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[The below paper is pdf-availed.]

Lipids and physical function in older adults.

Casas-Agustench P, Cherubini A, Andrés-Lacueva C.

Curr Opin Clin Nutr Metab Care. 2016 Oct 7.

PMID: 27753664

... In recent years, scientific evidence has increased concerning the ability of lipids, in particular omega 3 polyunsaturated fatty acids (n-3 PUFAs), to positively influence muscle and overall physical function in older patients. ...


Papers of particular interest, published within the annual period of review, have been highlighted as:

& of special interest

&& of outstanding interest

16.&& Logan SL, Spriet LL. Omega-3 fatty acid supplementation for 12 weeks

increases resting and exercise metabolic rate in healthy community-dwelling

older females. PLoS One 2015; 10:e0144828.

This interventional study explored the effects of fish oil supplementation on resting

metabolic rate, exercise-related energy expenditure, lean body mass and functional

capacity in healthy community-dwelling older women.

17.&& Smith GI, Julliand S, Reeds DN, et al. Fish oil-derived n-3 PUFA therapy

increases muscle mass and function in healthy older adults. Am J Clin Nutr

2015; 102:115–122.

This is a double-blind, randomized controlled study that evaluated the effects of the

supplementation of high doses of n-3 PUFA (4 g/day) for 6 months in healthy older

people, showing an improvement in muscle mass and performance in older adults.


Migraines linked to bacteria in mouth

People who suffer from migraines have more of certain bacteria in their mouths

By Darryl Hol, CBC News Posted: Oct 19, 2016



Migraines Are Correlated with Higher Levels of Nitrate-, Nitrite-, and Nitric Oxide-Reducing Oral Microbes in the American Gut Project Cohort

Antonio Gonzalez, Embriette Hyde, Naseer Sangwan, Jack A. Gilbert, Erik Viirre, Rob Knight

mSystems DOI: 10.1128/mSystems.00105-16



... we detected observable and significantly higher abundances of nitrate, nitrite, and nitric oxide reductase genes in migraineurs versus nonmigraineurs in samples collected from the oral cavity and a slight but significant difference in fecal samples.


Use of Sleep Medications and Mortality: The Hordaland Health Study.

Sivertsen B, Madsen IE, Salo P, Tell GS, Øverland S.

Drugs Real World Outcomes. 2015 Jun;2(2):123-128.

PMID: 27747767



... Compared with participants not using sleep medications, those who reported any use had a twofold risk for mortality (95 % confidence interval [CI] 1.1-3.7); the hazard ratio (HR) was 2.9 (95 % CI 1.4-5.9) for daily and 1.1 (95 % CI 0.3-3.4) for non-daily users. Mortality risk was higher for benzodiazepines (HR 3.1; 95 % CI 1.3-7.6), but not significant for short-acting benzodiazepine agonists (HR 1.5; 95 % CI 0.7-3.5).


Leisure-Time Physical Activity and Cardiovascular Mortality in an Elderly Population in Northern Manhattan: A Prospective Cohort Study.

Cheung YK, Moon YP, Kulick ER, Sacco RL, Elkind MS, Willey JZ.

J Gen Intern Med. 2016 Oct 17.

PMID: 27752879



... leisure-time physical activity (LTPA) ... energy-to-duration ratio (EDR) ... A high activity frequency was associated with reduced cardiovascular mortality (hazard ratio, HR = 0.93, P = 0.03), but demonstrated no effect on non-cardiovascular death. A high EDR was associated with increased risk of cardiovascular death (HR = 1.30, P = 0.01). A high number of activity types was beneficial in reducing all-cause mortality (HR = 0.87, P = 0.01).



[it is an abstract only.]


Zhang H, Wang Q, Guo Y, Li D, Zhang B, Dong Y, Huang X, Liu Y, Zhao J, Li W, Brunner HR, Liu L.

J Hypertens. 2016 Sep;34 Suppl 1 - ISH 2016 Abstract Book:e52-e53.

PMID: 27753914


... enriched potassium salt (KCL/NaCL = 1:1 by weight) ... baselines of age, SBP, DBP, and urinary sodium to potassium ratio (UNa/K) were not different between control and intervention groups. After using study salt for 3 years, the mean age, blood pressure and UNa/K are listed below. The proportion of impaired kidney function (ratio of microalbumin to creatinine> = 30 mg/g) was 26.8% and 16.2% for control and intervention group respectively (Chi square = 21.683, P < 0.001). The all causes mortality was 82.73/1000 p-y and 48.90/1000 p-y for control and intervention group respectively (Chi square = 28.626, p = 0.000).



The effects of almond consumption on fasting blood lipid levels: a systematic review and meta-analysis of randomised controlled trials.

Musa-Veloso K, Paulionis L, Poon T, Lee HY.

J Nutr Sci. 2016 Aug 16;5:e34. Review.

PMID: 27752301



... TC, LDL-C and TAG were significantly reduced by -0·153 mmol/l (P < 0·001), -0·124 mmol/l (P = 0·001) and -0·067 mmol/l (P = 0·042), respectively, and that HDL-C was not affected (-0·017 mmol/l; P = 0·207). ...


Review of Safety and Efficacy of Sleep Medicines in Older Adults.

Schroeck JL, Ford J, Conway EL, Kurtzhalts KE, Gee ME, Vollmer KA, Mergenhagen KA.

Clin Ther. 2016 Oct 14. pii: S0149-2918(16)30733-0. doi: 10.1016/j.clinthera.2016.09.010. Review.

PMID: 27751669


... Cognitive behavioral therapy and sleep hygiene are considered initial therapy for insomnia. Benzodiazepines are discouraged in the geriatric population, especially for long-term use. Although non-BzRAs have improved safety profiles compared with benzodiazepines, their side effects include dementia, serious injury, and fractures, which should limit their use. Ramelteon has a minimal adverse effect profile and is effective for sleep-onset latency and increased total sleep time, making it a valuable first-line option. Although the data on suvorexant are limited, this drug improves sleep maintenance and has mild adverse effects, including somnolence; residual daytime sedation has been reported, however. Sedating low-dose antidepressants should only be used for insomnia when the patient has comorbid depression. Antipsychotic agents, pramipexole, and tiagabine have all been used for insomnia, but none has been extensively studied in an older population, and all have considerable adverse effects. Gabapentin may be useful in patients with restless leg syndrome or chronic neuropathic pain and insomnia. Diphenhydramine should be avoided in the elderly. Valerian and melatonin are unregulated products that have a small impact on sleep latency and can produce residual sedation.


An ideal treatment for insomnia should help to improve sleep latency and sleep duration with limited awakenings and be without significant adverse effects such as daytime somnolence or decreased alertness. Cognitive behavioral therapy should always be first line treatment. Clinical inertia regarding previous prominent use of benzodiazepines and non-BzRAs will be a significant challenge for patients accustomed to their issuance. The future direction of insomnia treatment should have an emphasis on nonpharmacologic interventions, treating comorbid conditions, and focusing therapy on using benzodiazepines and non-BzRAs as last resorts.


Restricting feeding to the active phase in middle-aged mice attenuates adverse metabolic effects of a high-fat diet.

Duncan MJ, Smith JT, Narbaiza J, Mueez F, Bustle LB, Qureshi S, Fieseler C, Legan SJ.

Physiol Behav. 2016 Aug 30;167:1-9. doi: 10.1016/j.physbeh.2016.08.027.

PMID: 27586251


... three diets for 21-25weeks: 1) high-fat diet (60% total calories from fat) ad-libitum (HFD-AL), 2) HFD, time-restricted feeding (HFD-TRF), and 3) low-fat diet (10% total calories from fat) ad-libitum (LFD-AL) (n=15 each). HFD-TRF mice only had food access for 8h/day during their active period. HFD-TRF mice gained significantly less weight than HFD-AL mice (~20% vs 55% of initial weight, respectively). Caloric intake differed between these groups only during the first 8weeks and accounted for most but not all of their body weight difference during this time. TRF of a HFD lowered glucose tolerance in terms of incremental area under the curve (iAUC) (p<0.02) to that of LFD-AL mice. TRF of a HFD lowered liver weight (p<0.0001), but not retroperitoneal or epididymal fat pad weight, to that of LFD-AL mice. Neither HFD-AL nor HFD-TRF had any effect on performance in the novel object recognition or object location memory tests. Circulating corticosterone levels either before or after restraint stress were not affected by diet. ...

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Hi Everyone,


I was on a holiday visiting with my mother and brother for the last 3 weeks.  I have been casually following the Forums' messages and am getting quite disappointed with the skepticism expressed about serious CR's efficacy for following a relatively very low calorie diet in the ages of about 20-60 years and then a less restricted diet.  I would have appreciated Michael Rae addressing the criticism about the efficacy of serious CR.

Editors' Choice
Don’t mix zinc lozenges and antibiotics
Purna Kashyap
Science Translational Medicine  19 Oct 2016:
Vol. 8, Issue 361, pp. 361ec167
DOI: 10.1126/scitranslmed.aai9159
Clostridium difficile is a leading cause of nosocomial infection, with nearly half a million cases and 29,000 deaths, imposing a significant economic burden on the health system. The incidence and costs associated with C. difficile infection have been increasing over the past decade. A well-accepted risk factor for C. difficile infection is disruption of gut microbial communities following antibiotic use. According to a report from the U.S. Centers for Disease Control and Prevention, there are nearly 154 million antibiotic prescriptions written every year, nearly 30% of which are unnecessary. A majority of these excess antibiotic prescriptions are written for viral upper respiratory infections, such as the common cold, for which individuals are also likely to use zinc-based lozenges. Interestingly, a new study by Zackular et al. has identified high levels of zinc as playing a role in increasing susceptibility to C. difficile infection in a mouse model.
The authors found that giving mice a diet supplemented with zinc decreased microbial diversity and lowered the threshold of antibiotics needed to confer susceptibility to C. difficile infection. Further, the authors showed that calprotectin, a host-derived zinc-binding protein, inhibited growth of C. difficile in culture by decreasing the availability of zinc. This was supported by the increased disease severity and decreased survival of calprotectin-deficient mice following exposure to C. difficile. Whereas calprotectin has been associated with severity of C. difficile infection in human subjects, additional studies are needed to determine its role in zinc-dependent susceptibility to C. difficile.
This study highlights a potential cause for the increasing incidence of C. difficile infection and further brings attention to the need for the judicious use of antibiotics. It also raises concerns regarding the potential interaction of zinc-based lozenges with antibiotics, resulting in disruption of gut microbial communities, thus making gut conditions favorable for pathogen invasion. The tolerable upper limit of zinc intake in humans is 40 mg/day according to the U.S. Department of Health and Human Services, about four times the daily recommended dose, whereas this study examined the effect of supplementing the mouse diet with 12 times the standard dose of zinc for mice. Hence, future studies in human subjects will be needed to determine the validity of these findings at doses encountered in humans. So, don’t throw away the zinc lozenges just yet.
Dietary zinc alters the microbiota and decreases resistance to Clostridium difficile infection.
Zackular JP, Moore JL, Jordan AT, Juttukonda LJ, Noto MJ, Nicholson MR, Crews JD, Semler MW, Zhang Y, Ware LB, Washington MK, Chazin WJ, Caprioli RM, Skaar EP.
Nat Med. 2016 Sep 26. doi: 10.1038/nm.4174.
PMID: 27668938
Clostridium difficile is the most commonly reported nosocomial pathogen in the United States and is an urgent public health concern worldwide. Over the past decade, incidence, severity and costs associated with C. difficile infection (CDI) have increased dramatically. CDI is most commonly initiated by antibiotic-mediated disruption of the gut microbiota; however, non-antibiotic-associated CDI cases are well documented and on the rise. This suggests that unexplored environmental, nutrient and host factors probably influence CDI. Here we show that excess dietary zinc (Zn) substantially alters the gut microbiota and, in turn, reduces the minimum amount of antibiotics needed to confer susceptibility to CDI. In mice colonized with C. difficile, excess dietary Zn severely exacerbated C. difficile-associated disease by increasing toxin activity and altering the host immune response. In addition, we show that the Zn-binding S100 protein calprotectin has antimicrobial effects against C. difficile and is an essential component of the innate immune response to CDI. Taken together, these data suggest that nutrient Zn levels have a key role in determining susceptibility to CDI and severity of disease, and that calprotectin-mediated metal limitation is an important factor in the host immune response to C. difficile.

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Vitamin D Deficiency — Is There Really a Pandemic?
JoAnn E. Manson, M.D., Dr.P.H., Patsy M. Brannon, Ph.D., R.D., Clifford J. Rosen, M.D., and Christine L. Taylor, Ph.D.
N Engl J Med 2016; 375:1817-1820November 10, 2016DOI: 10.1056/NEJMp1608005
The claim that large proportions of North American and other populations are deficient in vitamin D is based on misinterpretation and misapplication of the Institute of Medicine reference values for nutrients — misunderstandings that can adversely affect patient care.

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Caloric restriction preserves memory and reduces anxiety of aging mice with early enhancement of neurovascular functions.
Parikh I, Guo J, Chuang KH, Zhong Y, Rempe RG, Hoffman JD, Armstrong R, Bauer B, Hartz AM, Lin AL.
Aging (Albany NY). 2016 Nov 8. doi: 10.18632/aging.101094. [Epub ahead of print]
PMID: 27829242
Neurovascular integrity plays an important role in protecting cognitive and mental health in aging. Lifestyle interventions that sustain neurovascular integrity may thus be critical on preserving brain functions in aging and reducing the risk for age-related neurodegenerative disorders. Here we show that caloric restriction (CR) had an early effect on neurovascular enhancements, and played a critical role in preserving vascular, cognitive and mental health in aging. In particular, we found that CR significantly enhanced cerebral blood flow (CBF) and blood-brain barrier function in young mice at 5-6 months of age. The neurovascular enhancements were associated with reduced mammalian target of rapamycin expression, elevated endothelial nitric oxide synthase signaling, and increased ketone bodies utilization. With age, CR decelerated the rate of decline in CBF. The preserved CBF in hippocampus and frontal cortex were highly correlated with preserved memory and learning, and reduced anxiety, of the aging mice treated with CR (18-20 months of age). Our results suggest that dietary intervention started in the early stage (e.g., young adults) may benefit cognitive and mental reserve in aging. Understanding nutritional effects on neurovascular functions may have profound implications in human brain aging and age-related neurodegenerative disorders.
anxiety; blood-brain barrier; caloric restriction; cerebral blood flow; cognition; magnetic resonance imaging (MRI); mammalian target of rapamcyin (mTOR)

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Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study.
Pearce SH, Razvi S, Yadegarfar ME, Martin-Ruiz C, Kingston A, Collerton J, Visser TJ, Kirkwood TB, Jagger C.
J Clin Endocrinol Metab. 2016 Nov;101(11):4385-4394.
PMID: 27552542
Perturbations in thyroid function are common in older individuals but their significance in the very old is not fully understood.
This study sought to determine whether thyroid hormone status and variation of thyroid hormones within the reference range correlated with mortality and disability in a cohort of 85-year-olds.
A cohort of 85-year-old individuals were assessed in their own homes (community or institutional care) for health status and thyroid function, and followed for mortality and disability for up to 9 years.
Six hundred and forty-three 85-year-olds registered with participating general practices in Newcastle and North Tyneside, United Kingdom.
All-cause mortality, cardiovascular mortality, and disability according to thyroid disease status and baseline thyroid hormone parameters (serum TSH, FT4, FT3, and rT3). Models were adjusted for age, sex, education, body mass index, smoking, and disease count.
After adjustment for age and sex, all-cause mortality was associated with baseline serum rT3 and FT3 (both P < .001), but not FT4 or TSH. After additional adjustment for potential confounders, only rT3 remained significantly associated with mortality (P = .001). Baseline serum TSH and rT3 predicted future disability trajectories in men and women, respectively.
Our study is reassuring that individuals age 85 y with both subclinical hypothyroidism and subclinical hyperthyroidism do not have a significantly worse survival over 9 years than their euthyroid peers. However, thyroid function tests did predict disability, with higher serum TSH levels predicting better outcomes. These data strengthen the argument for routine use of age-specific thyroid function reference ranges.

Community-acquired hyperkalemia in elderly patients: risk factors and clinical outcomes.
Turgutalp K, Bardak S, Helvacı I, İşgüzar G, Payas E, Demir S, Kıykım A.
Ren Fail. 2016 Oct;38(9):1405-1412.
PMID:  27494301
Although the risk and related factors of hyperkalemia developed in the hospital are known in elderly, risk and related factors of community-acquired hyperkalemia (CAH) in this population are not well known. This study was performed to investigate the risk of CAH in elderly and evaluate the related factors and clinical outcomes. Study design, setting and participants, intervention: Patients (aged ≥65 years) with hyperkalemia were screened. Group 1 (young-old); 65-74 years/old, Group 2 (middle-old); 75-84 years/old, Group 3 (oldest-old); ≥85 years/old, and Group 4 (control group); ≥65 years/old (normal serum potassium levels). The relation between CAH and hospital expenses (HE), the number of comorbid diseases (NCD), and all-cause of mortality rates (MR) were evaluated. We also investigated whether drugs, sex, and NCD are risk factors for the development of CAH.
There was a positive correlation between serum potassium levels and length of hospital stay, MR, HE, and NCD (p < 0.001). Risk factors for CAH were the use of non-steroidal-anti inflammatory drugs (NSAIDs) (Odds Ratio [OR]: 2.679), spironolactone (OR: 2.530), and angiotensin converting enzyme inhibitors (ACEI) (OR: 2.242), angiotensin receptor blockers (ARB) (OR: 2.679), ≥2 comorbid diseases (OR: 2.221), female gender (OR: 2.112), and renal injury (OR: 5.55). CAH risk was found to be increased 30.03 times when any of ACEI, ARB, NSAIDs, or spironolactone is given to a patient with a renal injury.
Use of NSAIDs, ACEI, ARB, spironolactone and increased NCD are all independent risk factors for CAH in the elderly, especially in patients with kidney diseases.
Community-acquired hyperkalemia; elderly; hospital expenses; mortality; risk factors

Particulate Air Pollution, Exceptional Aging, and Rates of Centenarians: A Nationwide Analysis of the United States, 1980-2010.
Baccarelli AA, Hales N, Burnett RT, Jerrett M, Mix C, Dockery DW, Pope CA.
Environ Health Perspect. 2016 Nov;124(11):1744-1750.
PMID: 27138440
Free PMC Article
Exceptional aging, defined as reaching age 85 years, shows geographic inequalities that may depend on local environmental conditions. Links between particulate pollution-a well-recognized environmental risk factor-and exceptional aging have not been investigated.
We conducted a nationwide analysis of ~28 million adults in 3,034 United States counties to determine whether local PM2.5 levels (particulate matter < 2.5 μm in aerodynamic diameter) affected the probability of becoming 85- to 94-year-olds or centenarians (100- to 104-year-olds) in 2010 for individuals who were 55-64 or 70-74 years old, respectively, in 1980.
We used population-weighted regression models including county-level PM2.5 from hybrid land-use regression and geostatistical interpolation, smoking, obesity, sociodemographic, and age-specific migration variables.
On average, 2,295 and 71.4 per 10,000 of the 55- to 64- and 70- to 74-year-olds in 1980, respectively, remained in the 85- to 94- and 100- to 104-year-old population in 2010. An interquartile range (4.19 μg/m3) increase in PM2.5 was associated with 93.7 fewer 85- to 94-year-olds (p < 0.001) and 3.5 fewer centenarians (p < 0.05). These associations were nearly linear, were stable to model specification, and were detectable below the annual PM2.5 national standard. Exceptional aging was strongly associated with smoking, with an interquartile range (4.77%) increase in population who smoked associated with 181.9 fewer 85- to 94-year-olds (p < 0.001) and 6.4 fewer centenarians (p < 0.001). Exceptional aging was also associated with obesity rates and median income.
Communities with the most exceptional aging have low ambient air pollution and low rates of smoking, poverty, and obesity. Improvements in these determinants may contribute to increasing exceptional aging.

Rapamycin reverses age-related increases in mitochondrial ROS production at complex I, oxidative stress, accumulation of mtDNA fragments inside nuclear DNA, and lipofuscin level, and increases autophagy, in the liver of middle-aged mice.
Martínez-Cisuelo V, Gómez J, García-Junceda I, Naudí A, Cabré R, Mota-Martorell N, López-Torres M, González-Sánchez M, Pamplona R, Barja G.
Exp Gerontol. 2016 Oct;83:130-8. doi: 10.1016/j.exger.2016.08.002.
PMID: 27498120
Rapamycin consistently increases longevity in mice although the mechanism of action of this drug is unknown. In the present investigation we studied the effect of rapamycin on mitochondrial oxidative stress at the same dose that is known to increase longevity in mice (14mgofrapamycin/kg of diet). Middle aged mice (16months old) showed significant age-related increases in mitochondrial ROS production at complex I, accumulation of mtDNA fragments inside nuclear DNA, mitochondrial protein lipoxidation, and lipofuscin accumulation compared to young animals (4months old) in the liver. After 7weeks of dietary treatment all those increases were totally or partially (lipofuscin) abolished by rapamycin, middle aged rapamycin-treated animals showing similar levels in those parameters to young animals. The decrease in mitochondrial ROS production was due to qualitative instead of quantitative changes in complex I. The decrease in mitochondrial protein lipoxidation was not due to decreases in the amount of highly oxidizable unsaturated fatty acids. Rapamycin also decreased the amount of RAPTOR (of mTOR complex) and increased the amounts of the PGC1-α and ATG13 proteins. The results are consistent with the possibility that rapamycin increases longevity in mice at least in part by lowering mitochondrial ROS production and increasing autophagy, decreasing the derived final forms of damage accumulated with age which are responsible for increased longevity. The decrease in lipofuscin accumulation induced by rapamycin adds to previous information suggesting that the increase in longevity induced by this drug can be due to a decrease in the rate of aging.
Aging; Free radicals; Lipofuscin; Mitochondria; Rapamycin; Tor


Effect of DHA supplementation in a very low-calorie ketogenic diet in the treatment of obesity: a randomized clinical trial.
de Luis D, Domingo JC, Izaola O, Casanueva FF, Bellido D, Sajoux I.
Endocrine. 2016 Oct;54(1):111-122.
PMID: 27117144
A VLCK diet supplemented with DHA, commercially available, was tested against an isocaloric VLCK diet without DHA. The main purpose of this study was to compare the effect of DHA supplementation in classic cardiovascular risk factors, adipokine levels, and inflammation-resolving eicosanoids. A total of obese patients were randomized into two groups: a group supplemented with DHA (n = 14) (PnK-DHA group) versus a group with an isocaloric diet free of supplementation (n = 15) (control group). The follow-up period was 6 months. The average weight loss after 6 months of treatment was 20.36 ± 5.02 kg in control group and 19.74 ± 5.10 kg in PnK-DHA group, without statistical differences between both groups. The VLCK diets induced a significant change in some of the biological parameters, such as insulin, HOMA-IR, triglycerides, LDL cholesterol, C-reactive protein, resistin, TNF alpha, and leptin. Following DHA supplementation, the DHA-derived oxylipins were significantly increased in the intervention group. The ratio of proresolution/proinflammatory lipid markers was increased in plasma of the intervention group over the entire study. Similarly, the mean ratios of AA/EPA and AA/DHA in erythrocyte membranes were dramatically reduced in the PnK-DHA group and the anti-inflammatory fatty acid index (AIFAI) was consistently increased after the DHA treatment (p < 0.05). The present study demonstrated that a very low-calorie ketogenic diet supplemented with DHA was significantly superior in the anti-inflammatory effect, without statistical differences in weight loss and metabolic improvement.
DHA; Ketosis; PnK method; Pronokal method; Protein diet; Weight loss

Incident hypertension and its prediction model in a prospective northern urban Han Chinese cohort study.
Chen Y, Wang C, Liu Y, Yuan Z, Zhang W, Li X, Yang Y, Sun X, Xue F, Zhang C.
J Hum Hypertens. 2016 Dec;30(12):794-800. doi: 10.1038/jhh.2016.23.
PMID: 27251078
Trends in incidence and prevalence of hypertension are grave in China and identifying high-risk, non-hypertension individuals for intervention may delay hypertension onset. We aimed to investigate the incidence of hypertension in northern urban Han Chinese population and construct multivariable hypertension prediction models through the prospective cohort, which included 7537 men and 4960 women free of hypertension at baseline between 2005 and 2010. During 38 958 person-years of follow-up, 2785 participants (men, 72.57%; women, 27.43%) developed hypertension. The incidence density of hypertension was 71.48 per 1000 person-year. In multivariable backward cox analyses, age, body mass index, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose and current drinking were retained for both men and women, while gamma-glutamyl transferase only for men, total cholesterol, neutrophil granulocyte and current smoking only for women. The area under receiver operating characteristic curve (AUC) was 0.761 (95% confidence interval (CI), 0.752–0.771) for men and 0.753 (95% CI, 0.741–0.765) for women, even after 10-fold cross-validation, the AUC was 0.760 (95% CI, 0.751–0.770) for men and 0.749 (95% CI, 0.737–0.761) for women. Through risk stratification, the absolute risk of incident hypertension in 5 years at moderate, high and very high risk level was 2.13, 3.84 and 6.14 times that of those who were at low risk in men, and 1.30, 2.56 and 6.01 times that of those who were at low risk in women. Our findings identified predictors of incident hypertension and indicated that the sex-specific multivariable prediction models would be simply used to estimate the risk of incident hypertension.

The impact of inflammation on the obesity paradox in coronary heart disease.
De Schutter A, Kachur S, Lavie CJ, Boddepalli RS, Patel DA, Milani RV.
Int J Obes (Lond). 2016 Nov;40(11):1730-1735. doi: 10.1038/ijo.2016.125.
PMID: 27453423
Despite the well-known adverse effects of obesity on almost all aspects of coronary heart disease, many studies of coronary heart disease cohorts have demonstrated an inverse relationship between obesity, as defined by body mass index (BMI), and subsequent prognosis: the 'obesity paradox'. The etiology of this and the potential role of inflammation in this process remain unknown.
We studied 519 patients with coronary heart disease before and after cardiac rehabilitation, dividing them into groups based on C-reactive protein ((CRP)⩾3 mg l-1 and CRP<3 mg l-1 after cardiac rehabilitation). BMI was calculated and body fat was measured using the skin-fold method. Lean mass index (LMI) was calculated as (1-%body fat) × BMI. The population was divided according to age- and gender-adjusted categories based on LMI and body fat and analyzed by total mortality over >3-year follow-up by National Death Index in both CRP groups.
During >3-year follow-up, all-cause mortality was higher in the high inflammation and in the low BMI group. In proportional hazard analysis, even after adjusting for ejection fraction and peak O2 consumption, higher BMI was associated with lower mortality in the entire population (hazard ratio (HR) 0.38; confidence interval 0.15-0.97) and a trend to lower mortality in both subgroups (HR 0.45 in low CRP, P=0.24 vs HR 0.32, P=0.06 in high CRP). High body fat, however, was associated with significantly lower mortality in the high CRP group (HR 0.22; P=0.03) but not in the low CRP group (HR 0.73; P=0.64). Conversely, high LMI was associated with markedly lower mortality in the low CRP group (HR 0.04; P=0.04).
The obesity paradox has multiple underlying etiologies. Body composition has a different role in different populations with an obesity paradox by BMI. Especially in the subpopulation with persistently high CRP levels, body fat seems protective.

Does a bit of alcohol turn off inflammation and improve health?
Bektas A, Sen R, Ferrucci L.
Age Ageing. 2016 Aug 29. [Epub ahead of print] No abstract available.
PMID: 27555047
• Unknown why inflammation increases with ageing
• Moderate alcohol use is associated with level of inflammation
lower than not drinking or heavy drinking
• It is not clear whether those who do not drink are ‘sick
quitters’ or whether moderate drinking is anti-inflammatory
• Important to show that causal pathways exist between
drinking, level of biomarkers of inflammation and protective
health effects
• More research needed
C-reactive protein level partially mediates the relationship between moderate alcohol use and frailty: the Health and Retirement Study.
Shah M, Paulson D.
Age Ageing. 2016 Jul 4. [Epub ahead of print]
PMID: 27496931
frailty is an indicator of late-life decline marked by higher rates of disability and healthcare utilisation. Research has linked health benefits with moderate alcohol use, including frailty risk reduction. Past work suggests inflammation, measured by C-reactive protein (CRP), as one candidate mechanism for this effect.
this study aims to elucidate a possible mechanism - CRP modulation - by which moderate alcohol consumption may protect against frailty.
a cross-sectional study using data from the 2008 wave of the Health and Retirement Study (HRS) conducted by the University of Michigan. The HRS is a cohort study on health, retirement and aging on adults aged 50 and older living in the USA. A final sample of 3,229 stroke-free participants, over the age of 65 years and with complete data, was identified from the 2008 wave. Alcohol use was measured via self-report. Frailty was measured using the Paulson-Lichtenberg Frailty Index. CRP was collected through the HRS protocol.
results from structural equation modelling support the hypothesised model that moderate alcohol use is associated with less frailty and lower CRP levels. Furthermore, the indirect relationship from moderate alcohol use to frailty through CRP was statistically significant.
overall findings suggest that inflammation measured by CRP is one mechanism by which moderate alcohol use may confer protective effects for frailty. These findings inform future research relating alcohol use and frailty, and suggest inflammation as a possible mechanism in the relationship between moderate alcohol use and other beneficial health outcomes.
inflammation; older adults; protective effect; risk reduction

Prevalence and risk factors for falls in older men and women: The English Longitudinal Study of Ageing.
Gale CR, Cooper C, Aihie Sayer A.
Age Ageing. 2016 Jul 19. [Epub ahead of print]
PMID: 27496938
Free Article
falls are a major cause of disability and death in older people. Women are more likely to fall than men, but little is known about whether risk factors for falls differ between the sexes. We used data from the English Longitudinal Study of Ageing to investigate the prevalence of falls by sex and to examine cross-sectionally sex-specific associations between a range of potential risk factors and likelihood of falling.
participants were 4,301 men and women aged 60 and over who had taken part in the 2012-13 survey of the English Longitudinal Study of Ageing. They provided information about sociodemographic, lifestyle and behavioural and medical factors, had their physical and cognitive function assessed and responded to a question about whether they had fallen down in the last two years.
in multivariable logistic regression models, severe pain and diagnosis of at least one chronic disease were independently associated with falls in both sexes. Sex-specific risk factors were incontinence (odds ratio (OR), 1.48; 95% CI, 1.19, 1.85) and frailty (OR 1.69, 95% CI 1.06, 2.69) in women, and older age (OR 1.02, 95% CI 1.04, 1.07), high levels of depressive symptoms (OR 1.33, 95% CI 1.05, 1.68), and being unable to perform a standing balance test (OR 3.32, 95% CI 2.09, 5.29) in men.
although we found some homogeneity between the sexes in the risk factors that were associated with falls, the existence of several sex-specific risk factors suggests that gender should be taken into account in designing fall-prevention strategies.
KEYWORDS: falls; older people; prevalence; risk factors
Prevalence of hyponatraemia in patients over the age of 65 who have an in-hospital fall.
Lobo-Rodríguez C, García-Pozo AM, Gadea-Cedenilla C, Moro-Tejedor MN, Pedraz Marcos A, Tejedor-Jorge A; Grupo Corporativo PRECAHI..
Nefrologia. 2016 May-Jun;36(3):292-8. doi: 10.1016/j.nefro.2016.03.014. English, Spanish.
PMID: 27161308
Free Article
Hyponatraemia is the most common electrolyte disorder. Some studies have found that it increases morbidity and mortality. There are new lines of research that are investigating the link between hyponatraemia and patient falls.
To determine if hyponatraemia is associated with falls in elderly hospitalised patients.
Design observational, analytical, case-control study.
Patients older than 65 years who had fallen during their hospitalisation at Gregorio Marañón Hospital (Madrid) were considered cases. Patients who did not fall were considered to be controls, paired according to the following variables: hospital ward, age, length of hospital stay, gender and Downton fall risk index. The sample size was 206 subjects.
Socio-demographic factors, variables included in the falls record sheet, Downton fall risk index and sodium levels were studied (hyponatraemia was considered Na(+)< 135mmol/l).
A descriptive analysis was performed to determine the sample homogeneity. The OR was calculated, and an analytical analysis using Chi-square test and a multivariate logistic regression analysis were also performed.
Of 103 cases recruited, 61 were men (50.4%) and 42 were women (49.4%). Hyponatraemia was detected in 29 cases with an association with falls of P: 0.002. The adjusted OR was 3.708 (1.6-8.3), 95% CI. Risk factors for falls were identified as hyponatraemia and limb sensory deficits.
Given that hyponatraemia could be considered a risk factor for falls, the inclusion of the determination of sodium level would be important for fall prevention strategies in the elderly.
Accidental Falls; Accidentes por caídas; Anciano; Elderly; Factores de riesgo; Hiponatremia; Hyponatraemia; Risk factors

Melatonin, hypnotics and their association with fracture: a matched cohort study.
Frisher M, Gibbons N, Bashford J, Chapman S, Weich S.
Age Ageing. 2016 Jul 26. [Epub ahead of print]
PMID: 27496941
although melatonin prescribing in England has been increasing in recent years, there have been no large scale studies on the safety of melatonin compared to other medical treatments for insomnia. The primary aim of this study was to examine the association between exposure to melatonin, hypnotic benzodiazepines (temazepam, nitrazepam) or Z-drugs (zolpidem, zopiclone) and fracture risk.
retrospective cohort study.
309 general practices contributing to The Health Improvement Network (THIN) between 2008 and 2013.
1,377 patients aged 45 years and older prescribed melatonin; 880 patients prescribed hypnotic benzodiazepines; 1,148 patients prescribed Z-drugs and 2,752 unexposed controls matched by age, gender and practice.
fracture following prescription of study drugs ascertained from practice records.
the unadjusted hazard ratios for fracture during the follow-up period were 1.90 (95% CI 1.41-2.57) for melatonin, 1.70 (95% CI 1.18-2.46) for hypnotic benzodiazepines and 2.03 (95% CI 1.45-2.84) for Z-drugs. After adjustment for 26 covariates, the hazard ratios were 1.44 (95% CI 1.01-2.04) for melatonin, 1.26 (95% CI 0.82-1.92) for hypnotic benzodiazepines and 1.52 (95% CI 1.04-2.23) for Z-drugs. Only patients with three or more melatonin prescriptions had elevated risk. The mean time to fracture was 1.04 years and there was no significant difference in mean time to fracture between the cohorts.
in this large cohort of patients attending UK primary care, prescriptions for melatonin and Z-drugs were associated with a significantly increased risk of fracture. With the use of melatonin increasing steadily overtime, this study adds to the literature on the safety profile of this drug.
cohort study; fracture; hypnotics; melatonin; older people

Blood pressure and all-cause mortality: a prospective study of nursing home residents.
Rådholm K, Festin K, Falk M, Midlöv P, Mölstad S, Östgren CJ.
Age Ageing. 2016 Jul 18. [Epub ahead of print]
PMID: 27496923
to explore the natural course of blood pressure development and its relation to mortality in a nursing home cohort.
a cohort of 406 nursing home residents in south east Sweden was followed prospectively for 30 months. Participants were divided into four groups based on systolic blood pressure (SBP) at baseline. Data were analysed using a Cox regression model with all-cause mortality as the outcome measurement; paired Student t-tests were used to evaluate blood pressure development over time.
during follow-up, 174 (43%) people died. Participants with SBP < 120 mmHg had a hazard ratio for mortality of 1.56 (95% confidence interval, 1.08-2.27) compared with those with SBP 120-139 mmHg, adjusted for age and sex. Risk of malnutrition or present malnutrition was most common in participants with SBP < 120 mmHg; risk of malnutrition or present malnutrition estimated using the Mini Nutritional Assessment was found in 78 (71%). The levels of SBP decreased over time independent of changes in anti-hypertensive medication.
in this cohort of nursing home residents, low SBP was associated with increased all-cause mortality. SBP decreased over time; this was not associated with altered anti-hypertensive treatment. The clinical implication from this study is that there is a need for systematic drug reviews in elderly persons in nursing homes, paying special attention to those with low SBP.
all-cause mortality; hypertension; hypotension; nursing home; older people; prospective study

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Do ω-3 PUFAs affect insulin resistance in a sex-specific manner? A systematic review and meta-analysis of randomized controlled trials.
Abbott KA, Burrows TL, Thota RN, Acharya S, Garg ML.
Am J Clin Nutr. 2016 Nov;104(5):1470-1484.
PMID: 27680989
Evidence has suggested that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) improve obesity-induced insulin resistance (IR); however, results from human intervention trials have been equivocal. Recently it has been reported that n-3 PUFA status is inversely associated with type 2 diabetes in women but not in men, suggesting a sex-dependent effect.
We aimed to determine whether n-3 PUFA interventions affect IR in a sex-dependent manner.
Five databases were searched (Medline, EMBASE, CINAHL, Scopus, and Pre-Medline) for randomized controlled trials. Searches were limited to the English language and to studies with adults aged >18 y. When possible, studies were pooled for a meta-analysis. The principle summary measure was the standardized mean difference (SMD) between groups.
Thirty-one eligible trials were identified with a total of 1848 participants [men: 45.1%; weighted mean ± SD age: 52.5 ± 8.2 y; weighted body mass index (in kg/m2): 28.8 ± 3.0]. Seven studies were conducted in women, 4 studies were conducted in men, and the remaining studies pooled men and women together. Twenty-six trials were pooled for the meta-analysis (men: n = 2; women: n = 6). With all studies (n = 26) pooled, there was no effect of n-3 PUFA on IR at the group level (SMD: 0.089; 95% CI: -0.105, 0.283; P = 0.367). In trials of ≥6 wk, a significant improvement in IR was seen in women (SMD: -0.266; 95% CI: -0.524, -0.007; P = 0.045) but not in men (SMD: 0.619; 95% CI: -0.583, 1.820; P = 0.313).
With this analysis, we provide preliminary evidence of a sex-dependent response of IR to an n-3 PUFA intervention. Additional studies are needed to confirm sex-dependent associations and to elucidate the potential mechanisms that are involved. This trial was registered at www.crd.york.ac.uk/PROSPERO/ as CRD42015017940.
DHA; EPA; adults; diabetes; insulin resistance; insulin sensitivity; omega-3 PUFAs

Leukocyte telomere length pattern in a Chuvash population that experienced mass famine in 1922-1923: a retrospective cohort study.
Kobyliansky E, Torchinsky D, Kalichman L, Karasik D.
Am J Clin Nutr. 2016 Nov;104(5):1410-1415.
PMID: 27733399
To our knowledge, there are no experimental studies that have addressed the effects of starvation on the maintenance of telomere length. Two epidemiologic studies that have addressed this topic gave controversial results.
We characterized leukocyte telomere length (LTL) in a Chuvash population that was comprised of survivors of the mass famine of 1922-1923 and in these survivors' descendants.
The tested cohort consisted of native Chuvash men (n = 687) and women (n = 647) who were born between 1909 and 1980 and who resided in small villages in the Chuvash Republic of the Russian Federation. Data were gathered during 3 expeditions undertaken in 1994, 1999, and 2002. With the use of this method of gathering the study cohort, we were able to treat age and birth year as independent variables (i.e., after adjustment for age, we were able to analyze how LTL correlates with a birth year in the interval between 1909 and 1980). The DNA of peripheral blood leukocytes was used to measure the telomere length with a quantitative polymerase chain reaction technique.
The main observations were as follows: 1) there were shorter leukocyte telomeres in men born after 1923 (i.e., after the mass famine) than in men born before 1922 (i.e., before the mass famine); 2) there was a stable inheritance of shorter telomeres by men of ensuing generations; and 3) there was an absence of a correlation between LTL and birth year in women.
Our study does not provide direct evidence for leukocyte telomere shortening in famine survivors. However, the comparative analysis of LTL in the survivors and their descendants suggests that such an effect did take place. The study also implies that mass famine may be associated with telomere shortening in male descendants of famine survivors. This observation is in agreement with the "thrifty telomere hypothesis" predicting that longer telomeres are disadvantageous in nutritionally marginal environments.
cohort study; famine; heritability; starvation; telomeres

Dietary protein intake and risk of type 2 diabetes: results from the Melbourne Collaborative Cohort Study and a meta-analysis of prospective studies.
Shang X, Scott D, Hodge AM, English DR, Giles GG, Ebeling PR, Sanders KM.
Am J Clin Nutr. 2016 Nov;104(5):1352-1365.
PMID: 27629053
Reported associations between protein intake from different sources and type 2 diabetes (T2D) have been inconsistent.
We prospectively examined the relations of total, animal, and plant protein intakes with incident T2D.
We followed 21,523 participants (women: 61.7%) between 1990 and 2007 from the Melbourne Collaborative Cohort Study who were free of diabetes, cardiovascular disease, cancer, and kidney stones at baseline. We also conducted a meta-analysis that included the results from our cohort and from 10 previous prospective studies.
A total of 929 new cases (4.3%) of T2D were documented during a mean of 11.7 y of follow-up. Multivariate-adjusted ORs for incident T2D in the highest compared with lowest quintiles of total and animal protein intakes as percentages of energy were 1.23 (95% CI: 0.96, 1.56; P-trend = 0.029) and 1.29 (95% CI: 0.99, 1.67; P-trend = 0.014), respectively. These associations appeared to be greater in men and in participants with normal baseline plasma glucose, body mass index, or blood pressure. Plant protein intake was inversely associated with incident T2D in women only (OR; 0.60; 95% CI: 0.37, 0.99). In the meta-analysis of 11 prospective cohort studies with 505,624 participants and 37,918 T2D cases (follow-up range: 5-24 y), pooled RRs for the comparison of the highest with lowest categories of total, animal, and plant protein intakes were 1.09 (95% CI: 1.06, 1.13), 1.19 (95% CI: 1.11, 1.28), and 0.95 (95% CI: 0.89, 1.02), respectively. Associations between animal protein intake and T2D were similar across sex, geographic region, length of follow-up, study quality, and method of expressing protein intake. An inverse association between plant protein intake and T2D was observed in women (RR: 0.93; 95% CI: 0.85, 1.00) and in US populations (RR: 0.91; 95% CI: 0.84, 0.97).
Higher intakes of total and animal protein were both associated with increased risks of T2D, whereas higher plant protein intake tended to be associated with lower risk of T2D.
animal protein; dietary protein; meta-analysis; plant protein; prospective study; type 2 diabetes

Potato consumption and risk of cardiovascular disease: 2 prospective cohort studies.
Larsson SC, Wolk A.
Am J Clin Nutr. 2016 Nov;104(5):1245-1252.
PMID: 27680993
Whether consumption of potatoes, which are rich in potassium and have a high glycemic index and glycemic load, is associated with the risk of cardiovascular disease (CVD) is unknown.
The aim was to examine the association between potato consumption and risk of total and specific CVD events as well as mortality from CVD in 2 prospective cohorts of Swedish adults, a population with a high consumption of potatoes.
Information on potato consumption was available from 69,313 men and women, free of CVD and diabetes, in the Cohort of Swedish Men and the Swedish Mammography Cohort. Nonfatal and fatal cases of CVD diagnosed over 13 y of follow-up were identified by linkage with the Swedish National Patient and Cause of Death Registers. Analyses were conducted by using a Cox proportional hazards regression model, controlled for potential confounders.
We ascertained 10,147 major CVD events [myocardial infarction (MI), heart failure (HF), and stroke] and 4003 deaths due to CVD. Total potato consumption was not associated with the risk of major CVD events, specific CVD endpoints, or CVD mortality in either men or women. Multivariable HRs (95% CIs) per an increment of 3 servings/wk of total potato consumption (boiled potatoes, fried potatoes, and French fries) were 1.00 (0.97, 1.02) for major CVD events, 1.01 (0.97, 1.04) for MI, 0.97 (0.93, 1.02) for HF, 1.01 (0.97, 1.05) for stroke, and 0.99 (0.95, 1.03) for CVD mortality. There were no significant trends between the consumption of boiled potatoes, fried potatoes, or French fries and risk of any CVD outcome.
Potato consumption was not associated with the risk of CVD in this population. The Swedish Mammography Cohort and the Cohort of Swedish Men are registered at clinicaltrials.gov as NCT01127698 and NCT01127711, respectively.
cardiovascular disease; heart failure; myocardial infarction; potatoes; prospective studies; stroke

Dairy fat and risk of cardiovascular disease in 3 cohorts of US adults.
Chen M, Li Y, Sun Q, Pan A, Manson JE, Rexrode KM, Willett WC, Rimm EB, Hu FB.
Am J Clin Nutr. 2016 Nov;104(5):1209-1217.
PMID: 27557656
Few prospective studies have examined dairy fat in relation to cardiovascular disease (CVD).
We aimed to evaluate the association between dairy fat and incident CVD in US adults.
We followed 43,652 men in the Health Professionals Follow-Up Study (1986-2010), 87,907 women in the Nurses' Health Study (1980-2012), and 90,675 women in the Nurses' Health Study II (1991-2011). Dairy fat and other fat intakes were assessed every 4 y with the use of validated food-frequency questionnaires.
During 5,158,337 person-years of follow-up, we documented 14,815 incident CVD cases including 8974 coronary heart disease cases (nonfatal myocardial infarction or fatal coronary disease) and 5841 stroke cases. In multivariate analyses, compared with an equivalent amount of energy from carbohydrates (excluding fruit and vegetables), dairy fat intake was not significantly related to risk of total CVD (for a 5% increase in energy from dairy fat, the RR was 1.02; 95% CI: 0.98, 1.05), coronary heart disease (RR: 1.03; 95% CI: 0.98, 1.09), or stroke (RR: 0.99; 95% CI: 0.93, 1.05) (P > 0.05 for all). In models in which we estimated the effects of exchanging different fat sources, the replacement of 5% of energy intake from dairy fat with equivalent energy intake from polyunsaturated fatty acid (PUFA) or vegetable fat was associated with 24% (RR: 0.76; 95% CI: 0.71, 0.81) and 10% (RR: 0.90; 95% CI: 0.87, 0.93) lower risk of CVD, respectively, whereas the 5% energy intake substitution of other animal fat with dairy fat was associated with 6% increased CVD risk (RR: 1.06; 95% CI: 1.02, 1.09).
The replacement of animal fats, including dairy fat, with vegetable sources of fats and PUFAs may reduce risk of CVD. Whether the food matrix may modify the effect of dairy fat on health outcomes warrants further investigation.
animal fat; cardiovascular disease; dairy fat; prospective; vegetable fat
Dairy fat: does it increase or reduce the risk of cardiovascular disease?
Givens DI, Soedamah-Muthu SS.
Am J Clin Nutr. 2016 Nov;104(5):1191-1192. No abstract available.
PMID: 27733390

Effects of calcium supplementation on body weight: a meta-analysis.
Li P, Fan C, Lu Y, Qi K.
Am J Clin Nutr. 2016 Nov;104(5):1263-1273.
PMID: 27733391
Whether calcium supplementation can reduce body weight and prevent obesity remains unclear because of inconsistent reports.
We performed a meta-analysis to investigate the correlations between calcium supplementation and changes in body weight on the basis of age, sex, body mass index (BMI) of the subjects, and length of calcium intervention.
PubMed, EMBASE, Web of Knowledge, and China National Knowledge Infrastructure databases were systematically searched to select relevant studies that were published from January 1994 to March 2016. Both randomized controlled trials and longitudinal studies of calcium supplementation were included, and random- or fixed-effects models in a software program were used for the data analysis.
Thirty-three studies involving a total of 4733 participants were included in this meta-analysis. No significant differences in weight changes were shown between calcium intervention and control groups (mean: -0.01 kg; 95% CI -0.02, 0.00 kg; P = 0.12). However, negative correlations between calcium supplementation and weight changes were shown in children and adolescents (mean: -0.26 kg; 95% CI: -0.41, -0.11 kg; P < 0.001) and in adult men and either premenopausal or old (>60 y of age) women (mean: -0.91 kg; 95% CI: -1.38, -0.44 kg; P < 0.001) but not in postmenopausal women (mean: -0.14 kg; 95% CI: -0.54, 0.26 kg; P = 0.50). When BMI was considered, a negative correlation between calcium supplementation and weight changes was observed in subjects with normal BMI (mean: -0.53 kg; 95% CI: -0.89, -0.16 kg; P = 0.005) but not in overweight or obese subjects (mean: -0.35 kg; 95% CI: -0.81, 0.11 kg; P = 0.14). Compared with the control groups, no differences in weight changes were shown in the calcium-intervention groups when the lengths of calcium interventions were <6 mo (mean: -0.09 kg; 95% CI: -0.45, 0.26 kg; P = 0.60) or ≥6 mo (mean: -0.01 kg; 95% CI: -0.02, 0.01 kg; P = 0.46).
Increasing calcium intake through calcium supplements can reduce body weight in subjects who have a normal BMI or in children and adolescents, adult men, or premenopausal women.
body mass index; body weight; calcium; meta-analysis; obesity

Association Between Life's Simple 7 and Noncardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis.
Ogunmoroti O, Allen NB, Cushman M, Michos ED, Rundek T, Rana JS, Blankstein R, Blumenthal RS, Blaha MJ, Veledar E, Nasir K.
J Am Heart Assoc. 2016 Oct 20;5(10). pii: e003954.
PMID: 27792654
Free Article
The American Heart Association introduced the Life's Simple 7 (LS7) metrics to assess and promote cardiovascular health. We examined the association between the LS7 metrics and noncardiovascular disease.
We studied 6506 men and women aged between 45 and 84 years, enrolled in the Multi-Ethnic Study of Atherosclerosis. Median follow-up time was 10.2 years. Each component of the LS7 metrics (smoking, body mass index, physical activity, diet, total cholesterol, blood pressure, and blood glucose) was assigned points, 0 indicates "poor" category; 1, "intermediate," and 2, "ideal." The LS7 score, ranged from 0 to 14, was created from the points and categorized as optimal (11-14), average (9-10), and inadequate (0-8). Hazard ratios and event rates per 1000 person-years were calculated for outcomes based on self-reported hospitalizations with the International Classification of Diseases, 9th Revision, diagnoses of cancer, chronic kidney disease, pneumonia, deep venous thromboembolism/pulmonary embolism, chronic obstructive pulmonary disease, dementia, and hip fracture. Analyses were adjusted for age, sex, race/ethnicity, income, and education. Overall, noncardiovascular disease event rates were lower with increasing LS7 scores. With the inadequate LS7 score as reference, an optimal score was associated with a decreased risk for noncardiovascular disease events. The hazard ratio for cancer was, 0.80 (0.64-0.98); chronic kidney disease, 0.38 (0.27-0.54); pneumonia, 0.57 (0.40-0.80); deep venous thromboembolism/pulmonary embolism, 0.52 (0.33-0.82), and chronic obstructive pulmonary disease, 0.51 (0.31-0.83).
The American Heart Association's LS7 score identified individuals who were vulnerable to multiple chronic nonvascular conditions. These results suggest that improving cardiovascular health will also reduce the burden of cancer and other chronic diseases.
Life's Simple 7; epidemiology; prevention; risk factor
"Ideal CVH is defined as the presence of 4
ideal health behaviors (nonsmoking, body mass index [bMI]
<25 kg/m2, physical activity at goal levels, and diet consistent
with recommended guidelines) and 3 ideal health factors
(untreated total cholesterol <200 mg/dL, blood pressure (BP)
<120/80 mm Hg, and fasting blood glucose <100 mg/dL)."

[The below paper is not pdf-availed.]
Associations of Accelerometry-Assessed and Self-Reported Physical Activity and Sedentary Behavior With All-Cause and Cardiovascular Mortality Among US Adults.
Evenson KR, Wen F, Herring AH.
Am J Epidemiol. 2016 Nov 1;184(9):621-632.
PMID: 27760774
The US physical activity (PA) recommendations were based primarily on studies in which self-reported data were used. Studies that include accelerometer-assessed PA and sedentary behavior can contribute to these recommendations. In the present study, we explored the associations of PA and sedentary behavior with all-cause and cardiovascular disease (CVD) mortality in a nationally representative sample. Among the 2003-2006 National Health and Nutrition Examination Survey cohort, 3,809 adults 40 years of age or older wore an accelerometer for 1 week and self-reported their PA levels. Mortality data were verified through 2011, with an average of 6.7 years of follow-up. We used Cox proportional hazards models to obtain adjusted hazard ratios and 95% confidence intervals. After excluding the first 2 years, there were 337 deaths (32% or 107 of which were attributable to CVD). Having higher accelerometer-assessed average counts per minute was associated with lower all-cause mortality risk: When compared with the first quartile, the adjusted hazard ratio was 0.37 (95% confidence interval: 0.23, 0.59) for the fourth quartile, 0.39 (95% confidence interval: 0.27, 0.57) for the third quartile, and 0.60 (95% confidence interval: 0.45, 0.80) second quartile. Results were similar for CVD mortality. Lower all-cause and CVD mortality risks were also generally observed for persons with higher accelerometer-assessed moderate and moderate-to-vigorous PA levels and for self-reported moderate-to-vigorous leisure, household and total activities, as well as for meeting PA recommendations. Accelerometer-assessed sedentary behavior was generally not associated with all-cause or CVD mortality in fully adjusted models. These findings support the national PA recommendations to reduce mortality.
accelerometry; aerobic exercise; cohort study; leisure activity; light activity; strength training; transportation activity; walking
nvited Commentary: Little Steps Lead to Huge Steps-It's Time to Make Physical Inactivity Our Number 1 Public Health Enemy.
Church TS.
Am J Epidemiol. 2016 Nov 1;184(9):633-635.
PMID:  27760775
The analysis plan and article in this issue of the Journal by Evenson et al. (Am J Epidemiol 2016;184(9):621-632) is well-conceived, thoughtfully conducted, and tightly written. The authors utilized the National Health and Nutrition Examination Survey data set to examine the association between accelerometer-measured physical activity level and mortality and found that meeting the 2013 federal Physical Activity Guidelines resulted in a 35% reduction in risk of mortality. The timing of these findings could not be better, given the ubiquitous nature of personal accelerometer devices. The masses are already equipped to routinely quantify their activity, and now we have the opportunity and responsibility to provide evidenced-based, tailored physical activity goals. We have evidenced-based physical activity guidelines, mass distribution of devices to track activity, and now scientific support indicating that meeting the physical activity goal, as assessed by these devices, has substantial health benefits. All of the pieces are in place to make physical inactivity a national priority, and we now have the opportunity to positively affect the health of millions of Americans.
accelerometers; activity; exercise; mortality

Flavanone Intake Is Inversely Associated with Risk of Incident Ischemic Stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study.
Goetz ME, Judd SE, Hartman TJ, McClellan W, Anderson A, Vaccarino V.
J Nutr. 2016 Nov;146(11):2233-2243.
PMID: 27655760
Flavonoids may have beneficial cerebrovascular effects, but evidence from racially and geographically representative cohorts in comprehensive flavonoid databases is lacking. Given racial and geographic disparities in stroke incidence, representative cohort studies are needed.
We evaluated the association between flavonoid intake and incident ischemic stroke in a biracial, national cohort using updated flavonoid composition tables and assessed differences in flavonoid intake by sex, race, and region of residence.
We evaluated 20,024 participants in the REGARDS (REasons for Geographic and Racial Differences in Stroke) study, a biracial prospective study. Participants with stroke history or missing dietary data were excluded. Flavonoid intake was estimated by using a Block98 food frequency questionnaire and the USDA's Provisional Flavonoid Addendum and Proanthocyanidin Database. Associations between quintiles of flavonoid intake and incident ischemic stroke were evaluated by using Cox proportional hazards models, adjusting for confounders.
Over 6.5 y, 524 acute ischemic strokes occurred. Flavanone intake was lower in the Southeastern United States but higher in blacks than in whites. After multivariable adjustment, flavanone intake was inversely associated with incident ischemic stroke (HR: 0.72; 95% CI: 0.55, 0.95; P-trend = 0.03). Consumption of citrus fruits and juices was inversely associated with incident ischemic stroke (HR: 0.69; 95% CI: 0.53, 0.91; P-trend = 0.02). Total flavonoids and other flavonoid subclasses were not associated with incident ischemic stroke. There was no statistical interaction with sex, race, or region for any flavonoid measure.
Greater consumption of flavanones, but not total or other flavonoid subclasses, was inversely associated with incident ischemic stroke. Associations did not differ by sex, race, or region for the association; however, regional differences in flavanone intake may contribute to regional disparities in ischemic stroke incidence. Higher flavanone intake in blacks suggests that flavanone intake is not implicated in racial disparities in ischemic stroke incidence.
epidemiology; flavonoid; ischemic stroke; plant-based diet; polyphenol

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Long-term outcome in anorexia nervosa in the community.
Mustelin L, Raevuori A, Bulik CM, Rissanen A, Hoek HW, Kaprio J, Keski-Rahkonen A.
Int J Eat Disord. 2015 Nov;48(7):851-9. doi: 10.1002/eat.22415.
PMID: 26059099
Few studies have assessed outcomes of anorexia nervosa (AN) outside clinical settings. We aimed to assess mortality, recovery, and socio-demographic outcomes of AN in a community sample.
Women in the nationwide FinnTwin16 cohort (born 1975-1979) were followed for 10 years after baseline diagnostic assessment (mean age at follow-up 34 years, N = 2188). We compared women with lifetime DSM-IV AN (N = 40) with unaffected women from the same cohort.
None of the women with AN had died and 88% were weight-recovered (BMI ≥ 18.5 kg/m(2) ), but their mean BMI (22.0 kg/m(2) ) was lower than among unaffected women (24.0 kg/m(2) , p = 0.008). University degrees (38 vs. 29%, p = 0.26), sickness absence during the past year (median 5 vs. 3 days, p = 0.21), or unemployment or disability pension (5 vs. 4%, p = 0.62) did not significantly differ between AN probands and their unaffected peers. More women with AN were still studying (15 vs. 4%, p = 0.003), and half of them had children, as compared to 66% of unaffected women (p = 0.05).
The long-term prognosis of AN in the community appears promising. Weight-restoration is common and socio-demographic outcomes are generally favorable. However, women with a history of AN may be less likely to have children.
anorexia nervosa; epidemiology; outcome; prognosis; twin study

Predictive Values of the New Sarcopenia Index by the Foundation for the National Institutes of Health Sarcopenia Project for Mortality among Older Korean Adults.
Moon JH, Kim KM, Kim JH, Moon JH, Choi SH, Lim S, Lim JY, Kim KW, Park KS, Jang HC.
PLoS One. 2016 Nov 10;11(11):e0166344. doi: 10.1371/journal.pone.0166344.
PMID: 27832145
We evaluated the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project's recommended criteria for sarcopenia's association with mortality among older Korean adults.
We conducted a community-based prospective cohort study which included 560 (285 men and 275 women) older Korean adults aged ≥65 years. Muscle mass (appendicular skeletal muscle mass-to-body mass index ratio (ASM/BMI)), handgrip strength, and walking velocity were evaluated in association with all-cause mortality during 6-year follow-up. Both the lowest quintile for each parameter (ethnic-specific cutoff) and FNIH-recommended values were used as cutoffs.
Forty men (14.0%) and 21 women (7.6%) died during 6-year follow-up. The deceased subjects were older and had lower ASM, handgrip strength, and walking velocity. Sarcopenia defined by both low lean mass and weakness had a 4.13 (95% CI, 1.69-10.11) times higher risk of death, and sarcopenia defined by a combination of low lean mass, weakness, and slowness had a 9.56 (3.16-28.90) times higher risk of death after adjusting for covariates in men. However, these significant associations were not observed in women. In terms of cutoffs of each parameter, using the lowest quintile showed better predictive values in mortality than using the FNIH-recommended values. Moreover, new muscle mass index, ASM/BMI, provided better prognostic values than ASM/height2 in all associations.
New sarcopenia definition by FNIH was better able to predict 6-year mortality among Korean men. Moreover, ethnic-specific cutoffs, the lowest quintile for each parameter, predicted the higher risk of mortality than the FNIH-recommended values.

Premature Adult Death in Individuals Born Preterm: A Sibling Comparison in a Prospective Nationwide Follow-Up Study.
Risnes KR, Pape K, Bjørngaard JH, Moster D, Bracken MB, Romundstad PR.
PLoS One. 2016 Nov 7;11(11):e0165051. doi: 10.1371/journal.pone.0165051.
PMID: 27820819
Free Article
Close to one in ten individuals worldwide is born preterm, and it is important to understand patterns of long-term health and mortality in this group. This study assesses the relationship between gestational age at birth and early adult mortality both in a nationwide population and within sibships. The study adds to existing knowledge by addressing selected causes of death and by assessing the role of genetic and environmental factors shared by siblings.
Study population was all Norwegian men and women born from 1967 to 1997 followed using nation-wide registry linkage for mortality through 2011 when they were between 15 and 45 years of age. Analyses were performed within maternal sibships to reduce variation in unobserved genetic and environmental factors shared by siblings. Specific outcomes were all-cause mortality and mortality from cardiovascular diseases, cancer and external causes including accidents, suicides and drug abuse/overdoses.
Compared with a sibling born in week 37-41, preterm siblings born before 34 weeks gestation had 50% increased mortality from all causes (adjusted Hazard Ratio (aHR) 1.54, 95% confidence interval (CI) 1.17, 2.03). The corresponding estimate for the entire population was 1.27 (95% CI 1.09, 1.47). The majority of deaths (65%) were from external causes and the corresponding risk estimates for these deaths were 1.52 (95% CI 1.08, 2.14) in the sibships and 1.20 (95% CI 1.01, 1.43) in the population.
Preterm birth before week 34 was associated with increased mortality between 15 and 45 years of age. The results suggest that increased premature adult mortality in this group is related to external causes of death and that the increased risks are unlikely to be explained by factors shared by siblings.

In vivo and in vitro evaluation for nutraceutical purposes of capsaicin, capsanthin, lutein and four pepper varieties.
Fernández-Bedmar Z, Alonso-Moraga A.
Food Chem Toxicol. 2016 Oct 13;98(Pt B):89-99. doi: 10.1016/j.fct.2016.10.011. [Epub ahead of print]
PMID: 27746329
The purpose of this study is to determine the nutraceutic potential of different Capsicum sp, capsaicin, capsanthin and lutein and provide data in order to clarify the conflicting results obtained for capsaicin by different authors. To achieve these objectives, in vivo (geno/antigenotoxicity and lifespan assays in the animal model Drosophila) and in vitro (cytotoxicity and DNA-fragmentation assays in HL60 promyelocytic cell line) assays were carried out. Results showed that i) none of the tested substances were genotoxic except green hot pepper and capsaicin at the highest tested concentration (5 mg/mL and 11.5 μM respectively), ii) all tested substances except green hot pepper are antimutagenic against H2O2-induced damage, iii) only red sweet pepper significantly extend the lifespan and healthspan of D. melanogaster at 1.25 and 2.5 mg/mL, iv) all pepper varieties induce dose-depended cytotoxic effect in HL60 cells with different IC50, and v) all pepper varieties and capsaicin exerted proapoptotic effect on HL60 cells.
(i) sweet peppers could be suggested as nutraceutical food, (ii) hot peppers should be moderately consumed, and (iii) supplementary studies are necessary to clarify the synergic effect of the carotenoids and capsaicinoids in the hot pepper food matrix.
Capsaicin; Carotenoids; Cytotoxicity; DNA-fragmentation; Genotoxicity; Pepper

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Influence of diet in acne vulgaris and atopic dermatitis.
Shokeen D.
Cutis. 2016 Sep;98(3):E28-E29.
PMID: 27814423
Diet has been considered as an influence in dermatology for several years. Unfortunately, although correlation has been breached, causation is yet to be determined. Over the last couple years, a few reviews of the literature have been published regarding the influence of diet in acne vulgaris and atopic dermatitis. This article reviews some dietary restrictions and supplements that may have beneficial effects in managing patients with acne vulgaris and atopic dermatitis.

Benefits of a hungry mind: When hungry, exposure to food facilitates proactive interference resolution.
Maran T, Sachse P, Martini M, Furtner M.
Appetite. 2016 Oct 18;108:343-352. doi: 10.1016/j.appet.2016.10.023. [Epub ahead of print]
PMID: 27769647
Hunger is an everyday motivational state, which biases cognition to detect food. Although evidence exists on how hunger affects basic attentional and mnemonic processes, less is known about how motivational drive for food modulates higher cognition. We aimed to investigate the effects of food deprivation on proactive interference resolution, in the presence and absence of food. Normal-weight participants performed a recency probes paradigm providing an experimental block with food and object stimuli as well as a control block with object stimuli only, in a fasted and a sated state. Results showed that the interaction of shifts in nutritional state with the perception of food cues evoked an altered resolution of proactive interference. Satiety led to impaired performance, whereas a hungry state resulted in strengthened resistance to proactive interference and lying in between, the control block presenting neutral objects remained unaffected by nutritional state manipulation. Additionally, a further increase in proactive interference resolution occurred when the conflicting probe depicted food compared to non-food objects. We conclude that when exposed to food, hunger initiates biased competition of active memory representations in favor of prioritized source information at cost of familiar, but irrelevant information. The implications of these findings are discussed in terms of an arousal-biased competition in working memory.
Cognitive control; Hunger; Motivation; Proactive interference; Working memory

Self-perception of uselessness and mortality among older adults in China.
Gu D, Dupre ME, Qiu L.
Arch Gerontol Geriatr. 2016 Nov 6;68:186-194. doi: 10.1016/j.archger.2016.10.015. [Epub ahead of print]
PMID: 27835771
Negative self-perceptions of aging among older adults have been associated with higher mortality in developed countries. However, it is unclear whether an association exists in developing countries where living to older age is more selective.
Using five waves of data (2000, 2002, 2005, 2008, and 2011) from a national survey of adults aged 65 and older in China (n=30,948), this study investigates how self-perceived feelings of uselessness are associated with subsequent mortality. Analyses were stratified by sex and age group (65-79, 80-89, 90-99, and 100+), and adjusted for a wide range of covariates.
Compared with women who never reported perceived uselessness, results from adjusted models shows that women who always reported perceived uselessness had 42% (p<0.001), 31% (p<0.001), and 24% (p<0.001) higher risks of mortality in each of the three oldest age groups, respectively. These associations were only slightly attenuated when covariates were adjusted, but non-significant once baseline health was further controlled for. For men, compared with those who never reported perceived uselessness, the adjusted models for those who always reported perceived uselessness had 62% (p<0.001), 62% (p<0.001), 69% (p<0.001), and 25% (p<0.1) higher risks of mortality in each of the four sequential age groups, respectively. The association was only slightly diminished-and many remained statistically significant-with further adjustments for psychological disposition and baseline health.
Self-perceived uselessness is associated with higher mortality risks in older adults in China. The association is stronger in men than in women and persists at very old ages.
China; Chinese Longitudinal Healthy Longevity Survey; Mortality; Negative perceptions; Older adults; Psychological resilience; Self-ageism; Usefulness; Uselessness
Self-perceived uselessness is associated with lower likelihood of successful aging among older adults in China.
Gu D, Brown BL, Qiu L.
BMC Geriatr. 2016 Oct 6;16(1):172.
PMID: 27716182
Free PMC Article
Plenty of evidence has shown that self-perceived uselessness among older adults is negatively associated with successful aging in terms of good health in Western societies. It is unclear whether these findings are valid in China where living into older age is more selective due to high mortality at younger ages.
Using five waves (2000, 2002, 2005, 2008/2009 and 2011/2012) of a large nationally representative survey in China with 29,954 observations from 19,070 older adults aged 65 and older, this study aimed to investigate the association between self-perceived uselessness and successful aging. Self-perceived uselessness was measured by a single item "with age, do you feel more useless?" with six answers: always, often, sometimes, seldom, never, and unable to answer. Successful aging was measured by independence in activities of daily living (ADL), independence in instrumental activities of daily living (IADL), unimpaired cognition, good life satisfaction, and good self-rated health. Logistic regression models were applied to each successful aging indicator after controlling for a rich set of covariates that included demographics, socioeconomic status, family/social support, and health practices. The models also adjusted for intraperson correlations across waves.
We found that self-perceived uselessness was negatively associated with successful aging among older adults aged 65 or older. Specifically, compared to never having self-perceived uselessness, always having such a perception was associated with 16-42 % lower odds of being ADL independent, IADL independent, cognitively unimpaired, and having good life satisfaction and good self-rated health. Often or sometimes having such a perception also reduced odds of aging successfully, although such reductions were less pronounced. The associations were similar among the oldest-old aged 80 or older with one exception for the case of IADL independence.
Self-perceived uselessness is negatively associated with successful aging among Chinese older adults as well as among the oldest-old. Our findings could be informative for China in the development of public health programs that aim to improve self-perceptions about aging and promote successful aging.
China; Negative perceptions; Older adults; Oldest-old; Psychological resilience; Self-ageism; Self-perceived uselessness; Successful aging; Usefulness

"What makes some rats live so long?" The mitochondrial contribution to longevity through balance of mitochondrial dynamics and mtDNA content.
Picca A, Pesce V, Sirago G, Fracasso F, Leeuwenburgh C, Lezza AM.
Exp Gerontol. 2016 Dec 1;85:33-40. doi: 10.1016/j.exger.2016.09.010.
PMID: 27620821
Extremely interesting for aging research are those individuals able to reach older ages still with functions similar to those of younger counterparts. We examined liver samples from ad libitum-fed old (28-month-old, AL-28) and ad libitum-fed very old (32-month-old, AL-32) rats for a number of markers, relevant for mitochondrial functionality and mitochondrial DNA (mtDNA) content. As for the mtDNA content and the protein amounts of the citrate synthase and the antioxidant peroxiredoxin III there were no significant changes in the AL-32 animals. No significant longevity-related change was found for TFAM amount, but a 50% reduction in the amount of the Lon protease, responsible for turnover of TFAM inside mitochondria, characterized the AL-32 rats. No longevity-related change was observed also for the amounts of the mtDNA repair enzymes OGG1 and APE1, whereas the intra-mitochondrial amount of the cytochrome c protein showed a 50% increase in the AL-32 rats, indicating a likely reduced initiation of the intrinsic apoptotic pathway. Totally unexpected was the doubling of two proteins, very relevant for mitochondrial dynamics, namely MFN2 and DRP1, in the AL-32 rats. This prompted us to the calculation of all individual fusion indexes that grouped together in the AL-32 rats, while in the AL-28 animals were very different. We found a strong positive correlation between the fusion indexes and the respective mtDNA contents in two AL-28 and four AL-32 rats. This supports the idea that the limited prevalence of fusion above a still active fission should have ensured a functional mitochondrial network and should have led to a quite narrow range of high mtDNA contents, likely the best-suitable for extended longevity. Our findings strongly suggest that, among the multiple causes leading to the longevity of the AL-32 rats, the maintenance of an adult-like balance of mitochondrial dynamics seems to be very relevant for the regulation of mtDNA content and functionality.
Aged liver mitochondria; Fusion index correlation with mtDNA content; Long-living rats; Mitochondrial dynamics; mtDNA and related proteins

Cognitive impairment and mortality among the oldest-old Chinese.
An R, Liu GG.
Int J Geriatr Psychiatry. 2016 Dec;31(12):1345-1353. doi: 10.1002/gps.4442.
PMID:  26891153
This study examined the relationship between cognitive impairment status and all-cause mortality among the oldest-old Chinese.
A total of 7474 survey participants 80 years of age and above came from the Chinese Longitudinal Healthy Longevity Survey 1998-2012 waves. Baseline cognitive impairment status was assessed using the Chinese version of the mini-mental state examination (MMSE), with total score ranging from 0 to 30. Cox proportional hazards regressions were performed to examine the relationship between baseline cognitive impairment status in 1998 and subsequent all-cause mortality during 1998-2012, adjusting for various individual characteristics at baseline.
Compared with those with no or mild cognitive impairment (18 ≤ MMSE score ≤ 30) at baseline, participants with moderate-to-severe cognitive impairment (0 ≤ MMSE score ≤ 17) were 28% (95% confidence interval = 20%, 37%) more likely to die during the follow-up period from 1998 to 2012. A dose-response relationship between baseline severity level of cognitive impairment and mortality was evident. Compared with those without cognitive impairment (25 ≤ MMSE score ≤ 30) at baseline, those having mild cognitive impairment (18 ≤ MMSE score ≤ 24), moderate cognitive impairment (10 ≤ MMSE score ≤ 17), and severe cognitive impairment (0 ≤ MMSE score ≤ 9), were 20% (13%, 28%), 38% (27%, 51%), and 47% (33%, 62%) more likely to die during the follow-up period. No statistically significant gender differences in the relationship between cognitive impairment status and mortality were found.
Baseline cognitive impairment was inversely associated with longevity among the oldest-old Chinese. Copyright © 2016 John Wiley & Sons, Ltd.
Chinese; cognitive impairment; mortality; oldest-old

Dietary Magnesium and Kidney Function Decline: The Healthy Aging in Neighborhoods of Diversity across the Life Span Study.
Rebholz CM, Tin A, Liu Y, Kuczmarski MF, Evans MK, Zonderman AB, Crews DC.
Am J Nephrol. 2016;44(5):381-387.
PMID: 27771720
Prior studies suggest that certain aspects of the diet related to magnesium intake, such as dietary acid load, protein intake and dietary patterns rich in fruits and vegetables, may impact kidney disease risk. We hypothesized that lower dietary magnesium intake would be prospectively associated with more rapid kidney function decline.
Among participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 at baseline (2004-2009), dietary magnesium intake was calculated from two 24-hour dietary recalls. Rapid decline was defined as ≥3% eGFR decline per year.
Median (25th-75th percentile) dietary magnesium intake was 116 (96-356) mg/1,000 kcal. Among 1,252 participants, those with lower dietary magnesium intake were younger, and were more likely to be African-American men. A total of 177 participants (14.1%) experienced rapid eGFR decline over a median follow-up of 5 years. Lower dietary magnesium intake was significantly associated with a greater odds of rapid eGFR decline (OR for tertile 1 vs. 3: 2.02, 95% CI 1.05-3.86, p value for trend across tertiles = 0.02) in analyses adjusted for sociodemographics (age, sex, race, education level, health insurance status, poverty status), kidney disease risk factors (smoking status, diabetes, hemoglobin A1c, hypertension, body mass index), baseline eGFR and dietary factors (total energy intake; diet quality; dietary intake of fiber, sodium, calcium, potassium and phosphorus).
In this urban population, lower dietary magnesium intake was independently associated with greater odds of rapid kidney function decline.
Results from the Atherosclerosis Risk in Communities study suggest that low serum magnesium is associated with incident kidney disease.
Tin A, Grams ME, Maruthur NM, Astor BC, Couper D, Mosley TH, Selvin E, Coresh J, Kao WH.
Kidney Int. 2015 Apr;87(4):820-7. doi: 10.1038/ki.2014.331.
PMID: 25272232
Free PMC Article
Low serum magnesium has been associated with kidney function decline in persons with diabetes as well as cardiovascular disease in the general population. As the association of serum magnesium with incident kidney disease in the general population is unknown, we assessed this in 13,226 participants (aged 45-65) in the Atherosclerosis Risk in Communities study with baseline estimated glomerular filtration rate of at least 60 ml/min per 1.73 m(2) in years 1987-89 and followed through 2010. The risks for incident chronic kidney disease (CKD) and end-stage renal disease (ESRD) associated with baseline total serum magnesium levels were evaluated using Cox regression. There were 1965 CKD and 208 ESRD events during a median follow-up of 21 years. In adjusted analysis, low serum magnesium levels (0.7 mmol/l or less) had significant associations with incident CKD and ESRD compared with the highest quartile with adjusted hazard ratio of 1.58 (95% CI: 1.35-1.87) for CKD and 2.39 (95% CI: 1.61-3.56) for ESRD. These associations remained significant after excluding users of diuretics and across subgroups stratified by hypertension, diabetes, and self-reported race. Thus, in a large sample of middle-aged adults, low total serum magnesium was independently associated with incident CKD and ESRD. Further studies are needed to determine whether modification of serum magnesium levels might alter subsequent incident kidney disease rates.

Circulating vitamin D in relation to cancer incidence and survival of the head and neck and oesophagus in the EPIC cohort.
Fanidi A, Muller DC, Midttun Ø, Ueland PM, Vollset SE, Relton C, Vineis P, Weiderpass E, Skeie G, Brustad M, Palli D, Tumino R, Grioni S, Sacerdote C, Bueno-de-Mesquita HB, Peeters PH, Boutron-Ruault MC, Kvaskoff M, Cadeau C, Huerta JM, Sánchez MJ, Agudo A, Lasheras C, Quirós JR, Chamosa S, Riboli E, Travis RC, Ward H, Murphy N, Khaw KT, Trichopoulou A, Lagiou P, Papatesta EM, Boeing H, Kuehn T, Katzke V, Steffen A, Johansson A, Brennan P, Johansson M.
Sci Rep. 2016 Nov 4;6:36017. doi: 10.1038/sre
PMID: 27812151
Experimental and epidemiological data suggest that vitamin D play a role in pathogenesis and progression of cancer, but prospective data on head and neck cancer (HNC) and oesophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants with blood samples between 1992 and 2000. This analysis includes 497 case-control pairs of the head and neck and oesophagus, as well as 443 additional controls. Circulating 25(OH)D3 were measured in pre-diagnostic samples and evaluated in relation to HNC and oesophagus cancer risk and post-diagnosis all-cause mortality. After controlling for risk factors, a doubling of 25(OH)D3 was associated with 30% lower odds of HNC (OR 0.70, 95% confidence interval [95% CI] 0.56-0.88, Ptrend = 0.001). Subsequent analyses by anatomical sub-site indicated clear inverse associations with risk of larynx and hypopharynx cancer combined (OR 0.55, 95CI% 0.39-0.78) and oral cavity cancer (OR 0.60, 95CI% 0.42-0.87). Low 25(OH)D3 concentrations were also associated with higher risk of death from any cause among HNC cases. No clear association was seen with risk or survival for oesophageal cancer. Study participants with elevated circulating concentrations of 25(OH)D3 had decreased risk of HNC, as well as improved survival following diagnosis.

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Female lung cancer mortality and long-term exposure to particulate matter in Italy.
Uccelli R, Mastrantonio M, Altavista P, Caiaffa E, Cattani G, Belli S, Comba P.
Eur J Public Health. 2016 Nov 11. pii: ckw203. [Epub ahead of print]
PMID: 27836971
Outdoor air pollution and particulate matter (PM) have recently been classified in Group 1 by IARC. In Italy there is no epidemiological study on the association between female lung cancer and PM as measured by the official monitoring stations.
We estimated the dose-response relationship between female lung cancer mortality and available long-term outdoor PM10 and/or PM2.5 concentrations for all the Italian province capital city municipalities (respectively, 64 and 32 municipalities). Multiple regression analysis of standardized mortality rates (SMRates) for the period 2000-11, as a function of PM concentrations, considering percentage of smokers and deprivation index as additional explanatory variables, was performed for PM10 only.
The number of province capital cities with available PM2.5 data was not sufficient to detect a significant increment of SMRates as a function of concentrations. An SMRate increase of 0.325 for 1 μg m-3 increment of PM10 concentration was calculated. Moreover, the attributable risk of the overall SMRates for the two subgroups of municipalities under/equal and above 20 μg m-3 value was evaluated. Attributable deaths were computed by both the unitary SMRate increase and the attributable risk. A rough estimate of the impact of PM10 exposure at level above the WHO guideline value of 20 μg m-3 in these 64 municipalities is between 2920 and 3449 lung cancer deaths out of 22 162 (13-16%).
Maintaining the PM10 concentrations below such WHO recommendation, an overall saving of nearly 300 lung cancer deaths per year in a population of 8 146 520 women living in the municipalities at study has been evaluated.

Statins for Prevention of Cardiovascular Disease in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force.
Chou R, Dana T, Blazina I, Daeges M, Jeanne TL.
JAMA. 2016 Nov 15;316(19):2008-2024. doi: 10.1001/jama.2015.15629.
PMID: 27838722
Cardiovascular disease (CVD), the leading cause of mortality and morbidity in the United States, may be potentially preventable with statin therapy.
To systematically review benefits and harms of statins for prevention of CVD to inform the US Preventive Services Task Force.
Data Sources:
Ovid MEDLINE (from 1946), Cochrane Central Register of Controlled Trials (from 1991), and Cochrane Database of Systematic Reviews (from 2005) to June 2016.
Study Selection:
Randomized clinical trials of statins vs placebo, fixed-dose vs titrated statins, and higher- vs lower-intensity statins in adults without prior cardiovascular events.
Data Extraction and Synthesis:
One investigator abstracted data, a second checked data for accuracy, and 2 investigators independently assessed study quality using predefined criteria. Data were pooled using random-effects meta-analysis.
Main Outcomes and Measures:
All-cause mortality, CVD-related morbidity or mortality, and harms.
Nineteen trials (n = 71 344 participants [range, 95-17 802]; mean age, 51-66 years) compared statins vs placebo or no statin. Statin therapy was associated with decreased risk of all-cause mortality (risk ratio [RR], 0.86 [95% CI, 0.80 to 0.93]; I2 = 0%; absolute risk difference [ARD], -0.40% [95% CI, -0.64% to -0.17%]), cardiovascular mortality (RR, 0.69 [95% CI, 0.54 to 0.88]; I2 = 54%; ARD, -0.43% [95% CI, -0.75% to -0.11%]), stroke (RR, 0.71 [95% CI, 0.62 to 0.82]; I2 = 0; ARD, -0.38% [95% CI, -0.53% to -0.23%]), myocardial infarction (RR, 0.64 [95% CI, 0.57 to 0.71]; I2 = 0%; ARD, -0.81% [95% CI, -1.19 to -0.43%]), and composite cardiovascular outcomes (RR, 0.70 [95% CI, 0.63 to 0.78]; I2 = 36%; ARD, -1.39% [95% CI, -1.79 to -0.99%]). Relative benefits appeared consistent in demographic and clinical subgroups, including populations without marked hyperlipidemia (total cholesterol level <200 mg/dL); absolute benefits were higher in subgroups at higher baseline risk. Statins were not associated with increased risk of serious adverse events (RR, 0.99 [95% CI, 0.94 to 1.04]), myalgias (RR, 0.96 [95% CI, 0.79 to 1.16]), or liver-related harms (RR, 1.10 [95% CI, 0.90 to 1.35]). In pooled analysis, statins were not associated with increased risk of diabetes (RR, 1.05 [95% CI, 0.91 to 1.20]), although statistical heterogeneity was present (I2 = 52%), and 1 trial found high-intensity statins associated with increased risk (RR, 1.25 [95% CI, 1.05 to 1.49]). No trial directly compared titrated vs fixed-dose statins, and there were no clear differences based on statin intensity.
Conclusions and Relevance:
In adults at increased CVD risk but without prior CVD events, statin therapy was associated with reduced risk of all-cause and cardiovascular mortality and CVD events, with greater absolute benefits in patients at greater baseline risk.

Vitamin E and the risk of pneumonia: using the I 2 statistic to quantify heterogeneity within a controlled trial.
Hemilä H.
Br J Nutr. 2016 Nov;116(9):1530-1536.
PMID: 27780487
Analyses in nutritional epidemiology usually assume a uniform effect of a nutrient. Previously, four subgroups of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of Finnish male smokers aged 50-69 years were identified in which vitamin E supplementation either significantly increased or decreased the risk of pneumonia. The purpose of this present study was to quantify the level of true heterogeneity in the effect of vitamin E on pneumonia incidence using the I 2 statistic. The I 2 value estimates the percentage of total variation across studies that is explained by true differences in the treatment effect rather than by chance, with a range from 0 to 100 %. The I 2 statistic for the effect of vitamin E supplementation on pneumonia risk for five subgroups of the ATBC population was 89 % (95 % CI 78, 95 %), indicating that essentially all heterogeneity was true variation in vitamin E effect instead of chance variation. The I 2 statistic for heterogeneity in vitamin E effects on pneumonia risk was 92 % (95 % CI 80, 97 %) for three other ATBC subgroups defined by smoking level and leisure-time exercise level. Vitamin E decreased pneumonia risk by 69 % among participants who had the least exposure to smoking and exercised during leisure time (7·6 % of the ATBC participants), and vitamin E increased pneumonia risk by 68 % among those who had the highest exposure to smoking and did not exercise (22 % of the ATBC participants). These findings refute there being a uniform effect of vitamin E supplementation on the risk of pneumonia.
AT DL-α-tocopheryl acetate; ATBC Alpha-Tocopherol; BC β-carotene; Beta-Carotene Cancer Prevention; Antioxidants; Dietary supplements; Effect modifiers (epidemiology); Population characteristics; Respiratory tract infections

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Substitution of meat and fish with vegetables or potatoes and risk of myocardial infarction.
Würtz AM, Hansen MD, Tjønneland A, Rimm EB, Schmidt EB, Overvad K, Jakobsen MU.
Br J Nutr. 2016 Nov;116(9):1602-1610.
PMID: 27774916
Red meat has been suggested to be adversely associated with risk of myocardial infarction (MI), whereas vegetable consumption has been found to be protective. The aim of this study was to investigate substitutions of red meat, poultry and fish with vegetables or potatoes for MI prevention. We followed up 29 142 women and 26 029 men in the Danish Diet, Cancer and Health study aged 50-64 years with no known history of MI at baseline. Diet was assessed by a validated 192-item FFQ at baseline. Adjusted Cox proportional hazard models were used to calculate hazard ratios (HR) and 95 % CI for MI associated with specified food substitutions of 150 g/week. During a median follow-up of 13·6 years, we identified 656 female and 1694 male cases. Among women, the HR for MI when replacing red meat with vegetables was 0·94 (95 % CI 0·90, 0·98). Replacing fatty fish with vegetables was associated with a higher risk of MI (HR 1·23; 95 % CI 1·05, 1·45), whereas an inverse, statistically non-significant association was found for lean fish (HR 0·93; 95 % CI 0·83, 1·05). Substituting poultry with vegetables was not associated with risk of MI (HR 1·00; 95 % CI 0·90, 1·11). Findings for substitution with potatoes were similar to findings for vegetables. Among men, a similar pattern was observed, but the associations were weak and mostly statistically non-significant. This study suggests that replacing red meat with vegetables or potatoes is associated with a lower risk of MI, whereas replacing fatty fish with vegetables or potatoes is associated with a higher risk of MI.
HR hazard ratio; MI myocardial infarction; Cohort studies; Fish; Meat; Myocardial infarction; Potatoes; Substitution models; Vegetables

[The below paper is not pdf-availed.]
Association between sucrose intake and acute coronary event risk and effect modification by lifestyle factors: Malmö Diet and Cancer Cohort Study.
Warfa K, Drake I, Wallström P, Engström G, Sonestedt E.
Br J Nutr. 2016 Nov;116(9):1611-1620.
PMID: 27774913
Previous studies have suggested that a high intake of sugar-sweetened beverages is positively associated with the risk of a coronary event. However, a few studies have examined the association between sucrose (the most common extrinsic sugar in Sweden) and incident coronary events. The objective of the present study was to examine the associations between sucrose intake and coronary event risk and to determine whether these associations are specific to certain subgroups of the population (i.e. according to physical activity, obesity status, educational level, alcohol consumption, smoking habits, intake of fat and intake of fruits and vegetables). We performed a prospective analysis on 26 190 individuals (62 % women) free from diabetes and without a history of CVD from the Swedish population-based Malmö Diet and Cancer cohort. Over an average of 17 years of follow-up (457 131 person-years), 2493 incident cases of coronary events were identified. Sucrose intake was obtained from an interview-based diet history method, including 7-d records of prepared meals and cold beverages and a 168-item diet questionnaire covering other foods. Participants who consumed >15 % of their energy intake (E%) from sucrose showed a 37 (95 % CI 13, 66) % increased risk of a coronary event compared with the lowest sucrose consumers (<5 E%) after adjusting for potential confounders. The association was not modified by the selected lifestyle factors. The results indicated that sucrose consumption higher than 15 E% (5 % of this population) is associated with an increased risk of a coronary event.
E% percentage of energy; HR hazard ratio; MDC Malmö Diet and Cancer; CVD; Effect modification; Risk factors; Sucrose

Lifelong Gender Gap in Risk of Incident Myocardial Infarction: The Tromsø Study.
Albrektsen G, Heuch I, Løchen ML, Thelle DS, Wilsgaard T, Njølstad I, Bønaa KH.
JAMA Intern Med. 2016 Nov 1;176(11):1673-1679. doi: 10.1001/jamainternmed.2016.5451.
PMID: 27617629
It is not clear to what extent the higher incidence of coronary heart disease (CHD) in men vs women is explained by differences in risk factor levels because few studies have presented adjusted risk estimates for sex. Moreover, the increase in risk of CHD in postmenopausal women, possibly hormone related, may eventually eliminate the sex contrast in risk, but age-specific risk estimates are scarce.
To quantify the difference in risk of incident myocardial infarction (MI) between men and women.
Design, Setting and Participants:
Population-based prospective study from Tromsø, Norway, comprising 33 997 individuals (51% women). Median follow-up time during ages 35 to 102 years was 17.6 years. Incidence rates (IRs) and incidence rate ratios (IRRs, relative risk) of MI were calculated in Poisson regression analysis of person-years at risk. The data analysis was performed in November 2015.
Sex, age, birth cohort, serum lipid levels, blood pressure, lifestyle factors, diabetes.
Main Outcomes and Measures:
Incident MI.
A total of 2793 individuals (886 women) received a diagnosis of MI during follow-up in the period 1979 through 2012. The IR increased with age in both sexes, with lower rates for women until age 95 years. Adjusted for age and birth cohort, the overall IRR for men vs women was 2.72 (95% CI, 2.50-2.96). Adjustment for high-density lipoprotein cholesterol and total cholesterol levels had the strongest impact on the risk estimate for sex, followed by diastolic blood pressure and smoking. However, the sex difference remained substantial even after adjustment for these factors (IRR, 2.07; 95% CI, 1.89-2.26). Men had higher risk throughout life, but the IRRs decreased with age (3.64 [95% CI, 2.85-4.65], 2.00 [95% CI, 1.76-2.28], and 1.66 [95% CI, 1.42-1.95] for age groups 35-54, 55-74, and 75-94 years, respectively). Adjustment for systolic blood pressure, diabetes, body mass index, and physical activity had no notable impact.
Conclusions and Relevance:
The observed sex contrast in risk of MI cannot be explained by differences in established CHD risk factors. The gender gap persisted throughout life but declined with age as a result of a more pronounced flattening of risk level changes in middle-aged men. The minor changes in IRs when moving from premenopausal to postmenopausal age in women make it unlikely that changes in female hormone levels influence the risk of MI.

[below papers are pdf-availed.]
Metabolically Healthy Obesity and Development of Chronic Kidney Disease: A Cohort Study.
Chang Y, Ryu S, Choi Y, Zhang Y, Cho J, Kwon MJ, Hyun YY, Lee KB, Kim H, Jung HS, Yun KE, Ahn J, Rampal S, Zhao D, Suh BS, Chung EC, Shin H, Pastor-Barriuso R, Guallar E.
Ann Intern Med. 2016 Mar 1;164(5):305-12. doi: 10.7326/M15-1323.
PMID: 26857595
The risk for chronic kidney disease (CKD) among obese persons without obesity-related metabolic abnormalities, called metabolically healthy obesity, is largely unexplored.
To investigate the risk for incident CKD across categories of body mass index in a large cohort of metabolically healthy men and women.
Prospective cohort study.
Kangbuk Samsung Health Study, Kangbuk Samsung Hospital, Seoul, South Korea.
62 249 metabolically healthy, young and middle-aged men and women without CKD or proteinuria at baseline.
Metabolic health was defined as a homeostasis model assessment of insulin resistance less than 2.5 and absence of any component of the metabolic syndrome. Underweight, normal weight, overweight, and obesity were defined as a body mass index less than 18.5 kg/m2, 18.5 to 22.9 kg/m2, 23 to 24.9 kg/m2, and 25 kg/m2 or greater, respectively. The outcome was incident CKD, defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m2.
During 369 088 person-years of follow-up, 906 incident CKD cases were identified. The multivariable-adjusted differences in 5-year cumulative incidence of CKD in underweight, overweight, and obese participants compared with normal-weight participants were -4.0 (95% CI, -7.8 to -0.3), 3.5 (CI, 0.9 to 6.1), and 6.7 (CI, 3.0 to 10.4) cases per 1000 persons, respectively. These associations were consistently seen in all clinically relevant subgroups.
Chronic kidney disease was identified by a single measurement at each visit.
Overweight and obesity are associated with an increased incidence of CKD in metabolically healthy young and middle-aged participants. These findings show that metabolically healthy obesity is not a harmless condition and that the obese phenotype, regardless of metabolic abnormalities, can adversely affect renal function.
"During 369 088 person-years of follow-up, 906 participants developed CKD, with an overall incidence rate of 2.5 cases per 1000 person-years. The average (SD) follow-up for participants without CKD was 6.0 years (3.0). After direct standardization to the overall sample distribution of age, sex, study center, year of screening examination, smoking status, alcohol intake, and physical activity at baseline, the cumulative incidence of CKD was consistently higher in persons with higher BMI over the entire follow-up (Figure 2). Compared with normal-weight participants, the adjusted differences in 5-year cumulative incidence of CKD for underweight, overweight, and obese participants were −4.0 (95% CI, −7.8 to −0.3), 3.5 (CI, 0.9 to 6.1), and 6.7 (CI, 3.0 to 10.4) cases per 1000 persons, respectively (Table 2, model 2). The adjusted differences in the time at which 1.0% of participants developed CKD for underweight, overweight, and obese participants compared with normal-weight participants were 2.0 (CI, −0.5 to 4.4), −1.2 (CI, −2.2 to −0.3), and −2.4 (CI, −3.4 to −1.5) years, respectively (Appendix Table, model 2)."
1: Stanford FC, Butsch WS. Metabolically Healthy Obesity and Development of
Chronic Kidney Disease. Ann Intern Med. 2016 Nov 15;165(10):742-743. doi:
10.7326/L16-0408. PubMed PMID: 27842408.
2: Kahn HS, Pavkov ME. Metabolically Healthy Obesity and Development of Chronic
Kidney Disease. Ann Intern Med. 2016 Nov 15;165(10):743. doi: 10.7326/L16-0407.
PubMed PMID: 27842407.
3: Little DJ, Deressa WT, Watson MA, Yuan CM. Metabolically Healthy Obesity and
Development of Chronic Kidney Disease. Ann Intern Med. 2016 Nov
15;165(10):743-744. doi: 10.7326/L16-0406. PubMed PMID: 27842406.
4: Chang Y, Ryu S, Cho J, Pastor-Barriuso R, Guallar E. Metabolically Healthy
Obesity and Development of Chronic Kidney Disease. Ann Intern Med. 2016 Nov
15;165(10):744-745. doi: 10.7326/L16-0405. PubMed PMID: 27842405.
We thank Drs. Stanford and Butsch, Drs. Kahn and Pavkov, and Dr. Little and colleagues for their interest in our study and for raising important points about the interpretation of our results. Several of the arguments address the use of Asian-specific cutoffs for BMI and the obesity paradox. For a given BMI, Asians have a higher percentage of total body fat (1) and a higher risk for cardiometabolic disease (2) than white persons. As a consequence, Asian Pacific–specific BMI criteria have gained widespread acceptance. As for more detailed analyses by degree of obesity, only 211 (0.3%) participants in our study had higher-grade obesity (BMI ≥ 30 kg/m2) and we could not perform a separate analysis of this subgroup.
The obesity paradox refers to the inverse association between obesity and mortality commonly found in participants older than 50 years or those with established cardiovascular disease or other comorbidities (3–5). It has raised concerns about selection, survival, treatment, and confounding biases (4, 6, 7). Our cohort comprised relatively young, metabolically healthy, asymptomatic Korean men and women, and our findings are less likely to be affected by survival biases or biases induced by comorbidities or treatment than studies in higher-risk populations. Furthermore, our findings are consistent with an extensive body of evidence indicating that BMI is linearly associated with the development of metabolic abnormalities, such as insulin resistance, type 2 diabetes, and hypertension (4, 8)—all risk factors for CKD.
Body mass index is an imperfect surrogate for adiposity, and we agree that body composition and fat distribution are important to understand the association between BMI and incident CKD. One of the study centers unfortunately did not measure waist circumference until 2012, and we could not evaluate the effect of fat distribution on CKD outcomes. With respect to body composition, the correlation of BMI with fat mass and with lean mass measured by an impedance analyzer (InBody 3.0 and 720 [biospace]) was 0.87 and 0.50, respectively, in women and 0.87 and 0.59, respectively, in men. The correlation between fat mass and lean mass was 0.34 in women and 0.41 in men. When fat mass and lean mass were simultaneously included in survival models adjusted for age, study center, year of screening examination, smoking status, alcohol intake, and physical activity, the adjusted 5-year risk differences for incident CKD comparing quartiles 2 to 4 of fat mass with quartile 1 were −3.3 (95% CI, −8.8 to 2.2), −3.4 (CI, −8.7 to 2.0), and −6.1 (CI, −11.2 to −1.1) cases per 1000 women, respectively, and −0.5 (CI, −4.9 to 4.0), −0.7 (CI, −5.1 to 3.6), and −3.2 (CI, −7.4 to 1.1) cases per 1000 men, respectively. The corresponding risk differences for lean mass were 4.6 (CI, 1.2 to 8.0), 9.2 (CI, 5.5 to 12.8), and 14.0 (CI, 9.7 to 18.4) cases per 1000 women, respectively, and 4.4 (CI, 1.8 to 6.9), 7.9 (CI, 4.8 to 11.0), and 13.6 (CI, 9.0 to 18.2) cases per 1000 men, respectively. In these analyses, lean mass was thus associated with increased risk for CKD, whereas fat mass was not.
The implications of these results for the interpretation of the association between BMI and CKD are unclear, because increased BMI is associated with increases in both fat and lean mass. However, these findings highlight the limitations of creatinine-based indices to assess kidney function as well as the need to evaluate the association between obesity and CKD using biomarkers that do not depend on muscle mass.

[Re: http://biomedgerontology.oxfordjournals.org/content/71/10.toc-- There were papers of interest to me, such as the below papers.]
Nutrition and Healthy Aging.
Kritchevsky SB.
J Gerontol A Biol Sci Med Sci. 2016 Oct;71(10):1303-5. doi: 10.1093/gerona/glw165. No abstract available.
PMID: 27621294
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

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Prostate Cancer and Socioeconomic Status in the Finnish Randomized Study of Screening for Prostate Cancer.
Kilpeläinen TP, Talala K, Raitanen J, Taari K, Kujala P, Tammela TL, Auvinen A.
Am J Epidemiol. 2016 Oct 24. [Epub ahead of print]
PMID: 27777219
Prostate cancer (PC) screening remains controversial. We investigated whether screening reduces the difference in prostate cancer risk by socioeconomic status (SES). In 1996-2011, a total of 72,139 men from the Finnish Randomized Study of Screening for Prostate Cancer were analyzed. Outcome measures were PC incidence, mortality, and participation in screening. SES indicators were educational level, income, and home ownership status (data obtained from the Statistics Finland registry). The mean duration of follow-up was 12.7 years. Higher SES was associated with a higher incidence of low- to moderate-risk PC but with a lower risk of advanced PC. Higher education was associated with significantly lower PC mortality in both control and screening arms (risk ratio = 0.48-0.69; P < 0.05). Higher income was also associated with lower PC mortality but only in the control arm (risk ratio = 0.45-0.73; P < 0.05). There were no significant differences in SES gradient by arm (Pinteraction = 0.33 and Pinteraction = 0.47 for primary vs. secondary education and primary vs. tertiary education, respectively; Pinteraction = 0.65 and Pinteraction = 0.09 for low vs. intermediate income and low vs. high income, respectively; and Pinteraction = 0.27 among home ownership status strata). Substantial gradients by SES in PC incidence and mortality were observed in the control arm. Higher SES was associated with overdiagnosis of low-risk PC and, conversely, lower risk of incurable PC and lower PC mortality. Special attention should be directed toward recruiting men with low SES to participate in population-based cancer screening.
incidence; mass screening; mortality; prostate-specific antigen; prostatic neoplasms; randomized controlled trials; socioeconomic status

[The results for the association of male plant food consumption with colon cancer risk surprised me.]
Association between meeting the WCRF/AICR cancer prevention recommendations and colorectal cancer incidence: results from the VITAL cohort.
Hastert TA, White E.
Cancer Causes Control. 2016 Nov;27(11):1347-1359.
PMID: 27752849
In 2007, the World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) published eight recommendations regarding body weight, physical activity, and dietary behaviors aimed at reducing cancer incidence worldwide. In this paper, we assess whether meeting the WCRF/AICR recommendations is associated with lower colorectal cancer (CRC) incidence; evaluate whether particular recommendations are most strongly associated with lower CRC incidence; and assess whether associations differ by sex.
We operationalized six of the recommendations (related to body weight, physical activity, energy density, plant foods, red and processed meat, and alcohol) and examined their association with CRC incidence over 7.6 years of follow-up in the prospective VITamins And Lifestyle Study cohort. Participants included 66,920 adults aged 50-76 years at baseline (2000-2002) with no history of CRC and with complete data for the recommendations evaluated. Incident colorectal cancers (n = 546) were tracked through 2009.
Compared with meeting no recommendations, meeting 1-3 recommendations was associated with 34-45 % lower CRC incidence, and meeting 4-6 was associated with 58 % lower incidence (95 % CI 34 %, 74 %) in fully adjusted analyses. The recommendations most strongly associated with lower CRC risk for women were related to body fatness and red and processed meat, while for men these were alcohol intake and red and processed meat. Differences by sex were statistically significant (p < 0.05) for the recommendations related to body weight and to alcohol.
Meeting the WCRF/AICR recommendations, particularly those related to alcohol, body weight, and red and processed meat, could substantially reduce CRC incidence; however, associations differ by sex.
Alcohol; Cancer prevention; Colorectal cancer; Obesity; Recommendations

Aspirin use and the incidence of breast, colon, ovarian, and pancreatic cancers in elderly women in the Iowa Women's Health Study.
Vaughan LE, Prizment A, Blair CK, Thomas W, Anderson KE.
Cancer Causes Control. 2016 Nov;27(11):1395-1402.
PMID: 27677628
Few studies have evaluated the chemopreventive effect of aspirin on the cancer risk in elderly women. We examined associations between frequency, dose, and duration of aspirin use with incidence of 719 aspirin-sensitive cancers (cancers of colon, pancreas, breast, and ovaries) in the Iowa Women's Health Study (IWHS), a prospective cohort of women over 70 years old.
Aspirin frequency, dose, and duration were self-reported in the 2004 IWHS questionnaire. Women were followed-up to 2011. Cancer cases were ascertained by linkage to the Iowa State Health Registry. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CI).
Among the 14,386 women, 30 % were nonusers of aspirin; 34 % used low-dose aspirin, and 36 % used regular- or high-dose aspirin. Compared with nonuse of aspirin, the HRs (95 % CI) for incidence of aspirin-sensitive cancers were 0.87 (0.72-1.06) for regular to high doses of aspirin use, 0.95 (0.80-1.13) for aspirin use 6+ times per week, and 0.93 (0.74-1.17) for aspirin use for 10+ years. For cumulative aspirin use, HR (95 % CI) was 0.87 (0.70-1.09) for >60,000 mg of aspirin per year and 0.95 (0.75-1.21) for >280,000 mg of aspirin in their lifetime, versus nonuse of aspirin. Results were similar for the all-cause cancer death as an endpoint, with a significant inverse association observed between lifetime aspirin dose and cancer mortality [<95,000 mg vs nonuser HR 0.76 (0.61-0.95)].
These findings suggest that aspirin use may prevent incident breast, colon, pancreatic, and ovarian cancer in elderly women.
Aspirin; Cancer; Cohort; Elderly; NSAIDs; Women
"when using death
from any type of cancer as an endpoint (Supplemental Table)
was examined, a significant inverse
association observed between lifetime aspirin dose and
cancer mortality (>95,000 mg vs nonuser HR 0.76; 95 %
CI 0.61–0.95)."

Classification for Longevity Potential: The Use of Novel Biomarkers.
Beekman M, Uh HW, van Heemst D, Wuhrer M, Ruhaak LR, Gonzalez-Covarrubias V, Hankemeier T, Houwing-Duistermaat JJ, Slagboom PE.
Front Public Health. 2016 Oct 28;4:233.
PMID: 27840811
In older people, chronological age may not be the best predictor of residual lifespan and mortality, because with age the heterogeneity in health is increasing. Biomarkers for biological age and residual lifespan are being developed to predict disease and mortality better at an individual level than chronological age. In the current paper, we aim to classify a group of older people into those with longevity potential or controls.
In the Leiden Longevity Study participated 1671 offspring of nonagenarian siblings, as the group with longevity potential, and 744 similarly aged controls. Using known risk factors for cardiovascular disease, previously reported markers for human longevity and other physiological measures as predictors, classification models for longevity potential were constructed with multiple logistic regression of the offspring-control status.
The Framingham Risk Score (FRS) is predictive for longevity potential [area under the receiver operating characteristic curve (AUC) = 64.7]. Physiological parameters involved in immune responses and glucose, lipid and energy metabolism further improve the prediction performance for longevity potential (AUCmale = 71.4, AUCfemale = 68.7).
Using the FRS, the classification of older people in groups with longevity potential and controls is moderate, but can be improved to a reasonably good classification in combination with markers of immune response, glucose, lipid, and energy metabolism. We show that individual classification of older people for longevity potential may be feasible using biomarkers from a wide variety of different biological processes.
Framingham Risk Score; biomarker; classification and prediction; human longevity potential; sex-specific analysis

Cardioprotection and lifespan extension by the natural polyamine spermidine.
Eisenberg T, Abdellatif M, Schroeder S, Primessnig U, Stekovic S, Pendl T, Harger A, Schipke J, Zimmermann A, Schmidt A, Tong M, Ruckenstuhl C, Dammbrueck C, Gross AS, Herbst V, Magnes C, Trausinger G, Narath S, Meinitzer A, Hu Z, Kirsch A, Eller K, Carmona-Gutierrez D, Büttner S, Pietrocola F, Knittelfelder O, Schrepfer E, Rockenfeller P, Simonini C, Rahn A, Horsch M, Moreth K, Beckers J, Fuchs H, Gailus-Durner V, Neff F, Janik D, Rathkolb B, Rozman J, de Angelis MH, Moustafa T, Haemmerle G, Mayr M, Willeit P, von Frieling-Salewsky M, Pieske B, Scorrano L, Pieber T, Pechlaner R, Willeit J, Sigrist SJ, Linke WA, Mühlfeld C, Sadoshima J, Dengjel J, Kiechl S, Kroemer G, Sedej S, Madeo F.
Nat Med. 2016 Nov 14. doi: 10.1038/nm.4222. [Epub ahead of print]
PMID: 27841876
Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends the lifespan of mice and exerts cardioprotective effects, reducing cardiac hypertrophy and preserving diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy and mitochondrial respiration, and it also improved the mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin phosphorylation and suppressed subclinical inflammation. Spermidine feeding failed to provide cardioprotection in mice that lack the autophagy-related protein Atg5 in cardiomyocytes. In Dahl salt-sensitive rats that were fed a high-salt diet, a model for hypertension-induced congestive heart failure, spermidine feeding reduced systemic blood pressure, increased titin phosphorylation and prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. In humans, high levels of dietary spermidine, as assessed from food questionnaires, correlated with reduced blood pressure and a lower incidence of cardiovascular disease. Our results suggest a new and feasible strategy for protection against cardiovascular disease.

Your money or your time? How both types of scarcity matter to physical activity and healthy eating.
Venn D, Strazdins L.
Soc Sci Med. 2016 Nov 2. pii: S0277-9536(16)30591-3. doi: 10.1016/j.socscimed.2016.10.023. [Epub ahead of print]
PMID: 27839899
Lack of time is one of the most common reasons people give for not exercising or eating healthy food, yet few studies explicitly test its relationship with health behaviours.
Conceptualising time as a social determinant we estimate how scarcity - of income or time - generate barriers to health behaviours.
Using longitudinal, nationally-representative survey data on Australians aged 25-54 years, our design addresses endogeneity and reverse causation by considering how new episodes of scarcity are related to changes in healthy eating and physical activity. Regression models estimated how scarcity of income (low income or feeling poor) or time (heavy time commitments or feeling rushed for time) predicted change over two consecutive years.
We find that both income and time scarcity reduce physical activity and, in some cases, lead people to consume less fruit and vegetables, eat out more and eat more discretionary calories (food high in salt, sugar or fat). Further, income and time scarcity operate independently to constrain healthy choices, although for more than one in ten people they synergistically increase risk.
Because income and time scarcity are patterned by socio-economic status and gender, our results underline the need to address both if public health interventions are to be more effective and fair.
Australia; Endogeneity; Gender inequality; Health inequality; Healthy eating; Physical activity; Social determinants of health; Time poverty

Edited by AlPater
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Demographic, Phenotypic, and Genetic Characteristics of Centenarians in Okinawa and Japan: Part 1 - Centenarians in Okinawa.

Willcox BJ, Willcox DC, Suzuki M.

Mech Ageing Dev. 2016 Nov 11. pii: S0047-6374(16)30220-2. doi: 10.1016/j.mad.2016.11.001. [Epub ahead of print] Review.

PMID: 27845177 


A study of elderly Okinawans has been carried out by the Okinawa Centenarian Study (OCS) research group for over four decades. The OCS began in 1975 as a population-based study of centenarians (99-year-olds and older) and other selected elderly persons residing in the main island of the Japanese prefecture of Okinawa. As of 2015, over 1000 centenarians have been examined. By several measures of health and longevity the Okinawans can claim to be the world's healthiest and longest-lived people. In this paper we explore the demographic, phenotypic, and genetic characteristics of this fascinating population.


Inclusion of walnut in the diets of adults at risk for type 2 diabetes and their dietary pattern changes: a randomized, controlled, cross-over trial.

Njike VY, Yarandi N, Petraro P, Ayettey RG, Treu JA, Katz DL.

BMJ Open Diabetes Res Care. 2016 Oct 19;4(1):e000293.

PMID: 27843557 



In our recently published study, including walnuts in the diets of adults with prediabetes led to overall improvement in diet quality. This report adds to those study findings by examining the food groups displaced during walnut inclusion in the diets of those adults with prediabetes.


Randomized, controlled, modified Latin square parallel design with 2 treatment arms. The 112 participants (31 men, 81 women) were randomly assigned to a diet with or without dietary counseling to regulate calorie intake in a 1:1 ratio. Within each treatment arm, participants were further randomized to 1 of 2 sequence permutations to receive a walnut-included diet with 56 g (366 kcal) of walnuts per day and a walnut-excluded diet. Participants in the calorie-regulated arm received advice from a dietitian to preserve an isocaloric condition while including walnuts. We analyzed the 12 components of the 2010 Healthy Eating Index to examine dietary pattern changes of study participants.


Seafood and plant protein foods intake significantly increased with walnut inclusion, compared with their exclusion (2.14±2.06 vs -0.49±2.33; p=0.003). The ingestion of healthful fatty acids also significantly increased with walnut inclusion, compared with their exclusion (1.43±4.53 vs -1.76±4.80; p=0.02). Dairy ingestion increased with walnut inclusion in the calorie-regulated phase, compared with walnut inclusion without calorie regulation (1.06±4.42 vs -2.15±3.64; p=0.02).


Our data suggest that walnut inclusion in the diets of adults at risk for diabetes led to an increase in intake of other healthful foods.


A1C; Nutrition; Nuts

"This study was conducted with funding from the

Centers for Disease Control and Prevention and the California Walnut

Commission. DLK has been compensated for public speaking by the

California Walnut Commission."


[The pdf is availed from the Medline site.]

The Combined Effects of Healthy Lifestyle Behaviors on All-Cause Mortality: The Golestan Cohort Study.

Fazel-Tabar Malekshah A, Zaroudi M, Etemadi A, Islami F, Sepanlou S, Sharafkhah M, Keshtkar AA, Khademi H, Poustchi H, Hekmatdoost A, Pourshams A, Feiz Sani A, Jafari E, Kamangar F, Dawsey SM, Abnet CC, Pharoah PD, Berennan PJ, Boffetta P, Esmaillzadeh A, Malekzadeh R.

Arch Iran Med. 2016 Nov;19(11):752-761.

PMID: 27845543 



Most studies that have evaluated the association between combined lifestyle factors and mortality outcomes have been conducted in populations of developed countries.


The aim of this study was to examine the association between combined lifestyle scores and risk of all-cause and cause-specific mortality for the first time among Iranian adults.


The study population included 50,045 Iranians, 40 - 75 years of age, who were enrolled in the Golestan Cohort Study, between 2004 and 2008. The lifestyle risk factors used in this study included cigarette smoking, physical inactivity, and Alternative Healthy Eating Index. The lifestyle score ranged from zero (non-healthy) to 3 (most healthy) points. From the study baseline up to analysis, a total of 4691 mortality cases were recorded. Participants with chronic diseases at baseline, outlier reports of calorie intake, missing data, and body mass index of less than 18.5 were excluded from the analyses. Cox regression models were fitted to establish the association between combined lifestyle scores and mortality outcomes.


After implementing the exclusion criteria, data from 40,708 participants were included in analyses. During 8.08 years of follow-up, 3,039 cases of all-cause mortality were recorded. The adjusted hazard ratio of a healthy lifestyle score, compared with non-healthy lifestyle score, was 0.68 (95% CI: 0.54, 0.86) for all-cause mortality, 0.53 (95% CI: 0.37, 0.77) for cardiovascular mortality, and 0.82 (95% CI: 0.53, 1.26) for mortality due to cancer. When we excluded the first two years of follow up from the analysis, the protective association between healthy lifestyle score and cardiovascular death did not change much 0.55 (95% CI: 0.36, 0.84), but the inverse association with all-cause mortality became weaker 0.72 (95% CI: 0.55, 0.94), and the association with cancer mortality was non-significant 0.92 (95% CI: 0.58, 1.48). In the gender-stratified analysis, we found an inverse strong association between adherence to healthy lifestyle and mortality from all causes and cardiovascular disease in either gender, but no significant relationship was seen with mortality from cancer in men or women. Stratified analysis of BMI status revealed an inverse significant association between adherence to healthy lifestyle and mortality from all causes, cardiovascular disease and cancer among non-obese participants.


We found evidence indicating that adherence to a healthy lifestyle, compared to non-healthy lifestyle, was associated with decreased risk of all-cause mortality and mortality from cardiovascular diseases in Iranian adults.


The incidence of hypertension and its risk factors in the German adult population: results from the German National Health Interview and Examination Survey 1998 and the German Health Interview and Examination Survey for Adults 2008-2011.

Diederichs C, Neuhauser H.

J Hypertens. 2016 Nov 14. [Epub ahead of print]

PMID: 27846042 



To analyze incident hypertension and its risk factors based on 11.9 years follow-up of a recent National Examination Survey cohort in Germany.


Out of 7124 participants of the German National Health Interview and Examination Survey 1998 (GNHIES98), 640 had died at follow-up 2008-2011 and 3045 were reexamined as part of the German Health Interview and Examination Survey for Adults 2008-2011 (DEGS1). Baseline and follow-up included standardized blood pressure (BP) measurements. Hypertension was defined as BP of at least 140/90 mmHg or intake of antihypertensive medication in participants with known hypertension.


Out of 2231 GNHIES98-DEGS1 participants aged 18-79 years without hypertension in 1998, 26.2% developed hypertension within a mean of 11.9 (range 10.0-14.1) years (men 29.0%, women 23.4%). In univariate analysis, hypertension incidence was positively associated with age, BMI, initial BP levels, pulse pressure, and alcohol consumption. Comorbidities such as diabetes and hyperlipidemia increased the chance to develop hypertension. In the multivariate model, initial SBP and DBP levels had the strongest influence on the development of future hypertension (7% increase in men and 5% in women per mmHg SBP). The percentage of aware, treated, and controlled hypertensive patients were 75.8, 62.1, and 50.3% in men and 83.8, 73.3, and 59.0% in women.


The high 11.9-year incidence in all age groups points to the lifelong potential for prevention of hypertension.


TABLE 3. Multivariate adjusted incidence of hypertension within 11.9 years for selected variables stratified for men and women

in the GNHIES98/DEGS1 cohort (n¼2231 without hypertension at baseline)a

Men Women


Age 39 1.00 – 1.00 –

40–49 2.06 0.013 2.58 0.002

50–59 2.58 0.001 4.77 0.000

60–79 2.96 0.002 4.66 0.000

Socioeconomic status Low 1.00 – 1.00 –

Medium 0.71 0.259 1.07 0.865

High 0.79 0.497 0.88 0.773

SPBa Per mmHg 1.07 0.001 1.05 0.016

DPBa Per mmHg 1.08 0.012 1.09 0.007

BMI (kg/m) <25 1.00 – 1.00 –

25 to <30 1.54 0.054 1.26 0.360

30 4.03 0.000 3.82 0.000

Diabetesb No 1.00 – 1.00 –

Yes 2.72 0.061 1.13 0.294

Hyperlipidemiac No 1.00 – 1.00 –

Yes 1.41 0.399 1.79 0.891

Smoking No 1.00 – 1.00 –

Yes 1.04 0.571 1.08 0.178

Alcohol consumption None 1.00 – 1.00 –

(men/women) <20/<10 g per day 2.42 0.021 2.05 0.035

20/10 g per day 2.88 0.014 2.13 0.092

Physical activity (hours per week) None/<1 1.00 – 1.00 –

1–2 0.76 0.306 1.31 0.035

2 0.84 0.399 1.04 0.092

Community size <20 000 1.00 – 1.00 –

20 000 to <100 000 1.15 0.542 0.98 0.916

100 000 1.39 0.176 0.71 0.211

Regionsd Central-East 1.00 – 1.00 –

Northwest 0.90 0.783 0.68 0.203

Central-West 0.72 0.372 0.75 0.358

South 1.09 0.811 0.69 0.152

Northeast 0.76 0.527 1.45 0.224

Health insurance Public 1.00 – 1.00 –

Private 0.79 0.405 0.78 0.409

OR, odds ratio.

aAll three blood pressure variables (SBP, DBP, pulse pressure) cannot be included in the multivariate model because of multicollinearity. Therefore, we chose the two variables with the

highest likelihood ratio x2, which were SBP and DBP.

bDiabetes (yes, if self-reported diagnose of diabetes by a physician or if they were taking antidiabetic medication [ATC code A10A/A10B] in the 7 days).

cHyperlipidemia (yes, if overall cholesterol level >190 mg/dl or self-reported diagnose of hyperlipidemia by a physician).

dRegions (Central-East: Sachsen-Anhalt, Sachsen, Thu¨ ringen versus Northwest: Schleswig-Holstein, Hamburg, Niedersachsen, Bremen versus Central-West: Nordrhein-Westfalen, Hessen,

Rheinland-Pfalz versus South: Bayern, Baden-Wu¨ rttemberg, Saarland versus Northeast: Mecklenburg-Vorpommern, Brandenburg, Berlin).


The Association between Renal Hyperfiltration and the Sources of Habitual Protein Intake and Dietary Acid Load in a General Population with Preserved Renal Function: The KoGES Study.

So R, Song S, Lee JE, Yoon HJ.

PLoS One. 2016 Nov 15;11(11):e0166495. doi: 10.1371/journal.pone.0166495.

PMID: 27846266 


Although the differential response of the kidney to the acute load of various sources of dietary protein in subjects with normal renal function is well known, the influence of habitual dietary protein intake and dietary acid load on renal function has not been tested well. The association between renal hyperfiltration (RHF), the earlier and possibly reversible stage of chronic kidney disease, and the sources of habitual dietary protein and dietary acid load was analyzed with the baseline data of 123,169 middle-aged healthy Koreans of a large prospective cohort study, who had a baseline estimated glomerular filtration rate (eGFR) >60 mL/min/m2 and no known history of diabetes and/or hypertension. eGFR was calculated with the Chronic Kidney Disease Epidemiology Collaboration equation using serum creatinine and RHF was defined as eGFR >95th percentile after adjustment for age, sex, height, and body weight. Dietary acid load was calculated with estimated net endogenous acid production (eNEAP). Although the level of habitual intake of animal protein was positively and vegetable protein was negatively associated with RHF, this association was significant only in women and younger participants (younger than sex-specific median age). The odds for RHF increased as the percentile rank of eNEAP increased until about the 50th percentile and then leveled off. The positive association between eNEAP and RHF was significant in both sexes and age groups. Dietary acid load was associated with RHF regardless of sex and age and rather than the amount of the total or the individual sources of habitual dietary protein, may be a better target for the dietary intervention of chronic kidney disease.


Caffeine Intake and Dementia Risk-A Health Benefit From One of Life's Simple Pleasures?

Morris MC.

J Gerontol A Biol Sci Med Sci. 2016 Dec;71(12):1595. No abstract available.

PMID: 27678291 


Relationships Between Caffeine Intake and Risk for Probable Dementia or Global Cognitive Impairment: The Women's Health Initiative Memory Study.

Driscoll I, Shumaker SA, Snively BM, Margolis KL, Manson JE, Vitolins MZ, Rossom RC, Espeland MA.

J Gerontol A Biol Sci Med Sci. 2016 Dec;71(12):1596-1602.

PMID: 27678290 



Nonhuman studies suggest a protective effect of caffeine on cognition. Although human literature remains less consistent, reviews suggest a possible favorable relationship between caffeine consumption and cognitive impairment or dementia. We investigated the relationship between caffeine intake and incidence of cognitive impairment or probable dementia in women aged 65 and older from the Women's Health Initiative Memory Study.


All women with self-reported caffeine consumption at enrollment were included (N = 6,467). In 10 years or less of follow-up with annual assessments of cognitive function, 388 of these women received a diagnosis of probable dementia based on a 4-phase protocol that included central adjudication. We used proportional hazards regression to assess differences in the distributions of times until incidence of probable dementia or composite cognitive impairment among women grouped by baseline level of caffeine intake, adjusting for risk factors (hormone therapy, age, race, education, body mass index, sleep quality, depression, hypertension, prior cardiovascular disease, diabetes, smoking, and alcohol consumption).


Women consuming above median levels (mean intake = 261mg) of caffeine intake for this group were less likely to develop incident dementia (hazard ratio = 0.74, 95% confidence interval [0.56, 0.99], p = .04) or any cognitive impairment (hazard ratio = 0.74, confidence interval [0.60, 0.91], p = .005) compared to those consuming below median amounts (mean intake = 64mg) of caffeine for this group.


Our findings suggest lower odds of probable dementia or cognitive impairment in older women whose caffeine consumption was above median for this group and are consistent with the existing literature showing an inverse association between caffeine intake and age-related cognitive impairment.


Aging; Cognitive function; Cognitive impairment; Dementia; Hormone therapy


Caffeine intake from coffee or tea and cognitive disorders: a meta-analysis of observational studies.

Kim YS, Kwak SM, Myung SK.

Neuroepidemiology. 2015;44(1):51-63.

PMID: 25721193

Free Article



Observational epidemiological studies such as cross-sectional, case-control, and cohort studies have reported inconsistent findings regarding the association between caffeine intake from coffee or tea and the risk of cognitive disorders such as dementia, Alzheimer's disease, cognitive impairment, and cognitive decline.


We searched PubMed and EMBASE in September 2014. Three evaluators independently extracted and reviewed articles, based on predetermined selection criteria.


Out of 293 articles identified through the search and bibliographies of relevant articles, 20 epidemiological studies from 19 articles, which involved 31,479 participants (8,398 in six cross-sectional studies, 4,601 in five case-control studies, and 19,918 in nine cohort studies), were included in the final analysis. The pooled odds ratio (OR) or relative risk (RR) of caffeine intake from coffee or tea for cognitive disorders (dementia, Alzheimer's disease, cognitive impairment, and cognitive decline) was 0.82 (95% confidence interval [CI], 0.67-1.01, I² = 63.2%) in a random-effects meta-analysis. In the subgroup meta-analysis by caffeine sources, the summary OR or RR of coffee intake was 0.83 (95% CI, 0.70-0.98; I² = 44.8%). However, in the subgroup meta-analysis by study design, the summary estimates (RR or OR) of coffee intake for cognitive disorders were 0.70 (95% CI, 0.50-0.98; I² = 42.0%) for cross-sectional studies, 0.82 (95% CI, 0.55-1.24; I² = 33.4%) for case-control studies, and 0.90 (95% CI, 0.59-1.36; I² = 60.0%) for cohort studies.


This meta-analysis found that caffeine intake from coffee or tea was not associated with the risk of cognitive disorders.


Lifestyle Factors and Dementia in the Oldest-old: The 90+ Study.

Paganini-Hill A, Kawas CH, Corrada MM.

Alzheimer Dis Assoc Disord. 2016 Jan-Mar;30(1):21-6. doi: 10.1097/WAD.0000000000000087.

PMID: 25710250 


Dementia incidence increases exponentially with age even in people aged 90 years and above. Because therapeutic regimens are limited, modification of lifestyle behaviors may offer the best means for disease control. To test the hypotheses that lifestyle factors are related to lower risk of dementia in the oldest-old, we analyzed data from The 90+ Study, a population-based longitudinal cohort study initiated in 2003. This analysis included 587 participants (mean age=93 y) seen in-person and determined not to have dementia at enrollment. Information on lifestyle factors (smoking, alcohol, caffeine, vitamin supplements, exercise, and other activities) was obtained at enrollment and was available from data collected 20 years previously. After an average follow-up of 36 months, 268 participants were identified with incident dementia. No variable measured 20 years previously was associated with risk. Engagement in specific social/mental activities and intakes of antioxidant vitamin supplements and caffeine at time of enrollment were, associated with significantly reduced risks. When these variables were analyzed together, the HRs changed little and remained significant for reading (0.54, P=0.01) and going to church/synagogue (HR=0.66, P<0.05) but not for caffeine (HR=0.61, P=0.15) and vitamin C (HR=0.68, P=0.07). While lifestyle behaviors around age 70 did not modify risk of late-life dementia, participation in activities and caffeine and supplemental vitamin intake around age 90 warrant further investigation. 

"Supported by grants R01CA32197 and R01AG21055 from the

National Institutes of Health, the Earl Carroll Trust Fund, and

Wyeth-Ayerst Laboratories."


Time of day and caffeine influence some neuropsychological tests in the elderly.

Walters ER, Lesk VE.

Psychol Assess. 2015 Mar;27(1):161-8. doi: 10.1037/a0038213.

PMID: 25346994 

We report that performance on neuropsychological tests used in the diagnosis of dementia can be influenced by external factors such as time of day (TOD) and caffeine. This study investigates TOD effects on cognitive performance in the elderly. The optimal TOD at which an individual is at his or her maximal arousal alters with age, and in the elderly, typically occurs in the morning. Neuropsychological test scores from healthy elderly participants were analyzed to determine whether TOD affected performance. Interactions between caffeine and TOD were also investigated. Across 2 data sets that were analyzed, significant TOD effects were noted for Pattern-Comparison Speed (PCS), Letter-Comparison Speed (LCS; Salthouse & Babcock, 1991), Trail Making Test Part A (Reitan, 1958), Mini-Mental State Examination (MMSE; Folstein, Folstein, & McHugh, 1975) and the Graded Naming Test (GNT; McKenna & Warrington, 1980), revealing a decline in test scores as TOD increases. Significant interactions between TOD, age, and the PCS, LCS, and Trail Making Part A were noted in Data Set 1. In Data Set 2, caffeine intake had been controlled for, and significant interactions between caffeine, TOD, and scores on the MMSE and GNT were found. The TOD and caffeine effects highlight the need to control for these external factors when scoring the assessments. This conclusion has implications for the clinical procedure of diagnosis and treatment of dementia and Alzheimer's.


Association between caffeine intake and age at onset in Huntington's disease.

Simonin C, Duru C, Salleron J, Hincker P, Charles P, Delval A, Youssov K, Burnouf S, Azulay JP, Verny C, Scherer C, Tranchant C, Goizet C, Debruxelles S, Defebvre L, Sablonnière B, Romon-Rousseaux M, Buée L, Destée A, Godefroy O, Dürr A, Landwehrmeyer B; REGISTRY Study of the European Huntington's Disease Network., Bachoud-Levi AC, Richard F, Blum D, Krystkowiak P; Huntington French Speaking Network..

Neurobiol Dis. 2013 Oct;58:179-82. doi: 10.1016/j.nbd.2013.05.013.

PMID: 23732677 


Habitual consumption of caffeine, a non-selective adenosine receptor (AR) antagonist, has been suggested to be beneficial in Parkinson's and Alzheimer's diseases. Experimental evidence support that ARs play a role in Huntington's disease (HD) raising the hypothesis that caffeine may be a life-style modifier in HD. To determine a possible relationship between caffeine consumption and age at onset (AAO) in HD, we retrospectively assessed caffeine consumption in 80 HD patients using a dietary survey and determined relationship with AAO. Following adjustment for gender, smoking status and CAG repeat length, caffeine consumption greater than 190mg/day was significantly associated with an earlier AAO. These data support an association between habitual caffeine intake and AAO in HD patients, but further studies are warranted to understand the link between these variables.


Adenosine receptors; Caffeine; Huntington's disease


Blood Pressure Trajectory, Gait Speed, and Outcomes: The Health, Aging, and Body Composition Study.

Odden MC, Wu C, Shlipak MG, Psaty BM, Katz R, Applegate WB, Harris T, Newman AB, Peralta CA; Health ABC Study..

J Gerontol A Biol Sci Med Sci. 2016 Dec;71(12):1688-1694. Erratum in: J Gerontol A Biol Sci Med Sci. 2016 Dec;71(12 ):e1.

PMID: 27142696



The present study aimed to (i) evaluate previous observations that the association of blood pressure (BP) with outcomes varies by gait speed and (ii) evaluate the association of subsequent changes in BP and cardiovascular risk.


Participants included 2,669 adults aged 70-79 years in the Health, Aging, and Body Composition (Health ABC) study. Gait speed was dichotomized at ≥1.0 m/s over a 20-m test at baseline. BP was measured at baseline, and changes in BP over 5 years were evaluated using (i) population-based trajectory models and (ii) intraindividual mean and slope.


Over a mean of 10 years, there were 1,366 deaths, 336 first myocardial infarctions, and 295 first strokes. There was a differential pattern of association between baseline systolic BP and diastolic BP and outcomes among brisk and moderate speed walkers. For example, the association between higher diastolic BP and mortality was in the protective direction for moderate speed walkers (hazard ratio = 0.75; 95% confidence interval: 0.63, 0.91) per 10 mmHg higher, whereas it was null in brisk walkers (hazard ratio = 1.05; 95% confidence interval: 0.98, 1.11), p value for interaction .01. The 5-year population-based trajectories did not add important information beyond baseline BP. Individual slopes in both systolic BP and diastolic BP did not appear to have important associations with the outcomes.


In this study, we found that the overall level of BP was associated with myocardial infarction, stroke, and death, and this association differed by baseline gait speed, whereas changes in BP were not associated with these outcomes.


Blood pressure; Epidemiology; Function; Gait speed; Hypertension.


Trajectories of Lower Extremity Physical Performance: Effects on Fractures and Mortality in Older Women.

Barbour KE, Lui LY, McCulloch CE, Ensrud KE, Cawthon PM, Yaffe K, Barnes DE, Fredman L, Newman AB, Cummings SR, Cauley JA; Study of Osteoporotic Fractures..

J Gerontol A Biol Sci Med Sci. 2016 Dec;71(12):1609-1615.

PMID: 27084313 



Prior studies have only considered one measurement of physical performance in its relationship to fractures and mortality. A single measurement is susceptible to large within-person changes over time, and thus, may not capture the true association between physical performance and the outcomes of interest.


Using data from the Study of Osteoporotic Fractures, we followed 7,015 women enrolled prior to age 80 years who had outcome information beyond this age. Trajectories of walking speed (m/s) and chair stand speed (stands/s) were estimated up to the last visit prior to age 80 years using mixed-effects linear regression. Physical performance at age 80 (PF_age80) was assessed at the last visit prior to age 80 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression and multivariate models adjusted for all other covariates.


Greatest walking speed decline and chair stand speed decline were both associated with higher risk of hip fracture (HR: 1.28; 95% CI: 1.03, 1.58 and HR: 1.26; 95% CI: 1.03, 1.54, respectively), but not nonspine fractures. Greatest walking speed decline and chair stand speed decline were both associated with a significant 29% (95% CI: 17-42%) and 27% (95% CI: 15-39%) increased risk of mortality, respectively.


Greatest declines in walking speed and chair stand speed were both associated with an increased risk of hip fracture and mortality independent of PF_age80 and other important confounders. Both physical performance change and the single physical performance measurement should be considered in the etiology of hip fracture and mortality.


Fractures; Mortality; Physical performance; Trajectories

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Effect of diet on mortality and cancer recurrence among cancer survivors: a systematic review and meta-analysis of cohort studies

Carolina Schwedhelm, Heiner Boeing, Georg Hoffmann, Krasimira Aleksandrova, and Lukas Schwingshackl

Nutr Rev 2016 74: 737-748



Context: Evidence of an association between dietary patterns and individual foods and the risk of overall mortality among cancer survivors has not been reviewed systematically. Objective: The aim of this meta-analysis of cohort studies was to investigate the association between food intake and dietary patterns and overall mortality among cancer survivors. Data Sources: The PubMed and Embase databases were searched. Study Selection: A total of 117 studies enrolling 209 597 cancer survivors were included. Data Extraction: The following data were extracted: study location, types of outcome, population characteristics, dietary assessment method, risk estimates, and adjustment factors. Results: Higher intakes of vegetables and fish were inversely associated with overall mortality, and higher alcohol consumption was positively associated with overall mortality (RR, 1.08; 95%CI, 1.02–1.16). Adherence to the highest category of diet quality was inversely associated with overall mortality (RR, 0.78; 95%CI, 0.72–0.85; postdiagnosis RR, 0.79; 95%CI, 0.71–0.89), as was adherence to the highest category of a prudent/healthy dietary pattern (RR, 0.81; 95%CI, 0.67–0.98; postdiagnosis RR, 0.77; 95%CI, 0.60–0.99). The Western dietary pattern was associated with increased risk of overall mortality (RR, 1.46; 95%CI, 1.27–1.68; postdiagnosis RR, 1.51; 95%CI, 1.24–1.85). Conclusion: Adherence to a high-quality diet and a prudent/healthy dietary pattern is inversely associated with overall mortality among cancer survivors, whereas a Western dietary pattern is positively associated with overall mortality in this population.

cancer survivorsfood intakedietary patternsoverall mortalitycancer recurrencemeta-analysis


Evidence for the vitamin D hypothesis: The NHANES III extended mortality follow-up.

Daraghmeh AH, Bertoia ML, Al-Qadi MO, Abdulbaki AM, Roberts MB, Eaton CB.

Atherosclerosis. 2016 Apr 9;255:96-101. doi: 10.1016/j.atherosclerosis.2016.04.007. [Epub ahead of print]

PMID: 27855294



Emerging evidence suggests that low levels of vitamin D may be an important risk factor for multiple chronic diseases and mortality, but the evidence is mixed. Vitamin D levels are associated with sun exposure, diet, and metabolic status. One potential explanation for the lack of consistent findings amongst various studies is that low vitamin levels may be associated with poor diets or other risk factors that we were not adequately controlled for in different analyses.


Prospective analysis of adults over the age of 35 in NHANES III data (1988-1994) with 20 year mortality follow-up. Sequential Cox proportional hazard models quartiles of 25OH vitamin D adjusted for age, season, geography, sociodemographic (SD), CVD risk factors (CVD) and nutritional factors (NF) were performed.


Gender, race, diabetes, anti-hypertensive meds, income, taking vitamin D supplements, physical activity, alcohol consumption, region, body mass index, blood pressure, creatinine, albumin, CRP, thyroxine, iron, RBC folate, vitamin A, E, alpha-carotene, and lycopene were all associated with different quartiles of vitamin D and as well as CHD and all-cause mortality and thus are important potential confounders of this relationship. Adjusting for the confounding factors, higher levels of vitamin D demonstrate an inverse relationship with all-cause mortality, but only the top quartile of vitamin D shows an inverse relationship with CHD mortality.


The highest quartile compared to the lowest quartile of 25OH vitamin D levels is inversely associated with CHD and all-cause mortality adjusting for multiple confounders. Whether supplementation of individuals with low vitamin D will result in similar benefits will require a randomized clinical trial.


Cohort studies; Mortality; Vitamin D


Body size over the life-course and the risk of endometrial cancer: the California Teachers Study.

Horn-Ross PL, Canchola AJ, Bernstein L, Deapen D, Lacey JV Jr, Lee E, Nelson DO, Reynolds P.

Cancer Causes Control. 2016 Dec;27(12):1419-1428.

PMID: 27804057



Physical activity may be associated with decreasing endometrial cancer risk; it remains unclear whether the association is modified by body size.


Among 93 888 eligible California Teachers Study participants, 976 were diagnosed with incident endometrial cancer between 1995-1996 and 2007. Cox proportional hazards regression methods were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for endometrial cancer associated with long-term (high school through age 54 years) and baseline (3 years prior to joining the cohort) strenuous and moderate recreational physical activity, overall and by body size.


Increased baseline strenuous recreational physical activity was associated with decreased endometrial cancer risk (Ptrend=0.006) with approximately 25% lower risk among women exercising >3 h per week per year than among those exercising <1/2 h per week per year (RR, 0.76; 95% CI, 0.63-0.92). This inverse association was observed among overweight/obese women (body mass index ≥25 kg m(-2); Ptrend=0.006), but not among thinner women (Ptrend=0.12). Baseline moderate activity was associated with lower risk among overweight/obese women.


Increasing physical activity, particularly strenuous activity, may be a lifestyle change that overweight and obese women can implement to reduce their endometrial cancer risk.


The association of diabetes and obesity with prostate cancer aggressiveness among Black Americans and White Americans in a population-based study.

Khan S, Cai J, Nielsen ME, Troester MA, Mohler JL, Fontham ET, Hendrix LH, Farnan L, Olshan AF, Bensen JT.

Cancer Causes Control. 2016 Dec;27(12):1475-1485.

PMID: 27830399



Few studies have investigated the role of race in the association of diabetes and obesity with prostate cancer aggressiveness. Here we evaluate the independent association between diabetes and obesity with prostate cancer aggressiveness in White Americans and Black Americans.


Our cross-sectional, case-only study consisted of 1,058 White Americans and 991 Black Americans from the North Carolina-Louisiana Prostate Cancer (PCaP) project. Diabetes status was determined by self-report. Obesity was determined using body mass index and calculated based on anthropometric measurements. High aggressive prostate cancer was defined as Gleason sum ≥8, or prostate-specific antigen >20 ng/ml, or Gleason sum = 7 and clinical stage cT3-cT4. The association between diabetes and obesity with high aggressive prostate cancer at diagnosis was evaluated using multivariable logistic regression and adjusted for potential confounders.


Diabetes was not associated with high aggressive prostate cancer in the overall sample (OR 1.04; 95% CI 0.79, 1.37), White Americans (OR 1.00; 95% CI 0.65, 1.57) or Black Americans (OR 1.07; 95% CI 0.75, 1.53). Obesity, independent of diabetes, was positively associated with high aggressive prostate cancer in White Americans (OR 1.98; 95% CI 1.14, 3.43), but not in the overall sample (OR 1.37; 95% CI 0.99, 1.92) or Black Americans (OR 1.09; 95% CI 0.71, 1.67).


Diabetes was not associated with prostate cancer aggressiveness, overall, or in either race group. Obesity, independent of diabetes, was associated with high aggressive prostate cancer only in White Americans.


Aggressiveness; Black Americans; Diabetes; Obesity; PCaP; Prostrate cancer


Careless skeptics: a dangerous breed.

de Grey AD.

Rejuvenation Res. 2016 Oct 12. [Epub ahead of print]

PMID: 27733078


1. Shermer M. 

Radical life-extension is not around the corner. 

Sci Am October 2016


Ageing, neurodegeneration and brain rejuvenation.

Wyss-Coray T.

Nature. 2016 Nov 9;539(7628):180-186. doi: 10.1038/nature20411.

PMID: 27830812


Although systemic diseases take the biggest toll on human health and well-being, increasingly, a failing brain is the arbiter of a death preceded by a gradual loss of the essence of being. Ageing, which is fundamental to neurodegeneration and dementia, affects every organ in the body and seems to be encoded partly in a blood-based signature. Indeed, factors in the circulation have been shown to modulate ageing and to rejuvenate numerous organs, including the brain. The discovery of such factors, the identification of their origins and a deeper understanding of their functions is ushering in a new era in ageing and dementia research.



Vitamin D Deficiency — Is There Really a Pandemic?

J.E. Manson, P.M. Brannon, C.J. Rosen, and C.L. Taylor

N Engl J Med 2016; 375:1817-1820 November 10, 2016 DOI: 10.1056/NEJMp1608005


Interpretation of the evidence for the efficacy and safety of statin therapy.

Collins R, Reith C, Emberson J, Armitage J, Baigent C, Blackwell L, Blumenthal R, Danesh J, Smith GD, DeMets D, Evans S, Law M, MacMahon S, Martin S, Neal B, Poulter N, Preiss D, Ridker P, Roberts I, Rodgers A, Sandercock P, Schulz K, Sever P, Simes J, Smeeth L, Wald N, Yusuf S, Peto R.

Lancet. 2016 Sep 8. pii: S0140-6736(16)31357-5. doi: 10.1016/S0140-6736(16)31357-5. [Epub ahead of print] Review.

PMID: 27616593


This Review is intended to help clinicians, patients, and the public make informed decisions about statin therapy for the prevention of heart attacks and strokes. It explains how the evidence that is available from randomised controlled trials yields reliable information about both the efficacy and safety of statin therapy. In addition, it discusses how claims that statins commonly cause adverse effects reflect a failure to recognise the limitations of other sources of evidence about the effects of treatment. Large-scale evidence from randomised trials shows that statin therapy reduces the risk of major vascular events (ie, coronary deaths or myocardial infarctions, strokes, and coronary revascularisation procedures) by about one-quarter for each mmol/L reduction in LDL cholesterol during each year (after the first) that it continues to be taken. The absolute benefits of statin therapy depend on an individual's absolute risk of occlusive vascular events and the absolute reduction in LDL cholesterol that is achieved. For example, lowering LDL cholesterol by 2 mmol/L (77 mg/dL) with an effective low-cost statin regimen (eg, atorvastatin 40 mg daily, costing about £2 per month) for 5 years in 10 000 patients would typically prevent major vascular events from occurring in about 1000 patients (ie, 10% absolute benefit) with pre-existing occlusive vascular disease (secondary prevention) and in 500 patients (ie, 5% absolute benefit) who are at increased risk but have not yet had a vascular event (primary prevention). Statin therapy has been shown to reduce vascular disease risk during each year it continues to be taken, so larger absolute benefits would accrue with more prolonged therapy, and these benefits persist long term. The only serious adverse events that have been shown to be caused by long-term statin therapy-ie, adverse effects of the statin-are myopathy (defined as muscle pain or weakness combined with large increases in blood concentrations of creatine kinase), new-onset diabetes mellitus, and, probably, haemorrhagic stroke. Typically, treatment of 10 000 patients for 5 years with an effective regimen (eg, atorvastatin 40 mg daily) would cause about 5 cases of myopathy (one of which might progress, if the statin therapy is not stopped, to the more severe condition of rhabdomyolysis), 50-100 new cases of diabetes, and 5-10 haemorrhagic strokes. However, any adverse impact of these side-effects on major vascular events has already been taken into account in the estimates of the absolute benefits. Statin therapy may cause symptomatic adverse events (eg, muscle pain or weakness) in up to about 50-100 patients (ie, 0·5-1·0% absolute harm) per 10 000 treated for 5 years. However, placebo-controlled randomised trials have shown definitively that almost all of the symptomatic adverse events that are attributed to statin therapy in routine practice are not actually caused by it (ie, they represent misattribution). The large-scale evidence available from randomised trials also indicates that it is unlikely that large absolute excesses in other serious adverse events still await discovery. Consequently, any further findings that emerge about the effects of statin therapy would not be expected to alter materially the balance of benefits and harms. It is, therefore, of concern that exaggerated claims about side-effect rates with statin therapy may be responsible for its under-use among individuals at increased risk of cardiovascular events. For, whereas the rare cases of myopathy and any muscle-related symptoms that are attributed to statin therapy generally resolve rapidly when treatment is stopped, the heart attacks or strokes that may occur if statin therapy is stopped unnecessarily can be devastating.


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A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility.

Desai MS, Seekatz AM, Koropatkin NM, Kamada N, Hickey CA, Wolter M, Pudlo NA, Kitamoto S, Terrapon N, Muller A, Young VB, Henrissat B, Wilmes P, Stappenbeck TS, Núñez G, Martens EC.

Cell. 2016 Nov 17;167(5):1339-1353.e21. doi: 10.1016/j.cell.2016.10.043.

PMID: 27863247


Despite the accepted health benefits of consuming dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a gnotobiotic mouse model, in which animals were colonized with a synthetic human gut microbiota composed of fully sequenced commensal bacteria, we elucidated the functional interactions between dietary fiber, the gut microbiota, and the colonic mucus barrier, which serves as a primary defense against enteric pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation, together with a fiber-deprived, mucus-eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium. Our work reveals intricate pathways linking diet, the gut microbiome, and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics.


Akkermansia; Citrobacter rodentium; bacteroides; dietary fiber; gylcans; microbiome; microbiota; mucin; mucus layer; polysaccharides


Effects of Statins on Cancer Mortality and Progression: A Systematic Review and Meta-analysis of 95 Cohorts Including 1111407 Individuals.

Mei Z, Liang M, Li L, Zhang Y, Wang Q, Yang W.

Int J Cancer. 2016 Nov 18. doi: 10.1002/ijc.30526. [Epub ahead of print]

PMID: 27859151


Statins have been implicated in the regulation of cell proliferation, apoptosis and tumor progression in cancer patients and statin use at the time of cancer diagnosis has been reported to be associated with reduced cancer risk and improved survival, irrespective of concomitant anti-cancer therapy. A systematic literature search of relevant databases through May 2015 was conducted to identify studies assessing the prognostic impact of statin use on prognostic outcomes in cancer patients. Literature search identified 95 cohort studies that met the inclusion criteria. A meta-analysis of 55 articles showed that statin use was significantly associated with decreased risk of all-cause mortality (HR 0.70, 95% Cl 0.66 to 0.74) compared with non-users. The observed pooled estimates were retained for cancer-specific mortality (HR 0.60, 95% Cl 0.47 to 0.77), progression-free survival (HR 0.67, 95% Cl 0.56 to 0.81), recurrence-free survial (HR 0.74, 95% Cl 0.65 to 0.83) and disease-free survival (HR 0.53, 95% Cl 0.40 to 0.72). These associations almost remained consistent across those outcomes when stratified by publication type, tumour location, study design, sample size, initiation of statins, disease stage, research country, follow-up duration or research hospital involved. Subgroup analyses according to initiation of statins showed postdiagnosis statin users (HR 0.65, 95% Cl 0.54 to 0.79) gained significantly more recurrence-free survival benefit than prediagnosis statin users (HR 0.86, 95% Cl 0.77 to 0.96) (P for interaction=0.018). Statin therapy has potential survival benefit for patients with malignancy. Further large-scale prospective studies emphasising survival outcomes of individual cancer type are strongly encouraged.


cancer; meta-analysis; mortality; progression; recurrence; statins


Change in body size and mortality: a systematic review and meta-analysis.

Karahalios A, English DR, Simpson JA.

Int J Epidemiol. 2016 Nov 17. pii: dyw246. [Epub ahead of print]

PMID: 27864401



Observational studies have reported that weight loss in later life is associated with an increased risk of mortality. However, the association with weight gain is unclear. We conducted a systematic review and meta-analysis of prospective studies assessing the association of weight gain and loss, and mortality.


We searched PubMed, Scopus and Web of Science for articles published before 5 September 2015. We included prospective studies that reported enough information to extract hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) for the association between weight gain and/or weight loss, and all-cause and cause-specific mortality. The estimates were pooled using a random-effects model. Meta-regression models were fitted to explore sources of potential between-study heterogeneity.


A total of 25 (providing data from 437 772 participants with 34 038 deaths from all causes) and 24 studies (434 694 participants with 31 978 deaths) presented results for the exposures, weight loss and weight gain. Weight loss compared with a stable weight was associated with an increased risk of all-cause (pooled HR: 1.45; 95% CI: 1.34, 1.58), and cardiovascular disease (CVD) mortality (1.50; 1.32, 1.70) and a slightly increased risk of cancer mortality (1.19; 0.97, 1.46). Weight gain was associated with an increased risk of CVD mortality (1.21; 1.07, 1.36) and a slightly increased risk of all-cause mortality (1.07; 1.01, 1.13) and cancer mortality (1.04; 0.96, 1.13). Considerable heterogeneity was observed; the method used to ascertain body size and the proportion of the baseline sample included in the final analysis explained most of the heterogeneity.


Weight loss and weight gain in midlife are associated with increased risk of all-cause and CVD mortality.


Meta-analysis; middle aged; mortality; systematic review; weight gain; weight loss


Diet-dependent acid load and type 2 diabetes: pooled results from three prospective cohort studies.

Kiefte-de Jong JC, Li Y, Chen M, Curhan GC, Mattei J, Malik VS, Forman JP, Franco OH, Hu FB.

Diabetologia. 2016 Nov 17. [Epub ahead of print]

PMID: 27858141



Studies suggest a potential link between low-grade metabolic acidosis and type 2 diabetes. A western dietary pattern increases daily acid load but the association between diet-dependent acid load and type 2 diabetes is still unclear. This study aimed to assess whether diet-dependent acid load is associated with the risk of type 2 diabetes.


We examined the association between energy-adjusted net endogenous acid production (NEAP), potential renal acid load (PRAL) and animal protein-to-potassium ratio (A:P) on incident type 2 diabetes in 67,433 women from the Nurses' Health Study, 84,310 women from the Nurses' Health Study II and 35,743 men from the Health Professionals' Follow-up Study who were free from type 2 diabetes, cardiovascular disease and cancer at baseline. Study-specific HRs were estimated using Cox proportional hazards models with time-varying covariates and were pooled using a random effects meta-analysis.


We documented 15,305 cases of type 2 diabetes during 4,025,131 person-years of follow-up. After adjustment for diabetes risk factors, dietary NEAP, PRAL and A:P were positively associated with type 2 diabetes (pooled HR [95% CI] for highest (Q5) vs lowest quintile (Q1): 1.29 [1.22, 1.37], p trend <0.0001; 1.29 [1.22, 1.36], p trend <0.0001 and 1.32 [1.24, 1.40], p trend <0.0001 for NEAP, PRAL and A:P, respectively). These results were not fully explained by other dietary factors including glycaemic load and dietary quality (HR [95% CI] for Q5 vs Q1: 1.21 [1.09, 1.33], p trend <0.0001; 1.19 [1.08, 1.30] and 1.26 [1.17, 1.36], p trend <0.0001 for NEAP, PRAL and A:P, respectively).


This study suggests that higher diet-dependent acid load is associated with an increased risk of type 2 diabetes. This association is not fully explained by diabetes risk factors and overall diet quality.


Acid–base balance; Dietary acid load; Glucose intolerance; Insulin resistance


Dietary trace element intake and liver cancer risk: results from two population-based cohorts in China.

Ma X, Yang Y, Li HL, Zheng W, Gao J, Zhang W, Yang G, Shu XO, Xiang YB.

Int J Cancer. 2016 Nov 15. doi: 10.1002/ijc.30522. [Epub ahead of print]

PMID: 27859272


Dietary factors have been hypothesized to affect the risk of liver cancer via various mechanisms, but the influence has been not well studied and the evidence is conflicting. We investigated associations of dietary trace element intake, assessed through a validated food frequency questionnaire, with risk of liver cancer in 2 prospective cohort studies of 132,765 women (1997-2013) and men (2002-2013) in Shanghai, China. The associations were first evaluated in cohort studies and further assessed in a case-control study nested within these cohorts adjusting for hepatitis B virus infection. For cohort analyses, Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals. For nested case-control analyses, conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. After a median follow-up time of 15.2 years for the Shanghai Women's Health Study and 9.3 years for the Shanghai Men's Health Study, 192 women and 344 men developed liver cancer. Dietary intake of manganese was inversely associated with liver cancer risk (highest vs. lowest quintile, HR = 0.51, 95% CI: 0.35-0.73; p trend = 0.001). Further adjustment for hepatitis B virus infection in the nested case-control study yielded a similar result (highest vs. lowest quintile, OR = 0.38, 95% CI: 0.21-0.69; p trend  < 0.001). No significant association was found between dietary intake of selenium, iron, zinc, copper and liver cancer risk. The results suggest that higher intake of manganese may be associated with a lower risk of liver cancer in China.


dietary trace elements; liver cancer; manganese; nested case-control study; prospective cohort study


[The below paper is not pdf-availed.]

Gamma-glutamyltransferase and risk of prostate cancer: Findings from the KIHD prospective cohort study.

Kunutsor SK, Laukkanen JA.

Int J Cancer. 2016 Nov 8. doi: 10.1002/ijc.30511. [Epub ahead of print]

PMID: 27861848


Increased circulating serum gamma-glutamyltransferase (GGT) has been linked with an increased risk of chronic disease outcomes, including overall and several site-specific cancers. However, the relationship of GGT with prostate cancer risk is uncertain. We aimed to assess the prospective association of GGT with risk of prostate cancer. Serum GGT activity was assessed at baseline in the Finnish Kuopio Ischemic Heart Disease prospective cohort of 2,390 men aged 42-61 years without a history of cancer at baseline. We corrected for within-person variability in GGT values using data from repeat measurements taken several years apart. During a median follow-up of 24.6 years, 230 cases of prostate cancer occurred. The age-adjusted regression dilution ratio for loge GGT was 0.69 [95% confidence interval (CI): 0.63-0.74]. Serum GGT was nonlinearly associated with risk of prostate cancer. In age-adjusted Cox regression analysis, the hazard ratio (95% CIs) for prostate cancer in a comparison of the top quartile versus bottom quartiles 1-3 of GGT values was 1.43 (1.07 to 1.93; p = 0.017), which persisted on adjustment for several established cancer risk factors 1.46 (1.06 to 2.02; p = 0.020). The association remained unchanged on further adjustment for total energy intake, socioeconomic status, physical activity and C-reactive protein. The association did not importantly vary across several clinical subgroups. GGT is positively and independently associated with future risk of prostate cancer in a middle-aged Finnish male population over long-term follow-up. Further research is needed to understand the mechanistic pathways involved and if GGT may have potential relevance in prostate cancer prevention.


gamma-glutamyltranferase; prostate cancer; risk factor


Daytime napping and mortality from all causes, cardiovascular disease, and cancer: a meta-analysis of prospective cohort studies.

Zhong G, Wang Y, Tao T, Ying J, Zhao Y.

Sleep Med. 2015 Jul;16(7):811-9. doi: 10.1016/j.sleep.2015.01.025. Review.

PMID: 26051864



The association between daytime napping and mortality remains controversial. We conducted a meta-analysis to examine the associations between daytime napping and the risks of death from all causes, cardiovascular disease (CVD), and cancer.


PubMed and Embase databases were searched through 19 September 2014. Prospective cohort studies that provided risk estimates of daytime napping and mortality were eligible for our meta-analysis. Two investigators independently performed study screening and data extraction. A random-effects model was used to estimate the combined effect size. Subgroup analyses were conducted to identify potential effect modifiers.


Twelve studies, involving 130,068 subjects, 49,791 nappers, and 19,059 deaths, were included. Our meta-analysis showed that daytime napping was associated with an increased risk of death from all causes [n = 9 studies; hazard ratio (HR), 1.22; 95% confidence interval (CI), 1.14-1.31; I(2) = 42.5%]. No significant associations between daytime napping and the risks of death from CVD (n = 6 studies; HR, 1.20; 95% CI, 0.96-1.50; I(2) = 75.0%) and cancer (n = 4 studies; HR, 1.07; 95% CI, 0.99-1.15; I(2) = 8.9%) were found. There were no significant differences in risks of all-cause and CVD mortality between subgroups stratified by the prevalence of napping, follow-up duration, outcome assessment, age, and sex.


Daytime napping is a predictor of increased all-cause mortality but not of CVD and cancer mortality. However, our findings should be treated with caution because of limited numbers of included studies and potential biases.


Cancer; Cardiovascular disease; Death; Meta-analysis; Mortality; Napping


Sleep Duration and All-Cause Mortality: A Systematic Review and Meta-Analysis of Prospective Studies.

Cappuccio FP, D'Elia L, Strazzullo P, Miller MA.

Sleep. 2010 May;33(5):585-92. Review.

PMID: 20469800 Free PMC Article



Increasing evidence suggests an association between both short and long duration of habitual sleep with adverse health outcomes.


To assess whether the population longitudinal evidence supports the presence of a relationship between duration of sleep and all-cause mortality, to investigate both short and long sleep duration and to obtain an estimate of the risk.


We performed a systematic search of publications using MEDLINE (1966-2009), EMBASE (from 1980), the Cochrane Library, and manual searches without language restrictions. We included studies if they were prospective, had follow-up >3 years, had duration of sleep at baseline, and all-cause mortality prospectively. We extracted relative risks (RR) and 95% confidence intervals (CI) and pooled them using a random effect model. We carried out sensitivity analyses and assessed heterogeneity and publication bias.


Overall, the 16 studies analyzed provided 27 independent cohort samples. They included 1,382,999 male and female participants (followup range 4 to 25 years), and 112,566 deaths. Sleep duration was assessed by questionnaire and outcome through death certification. In the pooled analysis, short duration of sleep was associated with a greater risk of death (RR: 1.12; 95% CI 1.06 to 1.18; P < 0.01) with no evidence of publication bias (P = 0.74) but heterogeneity between studies (P = 0.02). Long duration of sleep was also associated with a greater risk of death (1.30; [1.22 to 1.38]; P < 0.0001) with no evidence of publication bias (P = 0.18) but significant heterogeneity between studies (P < 0.0001).


Both short and long duration of sleep are significant predictors of death in prospective population studies.


Sleep duration and mortality in the elderly: a systematic review with meta-analysis.

da Silva AA, de Mello RG, Schaan CW, Fuchs FD, Redline S, Fuchs SC.

BMJ Open. 2016 Feb 17;6(2):e008119. doi: 10.1136/bmjopen-2015-008119.

PMID: 26888725 Free PMC Article



The purpose of our study was to evaluate the association between short and long sleep duration and all-cause and cardiovascular mortality among elderly individuals.


Systematic review and meta-analysis of population-based cohort studies.


Articles were retrieved from international and national electronic databases.


Studies were identified in PubMed, EMBASE, LILACS (Latin American and Caribbean Health Sciences Literature), IBECS (Bibliographic Index on Health Sciences from Spain) and CAPES (PhD thesis repository) between 1980 and 2015. Studies which met all criteria were eligible: participants aged 60 years or over, assessment of sleep duration as 24 h, nighttime or daytime sleep, evaluation of all-cause or cause-specific mortality, population-based cohort studies conducted on representative samples. There was no language restriction and studies published as abstracts were excluded.


Data were analysed using the Comprehensive Meta-Analysis software (V.3.3.070), and summary estimates (relative risk (RR), 95% CI) were calculated using a random effects model. Heterogeneity and consistency were evaluated through Cochran's Q and the I(2) statistics, respectively, and sensitivity analyses were conducted.


All-cause and cardiovascular mortality.


Overall, 27 cohort studies were selected, comprising >70,000 elderly individuals, and followed up from 3.4 to 35 years. In the pooled analysis, long and short sleep duration were associated with increased all-cause mortality (RR 1.33; 95% CI 1.24 to 1.43 and RR 1.07; 95% CI 1.03 to 1.11, respectively), compared with the reference category. For cardiovascular mortality, the pooled relative risks were 1.43 (95% CI 1.15 to 1.78) for long sleep, and 1.18 (95% CI 0.76 to 1.84) for short sleep. Daytime napping ≥ 30 min was associated with risk of all-cause mortality (RR 1.27; 95% CI 1.08 to 1.49), compared with no daytime sleep, but longer sleep duration (≥ 2.0 h) was not (RR 1.34; 95% CI 1.95 to 1.90).


Among elderly individuals, long and short sleep duration are associated with increased risk for all-cause mortality. Long sleep duration is associated with cardiovascular mortality.



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["What is the usefulness of the ratio of n-6 to n-3, which is a good divided by good?"]

Plasma eicosapentaenoic acid is negatively associated with all-cause mortality among men and women in a population-based prospective study.

Miura K, Hughes MC, Ungerer JP, Green AC.

Nutr Res. 2016 Sep 13. pii: S0271-5317(16)30435-3. doi: 10.1016/j.nutres.2016.09.006. [Epub ahead of print]

PMID: 27865614


Omega-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties, whereas omega-6 PUFAs appear to have proinflammatory properties. We aimed to assess plasma omega-3 and omega-6 PUFA status in relation to all-cause mortality in an Australian community-based study. We hypothesized that omega-3 PUFA would be inversely associated, and omega-6 PUFA positively associated with all-cause mortality. Plasma phospholipid omega-3 (eicosapentaenoic acid [EPA], docosapentaenoic acid [DPA], docosahexaenoic acid, α-linolenic acid, and total) and omega-6 PUFAs (linoleic acid, arachidonic acid, and total) were measured among 1008 adults (44% men) in 1996. Plasma PUFA composition was quantified using gas chromatography. During 17-year follow-up, 98 men and 81 women died. After adjustment for potential confounding factors, plasma EPA was inversely associated with all-cause mortality overall (adjusted hazard ratio {HR} per 1-SD increase, 0.81; 95% confidence interval [CI], 0.68-0.95), in men (HR, 0.78; 95% CI, 0.62-0.98), and in women (HR, 0.78; 95% CI, 0.65-0.94), separately. Inverse associations with mortality among men were also seen for DPA (HR, 0.76; 95% CI, 0.60-0.97) and α-linolenic acid (HR, 0.73; 95% CI, 0.57-0.94). No omega-6 PUFAs were significantly associated with mortality. Our findings of reduced all-cause mortality in men and women who have high EPA in plasma, and in men with high plasma DPA and α-linolenic acid, partially support our hypothesis that omega-3 PUFAs help reduce mortality but provide no evidence that omega-6 PUFAs may increase mortality.


Arachidonic acid; Biomarkers; Docosahexaenoic acid; Eicosapentaenoic acid; Linoleic acid; Omega-3 fatty acids; Omega-6 fatty acids


Plasma phospholipid long-chain ω-3 fatty acids and total and cause-specific mortality in older adults: a cohort study.

Mozaffarian D, Lemaitre RN, King IB, Song X, Huang H, Sacks FM, Rimm EB, Wang M, Siscovick DS.

Ann Intern Med. 2013 Apr 2;158(7):515-25. doi: 10.7326/0003-4819-158-7-201304020-00003.

PMID: 23546563 Free PMC Article



Long-chain ω-3 polyunsaturated fatty acids (ω3-PUFAs), including eicosapentaenoic acid (EPA) (20:5ω-3), docosapentaenoic acid (DPA) (22:5ω-3), and docosahexaenoic acid (DHA) (22:6ω-3), have been shown to reduce cardiovascular risk, but effects on cause-specific and total mortality and potential dose-responses remain controversial. Most observational studies have assessed self-reported dietary intake and most randomized trials have tested effects of adding supplements to dietary intake and evaluated secondary prevention, thus limiting inference for dietary ω3-PUFAs or primary prevention.


To investigate associations of plasma phospholipid EPA, DPA, DHA, and total ω3-PUFA levels with total and cause-specific mortality among healthy older adults not receiving supplements.


Prospective cohort study.


4 U.S. communities.


2692 U.S. adults aged 74 years (±5 years) without prevalent coronary heart disease (CHD), stroke, or heart failure at baseline.


Phospholipid fatty acid levels and cardiovascular risk factors were measured in 1992. Relationships with total and cause-specific mortality and incident fatal or nonfatal CHD and stroke through 2008 were assessed.


During 30 829 person-years, 1625 deaths (including 570 cardiovascular deaths), 359 fatal and 371 nonfatal CHD events, and 130 fatal and 276 nonfatal strokes occurred. After adjustment, higher plasma levels of ω3-PUFA biomarkers were associated with lower total mortality, with extreme-quintile hazard ratios of 0.83 for EPA (95% CI, 0.71 to 0.98; P for trend = 0.005), 0.77 for DPA (CI, 0.66 to 0.90; P for trend = 0.008), 0.80 for DHA (CI, 0.67 to 0.94; P for trend = 0.006), and 0.73 for total ω3-PUFAs (CI, 0.61 to 0.86; P for trend < 0.001). Lower risk was largely attributable to fewer cardiovascular than noncardiovascular deaths. Individuals in the highest quintile of phospholipid ω3-PUFA level lived an average of 2.22 more years (CI, 0.75 to 3.13 years) after age 65 years than did those in the lowest quintile.


Temporal changes in fatty acid levels and misclassification of causes of death may have resulted in underestimated associations, and unmeasured or imperfectly measured covariates may have caused residual confounding.


Higher circulating individual and total ω3-PUFA levels are associated with lower total mortality, especially CHD death, in older adults.


Circulating omega-6 polyunsaturated fatty acids and total and cause-specific mortality: the Cardiovascular Health Study.

Wu JH, Lemaitre RN, King IB, Song X, Psaty BM, Siscovick DS, Mozaffarian D.

Circulation. 2014 Oct 7;130(15):1245-53. doi: 10.1161/CIRCULATIONAHA.114.011590.

PMID: 25124495 Free PMC Article



Although omega-6 polyunsaturated fatty acids (n-6 PUFA) have been recommended to reduce coronary heart disease (CHD), controversy remains about benefits versus harms, including concerns over theorized proinflammatory effects of n-6 PUFA. We investigated associations of circulating n-6 PUFA including linoleic acid (the major dietary PUFA), γ-linolenic acid, dihomo-γ-linolenic acid, and arachidonic acid, with total and cause-specific mortality in the Cardiovascular Health Study, a community-based U.S. cohort.


Among 2792 participants(aged ≥65 years) free of cardiovascular disease at baseline, plasma phospholipid n-6 PUFA were measured at baseline using standardized methods. All-cause and cause-specific mortality, and total incident CHD and stroke, were assessed and adjudicated centrally. Associations of PUFA with risk were assessed by Cox regression. During 34 291 person-years of follow-up (1992-2010), 1994 deaths occurred (678 cardiovascular deaths), with 427 fatal and 418 nonfatal CHD, and 154 fatal and 399 nonfatal strokes. In multivariable models, higher linoleic acid was associated with lower total mortality, with extreme-quintile hazard ratio =0.87 (P trend=0.005). Lower death was largely attributable to cardiovascular disease causes, especially nonarrhythmic CHD mortality (hazard ratio, 0.51; 95% confidence interval, 0.32-0.82; P trend=0.001). Circulating γ-linolenic acid, dihomo-γ-linolenic acid, and arachidonic acid were not significantly associated with total or cause-specific mortality (eg, for arachidonic acid and CHD death, the extreme-quintile hazard ratio was 0.97; 95% confidence interval, 0.70-1.34; P trend=0.87). Evaluated semiparametrically, linoleic acid showed graded inverse associations with total mortality (P=0.005). There was little evidence that associations of n-6 PUFA with total mortality varied by age, sex, race, or plasma n-3 PUFA. Evaluating both n-6 and n-3 PUFA, lowest risk was evident with highest levels of both.


High circulating linoleic acid, but not other n-6 PUFA, was inversely associated with total and CHD mortality in older adults.


cardiovascular diseases; epidemiology; fatty acids, omega-6; mortality


Letter by Lucas Regarding Articles, "Dietary Linoleic Acid and Risk of Coronary Heart Disease: A Systematic Review and Meta-Analysis of Prospective Cohort Studies" and "Circulating Omega-6 Polyunsaturated Fatty Acids and Total and Cause-Specific Mortality: The Cardiovascular Health Study".

Lucas M.

Circulation. 2015 Jul 21;132(3):e21. doi: 10.1161/CIRCULATIONAHA.114.013446. No abstract available.

PMID: 26195492 Free Article

To the Editor:

Recently, 2 articles1,2 in your journal raised a fundamental question about polyunsaturated fatty acid (PUFA) ratios. For decades, the literature has recounted that humans have evolved on a PUFA diet containing a ratio of n-6 to n-3 of 1:1 and that an increase in this ratio is a major contributor to chronic diseases. Linoleic acid (LA; 18:2n-6), the primary source of n-6 PUFAs in human diets,3 is also the precursor of arachidonic acid (20:4n-6), from which proinflammatory eicosanoids and cytokines are derived, leading some to hypothesize that an imbalance between n-6 and n-3 intakes may cause cardiovascular disease and depression.4 However, a meta-analysis of prospective cohorts has shown that LA is associated with reduced risk of coronary heart disease in a dose–response manner.1 In another recent meta-analysis of prospective cohorts, circulating blood LA was not associated with risk for coronary outcomes, but arachidonic acid was associated with lower risk (relative risk, 0.83; 95% confidence interval, 0.74–0.92).5 In the Cardiovascular Health Study, higher plasma phospholipid LA, but not other n-6 PUFAs, was associated with lowered coronary heart disease and total mortality in older adults.2 In a 10-year prospective follow-up study of middle-aged women, we noted that LA intake was not associated with excess risk of clinical depression in the lowest quintiles of n-3 (in which the risk might be hypothesized to be the greatest).3 Three large US cohort studies found no evidence that n-6 PUFA intake increased the risk of suicide.4 Although we do not have all the evidence of relationships between n-6 dietary intake and health outcomes, it is clear that their contributions are not harmful and could even be rather protective. Moreover, the ratio of n-6 to n-3 is not a specific tool. Mathematically, there are infinite possibilities of numerators and denominators that will produce the same ratio of n-6 to n-3. Because LA might be viewed as good fat, a fundamental question arises: What is the usefulness of the ratio of n-6 to n-3, which is a good divided by good?


Response to Letters Regarding Article, "Circulating Omega-6 Polyunsaturated Fatty Acids and Total and Cause-Specific Mortality: The Cardiovascular Health Study".

Wu JH, Lemaitre RN, King IB, Song X, Psaty BM, Siscovick DS, Mozaffarian D.

Circulation. 2015 Jul 21;132(3):e25-6. doi: 10.1161/CIRCULATIONAHA.115.014853. No abstract available.

PMID: 26195495 Free PMC Article

Sertoglu and colleagues express concern about measurement of circulating fatty acid biomarkers in plasma. However, our investigation did not measure fatty acids in total plasma (the sum of fatty acids in non-esterified fatty acids, cholesterol esters, triglycerides, and phospholipids), but in the plasma phospholipid fraction. The plasma phospholipid fraction reflects fatty acid concentrations in cell membranes. Furthermore, phospholipid fatty acids in plasma and erythrocyte membranes inter-exchange, reflect fatty acid consumption over a similar period of time, and are reasonably correlated.1 Thus, either plasma phospholipid or erythrocyte fatty acid composition is a valid and reliable biomarker of dietary consumption. This explains why numerous longitudinal investigations have evaluated associations of fatty acids in plasma phospholipids or erythrocyte phospholipids in relation to cardio-metabolic disease risk.2, 3

We appreciate Sertoglu’s interest in omega-3 polyunsaturated fatty acids (n-3 PUFA). As described and cited in the present investigation, we previously measured and reported associations between plasma phospholipid n-3 PUFA biomarkers and risk of total and cardiovascular mortality in this cohort.4 In addition, in the current investigation we evaluated and found little evidence of interaction between linoleic acid (the major dietary omega-6 fatty acid) and n-3 PUFA (P=0.54). Indeed, our findings suggested an additive benefit, in that those with highest levels of both linoleic acid and n-3 PUFA had the lowest risk of total and cardiovascular mortality (figure 3, supplement figure 2).5 This important finding would have been obscured using an analysis based on the n-6/n-3 ratio. The conceptual and biologic flaws of the n-6/n-3 ratio have been described.6 A key flaw is the inability to discern very different conditions of dietary intake or underlying physiology: e.g., a ratio may be identical when consumption and circulating levels of both n-6 and n-3 are high or when both are low, two very different circumstances. In addition, the ratio cannot distinguish increases in the n-6 PUFA vs. decreases in n-3 PUFA. Finally, the conceptual basis of the ratio depends on the notion that n-6 PUFA and n-3 PUFA have opposing effects. However, substantial evidence indicates that both are beneficial;6 indeed, a recent meta-analysis found that individuals with higher circulating levels of arachidonic acid, the prototypical n-6 PUFA thought to be pro-inflammatory and harmful, had lower risk of coronary disease.7 Given these considerations, we agree with Dr Lucas that existing evidence suggest beneficial effect of dietary linoleic acid for cardiovascular outcomes, not harm, and use of the n-6/n-3 ratio is unlikely to impart meaningful information over and above assessment of the individual fatty acids alone.


Nut consumption is associated with lower incidence of type 2 diabetes: The Tehran Lipid and Glucose Study.

Asghari G, Ghorbani Z, Mirmiran P, Azizi F.

Diabetes Metab. 2016 Nov 16. pii: S1262-3636(16)30508-0. doi: 10.1016/j.diabet.2016.09.008. [Epub ahead of print]

PMID: 27865656



Nuts are rich in unsaturated fatty acids as well as other bioactive constituents. The present study investigated the association between nut consumption and the incidence of type 2 diabetes mellitus (T2DM) in a Middle Eastern population.


The study was conducted within the framework of the Tehran Lipid and Glucose Study (TLGS), in which 1984 participants (920 men and 1064 women) free of DM, aged≥20 years, were followed from phase III (2005-2008) to phase V (2011-2014). Dietary data were obtained from valid and reliable food-frequency questionnaires at baseline. Using multiple logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, with adjustments for age, gender, BMI, serum cholesterol and triglycerides, smoking and energy intake.


Study participants' means±SD of age and of BMI were 40.1±13.1 years and 27.0±4.8kg/m2, respectively. The median±SE of their total daily consumption of nuts was 1.19±0.11 servings. After 6.2±0.7 years of follow-up, 150 cases of T2DM were confirmed. On comparing those who consumed ≥4 servings/week with those who consumed <1 serving/week, the age-/energy-adjusted OR of incident T2DM for total nut consumption was 0.64 (95% CI: 0.36-1.12; P for trend = 0.03). In a fully adjusted model, nut consumption was associated with a lower risk of T2DM, and the ORs (95% CIs) of risk for those consuming 2-3.99 and ≥4 servings/week of nuts were 0.51 (0.26-0.97) and 0.47 (0.25-0.90), respectively, compared with those consuming <1 serving/week (P<0.001 for trend).


Our findings suggest that consuming ≥4 servings/week of nuts reduced the risk of T2DM compared with <1 serving/week.

"Nuts included all kinds of tree nuts and seeds, including

peanuts, almonds, walnuts, pistachios, hazelnuts, sunflower

seeds, watermelon seeds and pumpkin seeds, and the compounds

derived from them."

Edited by AlPater
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Dose-Response Relationship between Dietary Magnesium Intake and Risk of Type 2 Diabetes Mellitus: A Systematic Review and Meta-Regression Analysis of Prospective Cohort Studies.

Fang X, Han H, Li M, Liang C, Fan Z, Aaseth J, He J, Montgomery S, Cao Y.

Nutrients. 2016 Nov 19;8(11). pii: E739.

PMID: 27869762


The epidemiological evidence for a dose-response relationship between magnesium intake and risk of type 2 diabetes mellitus (T2D) is sparse. The aim of the study was to summarize the evidence for the association of dietary magnesium intake with risk of T2D and evaluate the dose-response relationship. We conducted a systematic review and meta-analysis of prospective cohort studies that reported dietary magnesium intake and risk of incident T2D. We identified relevant studies by searching major scientific literature databases and grey literature resources from their inception to February 2016. We included cohort studies that provided risk ratios, i.e., relative risks (RRs), odds ratios (ORs) or hazard ratios (HRs), for T2D. Linear dose-response relationships were assessed using random-effects meta-regression. Potential nonlinear associations were evaluated using restricted cubic splines. A total of 25 studies met the eligibility criteria. These studies comprised 637,922 individuals including 26,828 with a T2D diagnosis. Compared with the lowest magnesium consumption group in the population, the risk of T2D was reduced by 17% across all the studies; 19% in women and 16% in men. A statistically significant linear dose-response relationship was found between incremental magnesium intake and T2D risk. After adjusting for age and body mass index, the risk of T2D incidence was reduced by 8%-13% for per 100 mg/day increment in dietary magnesium intake. There was no evidence to support a nonlinear dose-response relationship between dietary magnesium intake and T2D risk. The combined data supports a role for magnesium in reducing risk of T2D, with a statistically significant linear dose-response pattern within the reference dose range of dietary intake among Asian and US populations. The evidence from Europe and black people is limited and more prospective studies are needed for the two subgroups.


cohort study; dietary intake; magnesium; meta-analysis; prospective study; type 2 diabetes


Maintaining a Healthy BMI: Data From a 16-Year Study of Young Australian Women.

Brown WJ, Kabir E, Clark BK, Gomersall SR.

Am J Prev Med. 2016 Dec;51(6):e165-e178. doi: 10.1016/j.amepre.2016.09.007.

PMID: 27866600



The aims of this prospective cohort study were to examine 16-year trajectories of weight and BMI in young adult women who had a healthy BMI in 1996 and determinants of remaining in the healthy BMI category.


A total of 4,881 women with healthy BMI at baseline and either healthy, overweight, or obese BMI at 16-year follow-up reported their weight, height, health, and health behaviors in six surveys of the Australian Longitudinal Study on Women's Health between 1996 (aged 18-23 years) and 2012 (aged 34-39 years). Determinants of BMI maintenance were estimated using binary logistic regression and generalized estimating equations in 2015.


Almost 60% remained in the healthy BMI category from 1996 to 2012, (mean weight gain, 0.19 kg/year), 29% transitioned to overweight BMI (0.83 kg/year), and 11.6% transitioned to obese (1.73 kg/year). The mean rates of annual weight gain in each group were consistent over time. Only three factors (low alcohol, moderate/high physical activity, having a university degree) were positively associated with maintaining a healthy BMI. Additional behavioral factors (smoking, high sitting time, energy intake, dieting, takeaway food, and use of oral contraceptives), as well as blue collar occupation, separation/divorce/widowhood, and major illness were negatively associated with BMI maintenance.


To prevent the transition from healthy to overweight/obese BMI, weight gain must be limited to <0.5 kg/year. Women with healthy BMI, but with higher rates of weight gain in their early 20s, could be identified by health professionals for assistance with prevention of becoming overweight/obese.


[The below paper is not pdf-availed.]

Caffeine as a Probable Factor for Increased Risk of OAB Development in Elderly People.

Kosilov KV, Loparev SA, Ivanovskaya MA, Kosilova LV.

Curr Urol. 2016 Oct;9(3):124-131.

PMID: 27867329



This study was conducted to compare overactive bladder (OAB) prevalence among people greater than 60 years of age who intake various doses of caffeine, as well as those who abstain from caffeine.


A randomized observational study was carried out in Vladivostok Gerontological Hospital. A total of 1,098 retired people greater than 60 years of age (659 women and 439 men, average age 67.1 years) took part in the study. They were admitted to the in-patient department with the purpose of annual physical examination performed in accordance with the order of the Ministry of Public Health of the Russian Federation. People over age 60, who at the moment of examination were in satisfactory health condition, were included into the study. People in which OAB had been detected or who used to take antimuscarinic were excluded from the study. Assessment tools for examining the patients' lower urinary tract condition were as follows: OAB-q SF, urination diaries, and uroflowmetry.


In the course of the experiment conducted, we found that 1/3 of people, both men and women greater than 60 years of age, who did not previously seek medical advice due to urination troubles, had symptoms of detrusor overactivity. These symptoms were moderate and did not bother patients too much in most cases (63.4%). It was also found that most patients consumed no more than 300mg caffeine with beverages per day, with 30% and 10% of patients suffering from OAB or severe detrusor overactivity, respectively. At the same time, almost 50% of patients taking more than 300 mg of caffeine per day suffer from OAB.


48.1% of people over 60 years of age suffering from overactive detrusor symptoms consume greater than 300 mg caffeine daily, which is significantly higher than that of their peers who do not intake excessive amounts of caffeine.


Antimuscarinic; Elderly patients; Overactive bladder


Effect of <i>Bifidobacterium animalis</i> ssp. <i>lactis</i> GCL2505 on visceral fat accumulation in healthy Japanese adults: a randomized controlled trial.

Takahashi S, Anzawa D, Takami K, Ishizuka A, Mawatari T, Kamikado K, Sugimura H, Nishijima T.

Biosci Microbiota Food Health. 2016;35(4):163-171.

PMID: 27867803


Bifidobacterium animalis ssp. lactis GCL2505 (B. lactis GCL2505) is able to survive passage through the intestine and then proliferate, leading to an increase in the amount of gut bifidobacteria. In the present study, we evaluated the impact of B. lactis GCL2505 on abdominal visceral fat storage in overweight and mildly obese Japanese adults. This clinical study was a double-blind, randomized, placebo-controlled, parallel-group comparative trial performed for 12 weeks. Healthy Japanese subjects (N=137) with body mass indices ranging from 23 to 30 kg/m2 consumed either fermented milk containing B. lactis GCL2505 or a placebo every day, and then visceral and subcutaneous abdominal fat areas were measured by computed tomography as the primary endpoints. The number of fecal bifidobacteria was also measured. Visceral fat area, but not subcutaneous fat area, was significantly reduced from baseline at 8 and 12 weeks in the GCL2505 group, compared with the placebo group. The total number of fecal bifidobacteria was significantly increased in the GCL2505 group. These results indicate that B. lactis GCL2505 reduces abdominal visceral fat, a key factor associated with metabolic disorders. This finding suggests that this probiotic strain can potentially serve as a specific functional food to achieve visceral fat reduction in overweight or mildly obese individuals.


Bifidobacterium; overweight; probiotics; randomized trial; visceral fat


Dietary Protein Sources and Incidence of Breast Cancer: A Dose-Response Meta-Analysis of Prospective Studies.

Wu J, Zeng R, Huang J, Li X, Zhang J, Ho JC, Zheng Y.

Nutrients. 2016 Nov 17;8(11). pii: E730.

PMID: 27869663


Protein is important to the human body, and different sources of protein may have different effects on the risk of breast cancer. Thus, we conducted a meta-analysis to investigate the association between different dietary protein sources and breast cancer risk. PubMed and several databases were searched until December 2015. Relevant articles were retrieved according to specific searching criteria. Forty-six prospective studies were included. The summary relative risk (RR) for highest versus lowest intake was 1.07 (95% confidence interval (CI) 1.01-1.14, I² = 34.6%) for processed meat, 0.92 (95% CI 0.84-1.00, I² = 0%) for soy food, 0.93 (95% CI 0.85-1.00, I² = 40.1%) for skim milk, and 0.90 (95% CI 0.82-1.00, I² = 0%) for yogurt. Similar conclusions were obtained in dose-response association for each serving increase: total red meat (RR: 1.07; 95% CI 1.01-1.14, I² = 7.1%), fresh red meat (RR: 1.13; 95% CI 1.01-1.26, I² = 56.4%), processed meat (RR: 1.09; 95% CI 1.02-1.17, I² = 11.8%), soy food (RR: 0.91; 95% CI 0.84-1.00, I² = 0%), and skim milk (RR: 0.96; 95% CI 0.92-1.00, I² = 11.9%). There was a null association between poultry, fish, egg, nuts, total milk, and whole milk intake and breast cancer risk. Higher total red meat, fresh red meat, and processed meat intake may be risk factors for breast cancer, whereas higher soy food and skim milk intake may reduce the risk of breast cancer.


breast cancer; dietary protein sources; meta-analysis; prospective studies


The Effects of Dietary Calcium Supplements Alone or With Vitamin D on Cholesterol Metabolism: A Meta-Analysis of Randomized Controlled Trials.

Chen C, Ge S, Li S, Wu L, Liu T, Li C.

J Cardiovasc Nurs. 2016 Nov 18. [Epub ahead of print]

PMID: 27870724



Evidence supports the role of lifestyle interventions as a primary intervention strategy among individuals with dyslipidemia. The role of micronutrients, and calcium in particular, on cholesterol metabolism is not clear and warrants further investigation.


The aim of this study is to conduct a meta-analysis of controlled clinical trials that have examined the effects of calcium supplements on blood lipids among adults.


MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases were searched up to March 2016 for calcium supplements clinical trials. Other trials were selected from searching bibliography of reviews, meta-analysis, and included trials. Clinical trials with random allocation to calcium supplementation or calcium plus vitamin D supplementation, or control were selected. Data collected included study design, participant characteristics, information of the intervention, and outcomes. Data synthesis was conducted using random effect models.


A total of 22 trials, representing 4071 participants, met the eligibility criteria. Compared with control group, calcium supplements significantly reduced low-density lipoprotein cholesterol level by -0.12 mmol/L (95% confidence interval, -0.22 to -0.02) and increased high-density lipoprotein cholesterol level by 0.05 mmol/L (95% confidence interval, 0.00 to 0.10). Subgroup analyses revealed that the associations were consistent across study duration and vitamin D cosupplementation status.


Calcium supplementation has beneficial effect on blood lipids. Such supplements may be useful as a nonpharmaceutical strategy in cholesterol control.


Healthy dietary patterns and incidence of biliary tract and gallbladder cancer in a prospective study of women and men.

Larsson SC, Håkansson N, Wolk A.

Eur J Cancer. 2016 Nov 18;70:42-47. doi: 10.1016/j.ejca.2016.10.012. [Epub ahead of print]

PMID: 27870981



Whether diet influences the risk of biliary tract cancer (BTC) is unknown. We examined the associations of two healthy dietary patterns, including a modified Dietary Approach to Stop Hypertension (mDASH) diet and a modified Mediterranean (mMED) diet, with the incidence of BTC in a population-based prospective study.


The study population comprised 76,014 Swedish adults who were 45-83 years of age and cancer-free at baseline. The mDASH and mMED diets were calculated from self-reported dietary data collected by a validated food-frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI) adjusted for potential confounders.


Over 1,010,777 person-years (mean 13.3 years) of follow-up, 140 extrahepatic BTC cases (including 77 gallbladder cancers) and 23 intrahepatic BTC cases were ascertained by linkage with the Swedish Cancer Register. Adherence to the mDASH and mMED diets was statistically significantly inversely associated with risk of extrahepatic BTC (Ptrend ≤ 0.0003) and gallbladder cancer (Ptrend ≤ 0.005) but not intrahepatic BTC (Ptrend ≥ 0.11). The multivariable HRs (95% CI) for the highest versus lowest tertile of the mDASH diet were 0.41 (0.26-0.64) for extrahepatic BTC and 0.36 (0.20-0.64) for gallbladder cancer. The corresponding HRs (95% CI) for the mMED diet were respectively 0.41 (0.25-0.67) and 0.42 (0.23-0.79).


Adherence to a healthy diet may play a role in reducing the risk of extrahepatic BTC.

Copyright © 2016 Elsevier Ltd. All rights reserved.


Biliary tract cancer; Diet; Foods; Gallbladder cancer; Prospective studies


Lowering the Bar on the Low-Fat Diet

David S. Ludwig

JAMA. 2016;316(20):2087-2088. doi:10.1001/jama.2016.15473

This Viewpoint by David Ludwig assesses the lessons learned from US nutrition recommendations to limit fat intake and the continuing increase in obesity and diabetes and discusses the challenges inherent in scientific evidence regarding nutrition.


Prevalence and Prognostic Implications of Coronary Artery Calcification in Low-Risk Women  -- A Meta-analysis

Maryam Kavousi, MD, PhD; Chintan S. Desai, MD, MS; Colby Ayers, MS; et al.

free access  

JAMA. 2016;316(20):2126-2134. doi:10.1001/jama.2016.17020

This meta-analysis of data from 5 population-based cohort studies assesses the associations between coronary artery calcium (CAC) score and atherosclerotic cardiovascular disease (CVD) in low-risk women and the changes in risk discrimination when CAC score is added to traditional CVD risk factors.

Key Points

Question  What is the value of coronary artery calcium (CAC) for cardiovascular risk assessment among women with 10-year atherosclerotic cardiovascular disease (ASCVD) risk less than 7.5% (low risk of CVD)?

Findings  Among 6739 low-risk women from 5 large population-based cohorts, compared with CAC absence, CAC presence was associated with an increased risk of ASCVD (incidence rates per 1000 person-years, 1.41 for CAC absence vs 4.33 for CAC presence). Addition of CAC to traditional risk factors led to modest improvement in prognostic accuracy.

Meaning  Among women at low risk of ASCVD, CAC was present in approximately one-third and was associated with an increased risk of ASCVD and modest improvement in prognostic accuracy compared with traditional risk factors.


Importance  The role of coronary artery calcium (CAC) testing for guiding preventive strategies among women at low cardiovascular disease (CVD) risk based on the American College of Cardiology and American Heart Association CVD prevention guidelines is unclear.

Objective  To assess the potential utility of CAC testing for CVD risk estimation and stratification among low-risk women.

Design, Setting, and Participants  Women with 10-year atherosclerotic CVD (ASCVD) risk lower than 7.5% from 5 large population-based cohorts: the Dallas Heart Study (United States), the Framingham Heart Study (United States), the Heinz Nixdorf Recall study (Germany), the Multi-Ethnic Study of Atherosclerosis (United States), and the Rotterdam Study (the Netherlands). The 5 cohorts were selected based on the availability of CAC data in a sizable group of low-risk women from the general population together with the long detailed follow-up data. Across the cohorts, events were assessed from the date of CAC scan (performed from 1998 through 2006) until January 1, 2012; January 1, 2014; or March 6, 2015. Fixed-effects meta-analysis was conducted to combine the results of the 5 studies.

Exposures  CAC score by computed tomography.

Main Outcomes and Measures  Main outcome was incident ASCVD, including nonfatal myocardial infarction, coronary heart disease (CHD) death, and stroke. Association of CAC with ASCVD was examined using Cox proportional hazards models. To assess whether CAC was associated with improved ASCVD risk predictions beyond the traditional risk factors, the C statistic and the continuous net reclassification improvement (cNRI) index were calculated.

Results  Among 6739 women with low ASCVD risk from the 5 studies, mean age ranged from 44 to 63 years and CAC was present in 36.1%. Across the cohorts, median follow-up ranged from 7.0 to 11.6 years. A total of 165 ASCVD events occurred (64 nonfatal myocardial infarctions, 29 CHD deaths, and 72 strokes), with the ASCVD incidence rates ranging from 1.5 to 6.0 per 1000 person-years. Compared with the absence of CAC (CAC = 0), presence of CAC (CAC >0) was associated with an increased risk of ASCVD (incidence rates per 1000 person-years, 1.41 for CAC absence vs 4.33 for CAC presence; difference, 2.92 [95% CI, 2.02-3.83]; multivariable-adjusted hazard ratio, 2.04 [95% CI, 1.44-2.90]). The addition of CAC to traditional risk factors improved the C statistic from 0.73 (95% CI, 0.69-0.77) to 0.77 (95% CI, 0.74-0.81) and provided a cNRI of 0.20 (95% CI, 0.09-0.31) for ASCVD prediction.

Conclusions and Relevance  Among women at low ASCVD risk, CAC was present in approximately one-third and was associated with an increased risk of ASCVD and modest improvement in prognostic accuracy compared with traditional risk factors. Further research is needed to assess the clinical utility and cost-effectiveness of this additional accuracy.


[The below paper is pdf-availed.]

Screening for Colorectal Cancer and Evolving Issues for Physicians and Patients -- A Review

David Lieberman, MD; Uri Ladabaum, MD, MS; Marcia Cruz-Correa, MD; et al.

JAMA. 2016;316(20):2135-2145. doi:10.1001/jama.2016.17418

This narrative review summarizes the most commonly used colorectal cancer screening tests in the United States and offers guidance about screening programs for higher-risk patients and management of antithrombotic therapy before colonoscopy.


Importance  Colorectal cancer (CRC) is the second-leading cause of cancer death in the United States. Screening can reduce CRC mortality and incidence, and numerous screening options, although available, complicate informed decision making. This review provides evidence-based tools for primary care physicians to identify patients with higher-than-average-risk and engage patients in informed decision making about CRC screening options.

Observations  Recently, the US Preventive Services Task Force recommended any of 8 CRC screening approaches for average-risk individuals, beginning at age 50 years. Only 2 methods have been shown in randomized clinical trials to reduce mortality: fecal occult blood testing and flexible sigmoidoscopy. Of the 8 programs, screenings using the fecal immunochemical test annually and colonoscopy every 10 years are now the most commonly used tests in the United States and among the most effective in reducing CRC mortality as determined by decision models. With the exception of primary screening using colonoscopy, all of the other screening approaches have multiple steps. Adherence to each phase of a multistep program is critical to achieving maximal effectiveness of the screening program. It is likely that each of the recommended programs can reduce CRC mortality, but other key outcomes may differ such as lifetime burden of colonoscopy, complications, patient acceptance, and cost. Decisions about the timing of screening cessation should be individualized.

Conclusions and Relevance  CRC screening is effective if patients adhere to the steps in each screening program. There is no evidence that one program is superior to another. Informed decision-making tools are provided to assist patients and clinicians with the goal of improving adherence to effective screening.


[The below paper is pdf-availed.]

Infectious Disease Mortality Trends in the United States, 1980-2014

Victoria Hansen, MS; Eyal Oren, PhD; Leslie K. Dennis, PhD; et al.

JAMA. 2016;316(20):2149-2151. doi:10.1001/jama.2016.12423

This study uses data from the US National Office of Vital Statistics and the Centers for Disease Control and Prevention WONDER database to characterize trends in infectious disease mortality from 1980 through 2014.

From 1900 through 1996, mortality from infectious diseases declined in the United States, except for a 1918 spike due to the Spanish flu pandemic.1 Since 1996, major changes in infectious diseases have occurred, such as the introduction of human immunodeficiency virus (HIV)/AIDS and West Nile virus into the United States, advances in HIV/AIDS treatment, changes in vaccine perceptions, and increased concern over drug-resistant pathogens. We investigated trends in infectious disease mortality from 1980 through 2014 to capture these changes.


From 1900 through 1996, mortality from infectious diseases declined in the United States, except for a 1918 spike due to the Spanish flu pandemic.1 Since 1996, major changes in infectious diseases have occurred, such as the introduction of human immunodeficiency virus (HIV)/AIDS and West Nile virus into the United States, advances in HIV/AIDS treatment, changes in vaccine perceptions, and increased concern over drug-resistant pathogens. We investigated trends in infectious disease mortality from 1980 through 2014 to capture these changes.


Using International Classification of Diseases codes, overall and infectious disease mortality data were extracted, based on underlying causes of death, from the National Office of Vital Statistics reports from 1900 through 1967 and from the Centers for Disease Control and Prevention (CDC) WONDER database from 1968 through 2014.2 The University of Arizona determined the study was exempt from review.

Crude mortality rates for infectious and noninfectious causes (per 100 000 population) from 1900 through 2014 were graphed along with selected infections from 1980 through 2014 based on overall burden (influenza, pneumonia) and emergence or reemergence (HIV/AIDS, vector-borne diseases, vaccine-preventable diseases, drug-resistant pathogens). Vaccine-preventable diseases included those for which vaccines are routinely provided in the United States. Pathogens with drug resistance were identified based on classification by the CDC.3 Average annual percentage change (AAPC) was calculated using a 2-sided permutation test. Joinpoint Trend Analysis Software (National Cancer Institute), version 4.2.0,4 was used to create a weighted regression of the time series. Segments were selected based on statistical significance (2-sided P < .05) except for HIV/AIDS (which was manually given a joinpoint in 1995 to capture the peak of the epidemic and AAPCs calculated before and after 1995) and vector-borne diseases (for which interannual variability made trend analysis inappropriate).


Overall and infectious disease mortality decreased from 1900 through 1950 (except for the 1918 spike) and then leveled off (Figure, A).

From 1980 through 2014, infectious diseases composed 5.4% (95% CI, 5.1% to 5.8%) of overall mortality. Per 100 000 population, infectious disease mortality increased from 42.0 in 1980 to 63.5 in 1995, paralleling trends in HIV/AIDS mortality. A decline in overall and HIV/AIDS mortality in 1995 was associated with the introduction of antiretroviral therapy (Figure, B). The overall AAPC was 0.4 (95% CI, −0.4 to 1.2) from 1980 through 2014.

Most infectious disease deaths (38.3% [95% CI, 37.1%-39.4%]) from 1980 through 2014 were due to influenza or pneumonia (Figure, B and Table).

>>>>>>>>>>>>>>>>>>>>>>>>>>>Table. Summary of Infectious Disease Mortality Rates and Average Annual Percentage Change in the United States Over Time


      Mortality Rate (per 100 000 Population)===AAPC (95% CI)a

      1980 2014===1980-2014


All infectious causes 42.0 45.6 0.4 (−0.4 to 1.2)

Influenza or pneumonia 17.1 17.3 0.1 (−0.5 to 0.7)

Influenza 1.2 1.4 −1.1 (−3.3 to 1.1)

Pneumonia 15.9 15.9 0.1 (−0.4 to 0.6)

HIV/AIDS 0 2.1

                ===1980-1995 85.2 (66.9 to 105.6)

                ===1995-2014 −10.4 (−12.7 to −8.0)

Vector-borne diseases 0.02 0.05 NRb

West Nile virus 0 0.03 NRb

Vaccine-preventable diseases 2.1 0.8 −2.4 (−2.8 to −2.1)

Pathogens with drug resistance 4.1 4.2 0.4 (−0.4 to 1.3)

Clostridium difficile 0 2.2 19.3 (15.2 to 23.5)

Other infectious causesc 18.7 21.1 0.8 (−0.2 to 1.7)


Abbreviation: AAPC, average annual

percentage change; HIV, human

immunodeficiency virus; NR, not


a With the exception of HIV/AIDS, for

which 1995 was selected as the

joinpoint, AAPCs were calculated

for 1980 through 2014.

bNot reported due to variability.

c Includes other infectious and

parasitic diseases, including

inflammatory diseases of the central

nervous system, diseases of the ear

and mastoid process, acute

rheumatic fever, acute and subacute

endocarditis, acute upper and lower

respiratory tract infections, acute

appendicitis, infections of the skin

and subcutaneous infections,

severe acute respiratory syndrome,

and infections specific to the

perinatal period.


Prior to the introduction of West Nile virus (1980-1999), mean vector-borne disease mortality was 0.01 per 100 000 population (95% CI, 0.01-0.02); primarily from spotted fevers (Figure, C). Since 2002, the mean rate was 0.05 per 100 000 population (95% CI, 0.04-0.06).

Vaccine-preventable disease death rates decreased since 1980 (Figure, D and Table). In 2014, the rate was 0.8 per 100 000 population for Streptococcus pneumoniae infection. Mortality due to hepatitis B alone showed an increase coincident with the HIV/AIDS epidemic (per 100 000 population: 0.13 in 1980 and 0.39 in 1995).

Mortality due to pathogens with drug-resistant strains remained stable since 1980 at about 4.0 per 100 000 population (95% CI, 3.80-4.13) (Figure, E and Table). Mortality from Clostridium difficile, a hospital-acquired infection with drug resistance, increased from almost none in 1989 (n = 74 deaths; 0.004 per 100 000 population) until reaching a plateau since 2007 (2.4 per 100 000 population [95% CI, 2.3-2.5]).


Infectious diseases represented a small proportion of overall US mortality from 1980 through 2014, with influenza or pneumonia accounting for approximately 40% of infectious disease mortality. Major changes in mortality from HIV/AIDS, West Nile virus, and C difficile occurred over this period. Mortality due to vaccine-preventable diseases declined, whereas mortality due to pathogens with resistant strains remained stable.

The study is limited to US mortality reported on death certificates, only partly capturing the true burden of these diseases. Globally, infectious diseases were the second (lower respiratory infections), fourth (diarrheal diseases) and fifth (HIV/AIDS) leading causes of lost disability-adjusted life-years.5

Grouping related diseases (eg, vector-borne disease) and using national-level data allow for the evaluation of general trends. However, trends in population subgroups and at the community level, such as measles outbreaks within low-vaccination communities, were not captured. Nonetheless, these trends illustrate the continued US vulnerability to infectious diseases.


Effects of Subsidies and Prohibitions on Nutrition in a Food Benefit Program: A Randomized Clinical Trial.

Harnack L, Oakes JM, Elbel B, Beatty T, Rydell S, French S.

JAMA Intern Med. 2016 Nov 1;176(11):1610-1618. doi: 10.1001/jamainternmed.2016.5633.

PMID: 27653735



Strategies to improve the nutritional status of those participating in the Supplemental Nutrition Assistance Program (SNAP) are of interest to policymakers.


To evaluate whether the proposed policy of incentivizing the purchase of fruits and vegetables and prohibiting the purchase of less nutritious foods in a food benefit program improves the nutritional quality of participants' diets.


Lower income participants (n = 279) not currently enrolled in SNAP were randomized to 1 of 4 experimental financial food benefit conditions: (1) incentive (30% financial incentive for fruits and vegetables purchased using food benefits); (2) restriction (not allowed to buy sugar sweetened beverages, sweet baked goods, or candies with food benefits); (3) incentive plus restriction (30% financial incentive on fruits and vegetables and restriction of purchase of sugar sweetened beverages, sweet baked goods, or candy with food benefits); or (4) control (no incentive or restrictions on foods purchased with food benefits). Participants in all conditions were given a study-specific debit card where funds were added every 4 weeks for a 12-week period. Outcome measures were collected at baseline and in the final 4 weeks of the experimental period.


Primary outcomes (from 24-hour dietary recalls) included intake of energy, discretionary calories, and overall diet quality.


A number of favorable changes were observed in the incentive plus restriction condition that were significantly different from changes in the control condition. These included (1) reduced intake of energy (-96 kcal/d, standard error [sE], 59.9); (2) reduced intake of discretionary calories (-64 kcal/d, SE 26.3); (3) reduced intake of sugar sweetened beverages, sweet baked goods, and candies (-0.6 servings/d, SE 0.2); (4) increased intake of solid fruit (0.2 servings/d, SE 0.1); and (5) improved Healthy Eating Index score (4.1 points, SE 1.4). Fewer improvements were observed in the incentive only and restriction only arms.


A food benefit program that pairs incentives for purchasing more fruits and vegetables with restrictions on the purchase of less nutritious foods may reduce energy intake and improve the nutritional quality of the diet of participants compared with a program that does not include incentives or restrictions.

Edited by AlPater
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Dose-Response Relationship between Alanine Aminotransferase Levels within the Reference Interval and Metabolic Syndrome in Chinese Adults.

Wu P, Chen Q, Chen L, Zhang P, Xiao J, Chen X, Liu M, Wang S.

Yonsei Med J. 2017 Jan;58(1):158-164. doi: 10.3349/ymj.2017.58.1.158.

PMID: 27873509



Elevation in serum alanine aminotransferase (ALT) levels is a biomarker for metabolic syndrome (MS); however, the relationship has not been fully investigated within the reference interval of ALT levels. Our objective was to explore the relationship between serum ALT levels within the reference interval and MS in Chinese adults.


This cross-sectional study included 16028 adults, who attended routine health check-ups at Shengli Oilfield Central Hospital from January 2006 to March 2012. The reference interval of serum ALT level was defined as less than 40 U/L. Logistic regression models and restricted cubic spline were used to evaluate the association of ALT with MS.


The prevalence of MS in the total population was 13.7% (6.4% for females and 18.4% for males). Multiple logistic regression showed that ALT levels were positively associated with MS after adjustment for potential confounding factors. The odds ratio of MS in the top quartile was 4.830 [95% confidence interval (CI): 2.980-7.829] in females and 3.168 (95% CI: 2.649-3.790) in males, compared with the ALT levels in the bottom quartile. The restricted cubic spline models revealed a positive non-linear dose-response relationship between ALT levels and the risk of MS in women (p for nonlinearity was 0.0327), but a positive linear dose-response relationship in men (p for nonlinearity was 0.0659).


Serum ALT levels within the reference interval are positively associated with MS in a dose-response manner. Elevated ALT levels, even within the reference interval, may reflect early dysmetabolic changes.


Alanine aminotransferase; metabolic syndrome; restricted cubic spline


Screening for abdominal aortic aneurysm in asymptomatic adults.

Ali MU, Fitzpatrick-Lewis D, Miller J, Warren R, Kenny M, Sherifali D, Raina P.

J Vasc Surg. 2016 Dec;64(6):1855-1868. doi: 10.1016/j.jvs.2016.05.101. Review.

PMID: 27871502



This report was produced for the Canadian Task Force on Preventive Health Care to provide guidelines on screening for abdominal aortic aneurysm (AAA) with ultrasound scan.


The aim of this systematic review is to examine the evidence on benefits and harms of AAA screening.


This systematic review considered studies from the most recent United States Preventive Services Task Force review on AAA screening and passed through the screening process with citations identified in our search up to April 2015 (PROSPERO Registration #CRD42015019047).


For benefits of one-time AAA screening in men compared with controls, pooled analyses from four randomized controlled trials with moderate quality evidence showed significant reductions in AAA-related mortality and AAA rupture rate up to 13 to 15 years of follow-up with 42% reduction (risk ratio [RR], 0.58; 95% confidence interval [CI], 0.39-0.88; number needed to screen = 212) and 38% reduction (RR, 0.62; 95% CI, 0.45-0.86; number needed to screen = 200), respectively. The effect of on all-cause mortality was marginally significant for longer follow-up. The Chichester trial examined the benefits of one-time AAA screening in women and found no significant differences between screening and control arms for up to 10 years of follow-up (RR, 0.88; 95% CI, 0.72-1.07). For consequences of one-time AAA screening in men compared with controls, there was a significant increase in the total number of AAA-related procedures over a follow-up of 13 to 15 years (2.16 times more likely) compared with controls. For harms of one-time AAA screening, no significant differences were observed in 30-day postoperative mortality for elective and emergency operations with compared control groups. Evidence from the Multicenter Aneurysm Screening Study trial using 13-year follow-up data showed that one-time AAA screening with ultrasound scan was potentially associated with an overdiagnosis of 45% (95% CI, 42%-47%) among screen-detected men.


Population-based screening for AAA with ultrasound scan in asymptomatic men aged 65 years and older showed statistically significant reductions in AAA-related mortality and rupture and, hence, avoids unnecessary AAA-related deaths. The current evidence showed no benefit of one-time AAA screening in woman. Limited evidence is available on the benefits of repeat AAA screening and targeted screening approaches based on risk factors for AAA. Future research should explore the differential benefits of AAA screening based on risk factors that increase risk for developing AAA.

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[There is nothing we can do about it but it is an prognostic indicator of sorts, I thought.]

Increased Paternal Age at Conception Is Associated with Transcriptomic Changes Involved in Mitochondrial Function in Elderly Individuals.

Nevalainen T, Kananen L, Marttila S, Jylhävä J, Jylhä M, Hervonen A, Hurme M.

PLoS One. 2016 Nov 23;11(11):e0167028. doi: 10.1371/journal.pone.0167028.

PMID: 27880854


The increased paternal age at conception (PAC) has been associated with autism spectrum disorder (ASD), schizophrenia and other neurodevelopmental disorders, thus raising questions that imply, potential health concerns in the offspring. As opposed to female oogonia, the male germ cells undergo hundreds of cell divisions during the fertile years. Thus, the advanced paternal age is associated with increase of point mutations in the male spermatogonia DNA, implying that this could be the major driving mechanism behind the paternal age effect observed in the offspring. In addition to replication errors, DNA replication fidelity and inefficient DNA repair machinery in the spermatogonia also contribute to the mutagenic load. Our study population consisted of 38 nonagenarians, participants in the Vitality 90+ Study, born in the year 1920 (women n = 25, men n = 13), for whom the parental birth dates were available. The gene expression profile of the study subjects was determined with HumanHT-12 v4 Expression BeadChip from peripheral blood mononuclear cells. We used Spearman's rank correlation to look for the associations of gene expression with paternal age at conception. Associated transcripts were further analyzed with GOrilla and IPA to determine enriched cellular processes and pathways. PAC was associated with the expression levels of 648 transcripts in nonagenarian subjects. These transcripts belonged to the process of mitochondrial translational termination and the canonical pathway of Mitochondrial dysfunction, more specifically of Oxidative phosphorylation. The observed systematic down-regulation of several mitochondrial respiratory chain components implies compromised function in oxidative phosphorylation and thus in the production of chemical energy.


Mouse Sirt3 promotes autophagy in AngII-induced myocardial hypertrophy through the deacetylation of FoxO1.

Li J, Chen T, Xiao M, Li N, Wang S, Su H, Guo X, Liu H, Yan F, Yang Y, Zhang Y, Bu P.

Oncotarget. 2016 Nov 17. doi: 10.18632/oncotarget.13429. [Epub ahead of print]

PMID: 27880725


Sirt3, a mitochondrial NAD+-dependent histone deacetylase, is the only member proven to promote longevity in mammalian Sirtuin family. The processed short form of Sirt3 has been demonstrated to target many mediators of energy metabolism and mitochondrial stress adaptive program. Autophagy serves as a dynamic recycling mechanism and provides energy or metabolic substrates. Among the mechanisms triggered by cardiac stress, opinions vary as to whether autophagy is a protective or detrimental response. Here, by inducing the Sirt3-knockout mice to myocardial hypertrophy with chronic angiotensin II infusion for four weeks, we determined the role of Sirt3 in myocardial hypertrophy and autophagy. In this study, the Sirt3-knockout mice developed deteriorated cardiac function and impaired autophagy compared to wild-type mice. What's more, the overexpression of Sirt3 by lentivirus transfection attenuated cardiomyocytes hypertrophy by promoting autophagy. We further demonstrated that Sirt3 could bind to FoxO1 and activate its deacetylation. Sequentially, deacetylated FoxO1 translocates to the nucleus where it facilitates downstream E3 ubiquitin ligases such as Muscle RING Finger 1 (MuRF1) and muscle atrophy F-box (MAFbx, Atrogin1). Altogether, these results revealed that Sirt3 activation is essential to improve autophagy flux by reducing the acetylation modification on FoxO1, which in turn alleviates myocardial hypertrophy.


FoxO1; Sirt3; autophagy; deacetylation modification; myocardial hypertrophy


A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape.

Ried JS, Jeff M J, Chu AY, Bragg-Gresham JL, van Dongen J, Huffman JE, Ahluwalia TS, Cadby G, Eklund N, Eriksson J, Esko T, Feitosa MF, Goel A, Gorski M, Hayward C, Heard-Costa NL, Jackson AU, Jokinen E, Kanoni S, Kristiansson K, Kutalik Z, Lahti J, Luan J, Mägi R, Mahajan A, Mangino M, Medina-Gomez C, Monda KL, Nolte IM, Pérusse L, Prokopenko I, Qi L, Rose LM, Salvi E, Smith MT, Snieder H, Stančáková A, Ju Sung Y, Tachmazidou I, Teumer A, Thorleifsson G, van der Harst P, Walker RW, Wang SR, Wild SH, Willems SM, Wong A, Zhang W, Albrecht E, Couto Alves A, Bakker SJ, Barlassina C, Bartz TM, Beilby J, Bellis C, Bergman RN, Bergmann S, Blangero J, Blüher M, Boerwinkle E, Bonnycastle LL, Bornstein SR, Bruinenberg M, Campbell H, Chen YI, Chiang CW, Chines PS, Collins FS, Cucca F, Cupples LA, D'Avila F, de Geus EJ, Dedoussis G, Dimitriou M, Döring A, Eriksson JG, Farmaki AE, Farrall M, Ferreira T, Fischer K, Forouhi NG, Friedrich N, Gjesing AP, Glorioso N, Graff M, Grallert H, Grarup N, Gräßler J, Grewal J, Hamsten A, Harder MN, Hartman CA, Hassinen M, Hastie N, Hattersley AT, Havulinna AS, Heliövaara M, Hillege H, Hofman A, Holmen O, Homuth G, Hottenga JJ, Hui J, Husemoen LL, Hysi PG, Isaacs A, Ittermann T, Jalilzadeh S, James AL, Jørgensen T, Jousilahti P, Jula A, Marie Justesen J, Justice AE, Kähönen M, Karaleftheri M, Tee Khaw K, Keinanen-Kiukaanniemi SM, Kinnunen L, Knekt PB, Koistinen HA, Kolcic I, Kooner IK, Koskinen S, Kovacs P, Kyriakou T, Laitinen T, Langenberg C, Lewin AM, Lichtner P, Lindgren CM, Lindström J, Linneberg A, Lorbeer R, Lorentzon M, Luben R, Lyssenko V, Männistö S, Manunta P, Leach IM, McArdle WL, Mcknight B, Mohlke KL, Mihailov E, Milani L, Mills R, Montasser ME, Morris AP, Müller G, Musk AW, Narisu N, Ong KK, Oostra BA, Osmond C, Palotie A, Pankow JS, Paternoster L, Penninx BW, Pichler I, Pilia MG, Polašek O, Pramstaller PP, Raitakari OT, Rankinen T, Rao DC, Rayner NW, Ribel-Madsen R, Rice TK, Richards M, Ridker PM, Rivadeneira F, Ryan KA, Sanna S, Sarzynski MA, Scholtens S, Scott RA, Sebert S, Southam L, Sparsø TH, Steinthorsdottir V, Stirrups K, Stolk RP, Strauch K, Stringham HM, Swertz MA, Swift AJ, Tönjes A, Tsafantakis E, van der Most PJ, Van Vliet-Ostaptchouk JV, Vandenput L, Vartiainen E, Venturini C, Verweij N, Viikari JS, Vitart V, Vohl MC, Vonk JM, Waeber G, Widén E, Willemsen G, Wilsgaard T, Winkler TW, Wright AF, Yerges-Armstrong LM, Hua Zhao J, Carola Zillikens M, Boomsma DI, Bouchard C, Chambers JC, Chasman DI, Cusi D, Gansevoort RT, Gieger C, Hansen T, Hicks AA, Hu F, Hveem K, Jarvelin MR, Kajantie E, Kooner JS, Kuh D, Kuusisto J, Laakso M, Lakka TA, Lehtimäki T, Metspalu A, Njølstad I, Ohlsson C, Oldehinkel AJ, Palmer LJ, Pedersen O, Perola M, Peters A, Psaty BM, Puolijoki H, Rauramaa R, Rudan I, Salomaa V, Schwarz PE, Shudiner AR, Smit JH, Sørensen TI, Spector TD, Stefansson K, Stumvoll M, Tremblay A, Tuomilehto J, Uitterlinden AG, Uusitupa M, Völker U, Vollenweider P, Wareham NJ, Watkins H, Wilson JF, Zeggini E, Abecasis GR, Boehnke M, Borecki IB, Deloukas P, van Duijn CM, Fox C, Groop LC, Heid IM, Hunter DJ, Kaplan RC, McCarthy MI, North KE, O'Connell JR, Schlessinger D, Thorsteinsdottir U, Strachan DP, Frayling T, Hirschhorn JN, Müller-Nurasyid M, Loos RJ.

Nat Commun. 2016 Nov 23;7:13357. doi: 10.1038/ncomms13357.

PMID: 27876822


Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.


Vitamin D3 Intake Dose and Common Cancer: A Population-Based Case Control Study in a Chinese Population.

Leung HW, Muo CH, Liu CF, Chan AL.

J Cancer. 2016 Oct 21;7(14):2028-2034.

PMID: 27877218


Objectives: Epidemiological studies suggest that vitamin D status is associated inversely with risk of common cancers in western populations. This study aimed to investigate whether vitamin D is associated with risk of common cancers in Chinese population. Methods: A population-based retrospective case-control study was conducted analyzing data retrieved from the Catastrophic Illness Patient Databases (CIPD) and longitudinal health insurance database (LHID) from January 1, 2010 to December 31, 2011and January 1, 2000 to December 31, 2011, respectively. Cases were identified as subjects diagnosed with site-specific cancers (International Classification of Diseases, Ninth Revision,) and frequency matched to select controls. Use of vitamin D3 was compared between two groups. Odds ratios (ORs) were employed to quantify the risk associated with exposure to vitamin D3 by logistic regression. Results: There were 1.21% (1961/161806) patients in cases and 0.67 % (1092/161806) patients in controls identified were vitamin D3 users. Overall risk of cancers associated with vitamin D3 users was 1.67 (95% CI:1.55 -1.81). Among these, the risk of kidney cancer and bladder cancer associated with intakes of vitamin D3 were significant (OR 2.59; 95% CI 1.81-3.70; OR 4.97; 95% CI 4.40-5.60) in an adjusted model. In further stratification analysis, we found a statistically significant risk of bladder cancer associated with high intake of vitamin D3. Except this, no statistically significant risk of other site-specific cancers associated with high intake of vitamin D3. Conclusion: Except bladder cancer in stratification analysis, we observed no statistically significant association between high intake of vitamin D3 and other site-specific cancers.


incidence.; odds ratio; population-based study; site-specific cancer; vitamin D


Comparative efficacy of vitamin D status in reducing the risk of bladder cancer: A systematic review and network meta-analysis.

Zhao Y, Chen C, Pan W, Gao M, He W, Mao R, Lin T, Huang J.

Nutrition. 2016 May;32(5):515-23. doi: 10.1016/j.nut.2015.10.023. Review.

PMID: 26822497


The optimal concentration of individual vitamin D intake for preventing bladder cancer has not, to our knowledge, been defined. To evaluate the comparative efficacy of different serum 25-hydroxyvitamin D concentrations in preventing bladder cancer, we conducted a systematic search of the literature published up to April 2015.


We applied a pairwise meta-analysis to estimate direct evidence from intervention-control studies and a network meta-analysis within a Bayesian framework to combine direct and indirect evidence. Moreover, a dose-response curve was utilized to predict the optimal median serum 25-hydroxyvitamin D concentration based on the odds ratio (OR) for each quintile concentration.


Seven studies of a total of 90757 participants, including 2509 bladder cancer patients, were included. Two prospective cohort studies with 57 591 participants and 494 bladder cancer patients, and five case-control studies with 33 166 participants and 2264 bladder cancer patients. From the network meta-analysis, we observed that sufficient serum 25-hydroxyvitamin D concentrations (>75 nmol/L) were superior to all other 25-hydroxyvitamin D concentrations in decreasing the risk of bladder cancer: OR = 0.68 and 95% credible interval (CrI) 0.52 to 0.87 compared with severely deficient concentrations (<25 nmol/L); OR = 0.65 and 95% CrI 0.49 to 0.86 compared with moderately deficient concentrations (25-37.5 nmol/L); OR = 0.61 and 95% CrI 0.47 to 0.80 compared with slightly deficient concentrations (37.5-50 nmol/L); and OR = 0.65 and 95% CrI 0.48 to 0.85 compared with insufficient concentrations (50-75 nmol/L). In addition, we noted a roughly inverse correlation between bladder cancer risk and 25-hydroxyvitamin D concentrations (R(2) = 0.98, P = 0.007).


Ensuring sufficient serum 25-hydroxyvitamin D concentrations might play an important role in decreasing the risk of bladder cancer. The serum 25-hydroxyvitamin D concentration ≥74 nmol/L was associated with a 60% lower risk of bladder cancer incidence.


Bladder cancer; Network meta-analysis; Serum 25-hydroxyvitamin D; Systematic review; Vitamin D


[The first below paper is pdf-availed.]

Fish consumption and prostate cancer risk and mortality in a Danish cohort study.

Outzen M, Tjønneland A, Christensen J, Olsen A.

Eur J Cancer Prev. 2016 Nov 22. [Epub ahead of print]

PMID: 27879495


Within the Danish 'Diet, Cancer and Health' cohort, we aimed to investigate the association between prediagnostic fish intake (total, lean, fatty) and (a) incidence of total and high-grade prostate cancer and (b) the risk of all-cause and prostate cancer-specific mortality among men with prostate cancer. Among 27 178 men, 1690 prostate cancer cases were identified through 2012. Of these, 1042 had a Gleason score of 7 or above and 498 had a Gleason score of 8 or above at the time of diagnosis; 364 died (n=228 from prostate cancer) during follow-up through 2013. Cox proportional hazard models were used for the statistical analyses. No association between any type of fish intake and risk of total prostate cancer or high-grade prostate cancer (Gleason score≥7 or ≥8) was found. For all-cause mortality, we found no association for any type of fish intake. For prostate cancer-specific mortality, only a higher intake of fatty fish was associated with a higher mortality [per daily 25 g increment in intake (mortality rate ratio=1.27; 95% confidence interval: 1.04-1.55; P=0.02)]. In conclusion, no strong association was found between fish consumption and the risk of or mortality from prostate cancer. Only a higher intake of fatty fish was associated with a higher risk of prostate cancer-specific mortality.


Nutrition, dietary interventions and prostate cancer: the latest evidence.

Lin PH, Aronson W, Freedland SJ.

BMC Med. 2015 Jan 8;13:3. doi: 10.1186/s12916-014-0234-y. Review.

PMID: 25573005 Free PMC Article


Prostate cancer (PCa) remains a leading cause of mortality in US men and the prevalence continues to rise world-wide especially in countries where men consume a 'Western-style' diet. Epidemiologic, preclinical and clinical studies suggest a potential role for dietary intake on the incidence and progression of PCa. 'This minireview provides an overview of recent published literature with regard to nutrients, dietary factors, dietary patterns and PCa incidence and progression. Low carbohydrates intake, soy protein, omega-3 (w-3) fat, green teas, tomatoes and tomato products and zyflamend showed promise in reducing PCa risk or progression. A higher saturated fat intake and a higher β-carotene status may increase risk. A 'U' shape relationship may exist between folate, vitamin C, vitamin D and calcium with PCa risk. Despite the inconsistent and inconclusive findings, the potential for a role of dietary intake for the prevention and treatment of PCa is promising. The combination of all the beneficial factors for PCa risk reduction in a healthy dietary pattern may be the best dietary advice. This pattern includes rich fruits and vegetables, reduced refined carbohydrates, total and saturated fats, and reduced cooked meats. Further carefully designed prospective trials are warranted.


Fish Consumption and Age-Related Macular Degeneration Incidence: A Meta-Analysis and Systematic Review of Prospective Cohort Studies.

Zhu W, Wu Y, Meng YF, Xing Q, Tao JJ, Lu J.

Nutrients. 2016 Nov 22;8(11). pii: E743. Review.

PMID: 27879656



The association between fish consumption and risk of age-related macular degeneration (AMD) is still unclear. The aim of the current meta-analysis and systematic review was to quantitatively evaluate findings from observational studies on fish consumption and the risk of AMD. Relevant studies were identified by searching electronic databases (Medline and EMBASE) and reviewing the reference lists of relevant articles up to August, 2016. Prospective cohort studies that reported relative risks (RRs) and 95% confidence intervals (CIs) for the link between fish consumption and risk of AMD were included. A total of 4202 cases with 128,988 individuals from eight cohort studies were identified in the current meta-analysis. The meta-analyzed RR was 0.76 (95% CI, 0.65-0.90) when any AMD was considered. Subgroup analyses by AMD stages showed that fish consumption would reduce the risk of both early (RR, 0.83; 95% CI, 0.72-0.96) and late (RR; 0.76; 95% CI, 0.60-0.97) AMD. When stratified by the follow-up duration, fish consumption was a protective factor of AMD in both over 10 years (n = 5; RR, 0.81; 95% CI, 0.67-0.97) and less than 10 years (n = 3; RR, 0.70; 95% CI, 0.51 to 0.97) follow-up duration. Stratified analyses by fish type demonstrated that dark meat fish (RR, 0.68, 95% CI, 0.46-0.99), especially tuna fish (RR, 0.58; 95% CI, 95% CI, 0.47-0.71) intake was associated with reduced AMD risk. Evidence of a linear association between dose of fish consumption and risk of AMD was demonstrated. The results of this meta-analysis demonstrated that fish consumption can reduce AMD risk. Advanced, well-designed, randomized clinical trials are required in order to validate the conclusions in this study.


age-related macular degeneration; fish; meta-analysis; nutrients


Chronic Low-Calorie Sweetener Use and Risk of Abdominal Obesity among Older Adults: A Cohort Study.

Chia CW, Shardell M, Tanaka T, Liu DD, Gravenstein KS, Simonsick EM, Egan JM, Ferrucci L.

PLoS One. 2016 Nov 23;11(11):e0167241. doi: 10.1371/journal.pone.0167241.

PMID: 27880832



Low-calorie sweetener use for weight control has come under increasing scrutiny as obesity, especially abdominal obesity, remain entrenched despite substantial low-calorie sweetener use. We evaluated whether chronic low-calorie sweetener use is a risk factor for abdominal obesity.


We used 8268 anthropometric measurements and 3096 food diary records with detailed information on low-calorie sweetener consumption in all food products, from 1454 participants (741 men, 713 women) in the Baltimore Longitudinal Study of Aging collected from 1984 to 2012 with median follow-up of 10 years (range: 0-28 years). At baseline, 785 were low-calorie sweetener non-users (51.7% men) and 669 participants were low-calorie sweetener users (50.1% men). Time-varying low-calorie sweetener use was operationalized as the proportion of visits since baseline at which low-calorie sweetener use was reported. We used marginal structural models to determine the association between baseline and time-varying low-calorie sweetener use with longitudinal outcomes-body mass index, waist circumference, obesity and abdominal obesity-with outcome status assessed at the visit following low-calorie sweetener ascertainment to minimize the potential for reverse causality. All models were adjusted for year of visit, age, sex, age by sex interaction, race, current smoking status, dietary intake (caffeine, fructose, protein, carbohydrate, and fat), physical activity, diabetes status, and Dietary Approaches to Stop Hypertension score as confounders.


With median follow-up of 10 years, low-calorie sweetener users had 0.80 kg/m2 higher body mass index (95% confidence interval [CI], 0.17-1.44), 2.6 cm larger waist circumference (95% CI, 0.71-4.39), 36.7% higher prevalence (prevalence ratio = 1.37; 95% CI, 1.10-1.69) and 53% higher incidence (hazard ratio = 1.53; 95% CI 1.10-2.12) of abdominal obesity than low-calorie sweetener non-users.


Low-calorie sweetener use is independently associated with heavier relative weight, a larger waist, and a higher prevalence and incidence of abdominal obesity suggesting that low-calorie sweetener use may not be an effective means of weight control.

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Familial Longevity Is Not Associated with Major Differences in the Hypothalamic-Pituitary-Gonadal Axis in Healthy Middle-Aged Men.

van der Spoel E, Roelfsema F, Jansen SW, Akintola AA, Ballieux BE, Cobbaert CM, Blauw GJ, Slagboom PE, Westendorp RG, Pijl H, van Heemst D.

Front Endocrinol (Lausanne). 2016 Nov 9;7:143.

PMID: 27881971



A trade-off between fertility and longevity possibly exists. The association of the male hypothalamic-pituitary-gonadal (HPG) axis with familial longevity has not yet been investigated.


To study 24-h hormone concentration profiles of the HPG axis in men enriched for familial longevity and controls.


We frequently sampled blood over 24 h in 10 healthy middle-aged male offspring of nonagenarian participants from the Leiden Longevity Study together with 10 male age-matched controls. Individual 24-h luteinizing hormone (LH) and testosterone concentration profiles were analyzed by deconvolution analyses to estimate secretion parameters. Furthermore, the temporal relationship between LH and testosterone was assessed by cross-correlation analysis. We used (cross-)approximate entropy to quantify the strength of feedback and/or feedforward control of LH and testosterone secretion.


Mean [95% confidence interval (CI)] total LH secretion of the offspring was 212 (156-268) U/L/24 h, which did not differ significantly (p = 0.51) from the total LH secretion of controls [186 (130-242) U/L/24 h]. Likewise, mean (95% CI) total testosterone secretion of the offspring [806 (671-941) nmol/L/24 h] and controls [811 (676-947) nmol/L/24 h] were similar (p = 0.95). Other parameters of LH and testosterone secretion were also not significantly different between offspring and controls. The temporal relationship between LH and testosterone and the strength of feedforward/feedback regulation within the HPG axis were similar between offspring of long-lived families and controls.


This relatively small study suggests that in healthy male middle-aged participants, familial longevity is not associated with major differences in the HPG axis. Selection on both fertility and health may in part explain the results.


approximate entropy; familial longevity; hormone secretion; hypothalamic–pituitary–gonadal axis; luteinizing hormone; temporal correlation; testosterone


Physical activity patterns and biomarkers of cardiovascular disease risk in hunter-gatherers.

Raichlen DA, Pontzer H, Harris JA, Mabulla AZ, Marlowe FW, Josh Snodgrass J, Eick G, Colette Berbesque J, Sancilio A, Wood BM.

Am J Hum Biol. 2016 Oct 9. doi: 10.1002/ajhb.22919. [Epub ahead of print]

PMID: 27723159



Time spent in moderate-to-vigorous physical activity (MVPA) is a strong predictor of cardiovascular health, yet few humans living in industrialized societies meet current recommendations (150 min/week). Researchers have long suggested that human physiological requirements for aerobic exercise reflect an evolutionary shift to a hunting and gathering foraging strategy, and a recent transition to more sedentary lifestyles likely represents a mismatch with our past in terms of physical activity. The goal of this study is to explore this mismatch by characterizing MVPA and cardiovascular health in the Hadza, a modern hunting and gathering population living in Northern Tanzania.


We measured MVPA using continuous heart rate monitoring in 46 participants recruited from two Hadza camps. As part of a larger survey of health in the Hadza, we measured blood pressure (n = 198) and biomarkers of cardiovascular health (n = 23) including C-reactive protein, cholesterol (Total, HDL, and LDL), and triglycerides.


We show that Hadza participants spend large amounts of time in MVPA (134.92 ± 8.6 min/day), and maintain these activity levels across the lifespan. In fact, the Hadza engage in over 14 times as much MVPA as subjects participating in large epidemiological studies in the United States. We found no evidence of risk factors for cardiovascular disease in this population (low prevalence of hypertension across the lifespan, optimal levels for biomarkers of cardiovascular health).


Our results provide evidence that the hunting and gathering foraging strategy involves high levels of MVPA, supporting the evolutionary medicine model for the relationship between MVPA and cardiovascular health.


C-reactive protein; blood pressure; cholesterol; energetics; exercise; flex heart rate; heart-rate


Association between prediabetes and risk of cardiovascular disease and all cause mortality: systematic review and meta-analysis.

Huang Y, Cai X, Mai W, Li M, Hu Y.

BMJ. 2016 Nov 23;355:i5953. doi: 10.1136/bmj.i5953.

PMID: 27881363



 To evaluate associations between different definitions of prediabetes and the risk of cardiovascular disease and all cause mortality.


 Meta-analysis of prospective cohort studies.


 Electronic databases (PubMed, Embase, and Google Scholar).


 Prospective cohort studies from general populations were included for meta-analysis if they reported adjusted relative risks with 95% confidence intervals for associations between the risk of composite cardiovascular disease, coronary heart disease, stroke, all cause mortality, and prediabetes.


 Two authors independently reviewed and selected eligible studies, based on predetermined selection criteria. Prediabetes was defined as impaired fasting glucose according to the criteria of the American Diabetes Association (IFG-ADA; fasting glucose 5.6-6.9 mmol/L), the WHO expert group (IFG-WHO; fasting glucose 6.1-6.9 mmol/L), impaired glucose tolerance (2 hour plasma glucose concentration 7.8-11.0 mmol/L during an oral glucose tolerance test), or raised haemoglobin A1c (HbA1c) of 39-47 mmol/mol : (5.7-6.4%) according to ADA criteria or 42-47 mmol/mol (6.0-6.4%) according to the National Institute for Health and Care Excellence (NICE) guideline. The relative risks of all cause mortality and cardiovascular events were calculated and reported with 95% confidence intervals.


 53 prospective cohort studies with 1 611 339 individuals were included for analysis. The median follow-up duration was 9.5 years. Compared with normoglycaemia, prediabetes (impaired glucose tolerance or impaired fasting glucose according to IFG-ADA or IFG-WHO criteria) was associated with an increased risk of composite cardiovascular disease (relative risk 1.13, 1.26, and 1.30 for IFG-ADA, IFG-WHO, and impaired glucose tolerance, respectively), coronary heart disease (1.10, 1.18, and 1.20, respectively), stroke (1.06, 1.17, and 1.20, respectively), and all cause mortality (1.13, 1.13 and 1.32, respectively). Increases in HBA1c to 39-47 mmol/mol or 42-47 mmol/mol were both associated with an increased risk of composite cardiovascular disease (1.21 and 1.25, respectively) and coronary heart disease (1.15 and 1.28, respectively), but not with an increased risk of stroke and all cause mortality.


 Prediabetes, defined as impaired glucose tolerance, impaired fasting glucose, or raised HbA1c, was associated with an increased risk of cardiovascular disease. The health risk might be increased in people with a fasting glucose concentration as low as 5.6 mmol/L or HbA1c of 39 mmol/mol.


Intake of individual saturated fatty acids and risk of coronary heart disease in US men and women: two prospective longitudinal cohort studies.

Zong G, Li Y, Wanders AJ, Alssema M, Zock PL, Willett WC, Hu FB, Sun Q.

BMJ. 2016 Nov 23;355:i5796. doi: 10.1136/bmj.i5796.

PMID: 27881409



 To investigate the association between long term intake of individual saturated fatty acids (SFAs) and the risk of coronary heart disease, in two large cohort studies.


 Prospective, longitudinal cohort study.


 Health professionals in the United States.


 73 147 women in the Nurses' Health Study (1984-2012) and 42 635 men in the Health Professionals Follow-up Study (1986-2010), who were free of major chronic diseases at baseline.


 Incidence of coronary heart disease (n=7035) was self-reported, and related deaths were identified by searching National Death Index or through report of next of kin or postal authority. Cases were confirmed by medical records review.


 Mean intake of SFAs accounted for 9.0-11.3% energy intake over time, and was mainly composed of lauric acid (12:0), myristic acid (14:0), palmitic acid (16:0), and stearic acid (18:0; 8.8-10.7% energy). Intake of 12:0, 14:0, 16:0 and 18:0 were highly correlated, with Spearman correlation coefficients between 0.38 and 0.93 (all P<0.001). Comparing the highest to the lowest groups of individual SFA intakes, hazard ratios of coronary heart disease were 1.07 (95% confidence interval 0.99 to 1.15; Ptrend=0.05) for 12:0, 1.13 (1.05 to 1.22; Ptrend<0.001) for 14:0, 1.18 (1.09 to 1.27; Ptrend<0.001) for 16:0, 1.18 (1.09 to 1.28; Ptrend<0.001) for 18:0, and 1.18 (1.09 to 1.28; Ptrend<0.001) for all four SFAs combined (12:0-18:0), after multivariate adjustment of lifestyle factors and total energy intake. Hazard ratios of coronary heart disease for isocaloric replacement of 1% energy from 12:0-18:0 were 0.92 (95% confidence interval 0.89 to 0.96; P<0.001) for polyunsaturated fat, 0.95 (0.90 to 1.01; P=0.08) for monounsaturated fat, 0.94 (0.91 to 0.97; P<0.001) for whole grain carbohydrates, and 0.93 (0.89 to 0.97; P=0.001) for plant proteins. For individual SFAs, the lowest risk of coronary heart disease was observed when the most abundant SFA, 16:0, was replaced. Hazard ratios of coronary heart disease for replacing 1% energy from 16:0 were 0.88 (95% confidence interval 0.81 to 0.96; P=0.002) for polyunsaturated fat, 0.92 (0.83 to 1.02; P=0.10) for monounsaturated fat, 0.90 (0.83 to 0.97; P=0.01) for whole grain carbohydrates, and 0.89 (0.82 to 0.97; P=0.01) for plant proteins.


 Higher dietary intakes of major SFAs are associated with an increased risk of coronary heart disease. Owing to similar associations and high correlations among individual SFAs, dietary recommendations for the prevention of coronary heart disease should continue to focus on replacing total saturated fat with more healthy sources of energy.


[it looked to me like the every other day cocoa intake improved ankle blood pressure indexes more.]

Habitual cocoa intake reduces arterial stiffness in postmenopausal women regardless of intake frequency: a randomized parallel-group study.

Okamoto T, Kobayashi R, Natsume M, Nakazato K.

Clin Interv Aging. 2016 Nov 14;11:1645-1652.

PMID: 27881914


Arterial stiffness is substantially higher in postmenopausal than in premenopausal women. Daily cocoa intake has been shown to reduce central arterial stiffness in health adults, regardless of age; however, the effect of cocoa-intake frequency on arterial stiffness in postmenopausal women remains unclear. Therefore, the purpose of this study was to investigate the effects of cocoa-intake frequency on arterial stiffness in postmenopausal women. A total of 26 postmenopausal women (mean age ± standard deviation 64±12 years) were randomly assigned to two groups with different cocoa-intake frequencies: one group ingested 17 g of cocoa once daily except on Sundays (every-day group, n=13), and the other ingested 17 g of cocoa twice daily every other day (every-other-day group, n=13). These intake regimens were maintained in both groups for 12 weeks. Carotid-femoral pulse-wave velocity and femoral-ankle pulse-wave velocity were measured in both groups at baseline and again at the end of the 12-week study period. Compared to baseline, both pulse-wave velocities had significantly decreased after the 12-week study period in both groups (P<0.05). However, no significant difference in degree of change was observed between the two groups. Although this study did not include a sedentary control group, these results suggest that regardless of frequency, habitual cocoa intake reduces central and peripheral arterial stiffness in postmenopausal women.


endothelin 1; flavanol-enriched cocoa; intake frequency; pulse-wave velocity


Intake of kale suppresses postprandial increases in plasma glucose: A randomized, double-blind, placebo-controlled, crossover study.

Kondo S, Suzuki A, Kurokawa M, Hasumi K.

Biomed Rep. 2016 Nov;5(5):553-558.

PMID: 27882216


Kale (Brassica oleracea var. acephala), a vegetable in the family Brassicaceae, has beneficial effects on health, including hypoglycemic effects. In our previous study with a limited number of subjects, intake of kale-containing food at a dose of 14 g decreased postprandial plasma glucose levels. In the present study, the effective dose of kale-containing food was investigated in a randomized, double-blind, placebo-controlled, crossover trial. The trial was conducted on 42 Japanese subjects aged 21-64 years with fasting plasma glucose levels of ≤125 mg/dl and 30-min postprandial plasma glucose levels of 140-187 mg/dl. The subjects consumed placebo or kale-containing food [7 or 14 g; low-dose (active-L) or high-dose (active-H) kale, respectively] together with a high-carbohydrate meal. At 30-120 min after the test meal intake, the plasma levels of glucose and insulin were determined. The postprandial plasma glucose levels in subjects with intake of active-L or active-H were significantly lower than those in subjects with intake of placebo, with the maximum plasma concentration (Cmax; 163±24 mg/dl for active-L and 162±23 mg/dl for active-H compared with 176±26 mg/dl for placebo [values presented as means ± standard deviation (SD); P<0.01]. The area under the plasma glucose concentration-time curve for 0-2 h (AUC0-2 h) values (means ± SD) were significantly lower for active-L (268±43 mg/h/dl) and active-H (266±42 mg/h/dl) than for the placebo (284±43 mg/h/dl; P<0.05). No significant differences were identified in the postprandial plasma insulin levels between the three conditions. No adverse events associated with intake of either dose of kale were observed. Our findings suggest that intake of kale suppresses postprandial increases in plasma glucose levels at a single dose of 7 g, and that a dose as high as 14 g is safe.


anti-diabetic; clinical study; kale; plasma glucose; postprandial hyperglycemia


Temporal Reduction in Chronotropic Index Predicts Risk of Cardiovascular Death Among Healthy Middle-Aged Men: a 28-Year Follow-Up Study.

Engeseth K, Hodnesdal C, Grundvold I, Liestøl K, Gjesdal K, Kjeldsen SE, Erikssen JE, Bodegard J, Skretteberg PT.

J Am Heart Assoc. 2016 Nov 23;5(12). pii: e004555.

PMID: 27881424 Free Article



Chronotropic index is a standardized measure of heart rate (HR) increment during exercise that reflects the combined effects of age, resting HR, and physical fitness. Low chronotropic index has been reported to predict disease and death. We tested whether temporal change in chronotropic index over 7 years influenced risk of cardiovascular death through up to 28 years.


Chronotropic index was calculated ([achieved maximal HR-resting HR]/[age-predicted maximal HR-resting HR]) after a symptom-limited bicycle ECG exercise test in 1420 healthy men at 2 examinations 7 years apart, in 1972 and 1979. Events of cardiovascular death were registered by manual scrutiny of all participants' hospital charts and the Norwegian Cause of Death Registry. The participants were divided into quartiles of temporal change in chronotropic index, with quartile one having the most negative value. Cox proportional hazard regression models were used to estimate risks and adjusted for classical cardiovascular risk factors. Incidence of cardiovascular death was 310 (22%) during median of 21 years of follow-up. After multivariable adjustment, and comparison with quartile four (mean +0.11), quartiles one (-0.16), two (-0.04), and three (+0.02) were associated with hazard ratios 1.50 (95% CI 1.10-2.05), 1.10 (0.79-1.53), and 1.04 (0.74-1.45) for cardiovascular death. Results remained robust also after exclusion of 31 participants with exercise ECG-induced signs of coronary ischemia.


Temporal reduction in chronotropic index was associated with increased long-term risk of cardiovascular death and might be a clinically important predictor when assessing risk in healthy individuals over a longer time.


all‐cause death prediction; cardiovascular outcomes; chronotropic index; exercise testing; heart rate; physical exercise; risk prediction

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[The below paper is pdf-availed.]

Cardiorespiratory fitness and death from cancer: a 42-year follow-up from the Copenhagen Male Study.

Jensen MT, Holtermann A, Bay H, Gyntelberg F.

Br J Sports Med. 2016 Nov 25. pii: bjsports-2016-096860. doi: 10.1136/bjsports-2016-096860. [Epub ahead of print]

PMID: 27888214



Poor cardiorespiratory fitness (CRF) is associated with death from cancer. If follow-up time is short, this association may be confounded by subclinical disease already present at the time of CRF assessment. This study investigates the association between CRF and death from cancer and any cause with 42 years and 44 years of follow-up, respectively.


Middle-aged, employed and cancer-free Danish men from the prospective Copenhagen Male Study, enrolled in 1970-1971, were included. CRF (maximal oxygen consumption (VO2max)) was estimated using a bicycle ergometer test and analysed in multivariable Cox models including conventional risk factors, social class and self-reported physical activity. Death from cancer and all-cause mortality was assessed using Danish national registers. Follow-up was 100% complete.


In total, 5131 men were included, mean (SD) age 48.8 (5.4) years. During 44 years of follow-up, 4486 subjects died (87.4%), 1527 (29.8%) from cancer. In multivariable models, CRF was highly significantly inversely associated with death from cancer and all-cause mortality ((HR (95% CI)) 0.83 (0.77 to 0.90) and 0.89 (0.85 to 0.93) per 10 mL/kg/min increase in estimated VO2max, respectively). A similar association was seen across specific cancer groups, except death from prostate cancer (1.00 (0.82 to 1.2); p=0.97; n=231). The associations between CRF and outcomes remained essentially unchanged after excluding subjects dying within 10 years (n=377) and 20 years (n=1276) of inclusion.


CRF is highly significantly inversely associated with death from cancer and all-cause mortality. The associations are robust for exclusion of subjects dying within 20 years of study inclusion, thereby suggesting a minimal influence of reverse causation.


Cancer; Fitness; Longevity; Physical fitness; VO2max


Insomnia and risk of dementia in older adults: Systematic review and meta-analysis.

de Almondes KM, Costa MV, Malloy-Diniz LF, Diniz BS.

J Psychiatr Res. 2016 Jun;77:109-15. doi: 10.1016/j.jpsychires.2016.02.021. Review.

PMID: 27017287


There are cross-sectional evidences of an association between sleep disorders and cognitive impairment on older adults. However, there are no consensus by means of longitudinal studies data on the increased risk of developing dementia related to insomnia. We conduct a systematic review and meta-analysis to evaluate the risk of incident all-cause dementia in individuals with insomnia in population-based prospective cohort studies. Five studies of 5.242 retrieved references were included in the meta-analysis. We used the generic inverse variance method with a random effects model to calculate the pooled risk of dementia in older adults with insomnia. We assessed heterogeneity in the meta-analysis by means of the Q-test and I2 index. Study quality was assessed with the Newcastle-Ottawa Scale The results showed that Insomnia was associated with a significant risk of all-cause dementia (RR = 1.53 CI95% (1.07-2.18), z = 2.36, p = 0.02). There was evidence for significant heterogeneity in the analysis (q-value = 2.4, p < 0.001 I2 = 82%). Insomnia is associated with an increased risk for dementia. This results provide evidences that future studies should investigate dementia prevention among elderly individuals through screening and proper management of insomnia.


Dementia; Elderly; Insomnia; Sleep disorders

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[i thank a kind off-list correspondent for the indirect heads-up for the below paper.]

Physical activity in adulthood: genes and mortality.

Karvinen S, Waller K, Silvennoinen M, Koch LG, Britton SL, Kaprio J, Kainulainen H, Kujala UM.

Sci Rep. 2015 Dec 15;5:18259. doi: 10.1038/srep18259.

PMID: 26666586 Free PMC Article


Observational studies report a strong inverse relationship between leisure-time physical activity and all-cause mortality. Despite suggestive evidence from population-based associations, scientists have not been able to show a beneficial effect of physical activity on the risk of death in controlled intervention studies among individuals who have been healthy at baseline. On the other hand, high cardiorespiratory fitness is known to be a strong predictor of reduced mortality, even more robust than physical activity level itself. Here, in both animals and/or human twins, we show that the same genetic factors influence physical activity levels, cardiorespiratory fitness, and risk of death. Previous observational follow-up studies in humans suggest that increasing fitness through physical activity levels could prolong life; however, our controlled interventional study with laboratory rats bred for low and high intrinsic fitness contrast with these findings. Also, we find no evidence for the suggested association using pairwise analysis among monozygotic twin pairs who are discordant in their physical activity levels. Based on both our animal and human findings, we propose that genetic pleiotropy might partly explain the frequently observed associations between high baseline physical activity and later reduced mortality in humans.

"Figure 2. Effects of genetic background and environment on lifespan.

Control rats {C} had longer lifespans than rats in the runner groups {R} of the same strain (HCR-C vs. HCR-R, P < 0.05 and LCR-C vs. LCR-R, P < 0.01). Mean lifespans were also significantly different between rat strains (HCR-C vs. LCR-C, P < 0.05)."


Higher morale is associated with lower risk of depressive disorders five years later among very old people.

Niklasson J, Näsman M, Nyqvist F, Conradsson M, Olofsson B, Lövheim H, Gustafson Y.

Arch Gerontol Geriatr. 2016 Nov 17;69:61-68. doi: 10.1016/j.archger.2016.11.008. [Epub ahead of print]

PMID: 27889589



The aim of this study was to investigate whether higher morale, i.e. future-oriented optimism, at baseline was associated with lower risk of depressive disorders five years later among very old people.Methods The Umeå85+/GErontological Regional Database, a population-based study with a longitudinal design, recruited participants in Sweden and Finland aged 85, 90 and ≥95 years. The sample in the present study included 647 individuals (89.1±4.4 years (Mean±SD), range 85-103). After five years, 216 were alive and agreed to a follow-up (92.6±3.4 years, range 90-104). The Philadelphia Geriatric Center Morale Scale (PGCMS) was used to assess morale. The depressive disorder diagnosis was determined according to DSM-IV based on medical records and interview data including assessment scales for depressive disorders. A number of sociodemographic, functional and health-related variables were analysed as possible confounders.Results For those with no depressive disorders at baseline, the only baseline variable significantly associated with depressive disorders five years later was the PGCMS score. A logistic regression model showed lower risk of depressive disorders five years later with higher baseline PGCMS scores (odds ratio 0.779 for one point increase in PGCMS, p<0.001). The association remained after adjusting for social isolation (p<0.1 association with depressive disorders five years later).Conclusion Our results indicate that the higher the morale, the lower the risk of depressive disorders five years later among very old people. The PGCMS seems to identify those very old individuals at increased risk of depressive disorders five years later. Preventive measures could befocused on this group.


Aged, 80 and over; Depressive disorders; Future-oriented optimism; Geriatric psychiatry; Morale; Salutogenic factor


[Looking at the last table in the paper made me skeptical that enough confounders were considered and it surprised me that some obvious risks were not associated with mortality.]

Self-Reported Masticatory Dysfunction and Mortality in Community Dwelling Elderly Adults: A 9-Year Follow-Up.

Laudisio A, Gemma A, Fontana DO, Rivera C, Bandinelli S, Ferrucci L, Incalzi RA.

J Am Geriatr Soc. 2016 Nov 27. doi: 10.1111/jgs.14331. [Epub ahead of print]

PMID: 27889908



To evaluate the association, if any, between masticatory dysfunction (MD) and mortality in older adults.


The Invecchiare in Chianti (InCHIANTI) Study, a cohort study with 9-year follow-up.


Tuscany, Italy.


Individuals aged 65 and older (N = 1,155).


MD was self-reported; Cox regression was used to assess the association between self-reported MD and 9-year all-cause mortality. This association was also evaluated after stratifying according to use of dentures. Analyses were adjusted for potential confounders, including demographic characteristics, lifestyle habits, comorbidities, nutrient intake, medications, and objective parameters.


Four hundred five (35%) participants reported MD. Over the 9-year follow-up, 475 (41%) subjects died. According to Cox regression analysis, self-reported MD was associated with higher mortality (relative risk (RR) = 1.23, 95% confidence interval (CI) = 1.02-1.48), after adjusting for potential confounders. In participants with self-reported MD, uncorrected edentulism was the condition associated with the greatest risk of mortality (RR = 2.10, 95% CI = 1.07-4.14); use of dentures seemed to blunt this association (RR = 1.12, 95% CI = 0.87-1.44).


Self-reported MD, chiefly when due to uncorrected edentulism, is associated with 9-year all-cause mortality in community-dwelling elderly adults. Further studies are needed to evaluate whether the timely correction of MD using adequate dentures can increase the survival of older adults.


community-dwelling elderly adults; epidemiology; masticatory dysfunction; mortality


Tocotrienols, health and ageing: A systematic review.

Georgousopoulou EN, Panagiotakos DB, Mellor DD, Naumovski N.

Maturitas. 2017 Jan;95:55-60. doi: 10.1016/j.maturitas.2016.11.003. Review.

PMID: 27889054



A systematic review of studies was undertaken to evaluate the potential effect of intake of tocotrienols or circulating levels of tocotrienols on parameters associated with successful ageing, specifically in relation to cognitive function, osteoporosis and DNA damage.


Following PRISMA guidelines a systematic review of epidemiological observational studies and clinical trials was undertaken. Inclusion criteria included all English language publications in the databases PubMed and Scopus, through to the end of July 2016.


Evidence from prospective and case-control studies suggested that increased blood levels of tocotrienols were associated with favorable cognitive function outcomes. A clinical trial of tocotrienol supplementation for 6 months suggested a beneficial effect of intake on DNA damage rates, but only in elderly people. Regarding osteoporosis, only in vitro studies with cultures of human bone cells were identified, and these demonstrated significant inhibition of osteoclast activity and promotion of osteoblast activity.


Research in middle-aged and elderly humans suggests that tocotrienols have a potential beneficial anti-ageing action with respect to cognitive impairment and DNA damage. Clinical trials are required to elucidate these effects.


Ageing; Cognitive function; Osteoporosis; Systematic review; Tocotrienols


Vitamin B3 May Delay Aging

Posted on Nov. 21, 2016, 6 a.m. in Anti-Aging Longevity Vitamins

Scientists have enhanced the global antioxidant capacity of cells, leading to a delay in aging and an increase in longevity.

Vitamin B3 foods - image from Shutterstock

Most attempts to show that oxidative damage is relevant for aging have not been successful, including many trials with antioxidant compounds. Because of this, although the accumulation of oxidative damage with aging is uncontested, most scientists believe that it is merely a minor, almost inconsequential, cause of aging. A team of scientists from the Spanish National Cancer Research Centre (CNIO) headed by Manuel Serrano, in collaboration with a group from the University of Valencia, directed by José Viña, and researchers at IMDEA Food from Madrid, have attempted to increase the global antioxidant capacity of the cells, instead of just one or a few antioxidant enzymes. They concentrated on increasing the levels of NADPH, which is a simple molecule that is of prime importance in antioxidant reactions, yet has also had not been yet studied in relation to aging. They employed a genetic approach to increase NADPH levels, generating transgenic mice with an increased expression throughout their bodies of one of the most crucial enzymes for the production of NADPH, glucose-6-phosphate dehydrogenase (otherwise known as G6PD).

The results, were published in the journal Nature Communications, and show that an increase in G6PD and as a result, in NADPH, increased the natural antioxidant defenses, shielding it from oxidative damage, decreasing aging-related processes such as insulin resistance, and increasing longevity. Furthermore, when the scientists analyzed long-lived transgenic animals, they found that their levels of oxidative damage were lower than in non-transgenic subjects of the same age. They found no difference in the tendency of these animals to develop cancer. The biggest surprise was when the team measured the aging process in the transgenic mice. They discovered that the animals with high levels of NADPH delayed their aging, metabolized sugar better and presented better coordination as they aged. Also, transgenic females lived 14% longer than the non-transgenic mice, though no significant effect was seen in the longevity of the males. "This increased longevity, although modest, is striking taking into account that until now attempts to increase longevity by manipulating individual antioxidant enzymes had failed," said Pablo Fernández-Marcos, co-first author of the study and researcher at IMDEA Food. The researchers in the study point to the use of pharmacological agents or nutritional supplements that increase NADPH levels as possible tools for delaying the aging process in humans and age-related diseases, such as diabetes, and others. Vitamin B3 and its derivatives are responsible for the synthesis of NADPH precursors and are potential candidates for future studies.


G6PD protects from oxidative damage and improves healthspan in mice.

Nóbrega-Pereira S, Fernandez-Marcos PJ, Brioche T, Gomez-Cabrera MC, Salvador-Pascual A, Flores JM, Viña J, Serrano M.

Nat Commun. 2016 Mar 15;7:10894. doi: 10.1038/ncomms10894.

PMID: 26976705 Free PMC Article


Reactive oxygen species (ROS) are constantly generated by cells and ROS-derived damage contributes to ageing. Protection against oxidative damage largely relies on the reductive power of NAPDH, whose levels are mostly determined by the enzyme glucose-6-phosphate dehydrogenase (G6PD). Here, we report a transgenic mouse model with moderate overexpression of human G6PD under its endogenous promoter. Importantly, G6PD-Tg mice have higher levels of NADPH, lower levels of ROS-derived damage, and better protection from ageing-associated functional decline, including extended median lifespan in females. The G6PD transgene has no effect on tumour development, even after combining with various tumour-prone genetic alterations. We conclude that a modest increase in G6PD activity is beneficial for healthspan through increased NADPH levels and protection from the deleterious effects of ROS.


4 Reasons to Go Vegetarian

Posted on Nov. 28, 2016, 6 a.m. in Diet Functional Foods Nutrition

Thinking about becoming a vegetarian? Here are some good reasons to make the switch.

 4 Reasons to Go Vegetarian 

If you have been thinking about becoming a vegetarian, there’s no better time to make the switch. For those of you have been on the fence, here are a few more reasons — like saving money and losing weight — to make the dietary transformation.

Reason #1: Vegetarian diets increase metabolism. Vegetarians have a lower body mass index compared to those eating meat, which has been previously attributed to eating less calories. But a study published in July showed that vegetarians also had a higher resting metabolism. By simply doing their everyday routine, vegetarians burned more calories compared to non-vegetarians. If your New Year’s Resolution included weight loss, becoming a vegetarian may be a good way to do just that.

Reason #2: Vegetarian diets can save you money. Contrary to popular belief, eating healthy doesn’t have to be costly. A study published earlier last year showed that a vegetarian meal plan can actually save money over a meat-based plan. According to the study published in the Journal of Hunger & Environmental Nutrition, vegetarians can save nearly $750 annually! Over a lifetime, this can add up to thousands of dollars in savings. Who doesn’t like a little extra money in their pocket?

Reason #3: Even the government is noticing vegetarian diets are sustainable and healthy. Since the infamous McGovern Report in 1977 — which unsuccessfully tried to incorporate a more plant based diet into formal nutritional guidelines, the meat industry has lobbied heavily to keep meat a mainstay of American dishes. However, things may be about to change. Earlier this year, the Dietary Guidelines Advisory Committee, which helps to create our Dietary Guidelines (think Food Pyramid and MyPlate), concluded that vegetarian diets are more healthy and environmentally friendly than their meaty alternatives. The formal Dietary Guidelines are still under review, but they may finally give vegetarians diets their due credit.

Reason #4: Processed meats cause colorectal cancer. If losing weight and saving money weren’t enough reasons to become a whole-hearted vegetarian, then maybe knowing that processed meats cause cancer might help you cut down on your total meat intake. Earlier this year, the World Health Organization released its landmark report denouncing bacon, hot dogs, sausages, ham, and other types of processed meat as Group 1 carcinogens – a category shared with cigarette smoking. Red meats were not far behind and were labelled as “probably carcinogenic to humans.” Given that colorectal cancer is the third most common type of cancer in America, who wouldn’t want to reduce their lifetime risk of getting cancer?

I have been a vegetarian for three years now, after making it my 2013 New Year’s Resolution in 2013, and it has been one of the best decisions of my life. For those of you who aren’t ready to make the switch, I am sure 2016 will have a few more reasons to jump on the veggie train.



Nutrients 2015, 7(7), 5933-5947; doi:10.3390/nu7075259

High Vegetable Fats Intake Is Associated with High Resting Energy Expenditure in Vegetarians

Tiziana Montalcini 1,*, Daniele De Bonis 2, Yvelise Ferro 2, Ilaria Carè 2, Elisa Mazza 2, Francesca Accattato 3, Marta Greco 3, Daniela Foti 3, Stefano Romeo 2,4, Elio Gulletta 3 and Arturo Pujia 2

Received: 6 May 2015 / Accepted: 10 July 2015 / Published: 17 July 2015

Abstract: It has been demonstrated that a vegetarian diet may be effective in reducing body weight, however, the underlying mechanisms are not entirely clear. We investigated whether there is a difference in resting energy expenditure between 26 vegetarians and 26 non-vegetarians and the correlation between some nutritional factors and inflammatory markers with resting energy expenditure. In this cross-sectional study, vegetarians and non-vegetarians were matched by age, body mass index and gender. All underwent instrumental examinations to assess the difference in body composition, nutrient intake and resting energy expenditure. Biochemical analyses and 12 different cytokines and growth factors were measured as an index of inflammatory state. A higher resting energy expenditure was found in vegetarians than in non-vegetarians (p = 0.008). Furthermore, a higher energy from diet, fibre, vegetable fats intake and interleukin-β (IL-1β) was found between the groups. In the univariate and multivariable analysis, resting energy expenditure was associated with vegetarian diet, free-fat mass and vegetable fats (p < 0.001; Slope in statistic (B) = 4.8; β = 0.42). After adjustment for cytokines, log10 interleukin-10 (IL-10) still correlated with resting energy expenditure (p = 0.02). Resting energy expenditure was positively correlated with a specific component of the vegetarian’s diet, i.e., vegetable fats. Furthermore, we showed that IL-10 was positively associated with resting energy expenditure in this population.

Keywords: vegetarians; plant rich diet; energy expenditure; obesity


Journal of Hunger & Environmental Nutrition 

Volume 10, 2015 - Issue 4

Economical Healthy Diets (2012): Including Lean Animal Protein Costs More Than Using Extra Virgin Olive Oil

Mary M. Flynn & Andrew R. Schiff

Pages 467-482 | Published online: 23 Sep 2015


Healthy diets are perceived to be expensive due to vegetables, fruits, whole grains, and low-fat animal protein. The cost for a 7-day meal plan for an economical version of MyPlate (MP) and a plant-based olive oil (PBOO) were calculated. Servings of vegetables, fruits, and whole grains were determined. MP cost $53.11, and PBOO cost $38.75. Lean animal protein contributed $11.20 (21%) of the total costs for MP. PBOO had more servings of vegetables (44.50 vs. 19.33), fruits (34.50 vs. 30.75), and whole grains (34.0 v 20.0). An economical version of MP costs $746.46 more per year while providing fewer servings of vegetables, fruits, and whole grains.

KEYWORDS: extra virgin olive oil, meat, low-income, diet



Association between inflammatory biomarkers and all-cause, cardiovascular and cancer-related mortality

Archana Singh-Manoux, PhD, Martin J. Shipley, MSc, Joshua A. Bell, PhD, Marianne Canonico, PhD, Alexis Elbaz, MD, PhD, Mika Kivimäki, PhD

First published November 28, 2016, doi: 10.1503/cmaj.160313

CMAJ November 28, 2016 cmaj.160313


Background: The inflammatory biomarker α1-acid glycoprotein (AGP) was found to have the strongest association with 5-year mortality in a recent study of 106 biomarkers. We examined whether AGP is a better biomarker of mortality risk than the more widely used inflammatory biomarkers interleukin-6 (IL-6) and C-reactive protein (CRP).

Methods: We analyzed data for 6545 men and women aged 45-69 (mean 55.7) years from the Whitehall II cohort study. We assayed AGP, IL-6 and CRP levels from fasting serum samples collected in 1997-1999. Mortality follow-up was until June 2015. Cox regression analysis was used to model associations of inflammatory biomarkers with all-cause, cardiovascular and cancer-related mortality.

Results: Over the mean follow-up of 16.7 years, 736 deaths occurred, of which 181 were from cardiovascular disease and 347 from cancer. In the model adjusted for all covariates (age, sex, socioeconomic status, body mass index, health behaviours and chronic disease), AGP did not predict mortality beyond the first 5 years of follow-up; over this period, IL-6 and CRP had stronger associations with mortality. When we considered all covariates and biomarkers simultaneously, AGP no longer predicted all-cause mortality over the entire follow-up period (adjusted hazard ratio {HR} 0.99, 95% confidence interval [CI] 0.90-1.08). Only IL-6 predicted all-cause mortality (adjusted HR 1.22, 95% CI 1.12-1.33) and cancer-related mortality (adjusted HR 1.13, 95% CI 1.00-1.29) over the entire follow-up period, whereas CRP predicted only cardiovascular mortality (adjusted HR 1.30, 95% CI 1.06-1.61).

Interpretation: Our findings suggest that AGP is not a better marker of short- or long-term mortality risk than the more commonly used biomarkers IL-6 and CRP.


Paul M. Ridker

Inflammation, cardiovascular disease and cancer: moving toward predictive medicine

CMAJ cmaj.161033; published ahead of print November 28, 2016,

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Somatic increase of CCT8 mimics proteostasis of human pluripotent stem cells and extends C. elegans lifespan.

Noormohammadi A, Khodakarami A, Gutierrez-Garcia R, Lee HJ, Koyuncu S, König T, Schindler C, Saez I, Fatima A, Dieterich C, Vilchez D.

Nat Commun. 2016 Nov 28;7:13649. doi: 10.1038/ncomms13649.

PMID: 27892468


Human embryonic stem cells can replicate indefinitely while maintaining their undifferentiated state and, therefore, are immortal in culture. This capacity may demand avoidance of any imbalance in protein homeostasis (proteostasis) that would otherwise compromise stem cell identity. Here we show that human pluripotent stem cells exhibit enhanced assembly of the TRiC/CCT complex, a chaperonin that facilitates the folding of 10% of the proteome. We find that ectopic expression of a single subunit (CCT8) is sufficient to increase TRiC/CCT assembly. Moreover, increased TRiC/CCT complex is required to avoid aggregation of mutant Huntingtin protein. We further show that increased expression of CCT8 in somatic tissues extends Caenorhabditis elegans lifespan in a TRiC/CCT-dependent manner. Ectopic expression of CCT8 also ameliorates the age-associated demise of proteostasis and corrects proteostatic deficiencies in worm models of Huntington's disease. Our results suggest proteostasis is a common principle that links organismal longevity with hESC immortality.


Impact of Mediterranean diet on metabolic syndrome, cancer and longevity.

Di Daniele N, Noce A, Vidiri MF, Moriconi E, Marrone G, Annicchiarico-Petruzzelli M, D'Urso G, Tesauro M, Rovella V, De Lorenzo A.

Oncotarget. 2016 Nov 24. doi: 10.18632/oncotarget.13553. [Epub ahead of print]

PMID: 27894098


Obesity symbolizes a major public health problem. Overweight and obesity are associated to the occurrence of the metabolic syndrome and to adipose tissue dysfunction. The adipose tissue is metabolically active and an endocrine organ, whose dysregulation causes a low-grade inflammatory state and ectopic fat depositions. The Mediterranean Diet represents a possible therapy for metabolic syndrome, preventing adiposopathy or "sick fat" formation.The Mediterranean Diet exerts protective effects in elderly subjects with and without baseline of chronic diseases. Recent studies have demonstrated a relationship between cancer and obesity. In the US, diet represents amount 30-35% of death causes related to cancer. Currently, the cancer is the second cause of death after cardiovascular diseases worldwide. Furthermore, populations living in the Mediterranean area have a decreased incidence of cancer compared with populations living in Northern Europe or the US, likely due to healthier dietary habits. The bioactive food components have a potential preventive action on cancer. The aims of this review are to evaluate the impact of Mediterranean Diet on onset, progression and regression of metabolic syndrome, cancer and on longevity.


Mediterranean diet; antioxidant; cancer; obesity; public health



Importance of Assessing Cardiorespiratory Fitness in Clinical Practice: A Case for Fitness as a Clinical Vital Sign: A Scientific Statement From the American Heart Association.

Ross R, Blair SN, Arena R, Church TS, Després JP, Franklin BA, Haskell WL, Kaminsky LA, Levine BD, Lavie CJ, Myers J, Niebauer J, Sallis R, Sawada SS, Sui X, Wisløff U; American Heart Association Physical Activity Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Clinical Cardiology; Council on Epidemiology and Prevention; Council on Cardiovascular and Stroke Nursing; Council on Functional Genomics and Translational Biology; and Stroke Council..

Circulation. 2016 Nov 21. pii: CIR.0000000000000461. [Epub ahead of print]

PMID: 27881567


Mounting evidence has firmly established that low levels of cardiorespiratory fitness (CRF) are associated with a high risk of cardiovascular disease, all-cause mortality, and mortality rates attributable to various cancers. A growing body of epidemiological and clinical evidence demonstrates not only that CRF is a potentially stronger predictor of mortality than established risk factors such as smoking, hypertension, high cholesterol, and type 2 diabetes mellitus, but that the addition of CRF to traditional risk factors significantly improves the reclassification of risk for adverse outcomes. The purpose of this statement is to review current knowledge related to the association between CRF and health outcomes, increase awareness of the added value of CRF to improve risk prediction, and suggest future directions in research. Although the statement is not intended to be a comprehensive review, critical references that address important advances in the field are highlighted. The underlying premise of this statement is that the addition of CRF for risk classification presents health professionals with unique opportunities to improve patient management and to encourage lifestyle-based strategies designed to reduce cardiovascular risk. These opportunities must be realized to optimize the prevention and treatment of cardiovascular disease and hence meet the American Heart Association's 2020 goals.

© 2016 American Heart Association, Inc.


AHA Scientific Statements; cardiovascular disease; physical fitness; risk factors


[i noticed that there was a lower risk in the third versus fourth quartile of fitness for non-fatal heart attack; ditto for the second and third quartile for non-fatal stroke.]

Cardiorespiratory fitness and nonfatal cardiovascular events: A population-based follow-up study.

Khan H, Jaffar N, Rauramaa R, Kurl S, Savonen K, Laukkanen JA.

Am Heart J. 2016 Nov 2;184:55-61. doi: 10.1016/j.ahj.2016.10.019. [Epub ahead of print]

PMID: 27892887



To examine the prognostic value of cardiorespiratory fitness (CRF) with risk of first major nonfatal myocardial infarction (MI), stroke, and heart failure (HF) events.


Cardiorespiratory fitness, as measured by maximal oxygen uptake, was assessed at baseline in a prospective cohort of 2,089 men aged 42 to 61years.


During a mean (SD) follow-up of 19.1(8.4) years, 522 nonfatal acute MI events, 198 acute all-cause nonfatal stroke events, and 221 nonfatal HF events were recorded. The hazard ratio per 1-metabolic-equivalent increase in CRF was 0.93 (95% CI 0.88-0.97) for nonfatal MI, 0.94 (95% CI0.87-1.01) for nonfatal stroke, and 0.84 (95% CI 0.78-0.91) for nonfatal HF events after adjustment for cardiovascular risk factors (age, systolic blood pressure, body mass index, history of cardiovascular disease, diabetes, smoking, alcohol use, serum creatinine, low-density lipoprotein levels, physical activity, and socioeconomic status). Further adjustment for left ventricular hypertrophy and resting heart rate did not attenuate these associations. Addition of CRF to conventional cardiovascular disease risk factors significantly improved both discrimination (C index) and category free net reclassification index (cf-NRI) for nonfatal MI (change in C index, 0.015 [95% CI 0.010-0.020] and change in cf-NRI 0.27, P<.01) and HF (change in C index 0.040 [95% CI 0.010-0.060] and change in cf-NRI 0.88, P<.01).


In this Finnish population, there is a strong, inverse, and independent association between CRF and acute nonfatal MI and HF risk.


Atorvastatin for high-risk statin-naïve patients undergoing noncardiac surgery: The Lowering the Risk of Operative Complications Using Atorvastatin Loading Dose (LOAD) randomized trial.

Berwanger O, de Barros E Silva PG, Barbosa RR, Precoma DB, Figueiredo EL, Hajjar LA, Kruel CD, Alboim C, Almeida AP, Dracoulakis MD, Filho HV, Carmona MJ, Maia LN, de Oliveira Filho JB, Saraiva JF, Soares RM, Damiani L, Paisani D, Kodama AA, Gonzales B, Ikeoka DT, Devereaux PJ, Lopes RD; LOAD Investigators..

Am Heart J. 2016 Nov 9;184:88-96. doi: 10.1016/j.ahj.2016.11.001. [Epub ahead of print]

PMID: 27892891


Preliminary evidence suggests that statins may prevent major perioperative vascular complications.


We randomized 648 statin-naïve patients who were scheduled for noncardiac surgery and were at risk for a major vascular complication. Patients were randomized to a loading dose of atorvastatin or placebo (80 mg anytime within 18hours before surgery), followed by a maintenance dose of 40 mg (or placebo), started at least 12hours after the surgery, and then 40 mg/d (or placebo) for 7days. The primary outcome was a composite of all-cause mortality, nonfatal myocardial injury after noncardiac surgery, and stroke at 30days.


The primary outcome was observed in 54 (16.6%) of 326 patients in the atorvastatin group and 59 (18.7%) of 316 patients in the placebo group (hazard ratio
0.87, 95% CI 0.60-1.26, P=.46). No significant effect was observed on the 30-day secondary outcomes of all-cause mortality (4.3% vs 4.1%, respectively; HR 1.14, 95% CI 0.53-2.47, P=.74), nonfatal myocardial infarction (3.4% vs 4.4%, respectively; HR 0.76, 95% CI 0.35-1.68, P=.50), myocardial injury after noncardiac surgery (13.2% vs 16.5%; HR 0.79, 95% CI 0.53-1.19, P=.26), and stroke (0.9% vs 0%, P=.25).


In contrast to the prior observational and trial data, the LOAD trial has neutral results and did not demonstrate a reduction in major cardiovascular complications after a short-term perioperative course of statin in statin-naïve patients undergoing noncardiac surgery. We demonstrated, however, that a large multicenter blinded perioperative statin trial for high-risk statin-naïve patients is feasible and should be done to definitely establish the efficacy and safety of statin in this patient population.


Dietary nitrate does not affect physical activity outcomes in health older adults in a randomized, crossover trial.

Siervo M, Oggioni C, Jakovljevic DG, Trenell M, Mathers JC, Houghton D, Celis-Morales C, Ashor AW, Ruddock A, Ranchordas M, Klonizakis M, Williams EA.

Nutr Res. 2016 Nov 14. pii: S0271-5317(16)30241-X. doi: 10.1016/j.nutres.2016.11.004. [Epub ahead of print]

PMID: 27890482


Although dietary nitrate (NO3-) ingestion appears to enhance exercise capacity and performance in young individuals, inconclusive findings have been reported in older people. Therefore, we conducted a double-blind, crossover randomized clinical trial using beetroot juice in older healthy participants, who were classified as normal weight and overweight. We tested whether consumption of beetroot juice (a rich source of NO3-) for 1 week would increase nitric oxide bioavailability via the nonenzymatic pathway and enhance (1) exercise capacity during an incremental exercise test, (2) physical capability, and (3) free-living physical activity. Twenty nonsmoking, healthy participants between 60 and 75 years of age and with a body mass index of 20.0 to 29.9 kg/m2 were included. Presupplementation and postsupplementation resting, submaximal, maximal, and recovery gas exchanges were measured. Physical capability was measured by hand-grip strength, time-up-and-go, repeated chair rising test, and 10-m walking speed. Free-living physical activity was assessed by triaxal accelerometry. Changes in urinary and plasmaNO3-concentrations were measured by gas chromatography-mass spectrometry. Nineteen participants (male-to-female ratio, 9:10) completed the study.Beetroot juice increased significantly both plasma and urinary NO3-concentrations (P<.001) when compared with placebo. Beetroot juice did not influence resting or submaximal and maximal oxygen consumption during the incremental exercise test. In addition, measures of physical capability and physical activity levels measured in free-living conditions were not modified by beetroot juice ingestion. The positive effects of beetroot juice ingestion on exercise performance seen in young individuals were not replicated in healthy, older adults. Whether aging represents a modifier of the effects of dietary NO3-on muscular performance is not known, and mechanistic studies and larger trials are needed to test this hypothesis.


Aging; Exercise; Inorganic nitrate; Nitric oxide; Oxygen consumption


Effect on body weight and composition in overweight/obese Australian adults over 12 months consumption of two different types of fibre supplementation in a randomized trial.

Pal S, Ho S, Gahler RJ, Wood S.

Nutr Metab (Lond). 2016 Nov 17;13:82.

PMID: 27891167



Higher fibre intakes are associated with risk reduction for chronic diseases. However, many people find difficulty in consuming sufficient fibre through their diet. Supplements may be an effective alternative. We aimed to investigate the effects of PolyGlycopleX® (PGX®), a proprietary polysaccharide complex and a proprietary Psyllium product (PgxSyl™) (PSY) on diet, body weight and composition in overweight and obese individuals.


This was a double-blind 52 weeks study with 159 people randomized to 3 groups: control (rice flour); PGX (PGX) and proprietary psyllium (PSY). Participants did not change any of their usual habits or diet except they consumed 5 g of supplement taken with a total of 500 ml of water 5-10 min before meals.


Weight was significantly lower in the PGX group compared to control at 3 (-1.6 kg [0.57, 2.67, p = 0.003]), 6 (-2.6 kg [1.01, 4.13, p = 0.001]) and 12 months (-2.6 kg [0.59, 4.64, p = 0.012]) and in the PSY group compared to control group at 3 (-1.1 kg [0.07, 2.12, p = 0.037]) and 6 months (-2.4 kg [0.95, 3.93, p = 0.002]). This was a difference of - 2.8% for the PGX group and - 1.5% for the PSY group compared to control after 12 months supplementation. Body Fat was significantly lower in PGX compared to control at 6 (-1.8 kg [0.63, 2.95, p = 0.003]) and 12 months (-1.9 kg [0.43, 3.36, p = 0.012]) and in PSY compared to control at 6 (-1.9 kg [0.84, 3.04, p = 0.001]) and 12 months (-1.4 kg [0.08, 2.71, p = 0.038]).


PGX was better than PSY at maintaining dietary changes and weight loss over the 12 month intervention period, with no change to exercise. A simple strategy of PGX supplementation may offer an effective solution to long-term weight-loss and then management without the need for other nutrient modification.


Body composition; Fibre; Obesity; PGX; Psyllium


Episodic memory of odors stratifies Alzheimer biomarkers in normal elderly.

Dhilla Albers A, Asafu-Adjei J, Delaney MK, Kelly KE, Gomez-Isla T, Blacker D, Johnson KA, Sperling RA, Hyman BT, Betensky RA, Hastings L, Albers MW.

Ann Neurol. 2016 Oct 1. doi: 10.1002/ana.24792. [Epub ahead of print]

PMID: 27696605



The objective of this study was to relate a novel test of identifying and recalling odor percepts to biomarkers of Alzheimer's disease (AD) in well-characterized elderly individuals, ranging from cognitively normal to demented.


One hundred eighty-three participants (cognitively normal: n = 70; subjective cognitive concerns: n = 74; mild cognitive impairment [MCI]: n = 29, AD dementia: n = 10) were administered novel olfactory tests: the Odor Percept IDentification (OPID) and the Percepts of Odor Episodic Memory (POEM) tests. Univariate cross-sectional analyses of performance across diagnoses; logistic regression modeling, including covariates of age, sex, education, APOE genotype, and neuropsychological test scores; and linear mixed modeling of longitudinal cognitive scores were performed. Amyloid deposition and MRI volumetrics were analyzed in a subset of participants.


Accuracy of identification and episodic memory of odor percepts differed significantly across diagnosis and age, with progressively worse performance across degrees of impairment. Among the participants who were cognitively normal or had subjective cognitive concerns, poorer than expected performance on the POEM test (based on the same individual's performance on the OPID and odor discrimination tests) was associated with higher frequencies of the APOE ε4 allele, thinner entorhinal cortices, and worse longitudinal trajectory of Logical Memory scores.


Selective impairment of episodic memory of odor percepts, relative to identification and discrimination of odor percepts revealed by this novel POEM battery, is associated with biomarkers of AD in a well-characterized pre-MCI population. These affordable, noninvasive olfactory tests offer potential to identify clinically normal individuals who have greater likelihood of future cognitive decline. Ann Neurol 2016.

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Patient Survival and Costs on Moderately Restricted Low-Protein Diets in Advanced CKD: Equivalent Survival at Lower Costs?

Barbara PG, Marta N, Irene C, Neve VF, Elena M, Marilisa B, Paolo A, Elisabetta V.

Nutrients. 2016 Nov 25;8(12). pii: E758.

PMID: 27898000


The indications for delaying the start of dialysis have revived interest in low-protein diets (LPDs). In this observational prospective study, we enrolled all patients with chronic kidney disease (CKD) who followed a moderately restricted LPD in 2007-2015 in a nephrology unit in Italy: 449 patients, 847 years of observation. At the start of the diet, the median glomerular filtration rate (GFR) was 20 mL/min, the median age was 70, the median Charlson Index was 7. Standardized mortality rates for the "on-diet" population were significantly lower than for patients on dialysis (United States Renal Data System (USRDS): 0.44 (0.36-0.54); Italian Dialysis Registry: 0.73 (0.59-0.88); French Dialysis Registry 0.70 (0.57-0.85)). Considering only the follow-up at low GFR (≤15 mL/min), survival remained significantly higher than in the USRDS, and was equivalent to the Italian and French registries, with an advantage in younger patients. Below the e-GFR of 15 mL/min, 50% of the patients reached a dialysis-free follow-up of ≥2 years; 25% have been dialysis-free for five years. Considering an average yearly cost of about 50,000 Euros for dialysis and 1200 Euros for the diet, and different hypotheses of "spared" dialysis years, treating 100 patients on a moderately restricted LPD would allow saving one to four million Euros. Therefore, our study suggests that in patients with advanced CKD, moderately restricted LPDs may allow prolonging dialysis-free follow-up with comparable survival to dialysis at a lower cost.


costs; dialysis start; low protein diet; mortality; registry; standardized mortality ratio


N-Acetyl Cysteine Attenuated the Deleterious Effects of Advanced Glycation End-Products on the Kidney of Non-Diabetic Rats.

Thieme K, Da Silva KS, Fabre NT, Catanozi S, Monteiro MB, Santos-Bezerra DP, Costa-Pessoa JM, Oliveira-Souza M, Machado UF, Passarelli M, Correa-Giannella ML.

Cell Physiol Biochem. 2016 Nov 30;40(3-4):608-620. [Epub ahead of print]

PMID: 27898405



To assess the renal effects of chronic exposure to advanced glycation end-products (AGEs) in the absence of diabetes and the potential impact of concomitant treatment with the antioxidant N-acetyl cysteine (NAC).


Wistar rats received intraperitoneally 20 mg/kg/day of albumin modified (AlbAGE) or not (AlbC) by advanced glycation for 12 weeks and oral NAC (600mg/L; AlbAGE+NAC and AlbC+NAC, respectively). Biochemical, urinary and renal morphological analyses; carboxymethyl-lysine (CML, an AGE), CD68 (macrophage infiltration), and 4-hydroxynonenal (4-HNE, marker of oxidative stress) immunostaining; intrarenal mRNA expression of genes belonging to pathways related to AGEs (Ager, Ddost, Nfkb1), renin-angiotensin system (Agt, Ren, Ace), fibrosis (Tgfb1, Col4a1), oxidative stress (Nox4, Txnip), and apoptosis (Bax, Bcl2); and reactive oxidative species (ROS) content were performed.


AlbAGE significantly increased urine protein-to-creatinine ratio; glomerular area; renal CML content and macrophage infiltration; expression of Ager, Nfkb1, Agt, Ren, Tgfb1, Col4a1, Txnip, Bax/Bcl2 ratio; and 4-HNE and ROS contents. Some of these effects were attenuated by NAC concomitant treatment.


Because AGEs are highly consumed in modern diets and implicated in the progression of different kidney diseases, NAC could be a therapeutic intervention to decrease renal damage, considering that long-term restriction of dietary AGEs is difficult to achieve in practice.


Prevalence and incidence of sarcopenia in the very old: findings from the Newcastle 85+ Study.

Dodds RM, Granic A, Davies K, Kirkwood TB, Jagger C, Sayer AA.

J Cachexia Sarcopenia Muscle. 2016 Nov 16. doi: 10.1002/jcsm.12157. [Epub ahead of print]

PMID: 27897431



Recognition that an older person has sarcopenia is important because this condition is linked to a range of adverse outcomes. Sarcopenia becomes increasingly common with age, and yet there are few data concerning its descriptive epidemiology in the very old (aged 85 years and above). Our aims were to describe risk factors for sarcopenia and estimate its prevalence and incidence in a British sample of the very old.


We used data from two waves (2006/07 and 2009/10) of the Newcastle 85+ Study, a cohort born in 1921 and registered with a Newcastle/North Tyneside general practice. We assessed sarcopenia status using the European Working Group on Sarcopenia in Older People (EWGSOP) definition. Grip strength was measured using a Takei digital dynamometer (Takei Scientific Instruments Ltd., Niigata, Japan), gait speed was calculated from the Timed Up and Go test, and lean mass was estimated using a Tanita-305 body fat analyzer. We used logistic regression to examine associations between risk factors for prevalent sarcopenia at baseline and incident sarcopenia at follow-up.


European Working Group on Sarcopenia in Older People sarcopenia was present in 21% of participants at baseline [149/719 participants, mean age 85.5 (0.4) years]. Many participants had either slow gait speed or weak grip strength (74.3%), and hence measurement of muscle mass was frequently indicated by the EWGSOP definition. Incidence data were available for 302 participants, and the incident rate was 3.7 cases per 100 person years at risk. Low Standardized Mini-Mental State Examination, lower occupational social class, and shorter duration of education were associated with sarcopenia at baseline, while low muscle mass was associated with incident sarcopenia. Low body mass index (BMI) was a risk factor for both in a graded fashion, with each unit decrease associated with increased odds of prevalent [odds ratio (OR) 1.29, 95% confidence interval (CI): 1.21, 1.37] and incident (OR 1.20, 95% CI: 1.08, 1.33) sarcopenia.


To our knowledge, this is the first study to describe prevalence and incidence of EWGSOP sarcopenia in the very old. Low BMI was a risk factor for both current and future sarcopenia; indeed, there was some evidence that low BMI may be a reasonable proxy for low lean mass. Overall, the high prevalence of sarcopenia among the very old suggests that this group should be a focus for future research.


Incidence; Prevalence; Risk factors; Sarcopenia; Very old


Efficacy of L-carnitine supplementation on frailty status and its biomarkers, nutritional status, and physical and cognitive function among prefrail older adults: a double-blind, randomized, placebo-controlled clinical trial.

Badrasawi M, Shahar S, Zahara AM, Nor Fadilah R, Singh DK.

Clin Interv Aging. 2016 Nov 17;11:1675-1686.

PMID: 27895474



Frailty is a biological syndrome of decreased reserve and resistance to stressors due to decline in multiple physiological systems. Amino acid deficiency, including L-carnitine, has been proposed to be associated with its pathophysiology. Nevertheless, the efficacy of L-carnitine supplementation on frailty status has not been documented. Thus, this study aimed to determine the effect of 10-week L-carnitine supplement (1.5 g/day) on frailty status and its biomarkers and also physical function, cognition, and nutritional status among prefrail older adults in Klang Valley, Malaysia.


This study is a randomized, double-blind, placebo-controlled clinical trial conducted among 50 prefrail subjects randomized into two groups (26 in L-carnitine group and 24 in placebo group). Outcome measures include frailty status using Fried criteria and Frailty Index accumulation of deficit, selected frailty biomarkers (interleukin-6, tumor necrosis factor-alpha, and insulin-like growth factor-1), physical function, cognitive function, nutritional status and biochemical profile.


The results indicated that the mean scores of Frailty Index score and hand grip test were significantly improved in subjects supplemented with L-carnitine (P<0.05 for both parameters) as compared to no change in the placebo group. Based on Fried criteria, four subjects (three from the L-carnitine group and one from the control group) transited from prefrail status to robust after the intervention.


L-carnitine supplementation has a favorable effect on the functional status and fatigue in prefrail older adults.


Frailty Index accumulation of deficit; Fried criteria; L-carnitine supplementation; frailty; frailty biomarkers; physical function; prefrail elderly; randomized controlled clinical trial


Effects of Hazelnut Consumption on Blood Lipids and Body Weight: A Systematic Review and Bayesian Meta-Analysis.

Perna S, Giacosa A, Bonitta G, Bologna C, Isu A, Guido D, Rondanelli M.

Nutrients. 2016 Nov 25;8(12). pii: E747. Review.

PMID: 27897978


Hazelnuts are rich in monounsaturated fatty acids and antioxidant bioactive substances: their consumption has been associated with a decreased risk of cardiovascular disease events. A systematic review and a meta-analysis was performed to combine the results from several trials and to estimate the pooled (overall) effect of hazelnuts on blood lipids and body weight outcomes. Specifically, a Bayesian random effect meta-analysis of mean differences of Δ-changes from baseline across treatment (MDΔ) (i.e., hazelnut-enriched diet vs. control diet) has been conducted. Nine studies representing 425 participants were included in the analysis. The intervention diet lasted 28-84 days with a dosage of hazelnuts ranging from 29 to 69 g/day. Out of nine studies, three randomized studies have been meta-analyzed showing a significant reduction in low-density lipoprotein (LDL) cholesterol (pooled MDΔ = -0.150 mmol/L; 95% highest posterior density interval (95%HPD) = -0.308; -0.003) in favor of a hazelnut-enriched diet. Total cholesterol showed a marked trend toward a decrease (pooled MDΔ = -0.127 mmol/L; 95%HPD = -0.284; 0.014) and high-density lipoprotein (HDL) cholesterol remained substantially stable (pooled MDΔ = 0.002 mmol/L; 95%HPD = -0.140; 0.147). No effects on triglycerides (pooled MDΔ = 0.045 mmol/L; 95%HPD = -0.195; 0.269) and body mass index (BMI) (pooled MDΔ = 0.062 kg/m²; 95%HPD = -0.293; 0.469) were found. Hazelnut-enriched diet is associated with a decrease of LDL and total cholesterol, while HDL cholesterol, triglycerides and BMI remain substantially unchanged.


BMI; Corylus avellana; body weight; cholesterol; hazelnut; lipid; obesity; triglyceride


Dietary intake of fiber in relation to knee pain trajectories.

Dai Z, Lu N, Niu J, Felson DT, Zhang Y.

Arthritis Care Res (Hoboken). 2016 Nov 29. doi: 10.1002/acr.23158. [Epub ahead of print]

PMID: 27899003


Objective Dietary fiber may reduce knee pain in part by lowering body weight and inflammation. In this study, we assessed whether fiber intake was associated with knee pain development patterns. Methods In a prospective, multicenter cohort of 4,796 men and women aged 45-79 years with or at risk of knee osteoarthritis in Osteoarthritis Initiative, participants were followed up annually for 8 years. Dietary fiber was estimated using a validated food frequency questionnaire at baseline. Group-based trajectory modeling was used to identify WOMAC pain trajectories, which were assessed for the associations with dietary fiber intake using polytomous regression models. Results Of the 4,470 eligible participants (8,940 knees) [mean age: 61.3 (SD: 9.1) years, 58% women], 4.9% underwent knee replacement and were censored at the time of surgery. Four distinct knee pain patterns were identified: no pain (34.5%), mild pain (38.1%), moderate pain (21.2%) and severe pain (6.2%). Dietary total fiber was inversely related to membership in the moderate or severe pain group (both p for trend ≤0.006). Subjects in the highest versus lowest quartile of total fiber had lower risks of belonging to moderate pain (OR=0.76, 95% CI: 0.61, 0.93) and severe pain patterns (OR=0.56, 95% CI: 0.41, 0.78). Similar results were found for grain fiber with these two pain patters. Conclusion Our findings suggest that high dietary total or grain fiber, particularly in the recommended daily fiber average intake of 25g per day, was associated with lower risks of belonging to moderate and severe knee pain development patterns over time.


Groundbreaking Research That May Make Aging Obsolete

Posted on Nov. 30, 2016, 6 a.m. in Anti-Aging Artificial Intelligence Longevity and Age Management

Is it possible that aging is preventable?

 Groundbreaking Research That May Make Aging Obsolete

Researchers are on the verge of cracking the aging code, and death caused by aging may become obsolete by as early as 2033. A synergy between two ground-breaking research fields is predicted to not only keep us alive; but to also keep us vivacious, youthful and healthy.

The Age Reversal Project Spearheads

The Maximum Life Foundation (www.maxlife.org), spearheaded by David Kekich, consists of a team of the leading anti-aging researchers and specialists from around the world. The team includes nanotechnology specialists, artificial intelligence developers, regenerative medicine specialists (including stem cell specialists), genetic experts, and specialists in the drug and nutritional supplement industries. According to the experts, a convergence of biotechnology, infotechnology and nanotechnology will provide a roadmap to halt aging in the very near future.

Gene therapy will also play an integral role in reversing aging. At the forefront of the genetic-based age reversal research is a company called BioViva, which is spearheaded by Liz Parrish (www.biovivasciences.com).

The Role of Artificial Intelligence

A.I. is the source technology in the age-reversal roadmap; it is necessary for the advancement of all the other tools required to stop aging

A.I. can take the discoveries and complexities of every field that is focused on aging, and handle them far better and far quicker than the human mind ever could

A company called Scicog Systems (www.scicogsystems.com) is creating an ‘Artificial Scientist’, that will essentially be the smartest scientist in the world

In approximately 3 years, the researchers will have gathered every bit of aging research available, and programmed them into the Artificial Scientist

The Artificial Scientist will be able to comprehend and dissect the quadrillions of chemical reactions that occur in the human body and unravel the code of the 20,000 human genes

It will be able to identify patterns that are unrecognizable to humans and form its own hypotheses from those patterns

It will be able to test its own hypotheses, to discover information and create new knowledge, which in turn, will turbocharge the age reversal development project

The Role of Gene Therapy

Gene therapy addresses the root cause of aging and encourages cellular and tissue regeneration

It offers the answer to correcting most if not all diseases (including diseases that are currently considered incurable), at their most basic level

Gene alterations (specifically, the shortening of the telomeres which are the protective tips of the chromosomes), are the leading risk factors of aging and disease

Telomerase prevent the shortening of telomeres, and Bioviva projects that delivering telomerase to the cells (which they are currently working on doing), will play an integral role in the age reversal development project


Compiling all the leading anti-aging data and research (including everything we currently know about gene therapy), into an Artificial Scientist, will help tremendously in the creation of an age reversal code. The code remains to be determined, but researchers theorize that it will combine gene chip technology with hormone balancing and other non-toxic interventions; all of which will put an end to aging as we know it!


Aging and death are two certainties in life that humans have shared since the beginning of time. But hard as it may be to believe, death caused by aging may become obsolete within the next 20 years, thanks to a synergy between two ground-breaking age reversal research fields. The first thing that this news may bring to mind is “Oh boy, we are going to keep people alive in nursing homes forever and ever,” or, “I don’t want to continue living when I’m old, frail and sick!” But that is not the projected outcome. Researchers are on the threshold of reversing the biological process of aging itself, so humans will not only stay alive, they will also remain vibrant, energetic, youthful and healthy.

The Spearhead of the Age Reversal Project

Since his 30’s David Kekich has been interested in reversing aging and in the prospect of creating technologies that would completely eliminate aging-related deaths. He has devoted the past two decades of his life to raising funds for, and researching, age reversal technologies. As a part of his efforts, he created the Maximum Life Foundation (www.maxlife.org), which consists of a team of the top anti-aging researchers from around the world. His panel of experts include regenerative medicine specialists (including stem cell specialists), nanotechnology specialists, artificial intelligence developers, genetic experts, and specialists in the nutritional supplement and drug industries.

In the last international ‘age-reversal’ brainstorming conference, Kekich and his team of experts created a complete scientific roadmap for the reversal of aging; a roadmap that merges biotechnology, infotechnology and nanotechnology. By converging those three fields, (including all the disciplines among and included in those fields), Kekich and his researchers forecast that they will be able to crack the aging code completely by 2033.

Research Field #1: Artificial Intelligence

Artificial Intelligence (A.I.) is the source technology in the age-reversal roadmap; it is not only supportive, but also essential for the development of all the other tools required to stop aging. The reason why it is so important is that it’s able to take the quadrillions of chemical reactions that are going on all the time and the other complexities in every field that is focused on aging, and to handle them far better and far faster than the human mind ever could.

There have been huge inroads in A.I. over the past decade, and a company called Scicog Systems (www.scicogsystems.com) is creating an ‘Artificial Scientist’, that will essentially be the smartest scientist in the world. It is estimated that within just 3 years, the researchers will have accumulated every bit of aging research pertaining to plants, animals and humans, into one massive A.I. database. The Artificial Scientist will be able to comprehend and dissect the quadrillion fragments of complex information pertaining to the human body and the study of age reversal. It will be able to quickly unravel the code of the 20,000 human genes; and it will be able to recognize patterns that are unrecognizable to humans and form its own hypotheses from those patterns. It will then be able to test its hypotheses, to uncover information and create new knowledge, which in turn, will turbocharge the age reversal development project.

Research Field # 2: Gene Therapy

According to some of the worlds leading anti-aging researchers, A.I. coupled with gene therapy, is the key to cracking the aging code and Liz Parrish is at the forefront of the genetic-based age reversal research. Her gene therapy approach at BioViva (www.biovivasciences.com) makes all the previous theories of telomerase activation nearly obsolete. In order to understand telomerase and their role in aging, you must first understand chromosomes and telomeres (which are different than telomerase). Chromosomes carry our DNA and at the end of chromosomes are telomeres, which protect our genetic data. An easy way to comprehend this is to think of telomeres as the protective plastic tips on shoelaces; they keep chromosome ends from fraying, which would destroy the genetic information. Every time a cell divides the telomeres get shorter, and when they get too short, the telomeres can no longer survive, which causes aging, cancer and a higher risk of death. Telomerase prevent and reverse the shortening of telomeres, thereby preventing the core cause of aging and many chronic diseases.

“We cannot cure the symptoms of aging without treating the underlying cause (telomere shortening). Cellular degeneration underlies biological aging and is behind the development of Alzheimer’s, heart disease, renal failure, and many others,” states Parrish. Her team of researchers are currently working on developing a one-time treatment tool, which will reverse arterial plaque for life, thereby making heart disease (America’s #1 killer) virtually obsolete. They are also working on a reversal for Alzheimer’s disease; and a tool to stop muscle wasting, which will help heal muscular dystrophy, spinal cord injuries, brain injuries, stroke, and more.


Parrish’s gene therapy research, combined with all of the other anti-aging data from medical experts, and technologists around the world, can be fed to the Artificial Scientist, so that it can crack the code to age reversal. The exact code remains to be determined; however, gene chip technology (that will allow for genetic alterations) will likely play a fundamental role. In the very near future, chip technology combined with hormonal balancing and other simple, non-toxic interventions, may just put an end to aging as we know it!



Unconventional Gas and Oil Drilling Is Associated with Increased Hospital Utilization Rates.

Jemielita T, Gerton GL, Neidell M, Chillrud S, Yan B, Stute M, Howarth M, Saberi P, Fausti N, Penning TM, Roy J, Propert KJ, Panettieri RA Jr.

PLoS One. 2015 Jul 15;10(7):e0131093. doi: 10.1371/journal.pone.0131093. Erratum in: PLoS One. 2015;10(8):e0137371.

PMID: 26176544 Free PMC Article


Over the past ten years, unconventional gas and oil drilling (UGOD) has markedly expanded in the United States. Despite substantial increases in well drilling, the health consequences of UGOD toxicant exposure remain unclear. This study examines an association between wells and healthcare use by zip code from 2007 to 2011 in Pennsylvania. Inpatient discharge databases from the Pennsylvania Healthcare Cost Containment Council were correlated with active wells by zip code in three counties in Pennsylvania. For overall inpatient prevalence rates and 25 specific medical categories, the association of inpatient prevalence rates with number of wells per zip code and, separately, with wells per km2 (separated into quantiles and defined as well density) were estimated using fixed-effects Poisson models. To account for multiple comparisons, a Bonferroni correction with associations of p<0.00096 was considered statistically significant. Cardiology inpatient prevalence rates were significantly associated with number of wells per zip code (p<0.00096) and wells per km2 (p<0.00096) while neurology inpatient prevalence rates were significantly associated with wells per km2 (p<0.00096). Furthermore, evidence also supported an association between well density and inpatient prevalence rates for the medical categories of dermatology, neurology, oncology, and urology. These data suggest that UGOD wells, which dramatically increased in the past decade, were associated with increased inpatient prevalence rates within specific medical categories in Pennsylvania. Further studies are necessary to address healthcare costs of UGOD and determine whether specific toxicants or combinations are associated with organ-specific responses.


Associations of specific types of sports and exercise with all-cause and cardiovascular-disease mortality: a cohort study of 80 306 British adults.

Oja P, Kelly P, Pedisic Z, Titze S, Bauman A, Foster C, Hamer M, Hillsdon M, Stamatakis E.

Br J Sports Med. 2016 Nov 28. pii: bjsports-2016-096822. doi: 10.1136/bjsports-2016-096822. [Epub ahead of print]

PMID: 27895075



Evidence for the long-term health effects of specific sport disciplines is scarce. Therefore, we examined the associations of six different types of sport/exercise with all-cause and cardiovascular disease (CVD) mortality risk in a large pooled Scottish and English population-based cohort.


Cox proportional hazards regression was used to investigate the associations between each exposure and all-cause and CVD mortality with adjustment for potential confounders in 80 306 individuals (54% women; mean±SD age: 52±14 years).


Significant reductions in all-cause mortality were observed for participation in cycling (HR=0.85, 95% CI 0.76 to 0.95), swimming (HR=0.72, 95% CI 0.65 to 0.80), racquet sports (HR=0.53, 95% CI 0.40 to 0.69) and aerobics (HR=0.73, 95% CI 0.63 to 0.85). No significant associations were found for participation in football and running. A significant reduction in CVD mortality was observed for participation in swimming (HR=0.59, 95% CI 0.46 to 0.75), racquet sports (HR=0.44, 95% CI 0.24 to 0.83) and aerobics (HR=0.64, 95% CI 0.45 to 0.92), but there were no significant associations for cycling, running and football. Variable dose-response patterns between the exposure and the outcomes were found across the sport disciplines.


These findings demonstrate that participation in specific sports may have significant benefits for public health. Future research should aim to further strengthen the sport-specific epidemiological evidence base and understanding of how to promote greater sports participation.


Cohort study; Epidemiology; Physical activity; Public health; Sports

Edited by AlPater
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