 2, 3, 4) throughout follow-up from ages 78 to 85, 85 to 90, and 90 to 95. Similarly, after adjusting for sex, education, self-rated health, body mass index, hypertension, diabetes mellitus, ischemic heart disease, and smoking, a low HGS was associated with significantly higher mortality.


Mean HGS declined progressively with age, and participants in the lowest age-specific quartile of HGS had a higher risk of subsequent functional decline and mortality.


cognitive status; depression; functional status; handgrip strength; longevity; mortality


Drosophila FIT is a protein-specific satiety hormone essential for feeding control.

Sun J, Liu C, Bai X, Li X, Li J, Zhang Z, Zhang Y, Guo J, Li Y.

Nat Commun. 2017 Jan 19;8:14161. doi: 10.1038/ncomms14161.

PMID: 28102207



Protein homeostasis is critical for health and lifespan of animals. However, the mechanisms for controlling protein feeding remain poorly understood. Here we report that in Drosophila, protein intake-induced feeding inhibition (PIFI) is specific to protein-containing food, and this effect is mediated by a fat body (FB) peptide named female-specific independent of transformer (FIT). Upon consumption of protein food, FIT expression is greatly elevated. Secreted FIT peptide in the fly haemolymph conveys this metabolic message to the brain, thereby promoting the release of Drosophila insulin-like peptide 2 (DILP2) and suppressing further protein intake. Interestingly, Fit is a sexually dimorphic gene, and consequently protein consumption-induced insulin release, as well as protein feeding behaviour, are also dimorphic between sexes. Thus, our findings reveal a protein-specific satiety hormone, providing important insights into the complex regulation of feeding decision, as well as the sexual dimorphism in feeding behaviour.


Role of Choline in the Modulation of Degenerative Processes: In Vivo and In Vitro Studies.

Merinas-Amo T, Tasset-Cuevas I, Díaz-Carretero AM, Alonso-Moraga Á, Calahorro F.

J Med Food. 2017 Jan 19. doi: 10.1089/jmf.2016.0075. [Epub ahead of print]

PMID: 28103133



The purpose of the present study was to examine the nutraceutical potential of choline as an added value to its well-known brain nutrient role. Several toxicity, antitoxicity, genotoxicity, antigenotoxicity, and longevity endpoints were checked in the somatic mutation and recombination test in in vivo Drosophila animal model. Cytotoxicity in human leukemia-60 cell line (HL-60) promyelocytic and NIH3T3 mouse fibroblast cells, proapoptotic DNA fragmentation, comet assay, methylation status, and macroautophagy (MA) activity were tested in in vitro assays. Choline is not only safe but it is also able to protect against the DNA damage caused by an oxidative genotoxin. Moreover, it improves the life extension in the animal model. The in vitro results show that it is able to exhibit genetic damage against leukemia HL-60 cells. Single-strand breaks in DNA are observed at the molecular level in treatments with choline, although only a significant hypermethylation on the long interspersed elements-1 and a hypomethylation on the satellite-alpha DNA repetitive DNA sequences of HL-60 cells at the lowest concentration (0.447 mM) were observed. Besides, choline decreased MA at the lower assayed concentration and the MA response to topoisomerase inhibitor (etoposide) is maintained in the presence of treatment with 0.22 mM choline. Taking into account the hopeful results obtained in the in vivo and in vitro assays, choline could be proposed as a substance with an important nutraceutical value for different purposes.


DNA damage; Drosophila melanogaster; HL-60 and NIH3T3 cell lines; antigenotoxicity; antitoxicity; choline; cytotoxicity; longevity; macroautophagy; methylation status


[Associations between airflow obstruction and total and cause-specific mortality in adults in China].

Lan FL, Li JC, Yu CQ, Guo Y, Bian Z, Tan YL, Pei P, Chen JS, Chen ZM, Cao WH, Lyu J, Li LM; China Kadoorie Biobank (CKB) Collaborative Group..

Zhonghua Liu Xing Bing Xue Za Zhi. 2017 Jan 10;38(1):13-19. doi: 10.3760/cma.j.issn.0254-6450.2017.01.003. Chinese.

PMID: 28100370


Objective: To examine the prospective associations between airflow obstruction and total and cause-specific mortality. Methods: The study was based on China Kadoorie Biobank, in which 199 099 men and 287 895 women aged 30-79 years at baseline survey were included after excluding those with heart disease, stroke and cancer. The Global Initiative on Obstructive Lung Disease (GOLD) guideline was used to classify airflow obstruction. Cox regression models were used to estimate adjusted HR and 95%CI. Results: During 3 494 079 person-years of follow-up between 2004 and 2013 (median 7.2 years), a total of 21 649 people died. Absolute mortality rates were 5.5, 9.9, 13.1, 32.4 and 63.3 deaths per 1 000 person-years for participants who had normal airflow, GOLD-1 to GOLD-4 airflow obstruction, respectively. After adjusting potential confounders, compared with participants with normal lung function, the HRs for death were 0.98 (95%CI: 0.88-1.09), 1.03 (95%CI: 0.97-1.09), 1.62 (95% CI: 1.53-1.73) and 2.83 (95% CI: 2.59-3.10) for those whose airflow obstruction were classified as GOLD-1 to GOLD-4, respectively. The airflow obstruction was also associated with increased risk for deaths due to ischemic heart disease, cerebrovascular disease and chronic obstructive pulmonary disease. Conclusion: Airflow obstruction is associated with total and certain cause-specific mortality, the higher the airflow obstruction degree is, the higher the death risk is.


Airflow obstruction; Chronic disease; Chronic obstructive pulmonary disease; Death


Living at a Geographically Higher Elevation Is Associated with Lower Risk of Metabolic Syndrome: Prospective Analysis of the SUN Cohort.

Lopez-Pascual A, Bes-Rastrollo M, Sayón-Orea C, Perez-Cornago A, Díaz-Gutiérrez J, Pons JJ, Martínez-González MA, González-Muniesa P, Martínez JA.

Front Physiol. 2017 Jan 4;7:658. doi: 10.3389/fphys.2016.00658.

PMID: 28101063



Living in a geographically higher altitude affects oxygen availability. The possible connection between environmental factors and the development of metabolic syndrome (MetS) feature is not fully understood, being the available epidemiological evidence still very limited. The aim of the present study was to evaluate the longitudinal association between altitude and incidence of MetS and each of its components in a prospective Spanish cohort, The Seguimiento Universidad de Navarra (SUN) project. Our study included 6860 highly educated subjects (university graduates) free from any MetS criteria at baseline. The altitude of residence was imputed with the postal code of each individual subject residence according to the data of the Spanish National Cartographic Institute and participants were categorized into tertiles. MetS was defined according to the harmonized definition. Cox proportional hazards models were used to assess the association between the altitude of residence and the risk of MetS during follow-up. After a median follow-up period of 10 years, 462 incident cases of MetS were identified. When adjusting for potential confounders, subjects in the highest category of altitude (>456 m) exhibited a significantly lower risk of developing MetS compared to those in the lowest tertile (<122 m) of altitude of residence [Model 2: Hazard ratio = 0.75 (95% Confidence interval: 0.58-0.97); p for trend = 0.029]. Living at geographically higher altitude was associated with a lower risk of developing MetS in the SUN project. Our findings suggest that geographical elevation may be an important factor linked to metabolic diseases.


cohort studies; environmental health; metabolic syndrome; morbidity; preventive medicine


[The below paper is pdf-availed.]

Low muscle mass and risk of type 2 diabetes in middle-aged and older adults: findings from the KoGES.

Son JW, Lee SS, Kim SR, Yoo SJ, Cha BY, Son HY, Cho NH.

Diabetologia. 2017 Jan 19. doi: 10.1007/s00125-016-4196-9. [Epub ahead of print]

PMID: 28102434



Asians have a propensity to develop type 2 diabetes with a lower BMI than Western populations. This discrepancy may be due to differences in body fat and muscle mass for a given BMI. However, unlike adiposity, it is unclear whether muscle mass affects the risk of type 2 diabetes in Asian populations.


We conducted a 2-yearly prospective assessment of 6895 participants who were free of diabetes at the baseline examination as part of the Korean Genome Epidemiology Study. The muscle mass index (MMI) was defined as the weight-adjusted appendicular skeletal muscle mass. Using Cox regression models, we evaluated the association between MMI and the risk of developing type 2 diabetes across sex-specific tertiles of MMI. Low muscle mass was defined as the sex-specific lowest tertile of MMI. Main covariates included age, sex, urban or rural residence, family history of diabetes, hypertension, smoking status, education level, monthly income, physical activity, alcohol consumption and diet. In addition, body fat mass, waist circumference and BMI were controlled as categorical variables. Obesity was defined as a BMI of ≥25 kg/m2 or a waist circumference of ≥90 cm for men and ≥85 cm for women.


During a median follow-up of 9.06 years, 1336 participants developed type 2 diabetes. At baseline, the mean age was 52.1 years and the mean BMI was 24.4 kg/m2. The mean MMI for men and women was 32.1% and 26.0%, respectively. There was an inverse association between MMI and the risk of type 2 diabetes. Multivariate-adjusted HRs for the risk of developing type 2 diabetes were 2.05 (95% CI 1.73, 2.43), 1.39 (95% CI 1.17, 1.66) and 1.0 from the lowest to highest sex-specific MMI tertile, with an HR of 1.35 (95% CI 1.26, 1.45) per SD decline in MMI. Further adjustments for fat mass, waist circumference and BMI as categorical variables did not modify the relationship (each p < 0.01). In BMI-stratified analyses, the population-attributable fraction of the lowest tertile of MMI for developing type 2 diabetes was increased by 11.9% in the non-obese group and 19.7% in the obese group.


Low muscle mass as defined by MMI was associated with an increased risk of type 2 diabetes, independent of general obesity, in middle-aged and older Korean adults.


[The below paper is pdf--availed.]

Maternal Characteristics and Incidence of Overweight/Obesity in Children: A 13-Year Follow-up Study in an Eastern Mediterranean Population.

Jalali-Farahani S, Amiri P, Abbasi B, Karimi M, Cheraghi L, Daneshpour MS, Azizi F.

Matern Child Health J. 2017 Jan 19. doi: 10.1007/s10995-016-2222-7. [Epub ahead of print]

PMID: 28102505


Objectives To investigate clustering of parental sociobehavioral factors and their relationship with the incidence of overweight and obesity in Iranian children. Methods Demographics, body weight, and certain medical characteristics of the parents of 2999 children were used to categorize parents by cluster; children's weights were assessed for each cluster. Specifically, survival analysis and Cox regression models were used to test the effect of parental clustering on the incidence of childhood overweight and obesity. Results Maternal metabolic syndrome, education level, age, body weight status, and paternal age had important roles in distinguishing clusters with low, moderate, and high risk. Crude incidence rates (per 10,000 person-years) of overweight and obesity were 416.8 (95% confidence interval (CI) 388.2-447.5) and 114.7 (95% CI 101.2-129.9), respectively. Children of parents with certain constellations of demographic and medical characteristics were 37.0 and 41.0% more likely to become overweight and obese, respectively. Conclusions for Practice The current study demonstrated the vital role of maternal characteristics in distinguishing familial clusters, which could be used to predict the incidence of overweight and obesity in children.


Children; Cluster analysis; Incidence; Overweight and obesity; Parental factors


This Week in Science

Science 20 Jan 2017:

Vol. 355, Issue 6322, pp. 257


Robots have a change of heart

Caitlin Czajka

A robotic sleeve supports the pumping heart without contacting the blood.


Ventricular assist devices help failing hearts function by pumping blood, but they require monitoring and anticoagulant therapy to prevent blood clot formation. Roche et al. created a soft robotic device with material properties similar to those of native heart tissue that sits snugly around the heart and provides ventricular assistance without ever contacting the blood. The robotic sleeve uses compressed air to power artificial silicone muscles that compress and twist, mimicking the movements of the normal human heart. The device increased cardiac ejection volume in vitro and when implanted in adult pigs during drug-induced cardiac arrest.


Sci. Transl. Med. 9, eaaf3925 (2017).


Soft robotic sleeve supports heart function.

Roche ET, Horvath MA, Wamala I, Alazmani A, Song SE, Whyte W, Machaidze Z, Payne CJ, Weaver JC, Fishbein G, Kuebler J, Vasilyev NV, Mooney DJ, Pigula FA, Walsh CJ.

Sci Transl Med. 2017 Jan 18;9(373). pii: eaaf3925. doi: 10.1126/scitranslmed.aaf3925.

PMID: 28100834




There is much interest in form-fitting, low-modulus, implantable devices or soft robots that can mimic or assist in complex biological functions such as the contraction of heart muscle. We present a soft robotic sleeve that is implanted around the heart and actively compresses and twists to act as a cardiac ventricular assist device. The sleeve does not contact blood, obviating the need for anticoagulation therapy or blood thinners, and reduces complications with current ventricular assist devices, such as clotting and infection. Our approach used a biologically inspired design to orient individual contracting elements or actuators in a layered helical and circumferential fashion, mimicking the orientation of the outer two muscle layers of the mammalian heart. The resulting implantable soft robot mimicked the form and function of the native heart, with a stiffness value of the same order of magnitude as that of the heart tissue. We demonstrated feasibility of this soft sleeve device for supporting heart function in a porcine model of acute heart failure. The soft robotic sleeve can be customized to patient-specific needs and may have the potential to act as a bridge to transplant for patients with heart failure.

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[The below paper is not pdf-availed.]

Cause of Death among Young-old, Old-old and Oldest-old Patients in a Single Center During 15 Years.

Zhang WX, Zhou W, Zhang ZQ, Shi BY.

West Indian Med J. 2015 Nov 9. pii: wimj.2015.072. doi: 10.7727/wimj.2015.072. [Epub ahead of print]

PMID: 28103355



The purpose of this study is to identify the cause of death in elderly patients stratified by age in a general hospital over a 15-year period.


The authors retrospectively analyzed the cause of death in a cohort of deceased patients aged 65 years and over, who were divided into three groups as young-old (65-74 years, n = 1050), old-old (75-84 years, n = 944), and oldest-old (≥85 years, n = 344), and who were admitted to a general hospital in Beijing from May 1996 to May 2011.


There were a total of 2338 patients (1409 male, 929 female) aged 65 years and older admitted to and eventually died in our hospital in this period. The five major causes of death by the order were neoplasm (777, 33.2%), circulatory (648, 27.7%), respiratory (541, 23.1%), digestive (163, 7.0%) and diseases and injuries (70, 3.0%). However, in the oldest-old group, they were respiratory (126, 36.6%), circulatory (95, 27.6%), neoplasm (61, 17.7%), digestive (28, 8.1%) diseases and injuries (26, 7.6%). The proportion of patients who died from neoplasm is significantly lower, while that of respiratory system diseases and injuries significantly higher in the older groups than in the younger groups (P < 0.01). The proportion of patients who died from neoplasm is negatively correlated with age (r = -0.938, P = 0.000), while that by respiratory diseases was positively correlated with age (r = 0.785, P = 0.000).


More attention should be paid to the prevention and management of neoplasm in younger group, while of respiratory system diseases for older group of elderly to fulfill their longevity.


Candidate SNP markers of aggressiveness-related complications and comorbidities of genetic diseases are predicted by a significant change in the affinity of TATA-binding protein for human gene promoters.

Chadaeva IV, Ponomarenko MP, Rasskazov DA, Sharypova EB, Kashina EV, Matveeva MY, Arshinova TV, Ponomarenko PM, Arkova OV, Bondar NP, Savinkova LK, Kolchanov NA.

BMC Genomics. 2016 Dec 28;17(Suppl 14):995. doi: 10.1186/s12864-016-3353-3.

PMID: 28105927




Aggressiveness in humans is a hereditary behavioral trait that mobilizes all systems of the body-first of all, the nervous and endocrine systems, and then the respiratory, vascular, muscular, and others-e.g., for the defense of oneself, children, family, shelter, territory, and other possessions as well as personal interests. The level of aggressiveness of a person determines many other characteristics of quality of life and lifespan, acting as a stress factor. Aggressive behavior depends on many parameters such as age, gender, diseases and treatment, diet, and environmental conditions. Among them, genetic factors are believed to be the main parameters that are well-studied at the factual level, but in actuality, genome-wide studies of aggressive behavior appeared relatively recently. One of the biggest projects of the modern science-1000 Genomes-involves identification of single nucleotide polymorphisms (SNPs), i.e., differences of individual genomes from the reference genome. SNPs can be associated with hereditary diseases, their complications, comorbidities, and responses to stress or a drug. Clinical comparisons between cohorts of patients and healthy volunteers (as a control) allow for identifying SNPs whose allele frequencies significantly separate them from one another as markers of the above conditions. Computer-based preliminary analysis of millions of SNPs detected by the 1000 Genomes project can accelerate clinical search for SNP markers due to preliminary whole-genome search for the most meaningful candidate SNP markers and discarding of neutral and poorly substantiated SNPs.


Here, we combine two computer-based search methods for SNPs (that alter gene expression) {i} Web service SNP_TATA_Comparator (DNA sequence analysis) and {ii} PubMed-based manual search for articles on aggressiveness using heuristic keywords. Near the known binding sites for TATA-binding protein (TBP) in human gene promoters, we found aggressiveness-related candidate SNP markers, including rs1143627 (associated with higher aggressiveness in patients undergoing cytokine immunotherapy), rs544850971 (higher aggressiveness in old women taking lipid-lowering medication), and rs10895068 (childhood aggressiveness-related obesity in adolescence with cardiovascular complications in adulthood).


After validation of these candidate markers by clinical protocols, these SNPs may become useful for physicians (may help to improve treatment of patients) and for the general population (a lifestyle choice preventing aggressiveness-related complications).


Aggressiveness; Candidate SNP marker; Gene; Keyword-based search; Prediction in silico; Promoter; Single nucleotide polymorphism; TATA-binding protein

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First Investigation to Focus on Role of Hypertension in Dementia in the “Oldest Old”

CHICAGO, January 17, 2017 –


Age of onset of hypertension and risk of dementia in the oldest-old: The 90+ Study.

Corrada MM, Hayden KM, Paganini-Hill A, Bullain SS, DeMoss J, Aguirre C, Brookmeyer R, Kawas CH.

Alzheimers Dement. 2017 Jan 6. pii: S1552-5260(16)32962-4. doi: 10.1016/j.jalz.2016.09.007. [Epub ahead of print]

PMID: 28108119



We investigated the association between age of onset of hypertension and dementia risk in an oldest-old cohort.


Participants are from The 90+ Study, a population-based longitudinal study of people aged 90+ who are survivors from the Leisure World Cohort Study. We estimated hypertension onset age using self-reported information from The 90+ Study and Leisure World Cohort Study, collected about 20 years earlier. A total of 559 participants without dementia were followed every 6 months for up to 10 years.


A total of 224 participants developed dementia during follow-up (mean = 2.8 years). Compared with those without hypertension, participants whose hypertension onset age was 80 to 89 years had a lower dementia risk (hazard ratio = 0.58, P = .04) and participants with an onset age of 90+ years had the lowest risk (hazard ratio = 0.37, P = .004).


Developing hypertension at older ages may protect against dementia. Understanding the mechanisms for this lower risk is important for determining ways to prevent dementia in the very elderly.


Blood pressure; Dementia; Epidemiology; Hypertension; Oldest-old; Risk factors


The Dietary Approaches to Stop Hypertension Diet, Cognitive Function, and Cognitive Decline in American Older Women.

Berendsen AA, Kang JH, van de Rest O, Feskens EJ, de Groot LC, Grodstein F.

J Am Med Dir Assoc. 2017 Jan 17. pii: S1525-8610(16)30558-8. doi: 10.1016/j.jamda.2016.11.026. [Epub ahead of print]

PMID: 28108204




To examine the association between long-term adherence to the Dietary Approaches to Stop Hypertension (DASH) diet with cognitive function and decline in older American women.


Prospective cohort study.


The Nurses' Health Study, a cohort of registered nurses residing in 11 US states.


A total of 16,144 women from the Nurses' Health Study, aged ≥70 years, who underwent cognitive testing a total of 4 times by telephone from 1995 to 2001 (baseline), with multiple dietary assessments between 1984 and the first cognitive examination. DASH adherence for each individual was based on scoring of intakes of 9 nutrient or food components.


Long-term DASH adherence was calculated as the average DASH adherence score from up to 5 repeated measures of diet. Primary outcomes were cognitive function calculated as the average scores of the 4 repeated measures, as well as cognitive change of the Telephone Interview for Cognitive Status score and composite scores of global cognition and verbal memory.


Greater adherence to long-term DASH score was associated with better average cognitive function, irrespective of apolipoprotein E ε4 allele status [multivariable-adjusted differences in mean z-scores between extreme DASH quintiles = 0.04 (95% confidence interval, CI 0.01-0.07), P trend = .009 for global cognition; 0.04 (95% CI 0.01-0.07), P trend = .002 for verbal memory and 0.16 (95% CI 0.03-0.29), and P trend = .03 for Telephone Interview for Cognitive Status, P interaction >0.24]. These differences were equivalent to being 1 year younger in age. Adherence to the DASH score was not associated with change in cognitive function over 6 years.


Our findings in the largest cohort on dietary patterns and cognitive function to date indicate that long-term adherence to the DASH diet is important to maintain cognitive function at older ages.


Cognition; DASH diet; aging; cohort; epidemiology

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Transcriptional profiling reveals protective mechanisms in brains of long-lived mice.

Frahm C, Srivastava A, Schmidt S, Mueller J, Groth M, Guenther M, Ji Y, Priebe S, Platzer M, Witte OW.

Neurobiol Aging. 2016 Dec 27;52:23-31. doi: 10.1016/j.neurobiolaging.2016.12.016. [Epub ahead of print]

PMID: 28110102



The brain plays a central role in organismal aging but is itself most sensitive to aging-related functional impairments and pathologies. Insights into processes underlying brain aging are the basis to positively impact brain health. Using high-throughput RNA sequencing and quantitative polymerase chain reaction (PCR), we monitored cerebral gene expression in mice throughout their whole lifespan (2, 9, 15, 24, and 30 months). Differentially expressed genes were clustered in 6 characteristic temporal expression profiles, 3 of which revealed a distinct change between 24 and 30 months, the period when most mice die. Functional annotation of these genes indicated a participation in protection against cancer and oxidative stress. Specifically, the most enriched pathways for the differentially expressed genes with higher expression at 30 versus 24 months were found to be glutathione metabolism and chemokine signaling pathway, whereas those lower expressed were enriched in focal adhesion and pathways in cancer. We therefore conclude that brains of very old mice are protected from certain aspects of aging, in particular cancer, which might have an impact on organismal health and lifespan.


Aging; Brain; Cancer; Glutathione; RNA-seq; Survival curve


Gut microbiota: A player in aging and a target for anti-aging intervention.

Vaiserman AM, Koliada AK, Marotta F.

Ageing Res Rev. 2017 Jan 18. pii: S1568-1637(16)30265-3. doi: 10.1016/j.arr.2017.01.001. [Epub ahead of print] Review.

PMID: 28109835



Aging-associated alterations in composition, diversity and functional features of intestinal microbiota are well-described in the modern literature. They are suggested to be caused by an age-related decline in immune system functioning (immunosenescence) and a low-grade chronic inflammation (inflammaging), which accompany many aging-associated pathologies. The microbiota-targeted dietary and probiotic interventions have been shown to favorably affect the host health and aging by an enhancement of antioxidant activity, improving immune homeostasis, suppression of chronic inflammation, regulation of fat deposition and metabolism and prevention of insulin resistance. Recently, a high effectiveness and safety of novel therapeutic application such as fecal microbiota transplantation in the prevention and treatment of age-related pathological conditions including atherosclerosis, type 2 diabetes and Parkinson's disease has been demonstrated. In this review, recent research findings are summarized on the role of gut micribiota in aging processes with emphasis on therapeutic potential of microbiome-targeted interventions in anti-aging medicine.


age-related disease; aging; gut microbiota; healthspan; lifespan; probiotic


Intestinal microbiota plays a crucial role in the host’s aging process.

Healthspan-promoting interventions are accompanied by normalization of gut microbiota.

Microbiota-targeted intervention is a promising anti-aging treatment option.



Gut microbes promote motor deficits in a mouse model of Parkinson's ...



he Scientist » News & Opinion » Daily News

Gut Microbes Linked to Neurodegenerative Disease

By Abby Olena | December 1, 2016


Bacteria in the intestine influence motor dysfunction and neuroinflammation in a mouse model of Parkinson’s disease.


Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease.

Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, Challis C, Schretter CE, Rocha S, Gradinaru V, Chesselet MF, Keshavarzian A, Shannon KM, Krajmalnik-Brown R, Wittung-Stafshede P, Knight R, Mazmanian SK.

Cell. 2016 Dec 1;167(6):1469-1480.e12. doi: 10.1016/j.cell.2016.11.018.


PMID: 27912057


The intestinal microbiota influence neurodevelopment, modulate behavior, and contribute to neurological disorders. However, a functional link between gut bacteria and neurodegenerative diseases remains unexplored. Synucleinopathies are characterized by aggregation of the protein α-synuclein (αSyn), often resulting in motor dysfunction as exemplified by Parkinson's disease (PD). Using mice that overexpress αSyn, we report herein that gut microbiota are required for motor deficits, microglia activation, and αSyn pathology. Antibiotic treatment ameliorates, while microbial re-colonization promotes, pathophysiology in adult animals, suggesting that postnatal signaling between the gut and the brain modulates disease. Indeed, oral administration of specific microbial metabolites to germ-free mice promotes neuroinflammation and motor symptoms. Remarkably, colonization of αSyn-overexpressing mice with microbiota from PD-affected patients enhances physical impairments compared to microbiota transplants from healthy human donors. These findings reveal that gut bacteria regulate movement disorders in mice and suggest that alterations in the human microbiome represent a risk factor for PD.


Parkinson’s disease; gut-brain axis; microbiome; microglia; mouse model; short chain fatty acids; synuclein


Dietary Protein Sources and All-Cause and Cause-Specific Mortality: The Golestan Cohort Study in Iran.

Farvid MS, Malekshah AF, Pourshams A, Poustchi H, Sepanlou SG, Sharafkhah M, Khoshnia M, Farvid M, Abnet CC, Kamangar F, Dawsey SM, Brennan P, Pharoah PD, Boffetta P, Willett WC, Malekzadeh R.

Am J Prev Med. 2017 Feb;52(2):237-248. doi: 10.1016/j.amepre.2016.10.041.

PMID: 28109460




Dietary protein comes from foods with greatly different compositions that may not relate equally with mortality risk. Few cohort studies from non-Western countries have examined the association between various dietary protein sources and cause-specific mortality. Therefore, the associations between dietary protein sources and all-cause, cardiovascular disease, and cancer mortality were evaluated in the Golestan Cohort Study in Iran.


Among 42,403 men and women who completed a dietary questionnaire at baseline, 3,291 deaths were documented during 11 years of follow up (2004-2015). Cox proportional hazards models estimated age-adjusted and multivariate-adjusted hazard ratios (HRs) and 95% CIs for all-cause and disease-specific mortality in relation to dietary protein sources. Data were analyzed from 2015 to 2016.


Comparing the highest versus the lowest quartile, egg consumption was associated with lower all-cause mortality risk (HR=0.88, 95% CI=0.79, 0.97, ptrend=0.03). In multivariate analysis, the highest versus the lowest quartile of fish consumption was associated with reduced risk of total cancer (HR=0.79, 95% CI=0.64, 0.98, ptrend=0.03) and gastrointestinal cancer (HR=0.75, 95% CI=0.56, 1.00, ptrend=0.02) mortality. The highest versus the lowest quintile of legume consumption was associated with reduced total cancer (HR=0.72, 95% CI=0.58, 0.89, ptrend=0.004), gastrointestinal cancer (HR=0.76, 95% CI=0.58, 1.01, ptrend=0.05), and other cancer (HR=0.66, 95% CI=0.47, 0.93, ptrend=0.04) mortality. Significant associations between total red meat and poultry intake and all-cause, cardiovascular disease, or cancer mortality rate were not observed among all participants.


These findings support an association of higher fish and legume consumption with lower cancer mortality, and higher egg consumption with lower all-cause mortality.


Activity Slows Cellular Aging

Posted on Jan. 23, 2017, 6 a.m.

in Anti-Aging Research Science

Anti-Aging Exercise

Mechanisms of Aging


For the first time, a study has explored the link between sedentary time, exercise, and telomeres.


Associations of Accelerometer-Measured and Self-Reported Sedentary Time With Leukocyte Telomere Length in Older Women.

Shadyab AH, Macera CA, Shaffer RA, Jain S, Gallo LC, LaMonte MJ, Reiner AP, Kooperberg C, Carty CL, Di C, Manini TM, Hou L, LaCroix AZ.

Am J Epidemiol. 2017 Jan 18. doi: 10.1093/aje/kww196. [Epub ahead of print]

PMID: 28100466




Few studies have assessed the association of sedentary time with leukocyte telomere length (LTL). In a cross-sectional study conducted in 2012-2013, we examined associations of accelerometer-measured and self-reported sedentary time with LTL in a sample of 1,481 older white and African-American women from the Women's Health Initiative and determined whether associations varied by level of moderate- to vigorous-intensity physical activity (MVPA). The association between sedentary time and LTL was evaluated using multiple linear regression models. Women were aged 79.2 (standard deviation, 6.7) years, on average. Self-reported sedentary time was not associated with LTL. In a model adjusting for demographic characteristics, lifestyle behaviors, and health-related factors, among women at or below the median level of accelerometer-measured MVPA, those in the highest quartile of accelerometer-measured sedentary time had significantly shorter LTL than those in the lowest quartile, with an average difference of 170 base pairs (95% confidence interval: 4, 340). Accelerometer-measured sedentary time was not associated with LTL in women above the median level of MVPA. Findings suggest that, on the basis of accelerometer measurements, higher sedentary time may be associated with shorter LTL among less physically active women.


accelerometry; leukocyte telomere length; moderate- to vigorous-intensity physical activity; sedentary time; telomeres


High dietary protein intake is associated with an increased body weight and total death risk.

Hernández-Alonso P, Salas-Salvadó J, Ruiz-Canela M, Corella D, Estruch R, Fitó M, Arós F, Gómez-Gracia E, Fiol M, Lapetra J, Basora J, Serra-Majem L, Muñoz MÁ, Buil-Cosiales P, Saiz C, Bulló M.

Clin Nutr. 2016 Apr;35(2):496-506. doi: 10.1016/j.clnu.2015.03.016.

PMID: 25886710




High dietary protein diets are widely used to manage overweight and obesity. However, there is a lack of consensus about their long-term efficacy and safety. Therefore, the aim of this study was to assess the effect of long-term high-protein consumption on body weight changes and death outcomes in subjects at high cardiovascular risk.


A secondary analysis of the PREDIMED trial was conducted. Dietary protein was assessed using a food-frequency questionnaire during the follow-up. Cox proportional hazard models were used to estimate the multivariate-adjusted hazard ratio (HR) and 95% confidence intervals (95%CI) for protein intake in relation to the risk of body weight and waist circumference changes, cardiovascular disease, cardiovascular death, cancer death and total death.


Higher total protein intake, expressed as percentage of energy, was significantly associated with a greater risk of weight gain when protein replaced carbohydrates (HR: 1.90; 95%CI: 1.05, 3.46) but not when replaced fat (HR: 1.69; 95%CI: 0.94, 3.03). However, no association was found between protein intake and waist circumference. Contrary, higher total protein intake was associated with a greater risk of all-cause death in both carbohydrate and fat substitution models (HR: 1.59; 95%CI: 1.08, 2.35; and HR: 1.66; 95%CI: 1.13, 2.43, respectively). A higher consumption of animal protein was associated with an increased risk of fatal and non-fatal outcomes when protein substituted carbohydrates or fat.


Higher dietary protein intake is associated with long-term increased risk of body weight gain and overall death in a Mediterranean population at high cardiovascular risk.


Body weight; Cardiovascular; Death; Protein; Risk

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Beyond Calories: An Integrated Approach to Promote Health, Longevity, and Well-Being.

Bertozzi B, Tosti V, Fontana L.

Gerontology. 2017;63(1):13-19.

PMID: 27173125 Free Article



In 1948, the World Health Organization defined health as 'a state of complete physical, mental, and social well-being, and not merely the absence of disease or infirmity'. Detractors claim that this definition of health is utopian and unrealistic. However, accumulating evidence from experimental studies suggests that aging is not inevitably linked with the development of chronic diseases, and the age-associated accumulation of molecular damage can be prevented or greatly delayed by dietary and genetic manipulations that downregulate key cellular nutrient-sensing pathways. Nonetheless, to obtain a state of complete physical, mental, and social well-being, we as human beings need to go beyond nutrition or pharmacological treatments and implement a combination of interventions that enhance not only our metabolic health but also our psychological, emotional, intellectual and spiritual development, our social relationships and cultural well-being. This perspective highlights a range of scientific research-based interventions that can potentially be used to promote human health and longevity. We will also briefly address the importance of environmental health in achieving this goal.


Efficacy of a novel formulation of L-Carnitine, creatine, and leucine on lean body mass and functional muscle strength in healthy older adults: a randomized, double-blind placebo-controlled study.

Evans M, Guthrie N, Pezzullo J, Sanli T, Fielding RA, Bellamine A.

Nutr Metab (Lond). 2017 Jan 18;14:7. doi: 10.1186/s12986-016-0158-y.

PMID: 28115977




Progressive decline in skeletal muscle mass and function are growing concerns in an aging population. Diet and physical activity are important for muscle maintenance but these requirements are not always met. This highlights the potential for nutritional supplementation. As a primary objective, we sought to assess the effect of a novel combination of L-Carnitine, creatine and leucine on muscle mass and performance in older subjects.


Forty-two healthy older adults aged 55-70 years were randomized to receive either a novel L-Carnitine (1500 mg), L-leucine (2000 mg), creatine (3000 mg), Vitamin D3 (10 μg) (L-Carnitine-combination) product (n = 14), L-Carnitine (1500 mg) (n = 14), or a placebo (n = 14) for eight weeks. We evaluated body mass by DXA, upper and lower strength by dynamometry, and walking distance by a 6-min walk test at baseline and after eight weeks of intervention. These measures, reflecting muscle mass, functional strength and mobility have been combined to generate a primary composite score. Quality of life, blood safety markers, and muscle biopsies for protein biomarker analysis were also conducted at baseline and the end of the study.


The primary composite outcome improved by 63.5 percentage points in the L-Carnitine-combination group vs. placebo (P = 0.013). However, this composite score did not change significantly in the L-Carnitine group (P = 0.232), and decreased slightly in the placebo group (P = 0.534). Participants supplemented with the L-Carnitine-combination showed a 1.0 kg increase in total lean muscle mass (P = 0.013), leg lean muscle mass (0.35 kg, P = 0.005), and a 1.0 kg increase in lower leg strength (P = 0.029) at week 8. In addition, these increases were significant when compared to the placebo group (P = 0.034, P = 0.026, and P = 0.002, respectively). Total mTOR protein expression was increased in participants in the L-Carnitine-combination group at the end of the study compared to the baseline (P = 0.017). This increase was also significant when compared to the placebo (P = 0.039), suggesting that the increase in muscle mass and strength was due to new protein synthesis and mTOR pathway activation.


The trial did reach its primary objective. L-Carnitine combined with creatine and L-leucine significantly improved the composite score which reflects muscle mass and strength, at the end of the study compared to placebo. The combination showed an increase in mTOR protein level, a driver for increased muscle mass which translated to an improvement in muscle strength. This new combination may provide a potential nutritional intervention to promote muscle growth and improved physical functioning in older adults.


Aging; Creatine; L-Carnitine; L-leucine; Lean body mass; Muscle strength; Older adults; Sarcopenia; mTOR


Subjective evaluation of the effectiveness of whole-body cryotherapy in patients with osteoarthritis.

Chruściak T.

Reumatologia. 2016;54(6):291-295. doi: 10.5114/reum.2016.64904.

PMID: 28115779




One of the treatments for osteoarthritis (OA) is whole-body cryotherapy (WBC). The aim of this study is to assess the effect of whole-body cryotherapy on the clinical status of patients with osteoarthritis (OA), according to their subjective feelings before and after the application of a 10-day cold treatment cycle. The aim is also to assess the reduction of intensity and frequency of pain, the reduction of the painkiller medication used, and to assess the possible impact on physical activity.


The study involved 50 people, including 30 women (60%) and 20 men (40%). Thirty-one patients had spondyloarthritis (62% of respondents), 10 had knee osteoarthritis (20%), and 9 hip osteoarthritis (18%). The overall average age was 50.1 ±10.9 years; the youngest patient was 29 years old and the oldest 73 years old. The average age of the women was 6 years higher. The study used a questionnaire completed by patients, and consisted of three basic parts. The modified Laitinen pain questionnaire contained questions concerning the intensity and frequency of pain, frequency of painkiller use and the degree of limited mobility. The visual analogue scale (VAS) was used in order to subjectively evaluate the therapy after applying the ten-day treatment cycle.


According to the subjective assessment of respondents, after the whole-body cryotherapy treatments, a significant improvement occurred in 39 patients (78%), an improvement in 9 patients (18%), and no improvement was only declared by 2 patients (4%).


Whole-body cryotherapy resulted in a reduction in the frequency and degree of pain perception in patients with osteoarthritis. WBC reduced the number of analgesic medications in these patients. It improved the range of physical activity and had a positive effect on the well-being of patients.


hip osteoarthritis; knee osteoarthritis; spondyloarthritis; whole-body cryotherapy


Assessing the Accuracy of a Wrist Motion Tracking Method for Counting Bites across Demographic and Food Variables.

Shen Y, Salley J, Muth E, Hoover A.

IEEE J Biomed Health Inform. 2016 Sep 21. doi: 10.1109/JBHI.2016.2612580. [Epub ahead of print]

PMID: 28113994



This paper describes a study to test the accuracy of a method that tracks wrist motion during eating to detect and count bites. The purpose was to assess its accuracy across demographic (age, gender, ethnicity) and bite (utensil, container, hand used, food type) variables. Data were collected in a cafeteria under normal eating conditions. A total of 271 participants ate a single meal while wearing a watch-like device to track their wrist motion. Video was simultaneously recorded of each participant and subsequently reviewed to determine the ground truth times of bites. Bite times were operationally defined as the moment when food or beverage was placed into the mouth. Food and beverage choices were not scripted or restricted. Participants were seated in groups of 2-4 and were encouraged to eat naturally. A total of 24,088 bites of 374 different food and beverage items were consumed. Overall the method for automatically detecting bites had a sensitivity of 75% with a positive predictive value of 89%. A range of 62-86% sensitivity was found across demographic variables, with slower eating rates trending towards higher sensitivity. Variations in sensitivity due to food type showed a modest correlation with the total wrist motion during the bite, possibly due to an increase in head-towards-plate motion and decrease in hand-towards-mouth motion for some food types. Overall, the findings provide the largest evidence to date that the method produces a reliable automated measure of intake during unrestricted eating.


Plant-based diets relatively low in bioavailable phosphate and calcium may aid prevention and control of prostate cancer by lessening production of fibroblast growth factor 23.

McCarty MF.

Med Hypotheses. 2017 Feb;99:68-72. doi: 10.1016/j.mehy.2017.01.001.

PMID: 28110703



Fibroblast growth factor 23 (FGF23), a hormonal regulator of phosphate and vitamin D metabolism produced primarily in bone by osteocytes and mature osteoblasts, is now known to have growth factor activity for many prostate cancers. In some of these cancers, autocrine production of FGF23 drives their proliferation. FGF23 synthesized within bone likely promotes the expansion of prostate cancer bone metastases. Hence, dietary or lifestyle factors which boost bone's production of FGF23 may encourage the induction and spread of prostate cancer. High dietary intakes of bioavailable phosphorus and of calcium have been found to boost FGF23 levels, and this accords well with prospective epidemiology pointing to high intakes of both phosphate and calcium as risk factors for aggressive prostate cancer. Hence, prospective studies correlating baseline FGF23 levels with subsequent risk for prostate cancer, or advanced prostate cancer, are needed. Natural plant-based diets, though not inherently low in calcium or phosphorus, provide forms of these that are less bioavailable than those in animal products, and hence may be expected to down-regulate bone's production of FGF23. This may play a role in the lower risk for clinical prostate cancer observed in vegans and quasi-vegan cultures. Other factors, such as decreased IGF-I levels and mTORC1 activity, may also play a role in this regard.


Calcium; FGF23; Phosphate; Plant-based diet; Prostate cancer; Vegan


Association Between Diabetes and Cause-Specific Mortality in Rural and Urban Areas of China.

Bragg F, Holmes MV, Iona A, Guo Y, Du H, Chen Y, Bian Z, Yang L, Herrington W, Bennett D, Turnbull I, Liu Y, Feng S, Chen J, Clarke R, Collins R, Peto R, Li L, Chen Z; China Kadoorie Biobank Collaborative Group..

JAMA. 2017 Jan 17;317(3):280-289. doi: 10.1001/jama.2016.19720.

PMID: 28114552




In China, diabetes prevalence has increased substantially in recent decades, but there are no reliable estimates of the excess mortality currently associated with diabetes.


To assess the proportional excess mortality associated with diabetes and estimate the diabetes-related absolute excess mortality in rural and urban areas of China.


A 7-year nationwide prospective study of 512 869 adults aged 30 to 79 years from 10 (5 rural and 5 urban) regions in China, who were recruited between June 2004 and July 2008 and were followed up until January 2014.


Diabetes (previously diagnosed or detected by screening) recorded at baseline.


All-cause and cause-specific mortality, collected through established death registries. Cox regression was used to estimate adjusted mortality rate ratio (RR) comparing individuals with diabetes vs those without diabetes at baseline.


Among the 512 869 participants, the mean (SD) age was 51.5 (10.7) years, 59% (n = 302 618) were women, and 5.9% (n = 30 280) had diabetes (4.1% in rural areas, 8.1% in urban areas, 5.8% of men, 6.1% of women, 3.1% had been previously diagnosed, and 2.8% were detected by screening). During 3.64 million person-years of follow-up, there were 24 909 deaths, including 3384 among individuals with diabetes. Compared with adults without diabetes, individuals with diabetes had a significantly increased risk of all-cause mortality (1373 vs 646 deaths per 100 000; adjusted RR, 2.00 [95% CI, 1.93-2.08]), which was higher in rural areas than in urban areas (rural RR, 2.17 [95% CI, 2.07-2.29]; urban RR, 1.83 [95% CI, 1.73-1.94]). Presence of diabetes was associated with increased mortality from ischemic heart disease (3287 deaths; RR, 2.40 [95% CI, 2.19-2.63]), stroke (4444 deaths; RR, 1.98 [95% CI, 1.81-2.17]), chronic liver disease (481 deaths; RR, 2.32 [95% CI, 1.76-3.06]), infections (425 deaths; RR, 2.29 [95% CI, 1.76-2.99]), and cancer of the liver (1325 deaths; RR, 1.54 [95% CI, 1.28-1.86]), pancreas (357 deaths; RR, 1.84 [95% CI, 1.35-2.51]), female breast (217 deaths; RR, 1.84 [95% CI, 1.24-2.74]), and female reproductive system (210 deaths; RR, 1.81 [95% CI, 1.20-2.74]). For chronic kidney disease (365 deaths), the RR was higher in rural areas (18.69 [95% CI, 14.22-24.57]) than in urban areas (6.83 [95% CI, 4.73-9.88]). Among those with diabetes, 10% of all deaths (16% rural; 4% urban) were due to definite or probable diabetic ketoacidosis or coma (408 deaths).


Among adults in China, diabetes was associated with increased mortality from a range of cardiovascular and noncardiovascular diseases. Although diabetes was more common in urban areas, it was associated with greater excess mortality in rural areas.


China's Burgeoning Epidemic of Diabetes-Associated Mortality.

Chan M.

JAMA. 2017 Jan 17;317(3):264-266. doi: 10.1001/jama.2016.19736. No abstract available.

PMID: 28114532



The association of male pattern baldness and risk of cancer and high-grade disease among men presenting for prostate biopsy.

Al Edwan G, Bhindi B, Margel D, Chadwick K, Finelli A, Zlotta A, Trachtenberg J, Fleshner N.

Can Urol Assoc J. 2016 Nov-Dec;10(11-12):E424-E427. doi: 10.5489/cuaj.3813.

PMID: 28096933 Free PMC Article





Androgens have been implicated in both male pattern baldness (MPB) and prostate cancer (PCa). We set out to prospectively determine if men with independently assessed MPB are at higher risk for PCa at biopsy and determine if any grade associations exist.


We prospectively enrolled 394 eligible patients presenting for prostate biopsy and independently determined their MPB pattern using the validated modified Norwood classification system (0: no balding; 1: frontal balding; 2: mild vertex balding; 3: moderate vertex balding; 4: sever vertex balding). Univariate and multivariable models, including Norwood score, age, prostate-specific antigen, and digital rectal examination abnormalities, were calculated for the outcomes of cancer and high-grade disease (Gleason >6). C-statistics analyses of our models were then compared with and without MPB pattern for marginal utility.


Norwood patterns were increasingly associated with cancer and high-grade disease with a dose-effect (p for trend <0.001 on univariate and multivariable analyses for cancer and p=0.001 and p=0.0036 for high-grade disease on univariate and multivariable analyses, respectively). On multivariable analyses, trends still held, with all patients exhibiting Norwood scale 3 and 4 at increased risk for cancer. In predicting risk of high-grade disease, only patients with Norwood pattern 4 exhibited an increased risk.


MPB appears to be a strong and independent risk factor for both cancer and high-grade disease for men presenting for prostate biopsy. Ours could be superior to marketed costly genetic tests. Further research is needed to understand the biology behind this observation and to incorporate these findings into clinical decision-making.


Competing interests: Dr. Zlotta has been an advisor for Amgen, Astellas, Ferring, Paladin Labs, and

Sanofi; has received educational grants from Red Leaf Medical and Sanofi; and has participated in clinical

trials for Sanofi. Dr. Fleshner has been an advisor for and received honoraria from Amgen, Astellas,

Eli Lilly, and Janssen; and has participated in clinical trials for Amgen, Janssen, Medivation, OICR, and

Prostate Cancer Canada. The remaining authors report no competing personal or financial interests.


The Microbiome and Risk for Obesity and Diabetes

Anthony L. Komaroff

JAMA January 24/31, 2017: Volume 317, Number 4, E1-E2


Obesity and type 2 diabetes mellitus are influenced

both by genes and lifestyle. That is not news. However,

the genes in the humanmicrobiome alsomay play an important

role, and that is news.

It has been known for decades that gut bacteria synthesize

essential vitamins and amino acids and help degrade

toxins.During the past decade, it has become clear

that the influence of the microbiome on health may be

even more profound.

Beginning at the moment of birth, each human

increasingly coexists with microbes. By the time individuals

reach adulthood, they are colonized by many

more microbial cells than the roughly 13 trillion human

cells. More important still, these microbial cells (the

microbiota), collectively, have exponentially more

genes (the microbiome) than do human cells, around

250 to 800 times more.

Moreover, many genes in the human microbiome

generate proteins, including hormones, neurotransmitters,

and molecules of inflammation, that can enter the

circulation and affect health. In light of this, it is reasonable

to question whether the genes of the microbiome

might play a greater role in health than do human genes.

Recent evidence suggests that the microbiome may

affect the probability of many major diseases, including

obesity and diabetes.


How could microbiota in the gut affect obesity? First,

microbiota could influence the calories the body

absorbs. Body weight is not affected by the calories

that are ingested, but rather by the calories that are

absorbed. Simple sugars in the diet are easily absorbed,

and human enzymes convert starches into simple sugars,

but human enzymes fail to digest many dietary

polysaccharides. Microbial enzymes can turn those

polysaccharides into digestible sources of energy, particularly

monosaccharides and short-chain fatty acids.

About 90% of gut bacteria are in 1 of 2 phyla: Bacteroidetes

and Firmicutes. Firmicutes generate more

harvestable energy than Bacteroidetes. Obese humans

have relatively more Firmicutes, as do rodents placed

on a high-fat diet.1

Various experiments suggest that microbiota may

powerfully affect obesity in mammals. For example:

• Gut microbiota from obese mice and from lean mice

were transplanted into germ-free, lean mice, all of

whom had the same daily caloric intake. Over the next

2 weeks, the mice receiving microbiota from obese

mice became obese, whereas those receiving microbiota

from lean mice remained lean.1

• Gut microbiota from conventionally raised farm animals

were placed in the guts of lean germ-free mice.

Without any increase in daily caloric intake, the body

fat content of the animals increased by 60% within 14

days, and they developed insulin resistance.2

• Obese mice underwent Roux-en-Y gastric bypass

(RYGB) surgery or sham surgery. Mice that underwent

RYGB surgery had the expected weight loss and

a characteristic change in the gutmicrobiome,whereas

mice that underwent the sham surgery did not. Transfer

of bacteria from mice that underwent RYGB surgery

to mice that underwent the sham surgery resulted

in weight loss, although not as great as seen

following RYGB surgery.3

• Investigators studied human twin pairs (mostly monozygotic)

in which 1 person was obese. Feces from the

fat twins and feces from the lean twins were fed to

the germ-free mice, which were of normal weight. The

mice fed feces from the fat twins became fat; those fed

feces from the lean twins remained lean. The fat and

lean mice were then housed together. Mice eat each

other’s feces. Gradually, the obese mice became lean,

and their gut flora came to resemble the flora of the lean

mice. This finding suggests that the flora of lean mice

may be able to dominate the flora of obese mice.4

These experiments suggest that the composition of

gutmicrobiota can influence obesity.However,other experiments

suggest that obesity can influence

the composition of gut microbiota.

For example, when obese people

diet and lose weight, the proportion of

Bacteroidetes increases relative to

Firmicutes.4 Conversely, when obese

people resume their previous diets and

gain weight, the proportion of Firmicutes

increases.4 These experiments suggest that the

microbiome may be a reflection of obesity (or leanness),

as well as a cause of it. In addition, low-grade gut

inflammation caused by gutmicrobiotamay increase the

risk of obesity along with the risk of type 2 diabetes.

Type 2 Diabetes Mellitus

Given the increased risk of developing type 2 diabetes

in obesity, it is not surprising that the microbiome might

also influence type 2 diabetes. However, more than enhanced

absorption of carbohydrates may be involved.

Relatively high ratios of Firmicutes to Bacteroidetes

not only influence carbohydrate metabolism, but

also alter the production of short-chain fatty acids. In

particular, acetate production is increased and butyrate

production decreased. A recent study5 found that

increased blood levels of acetate cause insulin resistance and

increase production of ghrelin (the appetite-stimulating hormone)

in the stomach. Lower butyrate levels in the gut encourage lowlevel

inflammation, which evokes insulin resistance.6

Gut inflammation has another effect. In rodent studies, inflammation

weakens epithelial tight junctions in the gut mucosa, facilitating

the entry of bacterial endotoxins into the blood. This “metabolic

endotoxemia” leads to increased activity of the innate immune

system, which leads to insulin resistance and weight gain.7

Studies in humans also suggest a role for the gut microbiota in

type 2 diabetes. Most studies have found that individuals with type

2 diabetes have a reduced abundance of butyrate-producing species,

leading to low-grade inflammation in the gut. This has been

found in people of different races and ethnicities and after controlling

for the effect ofmedications (particularlymetformin) on the gut

microbiome.8A prospective study of more than 7000 children has

linked the use of probiotics during the first month of life to a lower

risk of islet autoantibodies, suggesting that the gutmicrobiomemay

also play a role in type 1 diabetes mellitus.9

It is unlikely that a single species of gut bacteria plays a dominant

role in altering the risk of type 2 diabetes, although several studies

have found that increased numbers of Akkermansia muciniphila

reduce inflammation in adipose tissue and improve insulin signaling.

Even though many studies have reported associations between

the microbiome and type 2 diabetes in humans, only experimental

evidence can suggest a causal connection. At least 1 study

does. Treatment-naive men with the metabolic syndrome had their

gut flora eliminated by polyethylene glycol lavage. Then they were

randomized to receive small intestinal infusions (through a gastroduodenal

tube) either from lean male donors or from their own feces.Inmen

who received infusions from lean individuals, insulin sensitivity

increased. This effect declined over time, and there was

considerable individual variability. Recipients of feces from lean donors

had a higher abundance of butyrate-producing bacteria.10


It is plausible that the humanmicrobiomemay affect the risk of obesity

and type 2 diabetes and other diseases such as atherosclerosis,

and that manipulations of the microbiome might reduce that risk.

However,biomedical science isa longway from provingeither proposition.

Dissecting the possible role of the microbiome in these and

other diseases will be a great challenge, because (1) human genes

influence the composition of the gutmicrobiota, (2)microbial genes

influence the expression of human genes, (3) the metabolism of

some gut microbes influences the metabolism of other gut microbes,

and (4) diet influences both the microbiota and (possibly)

the expression of human genes. In short, human genes, microbial

genes, and diet share a complicated set of interdependencies.

It might seem unlikely, at first, that the microbiome could affect

the risk of major metabolic diseases. During the past decade, research

has revealed that it is not unlikely at all. In the end, disease is

the result of disordered biochemistry. Genes drive biochemistry, the

human microbiome contains exponentially more genes than there

are human genes, and thosemicrobial genes producemolecules that

affect human physiology.

New technologies (particularly rapid, inexpensive nucleic acid

sequencing) have provided the tools to understand how the microbiota

might affect health. Scientists have learned a great deal during

the past 50 years about modifiable risk factors for obesity and

type 2 diabetes. During the past decade, scientists have discovered

that perhaps the microbiota are the most important modifiable

risk factor of all.


Omega-3 Fatty Acid Could Increase One of Myokines in Male Patients with Coronary Artery Disease: A Randomized, Double-Blind, Placebo-Controlled Trial.

Agh F, Mohammadzadeh Honarvar N, Djalali M, Nematipour E, Gholamhoseini S, Zarei M, Ansari S, Javanbakht MH.

Arch Iran Med. 2017 Jan;20(1):28-33. doi: 0172001/AIM.007.

PMID: 28112528




Omega-3 fatty acids have a protective role against cardiovascular disease and these protective properties are attributed to its anti-inflammatory effects. Myokines have anti-inflammatory properties and thereby reduce low-grade inflammation. Irisin, as a myokine, is considered to be therapeutic for human metabolic diseases. This study was conducted to determine the effects of Omega-3 fatty acids supplementation on serum irisin in men with coronary artery disease (CAD).


This study was an 8-week randomized, double-blind, placebo-controlled trial. Forty-eight CAD male patients (Omega-3, n = 24; control, n = 24) were randomly assigned to either Omega-3 or control groups by permuted block randomization method. Only the participants with more than 50% stenosis in at least one major coronary vessel were included. A total of 3 participants in the control group were excluded from the study. Forty-five participants (Omega-3, n = 24; control, n = 21) completed the study. Participants took Omega-3 fatty acids supplement (720 mg eicosapentaenoic acid plus 480 mg docosahexaenoic acid) or placebo (edible paraffin) for 8 weeks. Serum irisin, high-sensitivity C-reactive protein (hs-CRP), lipid profile and anthropometric indices, body composition, and food intake were assessed before and after intervention. Statistical analyses were performed using SPSS software. Paired t-test was used for evaluating within-group effects from baseline. Variables with normal distribution were compared by independent t-test between 2 groups.


Compared to placebo, Omega-3 fatty acids increased serum irisin (P = 0.044) and decreased serum hs-CRP (P = 0.018) and LDL cholesterol (P = 0.031). Omega-3 fatty acids supplementation did not result in any significant changes in anthropometric measurements, blood pressure, serum lipids except for serum LDL, fasting blood glucose, body composition or serum insulin levels (all P > 0.05).


Omega-3 fatty acids supplementation could elevate serum irisin in male patients with CAD. Also, these fatty acids may able to decrease serum hs-CRP and LDL cholesterol.


[The below paper is pdf-availed. An increase versus the reference decrease in tertile of diet score was associated with not significant 0.67 and 0.64, respectively risk in radiography and DXA measured results, respectively. For no change versus reference, values were 0.9 and 0.96, respectively.]

Dietary Quality Is Associated with Abdominal Aortic Calcification: A Mean of 18-Year Longitudinal Study in Community-Dwelling Older Adults.

Shang X, Scott D, Hodge A, Khan B, Khan N, English DR, Giles GG, Ebeling PR, Sanders KM.

J Nutr Health Aging. 2017;21(2):147-151. doi: 10.1007/s12603-016-0738-6.

PMID: 28112768



This study aimed to examine the association between baseline and changes in dietary quality assessed by the Alternative Healthy Eating Index-2010 (AHEI-2010) and abdominal aortic calcification (AAC) among community-dwelling older adults.


Population-based longitudinal study.


A subset of the Melbourne Collaborative Cohort Study (MCCS).


262 community-dwelling adults (60% female) aged 53 ± 5 years at baseline.


Dietary intake was assessed using validated Food Frequency Questionnaires at baseline (1990-1994) and follow-up (2010-2011). AAC was evaluated by radiography and dual-energy x-ray absorptiometry (DXA) at follow-up.


Higher baseline AHEI-2010 score was associated with lower AAC severity by radiography [OR (95% CI) for Tertile 3 VS Tertile 1: 0.53 (0.29-0.99)] after adjustment for gender, age, physical activity, smoking, BMI, systolic blood pressure, plasma total cholesterol, calcium and energy intake. The association between AHEI-2010 and AAC severity by DXA was also significant in the multivariate-adjusted model [OR (95% CI) for Tertile 3 VS Tertile 1: 0.38 (0.20-0.70)]. Changes in AHEI-2010 over 18 years were not associated with AAC severity.


Baseline but not the changes in AHEI-2010 was inversely associated with the risk of AAC severity suggesting that a high quality diet might help prevent or delay the progression of AAC in community-dwelling older adults and the benefits might be manifested over the long-term.


Association of Docosahexaenoic Acid Supplementation With Alzheimer Disease Stage in Apolipoprotein E ε4 Carriers: A Review.

Yassine HN, Braskie MN, Mack WJ, Castor KJ, Fonteh AN, Schneider LS, Harrington MG, Chui HC.

JAMA Neurol. 2017 Jan 17. doi: 10.1001/jamaneurol.2016.4899. [Epub ahead of print]

PMID: 28114437




The apolipoprotein E ε4 (APOE4) allele identifies a unique population that is at significant risk for developing Alzheimer disease (AD). Docosahexaenoic acid (DHA) is an essential ω-3 fatty acid that is critical to the formation of neuronal synapses and membrane fluidity. Observational studies have associated ω-3 intake, including DHA, with a reduced risk for incident AD. In contrast, randomized clinical trials of ω-3 fatty acids have yielded mixed and inconsistent results. Interactions among DHA, APOE genotype, and stage of AD pathologic changes may explain the mixed results of DHA supplementation reported in the literature.


Although randomized clinical trials of ω-3 in symptomatic AD have had negative findings, several observational and clinical trials of ω-3 in the predementia stage of AD suggest that ω-3 supplementation may slow early memory decline in APOE4 carriers. Several mechanisms by which the APOE4 allele could alter the delivery of DHA to the brain may be amenable to DHA supplementation in predementia stages of AD. Evidence of accelerated DHA catabolism (eg, activation of phospholipases and oxidation pathways) could explain the lack of efficacy of ω-3 supplementation in AD dementia. The association of cognitive benefit with DHA supplementation in predementia but not AD dementia suggests that early ω-3 supplementation may reduce the risk for or delay the onset of AD symptoms in APOE4 carriers. Recent advances in brain imaging may help to identify the optimal timing for future DHA clinical trials.


High-dose DHA supplementation in APOE4 carriers before the onset of AD dementia can be a promising approach to decrease the incidence of AD. Given the safety profile, availability, and affordability of DHA supplements, refining an ω-3 intervention in APOE4 carriers is warranted.


Fiber Intake Linked to Successful Aging

Posted on Jan. 24, 2017, 6 a.m.

in Aging Diet Nutrition


Eating the right amount of fiber helps in avoiding disease and disability into old age.

Fiber Intake Linked to Successful Aging -- Fiber cereal - image from Shutterstock

It is well known that a diet with adequate fiber assists in keeping people “regular.” Increased dietary fiber may also reduce the risk of developing type-2 diabetes and has been shown to lower blood pressure. There is now evidence of a surprising additional benefit, discovered by the Australian researchers from the Westmead Institute for Medical Research. Associate Professor Bamini Gopinath, PhD, from the Institute's Centre for Vision Research compiled data from the Blue Mountains Eye Study, a benchmark population-based study that examined a group of more than 1,600 adults, ages 50 years and older, for systemic diseases and long-term sensory loss risk factors. The researchers explored the relationship between carbohydrate nutrition and healthy aging. The factors they examined included total carbohydrate intake, total fiber intake, glycemic index and load, and sugar intake. The fiber made the greatest difference in what the researchers called “successful aging”. They defined “successful aging” as including an absence of disability, cognitive impairment, depressive symptoms, respiratory symptoms, and chronic diseases including cancer coronary artery disease, and stroke.

According to the lead author of the paper, Gopinath, this study is the first to explore the relationship between carbohydrate intake and healthy aging, and the findings were significant enough to warrant further exploration. “Out of all the variables that we looked at, fiber intake -- which is a type of carbohydrate that the body can't digest -- had the strongest influence," she stated. "Essentially, we found that those who had the highest intake of fiber or total fiber actually had an almost 80 percent greater likelihood of living a long and healthy life over a 10-year follow-up. That is, they were less likely to suffer from hypertension, diabetes, dementia, depression, and functional disability."

Though there was likely an expectancy that the level of sugar intake would have the largest impact on successful aging, Gopinath pointed out that the particular group they studied were older adults, whose carbonated and sugary drink intake was fairly low. This study validates similar recent findings by the researchers, that emphasize the value of the overall diet and healthy aging.


Association Between Carbohydrate Nutrition and Successful Aging Over 10 Years.

Gopinath B, Flood VM, Kifley A, Louie JC, Mitchell P.

J Gerontol A Biol Sci Med Sci. 2016 Oct;71(10):1335-40. doi: 10.1093/gerona/glw091.

PMID: 27252308





We prospectively examined the relationship between dietary glycemic index (GI) and glycemic load (GL), carbohydrate, sugars, and fiber intake (including fruits, vegetable of breads/cereals fiber) with successful aging (determined through a multidomain approach).


A total of 1,609 adults aged 49 years and older who were free of cancer, coronary artery disease, and stroke at baseline were followed for 10 years. Dietary data were collected using a semiquantitative Food Frequency Questionnaire. Successful aging status was determined through interviewer-administered questionnaire at each visit and was defined as the absence of disability, depressive symptoms, cognitive impairment, respiratory symptoms, and chronic diseases (eg, cancer and coronary artery disease).


In all, 249 (15.5%) participants had aged successfully 10 years later. Dietary GI, GL, and carbohydrate intake were not significantly associated with successful aging. However, participants in the highest versus lowest (reference group) quartile of total fiber intake had greater odds of aging successfully than suboptimal aging, multivariable-adjusted odds ratio (OR), 1.79 (95% confidence interval [CI] 1.13-2.84). Those who remained consistently below the median in consumption of fiber from breads/cereal and fruit compared with the rest of cohort were less likely to age successfully, OR 0.53 (95% CI 0.34-0.84) and OR 0.64 (95% CI 0.44-0.95), respectively.


Consumption of dietary fiber from breads/cereals and fruits independently influenced the likelihood of aging successfully over 10 years. These findings suggest that increasing intake of fiber-rich foods could be a successful strategy in reaching old age disease free and fully functional.


Blue Mountains Eye Study; Carbohydrate; Fiber; Glycemic index; Successful aging


Adherence to Mediterranean diet and risk of developing cognitive disorders: An updated systematic review and meta-analysis of prospective cohort studies.

Wu L, Sun D.

Sci Rep. 2017 Jan 23;7:41317. doi: 10.1038/srep41317.

PMID: 28112268



Recent articles have presented inconsistent findings on the impact of Mediterranean diet in the occurrence of cognitive disorders; therefore, we performed an updated systematic review and meta-analysis to evaluate the potential association and dose-response pattern with accumulating evidence. We searched the PubMed and the Embase for the records relevant to this topic. A generic inverse-variance method was used to pool the outcome data for continuous variable, and categories of high vs. low, median vs. low of Mediterranean diet score with a random-effects model. Generalized least-squares trend estimation model was used to estimate the potential dose-response patterns of Mediterranean diet score on incident cognitive disorders. We identified 9 cohort studies involving 34,168 participants. Compared with the lowest category, the pooled analysis showed that the highest Mediterranean diet score was inversely associated with the developing of cognitive disorders, and the pooled RR (95% CI) was 0.79 (0.70, 0.90). Mediterranean diet score of the median category was not significantly associated with cognitive disorders. Dose-response analysis indicated a trend of an approximately linear relationship of the Mediterranean diet score with the incident risk of cognitive disorders. Further studies of randomized controlled trials are warranted to confirm the observed association in different populations.


A handheld and textile-enabled bioimpedance system for ubiquitous body composition analysis. An initial functional validation.

Ferreira Gonzalez J, Pau de la Cruz I, Lindecrantz K, Seoane F.

IEEE J Biomed Health Inform. 2016 Nov 15. doi: 10.1109/JBHI.2016.2628766. [Epub ahead of print]

PMID: 28113962



In recent years, many efforts have been made to promote a healthcare paradigm shift from the traditional reactive hospital-centered healthcare approach towards a proactive, patient-oriented and self-managed approach that could improve service quality and help reduce costs while contributing to sustainability. Managing and caring for patients with chronic diseases accounts over 75% of healthcare costs in developed countries. One of the most resource demanding diseases is chronic kidney disease (CKD), which often leads to a gradual and irreparable loss of renal function, with up to 12% of the population showing signs of different stages of this disease. Peritoneal dialysis and home haemodialysis are life-saving home-based renal replacement treatments that, compared to conventional in-center hemodialysis, provide similar long-term patient survival, less restrictions of life-style, such as a more flexible diet, and better flexibility in terms of treatment options and locations. Bioimpedance has been largely used clinically for decades in nutrition for assessing body fluid distributions. Moreover, bioimpedance methods are used to assess the overhydratation state of CKD patients, allowing clinicians to estimate the amount of fluid that should be removed by ultrafiltration. In this work, the initial validation of a handheld bioimpedance system for the assessment of body fluid status that could be used to assist the patient in home-based CKD treatments is presented. The body fluid monitoring system comprises a custom-made handheld tetrapolar bioimpedance spectrometer and a textile-based electrode garment for total body fluid assessment. The system performance was evaluated against the same measurements acquired using a commercial bioimpedance spectrometer for medical use on several voluntary subjects. The analysis of the measurement results and the comparison of the fluid estimations indicated that both devices are equivalent from a measurement performance perspective, allowing for its use on ubiquitous e-healthcare dialysis solutions.


Eat Well, or Get Roommates Who Do.

Kaplan LM, Brancale J.

Cell Host Microbe. 2017 Jan 16. pii: S1931-3128(17)30028-8. doi: 10.1016/j.chom.2017.01.006. [Epub ahead of print]

PMID: 28111204



In the January issue of Cell Host & Microbe, Griffin et al. (2017) report that the intestinal microbiome adapts to dietary practices. Restricted diversity induced by a typical American diet reflects a durable loss of taxa that is replenished only when dietary manipulation is accompanied by exposure to a healthier microbiota.




Prior Dietary Practices and Connections to a Human Gut Microbial Metacommunity Alter Responses to Diet Interventions.

Griffin NW, Ahern PP, Cheng J, Heath AC, Ilkayeva O, Newgard CB, Fontana L, Gordon JI.

Cell Host Microbe. 2017 Jan 11;21(1):84-96. doi: 10.1016/j.chom.2016.12.006.

PMID: 28041931



Ensuring that gut microbiota respond consistently to prescribed dietary interventions, irrespective of prior dietary practices (DPs), is critical for effective nutritional therapy. To address this, we identified DP-associated gut bacterial taxa in individuals either practicing chronic calorie restriction with adequate nutrition (CRON) or without dietary restrictions (AMER). When transplanted into gnotobiotic mice, AMER and CRON microbiota responded predictably to CRON and AMER diets but with variable response strengths. An individual's microbiota is connected to other individuals' communities ("metacommunity") by microbial exchange. Sequentially cohousing AMER-colonized mice with two different groups of CRON-colonized mice simulated metacommunity effects, resulting in enhanced responses to a CRON diet intervention and changes in several metabolic features in AMER animals. This response was driven by an influx of CRON DP-associated taxa. Certain DPs may impair responses to dietary interventions, necessitating the introduction of diet-responsive bacterial lineages present in other individuals and identified using the strategies described.

Serine Is an Essential Metabolite for Effector T Cell Expansion.

Ma EH, Bantug G, Griss T, Condotta S, Johnson RM, Samborska B, Mainolfi N, Suri V, Guak H, Balmer ML, Verway MJ, Raissi TC, Tsui H, Boukhaled G, Henriques da Costa S, Frezza C, Krawczyk CM, Friedman A, Manfredi M, Richer MJ, Hess C, Jones RG.

Cell Metab. 2017 Jan 12. pii: S1550-4131(16)30644-1. doi: 10.1016/j.cmet.2016.12.011. [Epub ahead of print]

PMID: 28111214


During immune challenge, T lymphocytes engage pathways of anabolic metabolism to support clonal expansion and the development of effector functions. Here we report a critical role for the non-essential amino acid serine in effector T cell responses. Upon activation, T cells upregulate enzymes of the serine, glycine, one-carbon (SGOC) metabolic network, and rapidly increase processing of serine into one-carbon metabolism. We show that extracellular serine is required for optimal T cell expansion even in glucose concentrations sufficient to support T cell activation, bioenergetics, and effector function. Restricting dietary serine impairs pathogen-driven expansion of T cells in vivo, without affecting overall immune cell homeostasis. Mechanistically, serine supplies glycine and one-carbon units for de novo nucleotide biosynthesis in proliferating T cells, and one-carbon units from formate can rescue T cells from serine deprivation. Our data implicate serine as a key immunometabolite that directly modulates adaptive immunity by controlling T cell proliferative capacity.


Phgdh; Shmt; T cell; glycolysis; immunometabolism; immunotherapy; metabolic reprogramming; metabolism; serine; serine biosynthesis

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Physical and mental health functioning after all-cause and diagnosis-specific sickness absence: a register-linkage follow-up study among ageing employees.

Mänty M, Lallukka T, Lahti J, Pietiläinen O, Laaksonen M, Lahelma E, Rahkonen O.

BMC Public Health. 2017 Jan 25;17(1):114. doi: 10.1186/s12889-017-4051-z.

PMID: 28118837




Sickness absence has been shown to be a risk marker for severe future health outcomes, such as disability retirement and premature death. However, it is poorly understood how all-cause and diagnosis-specific sickness absence is reflected in subsequent physical and mental health functioning over time. The aim of this study was to examine the association of all-cause and diagnosis-specific sickness absence with subsequent changes in physical and mental health functioning among ageing municipal employees.


Prospective survey and register data from the Finnish Helsinki Health Study and the Social Insurance Institution of Finland were used. Register based records for medically certified all-cause and diagnostic-specific sickness absence spells (>14 consecutive calendar days) in 2004-2007 were examined in relation to subsequent physical and mental health functioning measured by Short-Form 36 questionnaire in 2007 and 2012. In total, 3079 respondents who were continuously employed over the sickness absence follow-up were included in the analyses. Repeated-measures analysis was used to examine the associations.


During the 3-year follow-up, 30% of the participants had at least one spell of medically certified sickness absence. All-cause sickness absence was associated with lower subsequent physical and mental health functioning in a stepwise manner: the more absence days, the poorer the subsequent physical and mental health functioning. These differences remained but narrowed slightly during the follow-up. Furthermore, the adverse association for physical health functioning was strongest among those with sickness absence due to diseases of musculoskeletal or respiratory systems, and on mental functioning among those with sickness absence due to mental disorders.


Sickness absence showed a persistent adverse stepwise association with subsequent physical and mental health functioning. Evidence on health-related outcomes after long-term sickness absence may provide useful information for targeted interventions to promote health and workability.


Functioning; Health; Sickness absence


The Effects of Intensive Weight Reduction on Body Composition and Serum Hormones in Female Fitness Competitors.

Hulmi JJ, Isola V, Suonpää M, Järvinen NJ, Kokkonen M, Wennerström A, Nyman K, Perola M, Ahtiainen JP, Häkkinen K.

Front Physiol. 2017 Jan 10;7:689. doi: 10.3389/fphys.2016.00689.

PMID: 28119632




Worries about the potential negative consequences of popular fat loss regimens for aesthetic purposes in normal weight females have been surfacing in the media. However, longitudinal studies investigating these kinds of diets are lacking. The purpose of the present study was to investigate the effects of a 4-month fat-loss diet in normal weight females competing in fitness-sport. In total 50 participants finished the study with 27 females (27.2 ± 4.1 years) dieting for a competition and 23 (27.7 ± 3.7 years) acting as weight-stable controls. The energy deficit of the diet group was achieved by reducing carbohydrate intake and increasing aerobic exercise while maintaining a high level of protein intake and resistance training in addition to moderate fat intake. The diet led to a ~12% decrease in body weight (P < 0.001) and a ~35-50% decrease in fat mass (DXA, bioimpedance, skinfolds, P < 0.001) whereas the control group maintained their body and fat mass (diet × group interaction P < 0.001). A small decrease in lean mass (bioimpedance and skinfolds) and in vastus lateralis muscle cross-sectional area (ultrasound) were observed in diet (P < 0.05), whereas other results were unaltered (DXA: lean mass, ultrasound: triceps brachii thickness). The hormonal system was altered during the diet with decreased serum concentrations of leptin, triiodothyronine (T3), testosterone (P < 0.001), and estradiol (P < 0.01) coinciding with an increased incidence of menstrual irregularities (P < 0.05). Body weight and all hormones except T3 and testosterone returned to baseline during a 3-4 month recovery period including increased energy intake and decreased levels aerobic exercise. This study shows for the first time that most of the hormonal changes after a 35-50% decrease in body fat in previously normal-weight females can recover within 3-4 months of increased energy intake.


body composition; exercise; fat loss; fitness; nutrition; sex hormones; thyroid hormones


Does chronic physical activity level modify the airway inflammatory response to an acute bout of exercise in the postprandial period?

Kurti SP, Rosenkranz SK, Chapes SK, Teeman CS, Cull BJ, Emerson SR, Levitt MH, Smith JR, Harms CA.

Appl Physiol Nutr Metab. 2016 Oct 18:1-8. doi: 10.1139/apnm-2016-0335. [Epub ahead of print]

PMID: 28121185



Recent studies have confirmed that a single high-fat meal (HFM) leads to increased airway inflammation. However, exercise is a natural anti-inflammatory and may modify postprandial airway inflammation. The postprandial airway inflammatory response is likely to be modified by chronic physical activity (PA) level. This study investigated whether chronic PA modifies the airway inflammatory response to an acute bout of exercise in the postprandial period in both insufficiently active and active subjects. Thirty-nine nonasthmatic subjects (20 active, 13 males/7 females) who exceeded PA guidelines (≥150 min moderate-vigorous PA/week) and 19 insufficiently active (6 males/13 females) underwent an incremental treadmill test to exhaustion to determine peak oxygen uptake. Subjects were then randomized to a condition (COND), either remaining sedentary (CON) or exercising (EX) post-HFM. Exercise was performed at the heart rate corresponding to 60% peak oxygen uptake on a treadmill for 1 h post-HFM (63% fat, 10 kcal/kg body weight). Blood lipids and exhaled nitric oxide (eNO: marker of airway inflammation) were measured at baseline and 2 h and 4 h post-HFM. Sputum differential cell counts were performed at baseline and 4 h post-HFM. The mean eNO response for all groups increased at 2 h post-HFM (∼6%) and returned to baseline by 4 h (p = 0.03). There was a time × COND interaction (p = 0.04), where EX had a greater eNO response at 4 h compared with CON. Sputum neutrophils increased at 4 h post-HFM (p < 0.05). These findings suggest that airway inflammation occurs after an HFM when exercise is performed in the postprandial period, regardless of habitual activity level.


activité physique; energy balance; exercice physique; exercise; inflammation; physical activity; physiologie pulmonaire; pulmonary physiology; équilibre énergétique


[The below paper is pdf-availed.]

Omega-3 Supplementation and the Neural Correlates of Negative Affect and Impulsivity: A Double-Blind, Randomized, Placebo-Controlled Trial in Midlife Adults.

Ginty AT, Muldoon MF, Kuan DC, Schirda B, Kamarck TW, Jennings JR, Manuck SB, Gianaros PJ.

Psychosom Med. 2017 Jan 24. doi: 10.1097/PSY.0000000000000453. [Epub ahead of print]

PMID: 28121722



In clinical trials, omega-3 fatty acid supplementation improves symptoms in psychiatric disorders involving dysregulated mood and impulse control, yet it is unclear whether in healthy adults omega-3 fatty acid supplementation affects mood, impulse control and the brain systems supporting these processes. Accordingly, this study tested the hypotheses that eciosapentaenoic (EPA) and docosahexaenoic (DHA) acid supplementation reduces negative affect and impulsive behaviors in healthy adults and that these changes correspond to alterations in corticolimbic and corticostriatal brain systems which support affective and impulsive processes.


Healthy volunteers (N = 272) consuming 300 mg/day or less of EPA and DHA were enrolled in a double-blind, randomized, placebo controlled clinical trial. Participants received either capsules providing 1000 mg of EPA and 400 mg of DHA versus identical appearing soybean oil capsules per day for 18 weeks. Negative affect and impulsivity were measured by questionnaire and ecological momentary assessment (EMA), as well as functional alterations in corticolimbic and corticostriatal brain systems evoked by standardized fMRI tasks.


There were no group-by-time interactions for any questionnaire or EMA measures of mood and impulsivity. Likewise, no group-by-time interactions were observed for fMRI responses evoked within corticolimbic and corticostriatal systems.


In healthy adults with low intake of omega-3 fatty acids, moderate-dose supplementation for 18 weeks did not alter affect or impulsive behaviors, nor alter corticolimbic and corticostriatal brain functionality.


[The below paper is pdf-availed. Physical activity decreased HbA1c over twice as much in those with baseline values greater versus less than than 6%; for body weight the increased value was more than 4 times as great, mainly due to less affect with the value less than 6%.]

Change in Sedentary Time, Physical Activity, Bodyweight, and Hba1c in High-Risk Adults.

McCarthy M, Edwardson CL, Davies MJ, Henson J, Gray L, Khunti K, Yates T.

Med Sci Sports Exerc. 2017 Jan 24. doi: 10.1249/MSS.0000000000001218. [Epub ahead of print]

PMID: 28121795



In recent years, there has been a migration towards the use of glycated hemoglobin (HbA1c) in determining glycemic control. This study aimed to quantify the associations between changes in body weight, sedentary time and moderate to vigorous physical activity (MVPA) time with HbA1c levels over a three year period among adults at high risk of type 2 diabetes.


This study reports baseline and three year follow-up data from the Walking Away from Type 2 Diabetes study. ActiGraph GT3X accelerometers captured sedentary time and MVPA. Linear regression examined the independent associations of changes in sedentary time, MVPA and body weight with HbA1c between baseline and three year follow-up.


The sample comprised of 489 participants (mean age 64.2 ± 7.3 years, BMI 31.7 ± 5.1, 63.4% male) with valid baseline and follow-up accelerometer, body weight and HbA1c data. Following adjustment for known confounders, an increase in MVPA time (per 30mins/day) was associated with a decrease in HbA1c percentage(β = -0.11 (-0.18,-0.05), p=0.001) and an increase in body weight (per 6 kg) was associated with an increase in HbA1c percentage (β = 0.08 (0.04,0.12), p<0.001). Presence of dysglycemia at baseline (HbA1c ≥6.0%) strengthened these associations (p<0.001 for interactions). Change in sedentary time was not significantly associated with change in HbA1c after adjustment for change in MVPA time.


Increases in MVPA and body weight were associated with a reduction and increase in HbA1c respectively, particularly in those with dysglycemia. Quantifying the impact that health behavior changes have on HbA1c can be used to inform prevention programs.


Combined Impact of Traditional and Non-Traditional Healthy Behaviors on Health-Related Quality of Life: A Prospective Study in Older Adults.

Bayán-Bravo A, Pérez-Tasigchana RF, Sayón-Orea C, Martínez-Gómez D, López-García E, Rodríguez-Artalejo F, Guallar-Castillón P.

PLoS One. 2017 Jan 25;12(1):e0170513. doi: 10.1371/journal.pone.0170513.

PMID: 28122033




Combined exposure to several healthy behaviors (HB) is associated with reduced mortality in older adults but its impact on health-related quality of life (HRQL) is uncertain. This is a cohort study of 2,388 individuals aged ≥60 recruited in 2000-2001, whose data were updated in 2003 and 2009. At baseline, participants reported both traditional HB (non-smoking, being very or moderately active, healthy diet) and non-traditional HB (sleeping 7-8 h/d, being seated <8 h/d, and seeing friends every day). HRQL was measured with the SF-36 questionnaire at baseline, in 2003 (short-term) and in 2009 (long-term); a higher score on the SF-36 represents better HRQL. Linear regression models were used to assess the association between HB at baseline and HRQL in 2003 and 2009, with adjustment for the main confounders including baseline HRQL. In the short-term, being physically active, sleeping 7-8 h/d, and being seated <8 h/d was associated with better HRQL. Compared to having ≤1 of these HB, the β (95% confidence interval) for the score on the physical component summary of the SF-36 in 2003 was 1.42 (0.52-2.33) for 2 HB, and 2.06 (1.09-3.03) for 3 HB, p-trend <0.001. Corresponding figures for the mental component summary score were 1.89 (0.58-3.21) for 2 HB and 3.35 (1.95-4.76) for 3 HB, p-trend <0.001. Non-smoking, a healthy diet or seeing friends did not show an association with HRQL. In the long-term, being physically active was the only HB associated with better physical HRQL. As a conclusion, a greater number of HB, particularly more physical activity, adequate sleep duration, and sitting less, were associated with better short-term HRQL in older adults. However, in the long-term, being physically active was the only HB associated with better physical HRQL.


Assessing Sex Differences in the Risk of Cardiovascular Disease and Mortality per Increment in Systolic Blood Pressure: A Systematic Review and Meta-Analysis of Follow-Up Studies in the United States.

Wei YC, George NI, Chang CW, Hicks KA.

PLoS One. 2017 Jan 25;12(1):e0170218. doi: 10.1371/journal.pone.0170218.

PMID: 28122035




In the United States (US), cardiovascular (CV) disease accounts for nearly 20% of national health care expenses. Since costs are expected to increase with the aging population, informative research is necessary to address the growing burden of CV disease and sex-related differences in diagnosis, treatment, and outcomes. Hypertension is a major risk factor for CV disease and mortality. To evaluate whether there are sex-related differences in the effect of systolic blood pressure (SBP) on the risk of CV disease and mortality, we performed a systematic review and meta-analysis. We conducted a comprehensive search using PubMed and Google Scholar to identify US-based studies published prior to 31 December, 2015. We identified eight publications for CV disease risk, which provided 9 female and 8 male effect size (ES) observations. We also identified twelve publications for CV mortality, which provided 10 female and 18 male ES estimates. Our meta-analysis estimated that the pooled ES for increased risk of CV disease per 10 mmHg increment in SBP was 25% for women (95% Confidence Interval (CI): 1.18, 1.32) and 15% for men (95% CI: 1.11, 1.19). The pooled increase in CV mortality per 10 mm Hg SBP increment was similar for both women and men (Women: 1.16; 95% CI: 1.10, 1.23; Men: 1.17; 95% CI: 1.12, 1.22). After adjusting for age and baseline SBP, the results demonstrated that the risk of CV disease per 10 mm Hg SBP increment for women was 1.1-fold higher than men (P<0.01; 95% CI: 1.04, 1.17). Heterogeneity was moderate but significant. There was no significant sex difference in CV mortality.


Physical Exercise Performed Four Hours after Learning Improves Memory Retention and Increases Hippocampal Pattern Similarity during Retrieval.

van Dongen EV, Kersten IH, Wagner IC, Morris RG, Fernández G.

Curr Biol. 2016 Jul 11;26(13):1722-7. doi: 10.1016/j.cub.2016.04.071.

PMID: 27321998



Persistent long-term memory depends on successful stabilization and integration of new memories after initial encoding [1, 2]. This consolidation process is thought to require neuromodulatory factors such as dopamine, noradrenaline, and brain-derived neurotrophic factor [3-7]. Without the release of such factors around the time of encoding, memories will decay rapidly [3, 5, 6, 8]. Recent studies have shown that physical exercise acutely stimulates the release of several consolidation-promoting factors in humans [9-14], raising the question of whether physical exercise can be used to improve memory retention [15-17]. Here, we used a single session of physical exercise after learning to exogenously boost memory consolidation and thus long-term memory. Three groups of randomly assigned participants first encoded a set of picture-location associations. Afterward, one group performed exercise immediately, one 4 hr later, and the third did not perform any exercise. Participants otherwise underwent exactly the same procedures to control for potential experimental confounds. Forty-eight hours later, participants returned for a cued-recall test in a magnetic resonance scanner. With this design, we could investigate the impact of acute exercise on memory consolidation and retrieval-related neural processing. We found that performing exercise 4 hr, but not immediately, after encoding improved the retention of picture-location associations compared to the no-exercise control group. Moreover, performing exercise after a delay was associated with increased hippocampal pattern similarity for correct responses during delayed retrieval. Our results suggest that appropriately timed physical exercise can improve long-term memory and highlight the potential of exercise as an intervention in educational and clinical settings.


[Although the study was in drosophila, two of the authors published the related article studying mice.]

Growing more positive with age: The relationship between reproduction and survival in aging flies.

van den Heuvel J, Zandveld J, Brakefield PM, Kirkwood TB, Shanley DP, Zwaan BJ.

Exp Gerontol. 2017 Jan 22. pii: S0531-5565(16)30458-2. doi: 10.1016/j.exger.2017.01.016. [Epub ahead of print]

PMID: 28122252



Populations of laboratory animals that are selected for increased lifespan often show negative correlated responses in early fecundity. However, late fecundity and/or total lifetime fecundity can be higher in the populations selected for increased lifespan. This has been interpreted by some as being at odds with the disposable soma theory, which predicts decreased lifespan to increase total reproductive output. Alternatively, the Y-model explores the effects of variation in resource allocation and acquisition on life histories. In this model, a negative relationship between lifespan and reproduction can be viewed as variation in allocation, whereas a positive relationship is the result of variation in acquisition. However, a frequently neglected complication of the Y-model is that older individuals often show a decline in resource acquisition. Therefore, differential allocation to maintenance and survival might affect this decline in late-life acquisition which will affect resource availability across the whole lifespan. In this paper we show that a model which incorporates the ideas of the Y-model, the disposable soma theory, and an age-related decrease in resource acquisition, i.e. feeding senescence, can explain how the relationship between fecundity and lifespan changes with age. Furthermore, by modeling environments with contrasting extrinsic mortality rates, we explored how the outcome of the model depended on the relative importance of early and late-life reproduction. In high mortality environments a relatively higher early fecundity, lower late fecundity, and lower lifespans were more optimal, whereas the opposite was true for low mortality environments. We applied predictions from the model to a cohort of individually-housed female Drosophila melanogaster flies for which we measured age specific fecundity and lifespan. Early fecundity was negatively associated with lifespan, while late fecundity related positively with lifespan in the same cohort. This verified that the mechanism of feeding senescence could explain patterns for age specific relationships between lifespan and fecundity.


Disposable soma theory; Dynamic programming; Energy allocation Y-model; Lifespan; Reproduction; Trade-off


Calorie restriction and aging: a life-history analysis.

Shanley DP, Kirkwood TB.

Evolution. 2000 Jun;54(3):740-50.

PMID: 10937249



The disposable soma theory suggests that aging occurs because natural selection favors a strategy in which fewer resources are invested in somatic maintenance than are necessary for indefinite survival. However, laboratory rodents on calorie-restricted diets have extended life spans and retarded aging. One hypothesis is that this is an adaptive response involving a shift of resources during short periods of famine away from reproduction and toward increased somatic maintenance. The potential benefit is that the animal gains an increased chance of survival with a reduced intrinsic rate of senescence, thereby permitting reproductive value to be preserved for when the famine is over. We describe a mathematical life-history model of dynamic resource allocation that tests this idea. Senescence is modeled as a change in state that depends on the resources allocated to maintenance. Individuals are assumed to allocate the available resources to maximize the total number of descendants. The model shows that the evolutionary hypothesis is plausible and identifies two factors, both likely to exist, that favor this conclusion. These factors are that survival of juveniles is reduced during periods of famine and that the organism needs to pay an energetic "overhead" before any litter of offspring can be produced. If neither of these conditions holds, there is no evolutionary advantage to be gained from switching extra resources to maintenance. The model provides a basis to evaluate whether the life-extending effects of calorie-restriction might apply in other species, including humans.


Alcohol and Lung Cancer Risk Among Never Smokers: A Pooled Analysis from the International Lung Cancer Consortium and the SYNERGY Study.

Fehringer G, Brenner DR, Zhang ZF, Lee YA, Matsuo K, Ito H, Lan Q, Vineis P, Johansson M, Overvad K, Riboli E, Trichopoulou A, Sacerdote C, Stucker I, Boffetta P, Brennan P, Christiani DC, Hong YC, Landi MT, Morgenstern H, Schwartz AG, Wenzlaff AS, Rennert G, McLaughlin JR, Harris CC, Olivo-Marston S, Orlow I, Park BJ, Zauderer M, Barros Dios JM, Ruano Raviña A, Siemiatycki J, Koushik A, Lazarus P, Fernández-Somoano A, Tardon A, Le Marchand L, Brenner H, Saum KU, Duell EJ, Andrew AS, Szeszenia-Dabrowska N, Lissowska J, Zaridze D, Rudnai P, Fabianova E, Mates D, Foretova L, Janout V, Bencko V, Holcatova I, Pesatori AC, Consonni D, Olsson A, Straif K, Hung RJ.

Int J Cancer. 2017 Jan 24. doi: 10.1002/ijc.30618. [Epub ahead of print]

PMID: 28120396



It is not clear whether alcohol consumption is associated with lung cancer risk. The relationship is likely confounded by smoking, complicating the interpretation of previous studies. We examined the association of alcohol consumption and lung cancer risk in a large pooled international sample, minimizing potential confounding of tobacco consumption by restricting analyses to never smokers. Our study included 22 case-control and cohort studies with a total of 2548 never-smoking lung cancer patients and 9362 never-smoking controls from North America, Europe and Asia within the International Lung Cancer Consortium (ILCCO) and SYNERGY Consortium. Alcohol consumption was categorized into amounts consumed (grams per day) and also modelled as a continuous variable using restricted cubic splines for potential non-linearity. Analyses by histologic sub-type were included. Associations by type of alcohol consumed (wine, beer and liquor) were also investigated. Alcohol consumption was inversely associated with lung cancer risk with evidence most strongly supporting lower risk for light and moderate drinkers relative to non-drinkers (>0-4.9g per day: OR=0.80, 95% CI=0.70-0.90; 5-9.9g per day: OR=0.82, 95% CI=0.69-0.99; 10-19.9g per day: OR=0.79, 95% CI=0.65-0.96). Inverse associations were found for consumption of wine and liquor, but not beer. The results indicate that alcohol consumption is inversely associated with lung cancer risk, particularly among subjects with low to moderate consumption levels, and among wine and liquor drinkers, but not beer drinkers. Although our results should have no relevant bias from the confounding effect of smoking we cannot preclude that confounding by other factors contributed to the observed associations. Confounding in relation to the non-drinker reference category may be of particular importance.


Alcohol; beer; liquor; lung cancer; wine


The Opinion Pages

If Sugar Is Harmless, Prove It


David Bornstein

FIXES JAN. 25, 2017


Over the past half-century, the rate of obesity in America has nearly tripled, while the incidence of diabetes has increased roughly sevenfold. It’s estimated that the direct health care costs related to obesity and diabetes in the United States is $1 billion a day, while economists have calculated the indirect costs to society of these epidemics at over $1 trillion a year.

In recent years, some researchers have focused on the particular role refined sugar may play in these epidemics. Perhaps the most comprehensive analysis of this research has been put forth by the science journalist, Gary Taubes, author of the recent book, “The Case Against Sugar.” I spoke with Taubes about his research and what people should know about sugar to make better choices in their diets.

— David Bornstein

David Bornstein: What’s the essence of the case against sugar?

Gary Taubes: To understand the case against sugar, using a criminal justice metaphor, you have to understand the crimes committed: epidemics of diabetes and obesity worldwide. Wherever and whenever a population transitions from its traditional diet to a Western diet and lifestyle, we see dramatic increases in obesity, and diabetes goes from being a relatively rare disorder to a common one. One in 11 Americans now has diabetes. In some populations, one in three or four adults have diabetes. Stunning numbers.

So why sugar? Well, for starters, recent increases in sugar consumption are always at the scene of the crime on a population-wide level when these epidemics occur. And sugar is also at the scene of the crime biologically, and it’s got the mechanism necessary. But the evidence is not definitive; what I’m arguing is still a minority viewpoint.

D.B.: What’s the common explanation?

G.T.: The conventional wisdom is that obesity is a problem of energy imbalance. We eat too much, we’re too sedentary, so we get fatter — and this in turn causes the diabetes, Type 2, which is the common form. I don’t find this energy balance concept meaningful. It’s like saying when somebody gets richer, they make more money than they spend; they accumulate wealth. It’s a tautology; it tells you nothing about why it happens.

Still, it’s this energy balance thinking that leads us to blame the food industry for providing too much tasty food, and the individual who’s afflicted for not being able to eat in moderation and not being suitably active.

D.B.: Can you explain what you call the alternative hypothesis?

G.T.: Simple. Obesity is a hormonal/regulatory disorder just like any other growth defect. And the hormone that primarily drives fat accumulation is insulin, the same hormone that is disregulated in diabetes. Just as growth hormone is the primary driver of skeletal and muscular growth, insulin is the primary driver of our horizontal growth, the expansion of our fat tissue.

We secrete insulin in response to carbohydrates in our diet and there’s a condition called insulin resistance that is the fundamental defect in Type 2 diabetes and is so closely associated with obesity that we can speculate that it might be the cause. The Centers for Disease Control and Prevention estimates that 75 million American are insulin resistant.

D.B.: What is insulin resistance?

G.T.: Insulin is a hormone secreted by the pancreas that can be thought of as orchestrating how the body uses or partitions its fuel. It tells your cells to take up blood sugar and burn that sugar, technically glucose, for fuel. But it also tells your fat tissue to take up fat and inhibits the release of fat; it tells your muscles, your lean tissue, to use protein for rebuilding.

If you’re insulin resistant, your pancreas needs to secrete more insulin to control blood sugar, and that insulin will increase your fat accumulation as a consequence.

Researchers studying insulin resistance believe it begins in the liver, beginning with the accumulation of fat in the liver cells. As it turns out, the fructose constituent of sugar — half of cane or beet sugar, 55 percent of high fructose corn syrup — is metabolized primarily in the liver, and when it is delivered to the liver in high doses, the liver converts it into fat. So that’s what I mean when I say sugar is at the scene of the crime both in populations and biologically, in the body itself.

D.B.: Given the rates of obesity and diabetes in the United States, what do you think is called for today?

G.T.: I’m arguing the reason we’ve failed to curb the obesity and diabetes epidemics is we’ve misunderstood the cause. We blame eating too much and exercising too little, rather than the carbohydrate content of the diet, specifically sugar.

We need better research that asks the correct questions and rigorously, methodically and skeptically identifies the precise dietary causes of these disorders so we know what has to be removed to reverse or stop them. We need studies that can disassociate the physiological or toxic effects of sugar — on body fat, on insulin resistance status — from the calories it contains.

D.B.: Let’s say that happens. Then what?

G.T.: Then we have to get the message right. If we believe that sugar is just empty calories, then it’s reasonable to say eat it in moderation and balance the calories in sugary snacks by exercising more. We don’t have to steal Christmas, in effect, by removing sugar from our diets and our lives.

But I’m arguing that if sugar causes obesity and diabetes, then we should drop the “too much of,” or “overconsumption of,” or “excess of,” and just say sugar causes these diseases. (We could say added sugars, or refined sugars, if we don’t want to implicate fruit). We know that smoking too many cigarettes will cause lung cancer, but we don’t say “too many cigarettes” cause lung cancer; we say “cigarettes cause lung cancer.” The message is fundamentally different.

D.B.: What do you think the sugar industry should do?

G.T.: The sugar industry and its defenders argue that the evidence is ambiguous; therefore we should continue to believe that sugar is no more than empty calories at the very worst. What I would like them to do is suggest tests that could exonerate sugar, if it’s really harmless. It’s not enough just to say the evidence is ambiguous. And I think the industry now has an obligation to fund those tests.

D.B.: Do you think we should regulate sugar?

G.T.: I prefer education. Government regulation makes me nervous, as my books have documented how the ill-conceived efforts to limit our fat consumption, beginning in the 1970s and 1980s, may have helped put us in this situation. And government regulation based on ambiguous evidence makes me very nervous. It can set precedents for regulating other food products that might not be harmful or might even be beneficial to our health.

D.B.: What would help advance that education?

G.T.: We can put warning labels on sugary beverages as we’re trying to do in California. We can drop sugary drinks from kids’ menus at restaurants, as some chain restaurants already are. There are government campaigns, in various cities, and funded by the C.D.C. to discourage sugary drink consumptions. There are nonprofits creating ads and YouTube videos that help us understand quite how much sugar we’re consuming.

One possibility is that the Food and Drug Administration could reassess whether sugar should still be listed as “generally recognized as safe.” Foods need to have GRAS status to be used as additives. The F.D.A. granted sugar GRAS status in 1986, when most experts did generally recognize it as safe. But now they probably wouldn’t.

Clearly, we have to lower the sugar content in foods. Sugar is in virtually every processed food: peanut butter, salad dressing, white bread, ketchup, processed meats, barbecue sauces, canned soups, cold cuts, hot dogs, canned tomatoes, to name just a few.

One idea I like comes from a law professor at the University of California named, coincidentally, Stephen Sugarman, who has suggested a cap and trade approach for sugar. The idea is basically to have the markets and food industries agree to reduce the sugar that crosses the point of sale by, say, 5 percent every year. The idea is that we give food companies time to adapt to putting less sugar in their products, just like we give car companies time to reach higher gas mileage targets in their fleets.

D.B.: Do you have any advice to offer from personal experience?

G.T.: Clearly, the best approach is to learn to live without the obvious sources of sugar, in the sugary beverages, the candies and treats. But you have to do it long enough so that you can really know how you feel without it.

What’s it like to enjoy a meal without a dessert, or to drink water instead of juice or soda, to have a snack of nuts rather than a candy bar? When we try, and we can all do this as an experiment, we have to do it for long enough that we get over the initial cravings and get to the point where we can really experience what life is like without it. Only then can we decide if a healthy life without sugar is worth the apparent sacrifice.

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Nampt Expression Decreases Age-Related Senescence in Rat Bone Marrow Mesenchymal Stem Cells by Targeting Sirt1.

Ma C, Pi C, Yang Y, Lin L, Shi Y, Li Y, Li Y, He X.

PLoS One. 2017 Jan 26;12(1):e0170930. doi: 10.1371/journal.pone.0170930.

PMID: 28125705




Senescence restricts the development of applications involving mesenchymal stem cells (MSCs) in research fields, such as tissue engineering, and stem cell therapeutic strategies. Understanding the mechanisms underlying natural aging processes may contribute to the development of novel approaches to preventing age-related diseases or slowing individual aging processes. Nampt is a rate-limiting NAD biosynthetic enzyme that plays critical roles in energy metabolism, cell senescence and maintaining life spans. However, it remains unknown whether Nampt influences stem cell senescence. In this study, the function of Nampt was investigated using a rat model of natural aging. Our data show that Nampt expression was significantly lower in MSCs obtained from aged rats than in those obtained from young rats during physiological aging. Reducing the level of Nampt in aged MSCs resulted in lower intracellular concentrations of NAD+ and downregulated Sirt1 expression and activity. After the Nampt inhibitor FK866 was added, young MSCs were induced to become aged cells. The enhanced senescence was correlated with NAD+ depletion and Sirt1 activity attenuation. In addition, Nampt overexpression attenuated cell senescence in aged MSCs. Our findings provide a new explanation for the mechanisms underlying stem cell senescence and a novel target for delaying stem cell senescence and preventing and treating age-related diseases.


[Health Insurance in Old Age and Differences in Cognition, Depressive Symptoms and Health-Related Quality of Life].

Bock JO, Hajek A, Lühmann D, Ernst A, Mamone S, Wiese B, Weyerer S, Werle J, Pentzek M, Fuchs A, Stein J, Luck T, Bickel H, Weeg D, Wagner M, Scherer M, Riedel-Heller SG, Maier W, König HH; für die AgeCoDe & AgeQualiDe Study Group..

Psychiatr Prax. 2017 Jan 26. doi: 10.1055/s-0042-116219. [Epub ahead of print] German.

PMID: 28125847


Objective We aimed at identifying differences regarding cognition, depressive symptoms and health-related quality of life between members of private and statutory health insurance (SHI) in very old age in Germany. Methods Cross-sectional data were gathered from the multicenter prospective "Study on Needs, health service use, costs and health-related quality of life in a large sample of oldest-old primary care patients (85+)" (AgeQualiDe), covering primary care patients aged ≥ 85 years (n = 854; with 773 members of SHI). The Global Deterioration Scale measured cognition, the Geriatric Depression Scale assessed depressive symptoms, and health-related quality of life was measured by using a Visual Analogue Scale (EQ-VAS). Results While members of private health insurance showed slightly better cognitive function, less depressive symptoms and better health-related quality of life descriptively, regression models showed that none of these differences was statistically significant. Conclusions There are no differences between members of private health insurance and SHI regarding cognitive function, depressive symptoms and health-related quality of life in very old age.


Molecular Bases Underlying the Hepatoprotective Effects of Coffee.

Salomone F, Galvano F, Li Volti G.

Nutrients. 2017 Jan 23;9(1). pii: E85. doi: 10.3390/nu9010085. Review.

PMID: 28124992



Coffee is the most consumed beverage worldwide. Epidemiological studies with prospective cohorts showed that coffee intake is associated with reduced cardiovascular and all-cause mortality independently of caffeine content. Cohort and case-control studies reported an inverse association between coffee consumption and the degree of liver fibrosis as well as the development of liver cancer. Furthermore, the beneficial effects of coffee have been recently confirmed by large meta-analyses. In the last two decades, various in vitro and in vivo studies evaluated the molecular determinants for the hepatoprotective effects of coffee. In the present article, we aimed to critically review experimental evidence regarding the active components and the molecular bases underlying the beneficial role of coffee against chronic liver diseases. Almost all studies highlighted the beneficial effects of this beverage against liver fibrosis with the most solid results indicating a pivot role for both caffeine and chlorogenic acids. In particular, in experimental models of fibrosis, caffeine was shown to inhibit hepatic stellate cell activation by blocking adenosine receptors, and emerging evidence indicated that caffeine may also favorably impact angiogenesis and hepatic hemodynamics. On the other side, chlorogenic acids, potent phenolic antioxidants, suppress liver fibrogenesis and carcinogenesis by reducing oxidative stress and counteract steatogenesis through the modulation of glucose and lipid homeostasis in the liver. Overall, these molecular insights may have translational significance and suggest that coffee components need clinical evaluation.


caffeine; chlorogenic acid; liver cancer; liver fibrosis; liver steatosis

PMID: 28124992 DOI: 10.3390/nu9010085


The interventional relationship between frequent fish consumption and depression symptoms in aging adults: a randomized controlled trial.

Sharifan P, Hosseini MS, Sharifan A.

Int J Geriatr Psychiatry. 2017 Jan 26. doi: 10.1002/gps.4668. [Epub ahead of print]

PMID: 28124802




The present investigation was intended to test the hypothesis that the elderly provided with the frequent consumption of fishes marinated in essential oil of Perilla frutescens (EOPF) or not would experience fewer depressive symptoms after 6 months.


A total of 180 participants were recruited from Sina Hospital, Mashhad, Iran, who were diagnosed with depression based on Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision and Beck Depression Inventory. Participants (n = 180) were randomly assigned in a 1:1:1 ratio to Groups A, B, and C. The last two were provided with an instruction to consume Caspian white fish marinated in the presence or absence of EOPF (434 g each week or four meals per week). Group A served as the control with the common diet. The outcome measures were performed using the Beck Depression Inventory and the General Health Questionnaire.


There were no statistically significant differences in depressive symptom scores between groups with frequent fish consumption as compared with the control (p > 0.05). Yet adjustment for covariates showed that there was a significant reduction in depression among them (p < 0.05). Moreover, consumption of fish and EOPF was associated with more considerable improvements than Groups A and B (p < 0.05).


It could be concluded that high intakes of unsaturated fatty acids can afford to diminish likelihood of late-life depression.


controlled randomized trial; depression; elderly; frequent fish consumption; perilla


Effects of Coenzyme Q10 on Markers of Inflammation: A Systematic Review and Meta-Analysis.

Zhai J, Bo Y, Lu Y, Liu C, Zhang L.

PLoS One. 2017 Jan 26;12(1):e0170172. doi: 10.1371/journal.pone.0170172.

PMID: 28125601





Chronic inflammation contributes to the onset and development of metabolic diseases. Clinical evidence has suggested that coenzyme Q10 (CoQ10) has some effects on inflammatory markers. However, these results are equivocal. The aim of this systematic review was to assess the effects of CoQ10 on serum levels of inflammatory markers in people with metabolic diseases.


Electronic databases were searched up to February 2016 for randomized controlled trials (RCTs). The outcome parameters were related to inflammatory factors, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and C reactive protein (CRP). RevMan software was used for meta-analysis. Meta-regression analysis, Egger line regression test and Begg rank correlation test were performed by STATA software.


Nine trials involving 428 subjects were included in this meta-analysis. The results showed that compared with control group, CoQ10 supplementation has significantly improved the serum level of CoQ10 by 1.17μg/ml [MD = 1.17, 95% CI (0.47 to 1.87) μg/ml, I2 = 94%]. Meanwhile, it has significantly decreased TNF-α by 0.45 pg/ml [MD = -0.45, 95% CI (-0.67 to -0.24) pg/ml, I2 = 0%]. No significant difference was observed between CoQ10 and placebo with regard to CRP [MD = -0.21, 95% CI (-0.60 to 0.17) mg/L, I2 = 21%] and IL-6 [MD = -0.89, 95% CI (-1.95 to 0.16) pg/ml, I2 = 84%].


CoQ10 supplementation may partly improve the process of inflammatory state. The effects of CoQ10 on inflammation should be further investigated by conducting larger sample size and well-defined trials of long enough duration.


Saturated Fat Consumption and Risk of Coronary Heart Disease and Ischemic Stroke: A Science Update.

Nettleton JA, Brouwer IA, Geleijnse JM, Hornstra G.

Ann Nutr Metab. 2017 Jan 27;70(1):26-33. doi: 10.1159/000455681. [Epub ahead of print]

PMID: 28125802




At a workshop to update the science linking saturated fatty acid (SAFA) consumption with the risk of coronary heart disease (CHD) and ischemic stroke, invited participants presented data on the consumption and bioavailability of SAFA and their functions in the body and food technology. Epidemiological methods and outcomes were related to the association between SAFA consumption and disease events and mortality. Participants reviewed the effects of SAFA on CHD, causal risk factors, and surrogate risk markers. Higher intakes of SAFA were not associated with higher risks of CHD or stroke apparently, but studies did not take macronutrient replacement into account. Replacing SAFA by cis-polyunsaturated fatty acids was associated with significant CHD risk reduction, which was confirmed by randomized controlled trials. SAFA reduction had little direct effect on stroke risk. Cohort studies suggest that the food matrix and source of SAFA have important health effects.


[The below paper is pdf-availed. There were more than seven times as many negative as positive colorectal tumors for the bacterium.]

Association of Dietary Patterns With Risk of Colorectal Cancer Subtypes Classified by Fusobacterium Nucleatum in Tumor Tissue.

Mehta RS, Nishihara R, Cao Y, Song M, Mima K, Qian ZR, Nowak JA, Kosumi K, Hamada T, Masugi Y, Bullman S, Drew DA, Kostic AD, Fung TT, Garrett WS, Huttenhower C, Wu K, Meyerhardt JA, Zhang X, Willett WC, Giovannucci EL, Fuchs CS, Chan AT, Ogino S.

JAMA Oncol. 2017 Jan 26. doi: 10.1001/jamaoncol.2016.6374. [Epub ahead of print]

PMID: 28125762



Fusobacterium nucleatum appears to play a role in colorectal carcinogenesis through suppression of the hosts' immune response to tumor. Evidence also suggests that diet influences intestinal F nucleatum. However, the role of F nucleatum in mediating the relationship between diet and the risk of colorectal cancer is unknown.


To test the hypothesis that the associations of prudent diets (rich in whole grains and dietary fiber) and Western diets (rich in red and processed meat, refined grains, and desserts) with colorectal cancer risk may differ according to the presence of F nucleatum in tumor tissue.


A prospective cohort study was conducted using data from the Nurses' Health Study (June 1, 1980, to June 1, 2012) and the Health Professionals Follow-up Study (June 1, 1986, to June 1, 2012) on a total of 121 700 US female nurses and 51 529 US male health professionals aged 30 to 55 years and 40 to 75 years, respectively (both predominantly white individuals), at enrollment. Data analysis was performed from March 15, 2015, to August 10, 2016.


Prudent and Western diets.


Incidence of colorectal carcinoma subclassified by F nucleatum status in tumor tissue, determined by quantitative polymerase chain reaction.


Of the 173 229 individuals considered for the study, 137 217 were included in the analysis, 47 449 were male (34.6%), and mean (SD) baseline age for men was 54.0 (9.8) years and for women, 46.3 (7.2) years. A total of 1019 incident colon and rectal cancer cases with available F nucleatum data were documented over 26 to 32 years of follow-up, encompassing 3 643 562 person-years. The association of prudent diet with colorectal cancer significantly differed by tissue F nucleatum status (P = .01 for heterogeneity); prudent diet score was associated with a lower risk of F nucleatum-positive cancers (P = .003 for trend; multivariable hazard ratio of 0.43; 95% CI, 0.25-0.72, for the highest vs the lowest prudent score quartile) but not with F nucleatum-negative cancers (P = .47 for trend, the corresponding multivariable hazard ratio of 0.95; 95% CI, 0.77-1.17). There was no significant heterogeneity between the subgroups in relation to Western dietary pattern scores.


Prudent diets rich in whole grains and dietary fiber are associated with a lower risk for F nucleatum-positive colorectal cancer but not F nucleatum-negative cancer, supporting a potential role for intestinal microbiota in mediating the association between diet and colorectal neoplasms.


Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study.

Kang DW, Adams JB, Gregory AC, Borody T, Chittick L, Fasano A, Khoruts A, Geis E, Maldonado J, McDonough-Means S, Pollard EL, Roux S, Sadowsky MJ, Lipson KS, Sullivan MB, Caporaso JG, Krajmalnik-Brown R.

Microbiome. 2017 Jan 23;5(1):10. doi: 10.1186/s40168-016-0225-7.

PMID: 28122648




Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 1013 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children.


MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks).


This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact.


Autism spectrum disorders (ASD); Clinical trial; Fecal microbiota transplant (FMT); Gut bacteria; Gut bacteriophage; Microbiome; Virome

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