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Gut-Brain Cross-Talk in Metabolic Control.

Clemmensen C, Müller TD, Woods SC, Berthoud HR, Seeley RJ, Tschöp MH.

Cell. 2017 Feb 23;168(5):758-774. doi: 10.1016/j.cell.2017.01.025. Review.

PMID: 28235194




Because human energy metabolism evolved to favor adiposity over leanness, the availability of palatable, easily attainable, and calorically dense foods has led to unprecedented levels of obesity and its associated metabolic co-morbidities that appear resistant to traditional lifestyle interventions. However, recent progress identifying the molecular signaling pathways through which the brain and the gastrointestinal system communicate to govern energy homeostasis, combined with emerging insights on the molecular mechanisms underlying successful bariatric surgery, gives reason to be optimistic that novel precision medicines that mimic, enhance, and/or modulate gut-brain signaling can have unprecedented potential for stopping the obesity and type 2 diabetes pandemics.


appetite; bariatric surgery; brain; diabetes; energy balance; gut; metabolic syndrome; obesity; pharmacology; satiety

PMID: 28235194 DOI: 10.1016/j.cell.2017.01.025


Association of dietary vitamin E intake with risk of lung cancer: a dose-response meta-analysis.

Zhu YJ, Bo YC, Liu XX, Qiu CG.

Asia Pac J Clin Nutr. 2017 Mar;26(2):271-277. doi: 10.6133/apjcn.032016.04.

PMID: 28244705




Several epidemiological studies investigating the association between dietary vitamin E intake and the risk of lung cancer have demonstrated inconsistent results. Hence, a meta-analysis was conducted to summarise evidence of the association of dietary vitamin E intake with the risk of lung cancer.


In this meta-analysis, a systematic literature search of PubMed and Web of Science was conducted to identify relevant studies published from 1955 to April 2015. If p<0.05 or I2 >50%, a random effect model was used to estimate overall relative risks (RRs) and 95% confidence intervals (CIs). Otherwise, a fixed effect model was applied. Publication bias was estimated using the funnel plot and Egger's test. The doseresponse relationship was assessed using the method of restricted cubic splines with 4 knots at percentiles 5, 35, 65, and 95 of the distribution.


The pooled RR of lung cancer for the highest versus lowest categories of dietary vitamin E intake was 0.84 (95% CI=0.76-0.93). With every 2 mg/d increase in dietary vitamin E intake, the risk of lung cancer statistically decreased by 5% (RR=0.95, 95% CI =0.91-0.99, plinearity=0.0237).


Our analysis suggests that higher dietary vitamin E intake exerts a protective effect against lung cancer.


["next future" as opposed to "previous future" and "this future", I suppose.]

Centenarians as extreme phenotypes: an ecological perspective to get insight into the relationship between the genetics of longevity and age-associated diseases.

Giuliani C, Pirazzini C, Delledonne M, Xumerle L, Descombes P, Marquis J, Mengozzi G, Monti D, Bellizzi D, Passarino G, Luiselli D, Franceschi C, Garagnani P.

Mech Ageing Dev. 2017 Feb 24. pii: S0047-6374(16)30250-0. doi: 10.1016/j.mad.2017.02.007. [Epub ahead of print] Review.

PMID: 28242236



In this review we address the genetic continuum between aging and age-related diseases, with particular attention to the ecological perspective. We describe the connections between genes that promote longevity and genes associated to age-related diseases considering trade-off mechanisms in which the same genetic variants could have different effect according to the tissue considered and could be involved in several biological pathways. Then we describe mechanisms of antagonistic pleiotropy, focusing on the complex interplay between genetic variants and environmental changes (internal or external). We sustain the use of centenarians as "super-controls" for the study of the major age-related diseases, starting from the concept that the maximization of the phenotypic differences in the considered cohort, achieved by selecting the most divergent phenotypes, could be useful for increasing the significant differences observed in the genetic association study. We describe the potential impact of the population genetic variability in the study of human longevity and the possible contribution of the past selective pressures in shaping the current genomic background of individuals. In conclusion we illustrate recent findings emerged from whole genome sequencing of long-lived individuals and future perspectives for interpreting the huge amount of genetic data that will be generated in the next future.


Age-related diseases; Extreme-phenotypes; Gene-environment interactions; Longevity; Populations


[The below paper is pdf-availed.]

Reversible States of Physical and/or Cognitive Dysfunction: A 9-Year Longitudinal Study.

Qualls C, Waters DL, Vellas B, Villareal DT, Garry PJ, Gallini A, Andrieu S.

J Nutr Health Aging. 2017;21(3):271-275. doi: 10.1007/s12603-017-0878-3.

PMID: 28244566



To determine 1) age-adjusted transition probabilities to worsening physical/cognitive function states, reversal to normal cognition/physical function, or maintenance of normal state; 2) whether these transitions are modulated by sex, BMI, education, hypertension (HTN), health status, or APOE4; 3) whether worsening gait speed preceded cognition change, or vice versa.


Analysis of 9-year prospective cohort data from the New Mexico Aging Process Study.


Healthy independent-living adults.


60+ years of age (n= 598).


Gait speed, cognitive function (3MSE score), APOE4, HTN, BMI, education, health status.


Over 9 years, 2129 one-year transitions were observed. 32.6% stayed in the same state, while gait speed and cognitive function (3MSE scores) improved for 38% and 43% of participants per year, respectively. Transitions to improved function decreased with age (P< 0.001), APOE4 status (P=0.02), BMI (P=0.009), and health status (P=0.009). Transitions to worse function were significantly increased for the same factors (all P<0.05). Times to lower gait speed and cognitive function did not precede each other (P=0.91).


Transitions in gait speed and cognition were mutable with substantial likelihood of transition to improvement in physical and cognitive function even in oldest-old, which may have clinical implications for treatment interventions.


Cognitive function; gait speed; multi-state modelling; reversible transitions


[The below paper is pdf-availed.]

Factors Affecting Functional Impairment among Elderly Germans - Results of a Longitudinal Study.

Hajek A, Luck T, Brettschneider C, Posselt T, Lange C, Wiese B, Steinmann S, Weyerer S, Werle J, Pentzek M, Fuchs A, Stein J, Bickel H, Mösch E, Wagner M, Heser K, Maier W, Scherer JM, Riedel-Heller SG, König HH.

J Nutr Health Aging. 2017;21(3):299-306. doi: 10.1007/s12603-016-0771-5.

PMID: 28244570



To investigate causal factors of functional impairment in old age in a longitudinal approach.


A population-based prospective cohort study.


Elderly individuals were recruited via GP offices at six study centers in Germany. They were observed every 1.5 years over six waves.


Three thousand two hundred fifty-six people aged 75 years and older at baseline.


Functional impairment was quantified by the Lawton and Brody Instrumental Activities of Daily Living scale (IADL) and the Barthel-Index (BI).


Fixed effects regressions revealed that functional impairment (IADL; BI) increased significantly with ageing (β=-.2; β=-1.1), loss of a spouse (β= .5; β=-3.1), not living alone in private household (β=-1.2; β=-5.5), depression (solely significant for IADL: β= .6) and dementia (β=-2.3; β=-18.2). The comorbidity score did not affect functional impairment.


Our findings underline the relevance of changes in sociodemographic variables as well as the occurrence of depression or dementia for functional impairment. While several of these causal factors for functional decline in the oldest old are inevitable, some may not be, such as depression. Therefore, developing interventional strategies to prevent depression might be a fruitful approach in order to delay functional impairment in old age.


Functional impairment; dementia; depression; longitudinal study; older people


[The below paper is pdf-availed.]

The Role of Uric Acid for Predicting Future Metabolic Syndrome and Type 2 Diabetes in Older People.

Chang JB, Chen YL, Hung YJ, Hsieh CH, Lee CH, Pei D, Lin JD, Wu CZ, Liang YJ, Lin CM.

J Nutr Health Aging. 2017;21(3):329-335. doi: 10.1007/s12603-016-0749-3.

PMID: 28244574



Although it is known that high uric acid (UA) level is associated with type 2 diabetes (T2DM) and metabolic syndrome (MetS), most of the previous studies were focused on adults. Since aging becomes a major problem for many societies, in this longitudinal study, we investigated the role of UA in future T2DM and MetS in a large cohort of people who were older than 65 years.


A cross-sectional and longitudinal study.


18,907 elderly (9,732 men, 9,175 women) aged above 65 years, enrolled from health check-up centers, were classified into three subgroups by 10-year intervals (young old 65-74 years, YO; old old 75-84 years, OO; and oldest old 85-94 years, ODO), with the average follow-up period of 4.3 years.


The optimal cut-off values (CoVs) of baseline UA to predict future MetS and T2DM were determined by receiving operating characteristic (ROC) curve analysis. Using these CoVs of UA, the participants were divided into normal- and high-level groups of UA. Cox proportional hazard analysis was used to calculate hazard ratios (HRs) for the subjects with a high level of UA for the risk of future MetS and T2DM. In addition, Kaplan-Meier plots and log rank test were used to evaluate the time effect on the incidence of developing MetS and T2DM between the two groups.


In ROC curve analysis, the optimal CoVs of baseline UA were 6.0, 6.3 and 6.7 mg/dl in YO, OO, and ODO men, respectively; 5.5 and 4.9 mg/dl in YO and OO women, respectively (all p < 0.05). However, the CoVs of UA in ODO women (6.1 mg/dl) failed to show its discriminant power (p = 0.13). The Cox regression analysis showed the YO subjects with a higher baseline level of UA had a higher risk of developing MetS (HRs 1.56 and 1.58 for men and women, respectively, both p < 0.001); as for T2DM the HRs were 1.39 and 1.57. In OO men, the HRs was 1.89 for developing future MetS. However, no significant findings could be noted in the ODO group. Kaplan-Meier plots and log rank test also showed the same findings.


Our study showed that old subjects with high levels of UA will have a higher chance to have MetS and T2DM, particularly in the YO group (6.0 mg/dl for men and 5.5 mg/dl for women, respectively). Using UA as one of the metabolic biomarkers may help clinicians to early detect and prevent MetS and diabetes.


Diabetes; elderly; inflammation; metabolic syndrome; uric acid


Association of Serum Magnesium Level with Odds of Prediabetes and Diabetes in a Southern Chinese Population: a Prospective Nested Case-Control Study.

Fang C, Wang X, Wu W, Gu X, Ye T, Deng H, Wang X, Shen F.

Biol Trace Elem Res. 2016 Aug;172(2):307-14. doi: 10.1007/s12011-015-0594-y.

PMID: 26706038



Although emerging clinical evidence supports that magnesium deficiency is a risk factor for the development of type 2 diabetes, there are sparse studies concerning the dynamic change of serum magnesium with the risk of diabetes and its early stages. In this nested case-control study, we performed a 75-g oral glucose tolerance test or a standardized steamed bread meal test in 178 subjects with incident glucose metabolism impairment (33 with type 2 diabetes and 145 with prediabetes) and 178 matched controls at baseline and at 3-year follow-up and determined the associations between baseline serum magnesium levels as well as changes in serum magnesium levels at follow-up and odds of prediabetes and diabetes. After adjusting for potential confounders, the odds ratios of risk for prediabetes and type 2 diabetes in the highest quartile of serum magnesium levels were 0.22 (95 % confidence intervals [CI] 0.10-0.49; p for trend <0.001) and 0.02 (95 % CI 0.00-0.29; p for trend = 0.009), respectively, as compared with the lowest quartile. In addition, a significant decline in the serum magnesium level was detected in type 2 diabetes cases (p = 0.015) at 3 years as compared with at baseline. These results suggest that a low magnesium level is an independent risk factor for prediabetes and type 2 diabetes, and that the reduction of serum magnesium is associated with type 2 diabetes in a southern Chinese population.


Diabetes; Dynamic change; Magnesium; Prediabetes


'Strong evidence' of link between obesity and some major cancers, new study finds

Improved obesity treatment and prevention is needed, says expert

By Darryl Hol, CBC News Posted: Feb 28, 2017



Fresh evidence links adiposity with multiple cancers

BMJ 2017; 356 :j908; (Published 28 February 2017)

Yikyung Park, Graham A Colditz


The association is now clear; it’s time to get serious about prevention

The International Agency for Research on Cancer (IARC) working group recently reviewed epidemiological data, studies in experimental animals, and mechanistic data and concluded that excess body fatness causes cancer of the colon and rectum, liver, gallbladder, pancreas, kidney, thyroid, breast (postmenopausal), endometrium, ovary, oesophagus (adenocarcinoma), and gastric cardia, as well as meningioma and multiple myeloma.1 This potentially makes excess body fat the second most important modifiable cancer risk factor after tobacco use.

The study by Kyrgiou and colleagues2 took up the challenge of evaluating the robustness of multiple, sometimes overlapping, meta-analyses that reported an association between body adiposity measures (such as body mass index, weight gain, and waist circumference) and cancer. The authors conducted an umbrella review, also known as a “review of reviews” or “meta-review,”34 and initially identified a total of 204 individual meta-analyses from 49 papers. They further examined the 95 meta-analyses that reported the association between body fatness measured on a continuous scale (mostly body mass index in 5 kg/m2 increase) and cancer in cohort studies. After a rigorous evaluation for strength and validity of reported associations, 13% (12 of 95) of meta-analyses were judged to provide strong evidence on the basis of their statistical criteria. The rest of the meta-analyses were deemed to be highly suggestive (18%), suggestive (25%), and weak (20%). Twenty four per cent of meta-analyses found no association between body fatness and cancer.

Nine obesity related cancers were supported by strong evidence: oesophageal adenocarcinoma, colon and rectal cancer (in men), biliary tract system, pancreatic, and kidney cancer, endometrial cancer (premenopausal women), breast cancer (postmenopausal), and multiple myeloma. A positive association between body mass index and liver, ovarian, or thyroid cancer was highly suggestive or suggestive; a negative association with oesophageal squamous cell carcinoma or lung cancer was highly suggestive. In additional analyses using obesity categories (obesity versus normal weight), strong evidence also supported increased risks of gastric cardia and ovarian cancer in obese individuals.

Both the IARC report and Kyrgiou and colleagues’ umbrella review consistently and strongly concluded that excess body fat increases the risk of most digestive system cancers as well as endometrial and postmenopausal breast cancer. However, for gastric cardia, and cancers of the liver, ovary, or thyroid, the strength of evidence differed between the two approaches, which can be explained by differences in the method used to summarise the evidence.

Firstly, unlike the IARC report, Kyrgiou and colleagues’ review did not evaluate the quality of the original meta-analyses. Although it reviews meta-analyses that may be susceptible to publication bias, the IARC report clearly demonstrated the importance of assessing the quality of each meta-analysis, including search strategy, inclusion and exclusion criteria, and data extraction,5 which is often outside the scope of an umbrella review.

Secondly, inclusion of suboptimal studies in a review, such as those that inadequately control for smoking in analyses exploring body mass index and lung cancer, may still provide a precise estimate, but biased in the wrong direction. This also limits the quality of the evidence. In contrast to the study by Kyrgiou and colleagues, the IACR report judged the evidence linking higher body mass index with lower risk of oesophageal squamous cell carcinoma and lung cancer as inadequate and inconsistent, partly owing to inadequate control for confounding by smoking and potential bias in the published literature.

Lastly, Kyrgiou and colleagues did not appraise meta-analyses of individual participant data but reviewed meta-analyses that combined results from published studies. Pooled analyses of individual participant data can be an efficient way to examine associations between obesity and cancer, especially for rare cancers,67 cancer subtypes (different histologies),8 and subgroups such as never smokers9 where individual studies and meta-analyses often do not have sufficient power. Associations deemed to be less convincing in Kyrgiou and colleagues’ review, such as those linking adiposity with cancers of the liver, ovary, and thyroid, were mostly downgraded because of heterogeneity between studies or the small number of cancer cases in each meta-analysis. Both these shortcomings can be overcome by including large pooled analyses. Although an umbrella review can be useful in providing a snapshot of evidence to explore a broad research question, the findings from umbrella reviews should be interpreted with caution as they are less comprehensive than reviews based on all available data.

Though some specifics remain to be worked out, the unavoidable conclusion from these data is that preventing excess adult weight gain can reduce the risk of cancer. Furthermore, emerging evidence suggests that excess body fat in early life also has an adverse effect on risk of cancer in adulthood.6710 Given the critical role of healthcare providers in obesity screening and prevention,1112 clinicians, particularly those in primary care, can be a powerful force to lower the burden of obesity related cancers, as well as the many other chronic diseases linked to obesity such as diabetes, heart disease, and stroke. The data are clear. The time for action is now.


Adiposity and cancer at major anatomical sites: umbrella review of the literature

BMJ 2017; 356 doi: https://doi.org/10.1136/bmj.j477(Published 28 February 2017)

BMJ 2017;356:j477

Maria Kyrgiou, senior lecturer12, Ilkka Kalliala, clinical postdoctoral fellow1, Georgios Markozannes, research fellow3, Marc J Gunter, section and group head4, Evangelos Paraskevaidis, professor5, Hani Gabra, professor12, Pierre Martin-Hirsch, professor67, Konstantinos K Tsilidis, assistant professor38




To evaluate the strength and validity of the evidence for the association between adiposity and risk of developing or dying from cancer.


Umbrella review of systematic reviews and meta-analyses.

Data sources

PubMed, Embase, Cochrane Database of Systematic Reviews, and manual screening of retrieved references.

Eligibility criteria

Systematic reviews or meta-analyses of observational studies that evaluated the association between indices of adiposity and risk of developing or dying from cancer.

Data synthesis

Primary analysis focused on cohort studies exploring associations for continuous measures of adiposity. The evidence was graded into strong, highly suggestive, suggestive, or weak after applying criteria that included the statistical significance of the random effects summary estimate and of the largest study in a meta-analysis, the number of cancer cases, heterogeneity between studies, 95% prediction intervals, small study effects, excess significance bias, and sensitivity analysis with credibility ceilings.


204 meta-analyses investigated associations between seven indices of adiposity and developing or dying from 36 primary cancers and their subtypes. Of the 95 meta-analyses that included cohort studies and used a continuous scale to measure adiposity, only 12 (13%) associations for nine cancers were supported by strong evidence. An increase in body mass index was associated with a higher risk of developing oesophageal adenocarcinoma; colon and rectal cancer in men; biliary tract system and pancreatic cancer; endometrial cancer in premenopausal women; kidney cancer; and multiple myeloma. Weight gain and waist to hip circumference ratio were associated with higher risks of postmenopausal breast cancer in women who have never used hormone replacement therapy and endometrial cancer, respectively. The increase in the risk of developing cancer for every 5 kg/m2 increase in body mass index ranged from 9% (relative risk 1.09, 95% confidence interval 1.06 to 1.13) for rectal cancer among men to 56% (1.56, 1.34 to 1.81) for biliary tract system cancer. The risk of postmenopausal breast cancer among women who have never used HRT increased by 11% for each 5 kg of weight gain in adulthood (1.11, 1.09 to 1.13), and the risk of endometrial cancer increased by 21% for each 0.1 increase in waist to hip ratio (1.21, 1.13 to 1.29). Five additional associations were supported by strong evidence when categorical measures of adiposity were included: weight gain with colorectal cancer; body mass index with gallbladder, gastric cardia, and ovarian cancer; and multiple myeloma mortality.


Although the association of adiposity with cancer risk has been extensively studied, associations for only 11 cancers (oesophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract system, pancreas, breast, endometrium, ovary, and kidney) were supported by strong evidence. Other associations could be genuine, but substantial uncertainty remains. Obesity is becoming one of the biggest problems in public health; evidence on the strength of the associated risks may allow finer selection of those at higher risk of cancer, who could be targeted for personalised prevention strategies.

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Health Risk Assessment of Dietary Cadmium Intake: Do Current Guidelines Indicate How Much is Safe?

Satarug S, Vesey DA, Gobe GC.

Environ Health Perspect. 2017 Mar;125(3):284-288. doi: 10.1289/EHP108.

PMID: 28248635





Cadmium (Cd), a food-chain contaminant, is a significant health hazard. The kidney is one of the primary sites of injury after chronic Cd exposure. Kidney-based risk assessment establishes the urinary Cd threshold at 5.24 μg/g creatinine, and tolerable dietary intake of Cd at 62 μg/day per 70-kg person. However, cohort studies show that dietary Cd intake below a threshold limit and that tolerable levels may increase the risk of death from cancer, cardiovascular disease, and Alzheimer's disease.


We evaluated if the current tolerable dietary Cd intake guideline and urinary Cd threshold limit provide sufficient health protection.


Staple foods constitute 40-60% of total dietary Cd intake by average consumers. Diets high in shellfish, crustaceans, mollusks, spinach, and offal add to dietary Cd sources. Modeling studies predict the current tolerable dietary intake corresponding to urinary Cd of 0.70-1.85 μg/g creatinine in men and 0.95-3.07 μg/g creatinine in women. Urinary Cd levels of < 1 μg/g creatinine were associated with progressive kidney dysfunction and peripheral vascular disease. A urinary Cd of 0.37 μg/g creatinine was associated with breast cancer, whereas dietary Cd of 16-31.5 μg/day was associated with 25-94% increase in risk of estrogen receptor-positive breast cancer.


Modeling shows that dietary intake levels for Cd exceed the levels associated with kidney damage and many other adverse outcomes. Thus, the threshold level of urinary Cd should be re-evaluated. A more restrictive dietary intake guideline would afford enhanced health protection from this pervasive toxic metal.


Magnitude of Hypotension Based on Office and Ambulatory Blood Pressure Monitoring: Results From a Cohort of 5066 Treated Hypertensive Patients Aged 80 Years and Older.

Divisón-Garrote JA, Ruilope LM, de la Sierra A, de la Cruz JJ, Vinyoles E, Gorostidi M, Escobar-Cervantes C, Velilla-Zancada SM, Segura J, Banegas JR.

J Am Med Dir Assoc. 2017 Feb 25. pii: S1525-8610(17)30062-2. doi: 10.1016/j.jamda.2017.01.015. [Epub ahead of print]

PMID: 28246017




Elderly patients can be particularly susceptible to the adverse effects of excessive blood pressure (BP) lowering by antihypertensive treatment. The identification of hypotension is thus especially important. Ambulatory BP monitoring (ABPM) is a more accurate technique than office for classifying BP status. This study examined the prevalence of hypotension and associated demographic and clinical factors among very old treated hypertensive patients undergoing ABPM.


Cross-sectional study in which 5066 patients aged 80 years and older with treated hypertension drawn from the Spanish ABPM Registry were included.


Office BP and 24-hour ambulatory BP were determined using validated devices under standardized conditions. Based on previous studies, hypotension was defined as systolic/diastolic BP <110 and/or 70 mmHg with office measurement, <105 and/or 65 mmHg with daytime ABPM, <90 and/or 50 mmHg with nighttime ABPM, and <100 and/or 60 mmHg with 24-hour ABPM.


Participants' mean age was 83.2 ± 3.1 years (64.4% women). Overall, 22.8% of patients had office hypotension, 33.7% daytime hypotension, 9.2% nighttime hypotension, and 20.5% 24-hour ABPM hypotension. Low diastolic BP values were responsible for 90% of cases of hypotension. In addition, 59.1% of the cases of hypotension detected by daytime ABPM did not correspond to hypotension according to office BP. The variables independently associated with office and ABPM hypotension were diabetes, coronary heart disease, and a higher number of antihypertensive medications.


One in 3 very elderly treated hypertensive patients attended in usual clinical practice were potentially at risk of having hypotension according to daytime ABPM. More than half of them had masked hypotension; that is, they were not identified if relying on office BP alone. Thus, ABPM could be especially helpful for identifying ambulatory hypotension and avoiding overtreatment, in particular, in patients with diabetes, heart disease, or on antihypertensive polytherapy.


Hypotension; ambulatory blood pressure monitoring; elderly; epidemiology; office blood pressure


Development and validation of multivariable models to predict mortality and hospitalization in patients with heart failure.

Voors AA, Ouwerkerk W, Zannad F, van Veldhuisen DJ, Samani NJ, Ponikowski P, Ng LL, Metra M, Ter Maaten JM, Lang CC, Hillege HL, van der Harst P, Filippatos G, Dickstein K, Cleland JG, Anker SD, Zwinderman AH.

Eur J Heart Fail. 2017 Mar 1. doi: 10.1002/ejhf.785. [Epub ahead of print]

PMID: 28247565




From a prospective multicentre multicountry clinical trial, we developed and validated risk models to predict prospective all-cause mortality and hospitalizations because of heart failure (HF) in patients with HF.


BIOSTAT-CHF is a research programme designed to develop and externally validate risk models to predict all-cause mortality and HF hospitalizations. The index cohort consisted of 2516 patients with HF from 69 centres in 11 European countries. The external validation cohort consisted of 1738 comparable patients from six centres in Scotland, UK. Patients from the index cohort had a mean age of 69 years, 27% were female, 83% were in New York Heart Association (NYHA) class II-III and the mean left ventricular ejection fraction (LVEF) was 31%. The full prediction models for mortality, hospitalization owing to HF, and the combined outcome, yielded c-statistic values of 0.73, 0.69, and 0.71, respectively. Predictors of mortality and hospitalization owing to HF were remarkably different. The five strongest predictors of mortality were more advanced age, higher blood urea nitrogen and N-terminal pro-B-type natriuretic peptide, lower haemoglobin, and failure to prescribe a beta-blocker. The five strongest predictors of hospitalization owing to HF were more advanced age, previous hospitalization owing to HF, presence of oedema, lower systolic blood pressure and lower estimated glomerular filtration rate. Patients from the validation cohort were aged 74 years, 34% were female, 85% were in NYHA class II-III, and mean LVEF was 41%; c-statistic values for the full and compact model were comparable to the index cohort.


A small number of variables, which are usually readily available in the routine clinical setting, provide useful prognostic information for patients with HF. Predictors of mortality were remarkably different from predictors of hospitalization owing to HF.


Heart failure; Heart failure hospitalization; Mortality; Prediction model


Is tea consumption associated with the serum uric acid level, hyperuricemia or the risk of gout? A systematic review and meta-analysis.

Zhang Y, Cui Y, Li XA, Li LJ, Xie X, Huang YZ, Deng YH, Zeng C, Lei GH.

BMC Musculoskelet Disord. 2017 Feb 28;18(1):95. doi: 10.1186/s12891-017-1456-x.

PMID: 28245834





The aim of this study was to examine the associations of tea consumption with the serum uric acid (SUA) level, hyperuricemia (HU) and the risk of gout.


A comprehensive literature search up to June 2016, using PUBMED and EMBASE databases, was conducted to identify the relevant observational studies that examined the associations of tea consumption with the SUA level, HU and the risk of gout.


A total of fifteen observational studies were included in this study, and nine studies were extracted for meta-analysis. For the SUA level, seven studies were included. According to the combined weighted mean difference (WMD), there was no significant difference between the highest and the lowest tea intake category in terms of the SUA level (WMD = 7.41 μmol/L, 95%CI: -2.34 to 17.15; P = 0.136). In subgroup analysis including three studies, green tea consumption was positively associated with the SUA level (WMD = 17.20 μmol/L, 95%CI: 7.00 to 27.40; P = 0.01). For the prevalence of HU, five studies were included. The overall multi-variable adjusted odds ratio (OR) for the highest versus the lowest category of tea consumption was 0.98 (95%CI: 0.77 to 1.24; P = 0.839). For the risk of gout, two prospective cohort studies showed that there was no relationship between tea consumption and the risk of gout in males and females, respectively.


The current evidences suggest that tea consumption does not seem to be associated with the SUA level, HU and the risk of gout. However, due to the limited number of studies, green tea consumption might be positively associated with the SUA level. More well-designed prospective cohort studies are needed to elaborate these issues further.


Gout; Hyperuricemia; Meta-analysis; Serum uric acid; Systematic review; Tea


Three-Year Changes in Physical Activity and Decline in Physical Performance Over 9 Years of Follow-Up in Older Adults: The Invecchiare in Chianti Study.

Martinez-Gomez D, Bandinelli S, Del-Panta V, Patel KV, Guralnik JM, Ferrucci L.

J Am Geriatr Soc. 2017 Mar 1. doi: 10.1111/jgs.14788. [Epub ahead of print]

PMID: 28248412




To examine the associations between cumulative physical activity (PA) and its changes over 3 years and changes over 9 years of follow-up in physical performance in older adults.






Men and women aged 65 and older from the Invecchiare in Chianti study (N = 782).


Physical performance was assessed at baseline and at 3-, 6-, and 9-year follow-up using the Short Physical Performance Battery (SPPB). PA was assessed through an interviewer-administered questionnaire at baseline and 3-year follow-up. Analyses were adjusted for education, body mass index, smoking, alcohol intake, coronary heart disease, stroke, peripheral arterial disease, cancer, lung disease, lower extremity osteoarthritis, depression, and Mini-Mental State Examination.


Over 3 years of follow-up, 27.8% of participants were inactive, 52.2% were minimally active, and 20.0% were active, and the PA of 37.2% decreased, there was no change in PA of 50.1% and the PA of 12.7% increased. After adjustment for potential covariates, being mostly active (-1.08, 95% confidence interval (CI) = -1.43 to -0.73) and minimally active (-1.33, 95% CI = -1.53 to -1.12) over 3 years of follow-up was associated with less decline in SPPB score than being mostly inactive (-2.60, 95% CI = -2.92 to -2.27). When analyzing changes, increasing PA (-0.57, 95% CI = -1.01 to -0.12) was associated with less decline in SPPB score over 9 years than decreasing PA (-2.16, 95% CI = -2.42 to -1.89).


Maintaining or increasing PA levels may attenuate age-associated physical performance decline.


aging; physical activity; physical performance


The prospective impact of food pricing on improving dietary consumption: A systematic review and meta-analysis.

Afshin A, Peñalvo JL, Del Gobbo L, Silva J, Michaelson M, O'Flaherty M, Capewell S, Spiegelman D, Danaei G, Mozaffarian D.

PLoS One. 2017 Mar 1;12(3):e0172277. doi: 10.1371/journal.pone.0172277.

PMID: 28249003





While food pricing is a promising strategy to improve diet, the prospective impact of food pricing on diet has not been systematically quantified.


To quantify the prospective effect of changes in food prices on dietary consumption.


We systematically searched online databases for interventional or prospective observational studies of price change and diet; we also searched for studies evaluating adiposity as a secondary outcome. Studies were excluded if price data were collected before 1990. Data were extracted independently and in duplicate. Findings were pooled using DerSimonian-Laird's random effects model. Pre-specified sources of heterogeneity were analyzed using meta-regression; and potential for publication bias, by funnel plots, Begg's and Egger's tests.


From 3,163 identified abstracts, 23 interventional studies and 7 prospective cohorts with 37 intervention arms met inclusion criteria. In pooled analyses, a 10% decrease in price (i.e., subsidy) increased consumption of healthful foods by 12% (95%CI = 10-15%; N = 22 studies/intervention arms) whereas a 10% increase price (i.e. tax) decreased consumption of unhealthful foods by 6% (95%CI = 4-8%; N = 15). By food group, subsidies increased intake of fruits and vegetables by 14% (95%CI = 11-17%; N = 9); and other healthful foods, by 16% (95%CI = 10-23%; N = 10); without significant effects on more healthful beverages (-3%; 95%CI = -16-11%; N = 3). Each 10% price increase reduced sugar-sweetened beverage intake by 7% (95%CI = 3-10%; N = 5); fast foods, by 3% (95%CI = 1-5%; N = 3); and other unhealthful foods, by 9% (95%CI = 6-12%; N = 3). Changes in price of fruits and vegetables reduced body mass index (-0.04 kg/m2 per 10% price decrease, 95%CI = -0.08-0 kg/m2; N = 4); price changes for sugar-sweetened beverages or fast foods did not significantly alter body mass index, based on 4 studies. Meta-regression identified direction of price change (tax vs. subsidy), number of intervention components, intervention duration, and study quality score as significant sources of heterogeneity (P-heterogeneity<0.05 each). Evidence for publication bias was not observed.


These prospective results, largely from interventional studies, support efficacy of subsidies to increase consumption of healthful foods; and taxation to reduce intake of unhealthful beverages and foods. Use of subsidies and combined multicomponent interventions appear most effective.


Meal frequency patterns and glycemic properties of maternal diet in relation to preterm delivery: Results from a large prospective cohort study.

Englund-Ögge L, Birgisdottir BE, Sengpiel V, Brantsæter AL, Haugen M, Myhre R, Meltzer HM, Jacobsson B.

PLoS One. 2017 Mar 1;12(3):e0172896. doi: 10.1371/journal.pone.0172896.

PMID: 28249018





Dietary habits are linked to high maternal glucose levels, associated with preterm delivery. The aim of this study was to examine the associations between meal frequency and glycemic properties of maternal diet in relation to preterm delivery.


This prospective cohort study included 66,000 women from the Norwegian Mother and Child Cohort Study (MoBa). Meal frequency and food intake data were obtained from a validated food frequency questionnaire during mid-pregnancy. Principal component factor analysis was used with a data-driven approach, and three meal frequency patterns were identified: "snack meal", "main meal", and "evening meal". Pattern scores were ranked in quartiles. Glycemic index and glycemic load were estimated from table values. Intakes of carbohydrates, added sugar, and fiber were reported in grams per day and divided into quartiles. Gestational age was obtained from the Medical Birth Registry of Norway. Preterm delivery was defined as birth at <37 gestational weeks. A Cox regression model was used to assess associations with preterm delivery.


After adjustments, the "main meal" pattern was associated with a reduced risk of preterm delivery, with hazard ratios (HRs) of 0.89 (95% confidence interval (CI): 0.80, 0.98) and 0.90 (95% CI: 0.81, 0.99) for the third and fourth quartiles, respectively, and p for trend of 0.028. This was mainly attributed to the group of women with BMI ≥25 kg/m2, with HRs of 0.87 (95% CI: 0.79, 0.96) and 0.89 (95% CI: 0.80, 0.98) for the third and fourth quartiles, respectively, and p for trend of 0.010. There was no association between glycemic index, glycemic load, carbohydrates, added sugar, fiber, or the remaining meal frequency patterns and preterm delivery.


Regular consumption of main meals (breakfast, lunch, dinner) was associated with a lower risk of preterm delivery. Diet should be further studied as potential contributing factors for preterm delivery.


Exome-wide Association Study Identifies CLEC3B Missense Variant p.S106G as Being Associated With Extreme Longevity in East Asian Populations.

Tanisawa K, Arai Y, Hirose N, Shimokata H, Yamada Y, Kawai H, Kojima M, Obuchi S, Hirano H, Yoshida H, Suzuki H, Fujiwara Y, Ihara K, Sugaya M, Arai T, Mori S, Sawabe M, Sato N, Muramatsu M, Higuchi M, Liu YW, Kong QP, Tanaka M.

J Gerontol A Biol Sci Med Sci. 2016 May 6. pii: glw074. [Epub ahead of print]

PMID: 27154906




Life span is a complex trait regulated by multiple genetic and environmental factors; however, the genetic determinants of extreme longevity have been largely unknown. To identify the functional coding variants associated with extreme longevity, we performed an exome-wide association study (EWAS) on a Japanese population by using an Illumina HumanExome Beadchip and a focused replication study on a Chinese population. The EWAS on two independent Japanese cohorts consisting of 530 nonagenarians/centenarians demonstrated that the G allele of CLEC3B missense variant p.S106G was associated with extreme longevity at the exome-wide level of significance (p = 2.33×10-7, odds ratio [OR] = 1.50). The CLEC3B gene encodes tetranectin, a protein implicated in the mineralization process in osteogenesis as well as in the prognosis and metastasis of cancer. The replication study consisting of 448 Chinese nonagenarians/centenarians showed that the G allele of CLEC3B p.S106G was also associated with extreme longevity (p = .027, OR = 1.51), and the p value of this variant reached 1.87×10-8 in the meta-analysis of Japanese and Chinese populations. In conclusion, the present study identified the CLEC3B p.S106G as a novel longevity-associated variant, raising the novel hypothesis that tetranectin, encoded by CLEC3B, plays a role in human longevity and aging.


Centenarian; Human aging; Human genetics; Longevity


Enhanced Cognition and Hypoglutamatergic Signaling in a Growth Hormone Receptor Knockout Mouse Model of Successful Aging.

Hascup KN, Lynn MK, Fitzgerald PJ, Randall S, Kopchick JJ, Boger HA, Bartke A, Hascup ER.

J Gerontol A Biol Sci Med Sci. 2016 May 21. pii: glw088. [Epub ahead of print]

PMID: 27208894



Growth hormone receptor knockout (GHR-KO) mice are long lived with improved health span, making this an excellent model system for understanding biochemical mechanisms important to cognitive reserve. The purpose of the present study was to elucidate differences in cognition and glutamatergic dynamics between aged (20- to 24-month-old) GHR-KO and littermate controls. Glutamate plays a critical role in hippocampal learning and memory and is implicated in several neurodegenerative disorders, including Alzheimer's disease. Spatial learning and memory were assessed using the Morris water maze (MWM), whereas independent dentate gyrus (DG), CA3, and CA1 basal glutamate, release, and uptake measurements were conducted in isoflurane anesthetized mice utilizing an enzyme-based microelectrode array (MEA) coupled with constant potential amperometry. These MEAs have high temporal and low spatial resolution while causing minimal damage to the surrounding parenchyma. Littermate controls performed worse on the memory portion of the MWM behavioral task and had elevated DG, CA3, and CA1 basal glutamate and stimulus-evoked release compared with age-matched GHR-KO mice. CA3 basal glutamate negatively correlated with MWM performance. These results support glutamatergic regulation in learning and memory and may have implications for therapeutic targets to delay the onset of, or reduce cognitive decline, in Alzheimer's disease.


Alzheimer’s disease; Biosensor; Electrode; Health span; Longevity


Biological Aging and the Future of Geriatric Psychiatry.

Rutherford BR, Taylor WD, Brown PJ, Sneed JR, Roose SP.

J Gerontol A Biol Sci Med Sci. 2016 Dec 18. pii: glw241. doi: 10.1093/gerona/glw241. [Epub ahead of print] Review.

PMID: 27994004




Advances in understanding the biological bases of aging have intellectually revitalized the field of geriatric psychiatry and broadened its scope to include promoting successful aging and studying resilience factors in older adults. To describe the process by which this paradigm shift has occurred and illustrate its implications for treatment and research of late-life brain disorders, late-life depression is discussed as a prototype case. Prior phases of geriatric psychiatry research were focused on achieving depressive symptom relief, outlining pharmacokinetic and pharmacodynamic differences between older and younger adults, and identifying moderators of treatment response. Building on this work, current geriatric psychiatry researchers have begun to disentangle the etiologic complexity in late-life depression by focusing on the causative aging-related processes involved, identifying both neurobiological and behavioral intermediates, and finally delineating depression subtypes that are distinguishable by their underlying biology and the treatment approach required. In this review, we discuss several age-related processes that are critical to the development of late-life mood disorders, outline implications of these processes for the clinical evaluation and management of later-life psychiatric disorders, and finally put forth suggestions for better integrating aging and developmental processes into the National Institute of Mental Health's Research Domain Criteria.


Brain aging; Depression; Frailty; Successful aging


A Comparison of Objective Physical Performance Tests and Future Mortality in the Elderly People.

Veronese N, Stubbs B, Fontana L, Trevisan C, Bolzetta F, Rui M, Sartori L, Musacchio E, Zambon S, Maggi S, Perissinotto E, Corti MC, Crepaldi G, Manzato E, Sergi G.

J Gerontol A Biol Sci Med Sci. 2016 Jul 28. pii: glw139. [Epub ahead of print]

PMID: 27470299




Physical performance is an important predictor of mortality, but little is known on the comparative prognostic utility of different objective physical performance tests in community-dwelling older adults. We compared the prognostic usefulness of several objective physical performance tests on mortality, adjusting our analyses for potential confounders.


Among 3,099 older community-dwelling participants included in the Progetto Veneto Anziani study, 2,096 were followed for a mean of 4.4 years. Physical performance tests measured were Short Physical Performance Battery (SPPB), 4-meter gait speed, chair stands time, leg extension and flexion, handgrip strength, and 6-Minute Walking Test (6MWT), treated as continuous variables and categorized in gender-specific quartiles. The main outcome was mortality assessed with death certificates.


Participants who died during the follow-up (n = 327) scored significantly worse in all physical performance tests measured at baseline than those who survived (n = 1,769). Using a Harrell's C-index, the highest C-index was observed for 6MWT in men (C-index = 0.735; 95% confidence interval [CI]: 0.701-0.770, p < .0001) and SPPB in women (C-index = 0.781; 95% CI: 0.740-0.822, p = .0009). However, in both genders, only SPPB, 4-meter walking speed, and 6MWT are significant predictors of mortality. Analyses using sex-specific quartiles substantially confirmed these findings.


Slow gait speed, 6MWT, and SPPB are significant predictors for mortality in community-dwelling older men and women. Physicians should consider using these tests to identify elderly individuals who are at higher risk of death to improve clinical decision making.


Mortality; Physical activity; Physical performance


Physical Frailty, Cognitive Impairment, and the Risk of Neurocognitive Disorder in the Singapore Longitudinal Ageing Studies.

Feng L, Nyunt MS, Gao Q, Feng L, Lee TS, Tsoi T, Chong MS, Lim WS, Collinson S, Yap P, Yap KB, Ng TP.

J Gerontol A Biol Sci Med Sci. 2016 Mar 24. pii: glw050. [Epub ahead of print]

PMID: 27013397




The independent and combined effects of physical and cognitive domains of frailty in predicting the development of mild cognitive impairment (MCI) or dementia are not firmly established.


This study included cross-sectional and longitudinal analyses of physical frailty (Cardiovascular Health Study criteria), cognitive impairment (Mini-Mental State Examination [MMSE]), and neurocognitive disorder (DSM-5 criteria) among 1,575 community-living Chinese older adults from the Singapore Longitudinal Ageing Studies.


At baseline, 2% were frail, 32% were prefrail, and 9% had cognitive impairment (MMSE score < 23). Frailty at baseline was significantly associated with prevalent cognitive impairment. Physical frailty categories were not significantly associated with incident NCD, but continuous physical frailty score and MMSE score showed significant individual and joint associations with incident mild NCD and dementia. Compared with those who were robust and cognitively normal, prefrail or frail old adults without cognitive impairment had no increased risk of incident NCD, but elevated odds of association with incident NCD were observed for robust with cognitive impairment (odds ratio [OR] = 4.04, p < .001), prefrail with cognitive impairment (OR = 2.22, p = .044), and especially for frail with cognitive impairment (OR = 6.37, p = .005). The prevalence of co-existing frailty and cognitive impairment (cognitive frailty) was 1% (95% confidence interval [CI]: 0.5-1.4), but was higher among participants aged 75 and older at 5.0% (95% CI: 1.8-8.1).


Physical frailty is associated with increased prevalence and incidence of cognitive impairment, and co-existing physical frailty and cognitive impairment confers additionally greater risk of incident NCD.


Cognitive impairment; Frailty; Neurocognitive disorders


Reference Ranges for Thyroid-Stimulating Hormone and Free Thyroxine in Older Men: Results From the Health In Men Study.

Yeap BB, Manning L, Chubb SA, Hankey GJ, Golledge J, Almeida OP, Flicker L.

J Gerontol A Biol Sci Med Sci. 2016 Jul 20. pii: glw132. [Epub ahead of print]

PMID: 27440910




In older adults, thyroid-stimulating hormone (TSH) concentrations are raised and higher free thyroxine (FT4) is associated with poorer health outcomes. As use of nonage-appropriate reference ranges could lead to suboptimal management, we aimed to define reference intervals for TSH and FT4 in older men.


We conducted the study on community-dwelling men aged 70-89 years. Baseline TSH and FT4 levels were assayed (Elecsys 2010, Roche Diagnostics). Conventional reference intervals for TSH and FT4 were 0.4-4.0 mIU/L and 10-23 pmol/L, respectively. Incident deaths were ascertained using data linkage.


Of the 3,885 men included in the analysis, the 2.5th and 97.5th centiles for TSH and FT4 were 0.64-5.9 mIU/L and 12.1-20.6 pmol/L (0.94-1.60ng/dL), respectively. Of the 411 very healthy men defined by excellent or very good self-rated health and absence of major medical comorbidities, 2.5th to 97.5th centiles for TSH and FT4 were 0.67-4.98 mIU/L and 12.1-20.5 pmol/L (0.94-1.59ng/dL), respectively. TSH was not associated with mortality, whereas higher FT4 was associated with increased mortality. Applying intervals based on very healthy older men to the cohort as a whole led to the reclassification of 310 men (8.0%). More men were classified as being hyperthyroid or hypothyroid, or having subclinical hyperthyroidism, and fewer as having subclinical hypothyroidism.


In older men, the reference interval for TSH in older men is shifted upward, whereas the reference interval for FT4 is compressed compared with the conventional reference ranges. Applying reference intervals based on healthy older men identifies a substantial number of older men as having overt thyroid disease or subclinical hyperthyroidism and reduces the number classified as having subclinical hypothyroidism.

© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.


Free thyroxine; Mortality; Thyroid-stimulating hormone


Development and Validation of a 10-Year Mortality Prediction Model: Meta-Analysis of Individual Participant Data From Five Cohorts of Older Adults in Developed and Developing Countries.

Suemoto CK, Ueda P, Beltrán-Sánchez H, Lebrão ML, Duarte YA, Wong R, Danaei G.

J Gerontol A Biol Sci Med Sci. 2016 Aug 13. pii: glw166. [Epub ahead of print]

PMID: 27522061




Existing mortality prediction models for older adults have been each developed using a single study from the United States or Western Europe. We aimed to develop and validate a 10-year mortality prediction model for older adults using data from developed and developing countries.


We used data from five cohorts, including data from 16 developed and developing countries: ELSA (English Longitudinal Study of Aging), HRS (Health and Retirement Study), MHAS (Mexican Health and Aging Study), SABE-Sao Paulo (The Health, Well-being and Aging), and SHARE (Survey on Health, Ageing and Retirement in Europe). 35,367 older adults were split into training (two thirds) and test (one third) data sets. Baseline predictors included age, sex, comorbidities, and functional and cognitive measures. We performed an individual participant data meta-analysis using a sex-stratified Cox proportional hazards model, with time to death as the time scale. We validated the model using Harrell's C statistic (discrimination) and the estimated slope between observed and predicted 10-year mortality risk across deciles of risk (calibration).


During a median of 8.6 years, 8,325 participants died. The final model included age, sex, diabetes, heart disease, lung disease, cancer, smoking, alcohol use, body mass index, physical activity, self-reported health, difficulty with bathing, walking several blocks, and reporting date correctly. The model showed good discrimination (Harrell's C = 0.76) and calibration (slope = 1.005). Models for developed versus developing country cohorts performed equally well when applied to data from developing countries.


A parsimonious mortality prediction model using data from multiple cohorts in developed and developing countries can be used to predict mortality in older adults in both settings.


Mortality; Older adults; Prediction models; Prevention


The association of change in physical activity and body weight in the regulation of total energy expenditure.

Drenowatz C, Hill JO, Peters JC, Soriano-Maldonado A, Blair SN.

Eur J Clin Nutr. 2016 Dec 14. doi: 10.1038/ejcn.2016.228. [Epub ahead of print]

PMID: 27966573




The limited success in addressing the current obesity epidemic reflects the insufficient understanding of the regulation of energy balance. The present study examines the longitudinal association of body weight with physical activity (PA), total daily energy expenditure (TDEE) and total daily energy intake (TDEI).


A total of 195 adults (52% male) between 21 and 35 years of age with no intention for weight loss were followed over a 2-year period. Body weight, fat mass and fat-free mass were measured every 3 months. Participants were stratified into three groups based on change in body weight using a 5% cutpoint. TDEE and time spent in different PA intensities were determined via a multisensor device at each measurement time. TDEI was calculated based on change in body composition and TDEE.


At 2-year follow-up, 57% of the participants maintained weight, 14% lost weight and 29% gained weight. Average weight change was -6.9±3.4 and 7.1±3.6 kg in the weight-loss and weight-gain groups, respectively. Average TDEE and TDEI did not change significantly in any weight change group (P>0.16). Moderate-to-vigorous PA, however, increased significantly in the weight-loss group (35±49 min/day; P<0.01) and decreased in the weight-gain group (-35±46 min/day; P<0.01).


Results of this observational study indicate an inverse association between body weight and PA to maintain a stable TDEE and allow for a stable TDEI over time. Sufficient PA levels, therefore, are an important contributor to weight loss maintenance.

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Do symbiotic and Vitamin E supplementation have favorite effects in nonalcoholic fatty liver disease? A randomized, double-blind, placebo-controlled trial.

Ekhlasi G, Kolahdouz Mohammadi R, Agah S, Zarrati M, Hosseini AF, Arabshahi SS, Shidfar F.

J Res Med Sci. 2016 Nov 2;21:106. doi: 10.4103/1735-1995.193178.

PMID: 28250783




Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Oral administration of symbiotic and Vitamin E has been proposed as an effective treatment in NAFLD patients. This study was carried out to assess the effects of symbiotic and/or Vitamin E supplementation on liver enzymes, leptin, lipid profile, and some parameters of insulin resistance (IR) in NAFLD patients.


We randomly assigned sixty NAFLD adult patients to receive (1) symbiotic twice daily + Vitamin E-like placebo capsule; (2) 400 IU/d Vitamin E + symbiotic-like placebo; (3) symbiotic twice daily + 400 IU/d Vitamin E; and (4) symbiotic-like placebo + Vitamin E-like placebo for 8 weeks.


Symbiotic plus Vitamin E supplementation led to a significant decrease in concentrations of liver transaminase (P ≤ 0.05). Mean difference of apolipoprotein A-1 was more significant in symbiotic group compared to control. However, mean difference of apolipoprotein B100/A-1 was only significant in symbiotic group compared to control. At the end of the study, significant differences in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were seen between the symbiotic plus Vitamin E and control groups (P < 0.001). Furthermore, intake of symbiotic plus Vitamin E supplements led to a significant decrease in concentrations of triglycerides (TG) after the intervention. Significant differences in leptin, fasting blood sugar (FBS), and insulin levels were seen between the symbiotic plus Vitamin E and control groups at the end of the study (P < 0.001). In contrast, symbiotic and/or Vitamin E supplementation did not affect high-density lipoprotein cholesterol and homeostasis model assessment for IR levels.


In our study, symbiotic plus Vitamin E supplementation was the most effective treatment in lowering liver enzymes, leptin, FBS, insulin, TG, TC, and LDL-C among NAFLD patients.


Leptin; Vitamin E; lipid profile; nonalcoholic fatty liver disease; symbiotic


Nutrition and physical activity in the prevention and treatment of sarcopenia: systematic review.

Beaudart C, Dawson A, Shaw SC, Harvey NC, Kanis JA, Binkley N, Reginster JY, Chapurlat R, Chan DC, Bruyère O, Rizzoli R, Cooper C, Dennison EM; IOF-ESCEO Sarcopenia Working Group..

Osteoporos Int. 2017 Mar 1. doi: 10.1007/s00198-017-3980-9. [Epub ahead of print] Review.

PMID: 28251287




This systematic review summarizes the effect of combined exercise and nutrition intervention on muscle mass and muscle function. A total of 37 RCTs were identified. Results indicate that physical exercise has a positive impact on muscle mass and muscle function in subjects aged 65 years and older. However, any interactive effect of dietary supplementation appears to be limited.


In 2013, Denison et al. conducted a systematic review including 17 randomized controlled trials (RCTs) to explore the effect of combined exercise and nutrition intervention to improve muscle mass, muscle strength, or physical performance in older people. They concluded that further studies were needed to provide evidence upon which public health and clinical recommendations could be based. The purpose of the present work was to update the prior systematic review and include studies published up to October 2015.


Using the electronic databases MEDLINE and EMBASE, we identified RCTs which assessed the combined effect of exercise training and nutritional supplementation on muscle strength, muscle mass, or physical performance in subjects aged 60 years and over. Study selection and data extraction were performed by two independent reviewers.


The search strategy identified 21 additional RCTs giving a total of 37 RCTs. Studies were heterogeneous in terms of protocols for physical exercise and dietary supplementation (proteins, essential amino acids, creatine, β-hydroxy-β-methylbuthyrate, vitamin D, multi-nutrients, or other). In 79% of the studies (27/34 RCTs), muscle mass increased with exercise but an additional effect of nutrition was only found in 8 RCTs (23.5%). Muscle strength increased in 82.8% of the studies (29/35 RCTs) following exercise intervention, and dietary supplementation showed additional benefits in only a small number of studies (8/35 RCTS, 22.8%). Finally, the majority of studies showed an increase of physical performance following exercise intervention (26/28 RCTs, 92.8%) but interaction with nutrition supplementation was only found in 14.3% of these studies (4/28 RCTs).


Physical exercise has a positive impact on muscle mass and muscle function in healthy subjects aged 60 years and older. The biggest effect of exercise intervention, of any type, has been seen on physical performance (gait speed, chair rising test, balance, SPPB test, etc.). We observed huge variations in regard to the dietary supplementation protocols. Based on the included studies, mainly performed on well-nourished subjects, the interactive effect of dietary supplementation on muscle function appears limited.


Dietary; Intervention; Physical activity; Sarcopenia


[The below paper is pdf-availed.]

Effects of feedback-based balance and core resistance training vs. Pilates training on cognitive functions in older women with mild cognitive impairment: a pilot randomized controlled trial.

Greblo Jurakic Z, Krizanic V, Sarabon N, Markovic G.

Aging Clin Exp Res. 2017 Mar 1. doi: 10.1007/s40520-017-0740-9. [Epub ahead of print]

PMID: 28251569



There is limited research about beneficial effects of physical activity in older adults suffering from mild cognitive impairment (MCI).


The aim of the study was to provide preliminary evidence on the effects of two types of non-aerobic training on cognitive functions in older women suffering from MCI.


Twenty-eight participants aged 66-78 years with MCI were randomly assigned to a combined balance and core resistance training group (n = 14) or to a Pilates group (n = 14).


Following completion of the 8-week exercise programme, both groups showed significant improvements in global and specific cognitive domains.


Findings suggest that non-aerobic training should be further explored as a beneficial intervention for older adults suffering from MCI.


Cognitive functions; Exercise; Mild cognitive impairment; Physical activity


[The below paper is pdf-availed.]

Dietary Supplementation With Nonfermentable Fiber Alters the Gut Microbiota and Confers Protection in Murine Models of Sepsis.

Morowitz MJ, Di Caro V, Pang D, Cummings J, Firek B, Rogers MB, Ranganathan S, Clark RS, Aneja RK.

Crit Care Med. 2017 Mar 1. doi: 10.1097/CCM.0000000000002291. [Epub ahead of print]

PMID: 28252538



Links between microbial alterations and systemic inflammation have been demonstrated in chronic disease, but little is known about these interactions during acute inflammation. This study investigates the effect of dietary supplementation with cellulose, a nonfermentable fiber, on the gut microbiota, inflammatory markers, and survival in two murine models of sepsis.


Prospective experimental study.


University laboratory.


Six-week-old male C57BL/6 wild-type mice.


Mice were assigned to low-fiber, normal-fiber, or high-fiber diets with or without antibiotics for 2 weeks and then subjected to sepsis by cecal ligation and puncture or endotoxin injection. Fecal samples were collected for microbiota analyses before and after dietary interventions.


Mice that received a high-fiber diet demonstrated increased survival after cecal ligation and puncture relative to mice receiving low-fiber or normal-fiber diets. The survival benefit was associated with decreased serum concentration of pro-inflammatory cytokines, reduced neutrophil infiltration in the lungs, and diminished hepatic inflammation. The high-fiber diet also increased survival after endotoxin injection. Bacterial 16S ribosomal RNA gene sequences from each sample were amplified, sequenced, and analyzed. Fiber supplementation yielded an increase in relative abundance of the genera Akkermansia and Lachnospiraceae, taxa commonly associated with metabolic health. Administration of antibiotics to mice on the high-fiber diet negated the enrichment of Akkermansia species and the survival benefit after cecal ligation and puncture.


Dietary supplementation with cellulose offers a microbe-mediated survival advantage in murine models of sepsis. Improved understanding of the link between diet, the microbiota, and systemic illness may yield new therapeutic strategies for patients with sepsis.


Urinary metabolomics reveals glycemic and coffee associated signatures of thyroid function in two population-based cohorts.

Friedrich N, Pietzner M, Cannet C, Thuesen BH, Hansen T, Wallaschofski H, Grarup N, Skaaby T, Budde K, Pedersen O, Nauck M, Linneberg A.

PLoS One. 2017 Mar 2;12(3):e0173078. doi: 10.1371/journal.pone.0173078.

PMID: 28253303





Triiodothyronine (T3) and thyroxine (T4) as the main secretion products of the thyroid affect nearly every human tissue and are involved in a broad range of processes ranging from energy expenditure and lipid metabolism to glucose homeostasis. Metabolomics studies outside the focus of clinical manifest thyroid diseases are rare. The aim of the present investigation was to analyze the cross-sectional and longitudinal associations of urinary metabolites with serum free T4 (FT4) and thyroid-stimulating hormone (TSH).


Urine Metabolites of participants of the population-based studies Inter99 (n = 5620) and Health2006/Health2008 (n = 3788) were analyzed by 1H-NMR spectroscopy. Linear or mixed linear models were used to detect associations between urine metabolites and thyroid function.


Cross-sectional analyses revealed positive relations of alanine, trigonelline and lactic acid with FT4 and negative relations of dimethylamine, glucose, glycine and lactic acid with log(TSH). In longitudinal analyses, lower levels of alanine, dimethylamine, glycine, lactic acid and N,N-dimethylglycine were linked to a higher decline in FT4 levels over time, whereas higher trigonelline levels were related to a higher FT4 decline. Moreover, the risk of hypothyroidism was higher in subjects with high baseline trigonelline or low lactic acid, alanine or glycine values.


The detected associations mainly emphasize the important role of thyroid hormones in glucose homeostasis. In addition, the predictive character of these metabolites might argue for a potential feedback of the metabolic state on thyroid function. Besides known metabolic consequences of TH, the link to the urine excretion of trigonelline, a marker of coffee consumption, represents a novel finding of this study and given the ubiquitous consumption of coffee requires further research.


Can pulses play a role in improving cardiometabolic health? Evidence from systematic reviews and meta-analyses.

Viguiliouk E, Blanco Mejia S, Kendall CW, Sievenpiper JL.

Ann N Y Acad Sci. 2017 Mar 2. doi: 10.1111/nyas.13312. [Epub ahead of print]

PMID: 28253436




Obesity, diabetes, and cardiovascular disease (CVD) present important unmet prevention and treatment challenges. Dietary pulses are sustainable, affordable, and nutrient-dense foods that have shown a wide range of health benefits in the prevention and management of these conditions. Despite these findings, recommendations for pulse intake continue to vary across chronic disease guidelines, and intake levels continue to remain low. Here, we summarize findings from recent systematic reviews and meta-analyses assessing the relationship between dietary pulse consumption and cardiometabolic health and assess the overall strength of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation tool. We conclude that systematic reviews and meta-analyses of prospective cohort studies assessing the relationship between legumes and the risk of coronary heart disease appear to provide moderate-quality evidence of a benefit, and several systematic reviews and meta-analyses of randomized controlled trials assessing the effect of pulses on cardiometabolic risk factors provide low- to moderate-quality evidence of a benefit. There remains an urgent need, however, for more high-quality prospective cohort studies and large, high-quality, randomized trials to clarify the benefits of dietary pulses in the prevention and management of overweight/obesity, diabetes, and CVD.


GRADE; cardiometabolic health; dietary pulses; review


Understanding the mechanisms underlying the neuroprotective role of calorie restriction in Parkinson’s Disease

Jacqueline Alyce Bayliss

PhD thesis for Monash University, 2016

pdf availed from: https://figshare.com/articles/Understanding_the_mechanisms_underlying_the_neuroprotective_role_of_calorie_restriction_in_Parkinson_s_Disease/4719760


Parkinson’s Disease (PD) is a debilitating neurological condition classified by a reduction of dopamine in the nigrostriatal region of the brain, resulting in movement disorders. Calorie restriction (CR) has shown to be neuroprotective during PD however, adhering to CR is difficult. In this thesis we attempted to create an alternative option that can mimic CR without having to reduce the amount of calories we consume. Initially we focused on the “hunger hormone” ghrelin, as it is elevated in the plasma during CR and is known to be protective in PD. Ghrelin exists in two distinctive isoforms, each with its own metabolic profile. In PD acyl ghrelin administration is neuroprotective, however, the role of des-acylated ghrelin is unknown. We wanted to identify the relative contributions each isoform plays using the MPTP model of PD. Chronic administration of acyl ghrelin in mice lacking both isoforms of ghrelin (Ghrelin KO) attenuated the MPTP-induced loss on Tyrosine Hydroxylase (TH; marker for dopamine) neuronal number and volume and TH protein concentration in the nigrostriatal pathway. However, injection of acyl ghrelin also elevated plasma des-acylated ghrelin, indicating in vivo deacetylation. Next, we chronically administered des-acylated ghrelin to Ghrelin KO mice and observed no neuroprotective effects. The lack of a protective effect was mirrored in Ghrelin-O-Acyltransferase (GOAT) KO mice, which lacks the ability to acylate ghrelin and consequently chronically increases plasma des-acyl ghrelin. Using this information we wanted to determine if acyl ghrelin was responsible for the neuroprotective actions of CR. CR attenuated the MPTP-induced loss of substantia nigra (SN) dopamine neurons and striatal dopamine turnover in Ghrelin WT but not KO mice, demonstrating that ghrelin mediates CR’s neuroprotective effect. CR elevated phosphorylated AMPK-activated kinase (AMPK) levels in the SN of WT but not KO mice suggesting that AMPK is a target for ghrelin-induced neuroprotection. Indeed, exogenous acyl ghrelin significantly increased pAMPK in the SN. Genetic deletion of AMPKβ1 and 2 subunits only in dopamine neurons (AMPK KO) prevented ghrelin-induced AMPK phosphorylation and neuroprotection. Hence, ghrelin signaling through AMPK in SN dopamine neurons mediates CR’s neuroprotective effects. Next we wanted to recreate the neuroprotective actions of CR with an already safe therapeutic. Metformin is the most commonly used drug to treat type 2 diabetes. It acts via AMPK activation in the periphery to ultimately lower blood glucose levels. Recently Metformin has been shown to be neuroprotective in PD. We wanted to determine if this was due to a direct effect on AMPK activity in dopaminergic neurons. We show that Metformin is neuroprotective in a mouse model of PD by attenuating dopaminergic cell loss and gliosis. This effect was present in both AMPK WT and KO mice indicating that Metformin’s neuroprotective actions are not due to AMPK activation in the SN dopaminergic neurons. Overall, these studies suggest a pathway linking CR with elevated acyl ghrelin which in turn phosphorylates AMPK in dopaminergic neurons to elicit a neuroprotective effect. CR mimetics should focus on AMPK activation in dopaminergic neurons as one potential target for the treatment of PD.


Dietary Patterns and Risk of Colorectal Cancer: Analysis by Tumor Location and Molecular Subtypes.

Mehta RS, Song M, Nishihara R, Drew DA, Wu K, Qian ZR, Fung TT, Hamada T, Masugi Y, da Silva A, Shi Y, Li W, Gu M, Willett WC, Fuchs CS, Giovannucci EL, Ogino S, Chan AT.

Gastroenterology. 2017 Feb 26. pii: S0016-5085(17)30179-8. doi: 10.1053/j.gastro.2017.02.015. [Epub ahead of print]

PMID: 28249812




Western and prudent dietary patterns have been associated with higher and lower risks of colorectal cancer (CRC), respectively. However, little is known about associations between dietary patterns and specific anatomic subsite or molecular subtypes of CRC.


We used multivariable Cox proportional hazards models to examine associations between Western and prudent dietary patterns and CRC risk in the Health Professionals Follow-up Study and Nurses' Health Study.


After up to 32 years of follow-up of 137,217 men and women, we documented 3260 cases of CRC. Among individuals from whom subsite data were available, we observed 1264 proximal colon, 866 distal colon, and 670 rectal tumors. Western diet was associated with an increased incidence of CRC (Ptrend<.0001), with a relative risk (RR) of 1.31 (95% CI, 1.15-1.48, comparing the highest to lowest quartile). The association of Western diet with CRC was evident for tumors of the distal colon (RR, 1.55; 95% CI, 1.22-1.96; Ptrend=.0004) and rectum (RR, 1.35; 95% CI, 1.03-1.77; Ptrend=.01) but not proximal colon (RR, 1.11; 95% CI, 0.91-1.35; Ptrend=.51) when we compared extreme quartiles. In contrast, for the prudent pattern, we observed a RR of 0.86 for overall CRC (95% CI, 0.77-0.95; Ptrend=.01), with similar trends at anatomic subsites. However, the trend appeared stronger among men than women. Among 1285 cases (39%) with tissue available for molecular profiling, Western diet appeared to be more strongly associated with some CRC molecular subtypes (no mutations in KRAS [KRAS wildtype] or BRAF [bRAF wildtype], no or a low CpG island methylator phenotype, and microsatellite stability), although formal tests for heterogeneity did not produce statistically significant results.


Western dietary patterns are associated with an increased risk of CRC, particularly distal colon and rectal tumors. Western dietary patterns also appear more strongly associated with tumors that are KRAS wildtype, BRAF wildtype, have no or a low CpG island methylator phenotype, and microsatellite stability. In contrast, prudent dietary patterns are associated with a lower risk of CRC that does not vary according to anatomic subsite or molecular subtype.


colon cancer risk; molecular epidemiology; processed meat; red meat


An Adolescent and Early Adulthood Dietary Pattern Associated with Inflammation and the Incidence of Breast Cancer.

Harris HR, Willett WC, Vaidya RL, Michels KB.

Cancer Res. 2017 Mar 1;77(5):1179-1187. doi: 10.1158/0008-5472.CAN-16-2273.

PMID: 28249935



Adolescence is a highly susceptible period for mammary carcinogenesis, but few prospective studies have examined the role of adolescent diet in breast cancer risk. Reduced rank regression has previously been used to identify a dietary pattern associated with markers of inflammation (C-reactive protein, IL6, and TNFα receptor 2). We investigated whether an adolescent and early adulthood inflammatory dietary pattern was associated with breast cancer among 45,204 women in the Nurses' Health Study II using reduced rank regression. Participants completed a food frequency questionnaire in 1998 about their high school diet (HS-FFQ) and a FFQ in 1991 when they were ages 27-44 years. Among women who completed the HS-FFQ, 1,477 cases of breast cancer were diagnosed during 22 years of follow-up. An adolescent and early adulthood dietary pattern characterized by inflammation was associated with an increased incidence of premenopausal but not postmenopausal breast cancer. Women in the fifth quintile of the inflammatory pattern score had multivariable adjusted HRs for premenopausal breast cancer of 1.35 for adolescent diet [95% confidence interval (95% CI), 1.06-1.73; Ptrend = 0.002] and 1.41 for early adulthood diet (95% CI, 1.11-1.78; Ptrend = 0.006) compared with women in the first quintile. The corresponding RRs for postmenopausal breast cancer were 0.84 (95% CI, 0.60-1.17) for adolescent and 0.76 (95% CI, 0.54-1.06) for adult intake. Overall, our findings support the notion that an adolescent and early adulthood diet characterized by high intake of sugar-sweetened and diet soft drinks, refined grains, red and processed meat, and margarine, and low intake of green leafy vegetables, cruciferous vegetables, and coffee may increase the incidence of premenopausal breast cancer.

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The association between adult attained height and sitting height with mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Sawada N, Wark PA, Merritt MA, Tsugane S, Ward HA, Rinaldi S, Weiderpass E, Dartois L, His M, Boutron-Ruault MC, Turzanski-Fortner R, Kaaks R, Overvad K, Redondo ML, Travier N, Molina-Portillo E, Dorronsoro M, Cirera L, Ardanaz E, Perez-Cornago A, Trichopoulou A, Lagiou P, Valanou E, Masala G, Pala V, Hm Peeters P, T van der Schouw Y, Melander O, Manjer J, da Silva M, Skeie G, Tjønneland A, Olsen A, J Gunter M, Riboli E, J Cross A.

PLoS One. 2017 Mar 3;12(3):e0173117. doi: 10.1371/journal.pone.0173117.

PMID: 28257491




Adult height and sitting height may reflect genetic and environmental factors, including early life nutrition, physical and social environments. Previous studies have reported divergent associations for height and chronic disease mortality, with positive associations observed for cancer mortality but inverse associations for circulatory disease mortality. Sitting height might be more strongly associated with insulin resistance; however, data on sitting height and mortality is sparse. Using the European Prospective Investigation into Cancer and Nutrition study, a prospective cohort of 409,748 individuals, we examined adult height and sitting height in relation to all-cause and cause-specific mortality. Height was measured in the majority of participants; sitting height was measured in ~253,000 participants. During an average of 12.5 years of follow-up, 29,810 deaths (11,931 from cancer and 7,346 from circulatory disease) were identified. Hazard ratios (HR) with 95% confidence intervals (CI) for death were calculated using multivariable Cox regression within quintiles of height. Height was positively associated with cancer mortality (men: HRQ5 vs. Q1 = 1.11, 95%CI = 1.00-1.24; women: HRQ5 vs. Q1 = 1.17, 95%CI = 1.07-1.28). In contrast, height was inversely associated with circulatory disease mortality (men: HRQ5 vs. Q1 = 0.63, 95%CI = 0.56-0.71; women: HRQ5 vs. Q1 = 0.81, 95%CI = 0.70-0.93). Although sitting height was not associated with cancer mortality, it was inversely associated with circulatory disease (men: HRQ5 vs. Q1 = 0.64, 95%CI = 0.55-0.75; women: HRQ5 vs. Q1 = 0.60, 95%CI = 0.49-0.74) and respiratory disease mortality (men: HRQ5 vs. Q1 = 0.45, 95%CI = 0.28-0.71; women: HRQ5 vs. Q1 = 0.60, 95%CI = 0.40-0.89). We observed opposing effects of height on cancer and circulatory disease mortality. Sitting height was inversely associated with circulatory disease and respiratory disease mortality.


Adherence to Healthy Lifestyle and Cardiovascular Diseases in the Chinese Population.

Lv J, Yu C, Guo Y, Bian Z, Yang L, Chen Y, Tang X, Zhang W, Qian Y, Huang Y, Wang X, Chen J, Chen Z, Qi L, Li L; China Kadoorie Biobank Collaborative Group..

J Am Coll Cardiol. 2017 Mar 7;69(9):1116-1125. doi: 10.1016/j.jacc.2016.11.076.

PMID: 28254173





Adherence to a combination of healthy lifestyle factors has been related to a considerable reduction of cardiovascular risk in white populations; however, little is known whether such associations persist in nonwhite populations like the Asian population.


This study aimed to examine the associations of a combination of modifiable, healthy lifestyle factors with the risks of ischemic cardiovascular diseases and estimate the proportion of diseases that could potentially be prevented by adherence to these healthy lifestyle patterns.


This study examined the associations of 6 lifestyle factors with ischemic heart disease and ischemic stroke (IS) in the China Kadoorie Biobank of 461,211 participants 30 to 79 years of age who did not have cardiovascular diseases, cancer, or diabetes at baseline. Low-risk lifestyle factors were defined as nonsmoking status or having stopped smoking for reasons other than illness, alcohol consumption of <30 g/day, a median or higher level of physical activity, a diet rich in vegetables and fruits and limited in red meat, a body mass index of 18.5 to 23.9 kg/m2, and a waist-to-hip ratio <0.90 for men and <0.85 for women.


During a median of 7.2 years (3.3 million person-years) of follow-up, this study documented 3,331 incident major coronary events (MCE) and 19,348 incident ISs. In multivariable-adjusted analyses, current nonsmoking status, light to moderate alcohol consumption, high physical activity, a diet rich in vegetables and fruits and limited in red meat, and low adiposity were independently associated with reduced risks of MCE and IS. Compared with participants without any low-risk factors, the hazard ratio for participants with ≥4 low-risk factors was 0.42 (95% confidence interval: 0.34 to 0.52) for MCE and 0.61 (95% confidence interval: 0.56 to 0.66) for IS. Approximately 67.9% (95% confidence interval: 46.5% to 81.9%) of the MCE and 39.1% (95% confidence interval: 26.4% to 50.4%) of the IS cases were attributable to poor adherence to healthy lifestyle.


Adherence to healthy lifestyle may substantially lower the burden of cardiovascular diseases in Chinese.


cardiovascular diseases; cohort studies; health behavior; lifestyle


[The below paper is not pdf-availed.]

Meat consumption and colorectal cancer risk in Japan: The Takayama study.

Wada K, Oba S, Tsuji M, Tamura T, Konishi K, Goto Y, Mizuta F, Koda S, Hori A, Tanabashi S, Matsushita S, Tokimitsu N, Nagata C.

Cancer Sci. 2017 Mar 3. doi: 10.1111/cas.13217. [Epub ahead of print]

PMID: 28256076


Compared with the abundant data from Western countries, evidence regarding meat consumption and colorectal cancer is limited in the Japanese population. We evaluated colorectal cancer risk in relation to meat consumption in a population-based prospective cohort study in Japan. Participants were 13,957 men and 16,374 women aged ≥35 years in September 1992. Meat intake, assessed with a validated food frequency questionnaire, was controlled for the total energy intake. The incidence of colorectal cancer was confirmed through regional population-based cancer registries and histological identification from colonoscopy in two main hospitals in the study area. From September 1992 to March 2008, 429 men and 343 women developed colorectal cancer. After adjustments for multiple confounders, a significantly increased relative risk of colorectal cancer was observed in the highest vs. lowest quartile of the intake of total and red meat among men; the estimated hazard ratios were 1.36 (95% CI: 1.03,1.79) for total meat (p for trend=0.022), and 1.44 (95% CI: 1.10, 1.89) for red meat (p for trend=0.009). A positive association between processed meat intake and colon cancer risk was also observed in men. There was no significant association between colorectal cancer and meat consumption in women. These results suggest that the intake of red and processed meat increases the risk of colorectal or colon cancer among Japanese men. Abstaining from excessive consumption of meat might be protective against developing colorectal cancer.


cohort studies; colorectal cancer; epidemiology; processed meat; red meat

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The modelled impact of increases in physical activity: the effect of both increased survival and reduced incidence of disease.

Mytton OT, Tainio M, Ogilvie D, Panter J, Cobiac L, Woodcock J.

Eur J Epidemiol. 2017 Mar 3. doi: 10.1007/s10654-017-0235-1. [Epub ahead of print]

PMID: 28258521




Physical activity can affect 'need' for healthcare both by reducing the incidence rate of some diseases and by increasing longevity (increasing the time lived at older ages when disease incidence is higher). However, it is common to consider only the first effect, which may overestimate any reduction in need for healthcare. We developed a hybrid micro-simulation lifetable model, which made allowance for both changes in longevity and risk of disease incidence, to estimate the effects of increases in physical activity (all adults meeting guidelines) on measures of healthcare need for diseases for which physical activity is protective. These were compared with estimates made using comparative risk assessment (CRA) methods, which assumed that longevity was fixed. Using the lifetable model, life expectancy increased by 95 days (95% uncertainty intervals: 68-126 days). Estimates of the healthcare need tended to decrease, but the magnitude of the decreases were noticeably smaller than those estimated using CRA methods (e.g. dementia: change in person-years, -0.6%, 95% uncertainty interval -3.7% to +1.6%; change in incident cases, -0.4%, -3.6% to +1.9%; change in person-years (CRA methods), -4.0%, -7.4% to -1.6%). The pattern of results persisted under different scenarios and sensitivity analyses. For most diseases for which physical activity is protective, increases in physical activity are associated with decreases in indices of healthcare need. However, disease onset may be delayed or time lived with disease may increase, such that the decreases in need may be relatively small and less than is sometimes expected.


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

Canada T.

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

PMID: 28256953




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


Prospective cohort study.


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


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


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


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


Not so fast: The impact of impulsivity on weight loss varies by treatment type.

Manasse SM, Flack D, Dochat C, Zhang F, Butryn ML, Forman EM.

Appetite. 2017 Feb 28. pii: S0195-6663(17)30326-4. doi: 10.1016/j.appet.2017.02.042. [Epub ahead of print]

PMID: 28257940



Behavioral weight loss (BWL) treatments result in suboptimal weight losses for many individuals. Impulsivity appears to be a maintenance factor of obesity, yet few studies have examined impulsivity as a predictor of outcomes from BWL. We examined specific facets of impulsivity (inhibitory control and delay discounting) as moderators of outcome in BWL. Overweight adults (n = 190) were randomized to standard behavioral treatment (SBT) or acceptance-based behavioral treatment (ABT). We hypothesized that impulsivity would be inversely associated with weight loss, and that the association between impulsivity and outcome would be attenuated in the ABT condition. Poorer general inhibitory control predicted lower percent weight lost at 12 months across conditions at the trend level (b = -0.003, p = 0.06). The negative impact of low inhibitory control on weight loss was attenuated by assignment to ABT versus SBT (b = 0.004, p = 0.03). Treatment condition, at trend level, also moderated the impact of delay discounting (b = -0.011, p = .098) and food-specific inhibitory control (b = 0.003, p = 0.06) on percent weight loss such that those with greater impulsivity benefitted most from ABT. Results reveal a potential pattern that impulsivity reduces benefit derived from SBT but not ABT. Further research on the moderating effect of impulsivity is necessary to inform the development of targeted treatments for clinically meaningful subtypes of patients.


Acceptance-based treatment; Behavioral weight loss; Delay discounting; Impulsivity; Inhibitory control; Obesity


[i thought it might be interesting to compare the effects to the effects of number of fast food joints.]

Liquor landscapes: Does access to alcohol outlets influence alcohol consumption in young adults?

Foster S, Trapp G, Hooper P, Oddy WH, Wood L, Knuiman M.

Health Place. 2017 Feb 28;45:17-23. doi: 10.1016/j.healthplace.2017.02.008. [Epub ahead of print]

PMID: 28258014



Few longitudinal studies have examined the impact of liquor licences on alcohol consumption, and none in young adults, the life stage when alcohol intake is at its highest. We examined associations between liquor licences (i.e., general licences, on-premise licences, liquor stores, and club licences) and alcohol consumption at 20-years (n=988) and 22-years (n=893), and whether changes in the licences between time-points influenced alcohol consumption (n=665). Only general licences were associated with alcohol consumption at 20-years (p=0.037), but by 22-years, all licences types were positively associated with alcohol consumption (p<0.05). Longitudinal analyses showed that for each increase in liquor stores over time, alcohol consumption increased by 1.22g/day or 8% (p=0.030), and for each additional club licence, consumption increased by 0.90g/day or 6% (p=0.007). Limiting liquor licences could contribute to a reduction in young adults' alcohol intake.


Alcohol; Alcohol outlet density; Licence types; Longitudinal; Neighbourhood; Young adults


Multiple Risk Behavior Interventions: Meta-analyses of RCTs.

Meader N, King K, Wright K, Graham HM, Petticrew M, Power C, White M, Sowden AJ.

Am J Prev Med. 2017 Feb 28. pii: S0749-3797(17)30091-0. doi: 10.1016/j.amepre.2017.01.032. [Epub ahead of print] Review.

PMID: 28258777




Multiple risk behaviors are common and associated with developing chronic conditions such as heart disease, cancer, or Type 2 diabetes. A systematic review, meta-analysis, and meta-regression of the effectiveness of multiple risk behavior interventions was conducted.


Six electronic databases including MEDLINE, EMBASE, and PsycINFO were searched to August 2016. RCTs of non-pharmacologic interventions in general adult populations were selected. Studies targeting specific at-risk groups (such as people screened for cardiovascular risk factors or obesity) were excluded. Studies were screened independently. Study characteristics and outcomes were extracted and risk of bias assessed by one researcher and checked by another. The Behaviour Change Wheel and Oxford Implementation Index were used to code intervention content and context.


Random-effects meta-analyses were conducted. Sixty-nine trials involving 73,873 individuals were included. Interventions mainly comprised education and skills training and were associated with modest improvements in most risk behaviors: increased fruit and vegetable intake (0.31 portions, 95% CI=0.17, 0.45) and physical activity (standardized mean difference, 0.25; 95% CI=0.13, 0.38), and reduced fat intake (standardized mean difference, -0.24; 95% CI= -0.36, -0.12). Although reductions in smoking were found (OR=0.78, 95% CI=0.68, 0.90), they appeared to be negatively associated with improvement in other behaviors (such as diet and physical activity). Preliminary evidence suggests that sequentially changing smoking alongside other risk behaviors was more effective than simultaneous change. But most studies assessed simultaneous rather than sequential change in risk behaviors; therefore, comparisons are sparse. Follow-up period and intervention characteristics impacted effectiveness for some outcomes.


Interventions comprising education (e.g., providing information about behaviors associated with health risks) and skills training (e.g., teaching skills that equip participants to engage in less risky behavior) and targeting multiple risk behaviors concurrently are associated with small changes in diet and physical activity. Although on average smoking was reduced, it appeared changes in smoking were negatively associated with changes in other behaviors, suggesting it may not be optimal to target smoking simultaneously with other risk behaviors.


Association between a dietary quality index based on the food standard agency nutrient profiling system and cardiovascular disease risk among French adults.

Adriouch S, Julia C, Kesse-Guyot E, Ducrot P, Péneau S, Méjean C, Assmann KE, Deschasaux M, Hercberg S, Touvier M, Fezeu LK.

Int J Cardiol. 2017 Feb 24. pii: S0167-5273(17)31122-1. doi: 10.1016/j.ijcard.2017.02.092. [Epub ahead of print]

PMID: 28258849




In France, the implementation of a front-of-pack (FOP) nutrition label-the 5-Colour Nutrition Label (5-CNL) is currently under consideration as a strategic tool to allow consumers making healthier food choices. This FOP label is based on the British Food Standards Agency Nutrient Profiling System (FSA-NPS), reflecting the overall nutritional quality of foods. At the individual level, an energy-weighted mean of all FSA-NPS scores of foods usually consumed has been elaborated (FSA-NPS DI). Our objective was to investigate the prospective association between the FSA-NPS DI and cardiovascular disease (CVD) risk.


75,801 participants to the NutriNet-Santé cohort, who completed at least three 24h dietary records during the first 2y of the follow-up, were followed between 2009 and 2016. Multivariable Cox proportional hazards models were used to characterize the associations between FSA-NPS DI and the incidence of CVDs.


509 major cardiovascular events were diagnosed (262 coronary heart diseases and 247 strokes). A higher FSA-NPS DI, characterizing lower dietary quality, was associated with increased CVD risk (HRfor a 1-point increment=1.08 (1.03-1.13); HRQ4vs.Q1=1.40 (1.06-1.84), Ptrend Q4-Q1=0.01). This association tended to be stronger in overweight subjects (HRfor a 1-point increment=1.12 (1.04-1.19); Pinteraction=0.003).


These results suggest that lower dietary quality, as reflected by a higher FSA-NPS DI, may be associated with a significant increase in cardiovascular risk, especially in at-risk individuals (overweight population). They support the public health relevance of developing a front-of-pack nutrition label based on this score.


Cardiovascular risk; FSA-NPS; Nutrient profiling system; Nutrition policy; Prospective study


Effects of Anabolic Androgenic Steroids on the Reproductive System of Athletes and Recreational Users: A Systematic Review and Meta-Analysis.

Christou MA, Christou PA, Markozannes G, Tsatsoulis A, Mastorakos G, Tigas S.

Sports Med. 2017 Mar 4. doi: 10.1007/s40279-017-0709-z. [Epub ahead of print] Review.

PMID: 28258581




Anabolic androgenic steroids (AAS) are testosterone derivatives used by athletes and recreational users to improve athletic performance and/or enhance appearance. Anabolic androgenic steroids use may have serious and potentially irreversible adverse effects on different organs and systems, including the reproductive system.


This systematic review and meta-analysis aimed to critically assess the impact of AAS use on the reproductive system of athletes and recreational users.


An electronic literature search was conducted using the databases MEDLINE, CENTRAL, and Google Scholar. Studies were included when the following criteria were fulfilled: participants were athletes or recreational users of any age, sex, level or type of sport; AAS use of any type, dose, form or duration; AAS effects on the reproductive system were assessed as stated by medical history, clinical examination, hormone and/or semen analysis. Random-effects meta-analysis was performed to assess the weighted mean difference (WMD) of serum gonadotropin (luteinizing hormone, follicle-stimulating hormone) and testosterone levels compared with baseline, during the period of AAS use, as well as following AAS discontinuation.


Thirty-three studies (three randomized clinical trials, 11 cohort, 18 cross-sectional, and one non-randomized parallel clinical trial) were included in the systematic review (3879 participants; 1766 AAS users and 2113 non-AAS users). The majority of the participants were men; only six studies provided data for female athletes. A meta-analysis (11 studies) was conducted of studies evaluating serum gonadotropin and testosterone levels in male subjects: (1) prior to, and during AAS use (six studies, n = 65 AAS users; seven studies, n = 59, evaluating gonadotropin and testosterone levels respectively); (2) during AAS use and following AAS discontinuation (four studies, n = 35; six studies, n = 39, respectively); as well as (3) prior to AAS use and following AAS discontinuation (three studies, n = 17; five studies, n = 27, respectively). During AAS intake, significant reductions in luteinizing hormone [weighted mean difference (WMD) -3.37 IU/L, 95% confidence interval (CI) -5.05 to -1.70, p < 0.001], follicle-stimulating hormone (WMD -1.73 IU/L, 95% CI -2.67 to -0.79, p < 0.001), and endogenous testosterone levels (WMD -10.75 nmol/L, 95% CI -15.01 to -6.49, p < 0.001) were reported. Following AAS discontinuation, serum gonadotropin levels gradually returned to baseline values within 13-24 weeks, whereas serum testosterone levels remained lower as compared with baseline (WMD -9.40 nmol/L, 95% CI -14.38 to -4.42, p < 0.001). Serum testosterone levels remained reduced at 16 weeks following discontinuation of AAS. In addition, AAS abuse resulted in structural and functional sperm changes, a reduction in testicular volume, gynecomastia, as well as clitoromegaly, menstrual irregularities, and subfertility.


The majority of AAS users demonstrated hypogonadism with persistently low gonadotropin and testosterone levels, lasting for several weeks to months after AAS withdrawal. Anabolic androgenic steroid use results in profound and prolonged effects on the reproductive system of athletes and recreational users and potentially on fertility.


A Systematic Review of the Effects of Plant Compared with Animal Protein Sources on Features of Metabolic Syndrome.

Chalvon-Demersay T, Azzout-Marniche D, Arfsten J, Egli L, Gaudichon C, Karagounis LG, Tomé D.

J Nutr. 2017 Mar;147(3):281-292. doi: 10.3945/jn.116.239574. Review.

PMID: 28122929 Free Article




Dietary protein may play an important role in the prevention of metabolic dysfunctions. However, the way in which the protein source affects these dysfunctions has not been clearly established. The aim of the current systematic review was to compare the impact of plant- and animal-sourced dietary proteins on several features of metabolic syndrome in humans. The PubMed database was searched for both chronic and acute interventional studies, as well as observational studies, in healthy humans or those with metabolic dysfunctions, in which the impact of animal and plant protein intake was compared while using the following variables: cholesterolemia and triglyceridemia, blood pressure, glucose homeostasis, and body composition. Based on data extraction, we observed that soy protein consumption (with isoflavones), but not soy protein alone (without isoflavones) or other plant proteins (pea and lupine proteins, wheat gluten), leads to a 3% greater decrease in both total and LDL cholesterol compared with animal-sourced protein ingestion, especially in individuals with high fasting cholesterol concentrations. This observation was made when animal proteins were provided as a whole diet rather than given supplementally. Some observational studies reported an inverse association between plant protein intake and systolic and diastolic blood pressure, but this was not confirmed by intervention studies. Moreover, plant protein (wheat gluten, soy protein) intake as part of a mixed meal resulted in a lower postprandial insulin response than did whey. This systematic review provides some evidence that the intake of soy protein associated with isoflavones may prevent the onset of risk factors associated with cardiovascular disease, i.e., hypercholesterolemia and hypertension, in humans. However, we were not able to draw any further conclusions from the present work on the positive effects of plant proteins relating to glucose homeostasis and body composition.


animal protein; blood pressure; body composition; cholesterol; glucose homeostasis; metabolic syndrome; plant protein


Longitudinal association between fasting blood glucose concentrations and first stroke in hypertensive adults in China: effect of folic acid intervention.

Xu RB, Kong X, Xu BP, Song Y, Ji M, Zhao M, Huang X, Li P, Cheng X, Chen F, Zhang Y, Tang G, Qin X, Wang B, Hou FF, Dong Q, Chen Y, Yang T, Sun N, Li X, Zhao L, Ge J, Ji L, Huo Y, Li J.

Am J Clin Nutr. 2017 Mar;105(3):564-570. doi: 10.3945/ajcn.116.145656.

PMID: 28122783



Background: Diabetes is a known risk factor for stroke, but data on its prospective association with first stroke are limited. Folic acid supplementation has been shown to protect against first stroke, but its role in preventing first stroke in diabetes is unknown.Objectives: This post hoc analysis of the China Stroke Primary Prevention Trial tested the hypotheses that the fasting blood glucose (FBG) concentration is positively associated with first stroke risk and that folic acid treatment can reduce stroke risk associated with elevated fasting glucose concentrations.Design: This analysis included 20,327 hypertensive adults without a history of stroke or myocardial infarction, who were randomly assigned to a double-blind daily treatment with 10 mg enalapril and 0.8 mg folic acid (n = 10,160) or 10 mg enalapril alone (n = 10,167). Kaplan-Meier survival analysis and Cox proportionate hazard models were used to test the hypotheses with adjustment for pertinent covariables.Results: During a median treatment duration of 4.5 y, 616 participants developed a first stroke (497 ischemic strokes). A high FBG concentration (≥7.0 mmol/L) or diabetes, compared with a low FBG concentration (<5.0 mmol/L), was associated with an increased risk of first stroke (6.0% compared with 2.6%, respectively; HR: 1.9; 95% CI: 1.3, 2.8; P < 0.001). Folic acid treatment reduced the risk of stroke across a wide range of FBG concentrations ≥5.0 mmol/L, but risk reduction was greatest in subjects with FBG concentrations ≥7.0 mmol/L or with diabetes (HR: 0.66; 95% CI: 0.46, 0.97; P < 0.05). There was a significant interactive effect of FBG and folic acid treatment on first stroke (P = 0.01).Conclusions: In Chinese hypertensive adults, an FBG concentration ≥7.0 mmol/L or diabetes is associated with an increased risk of first stroke; this increased risk is reduced by 34% with folic acid treatment. These findings warrant additional investigation.


Chinese; folic acid; hyperglycemia; hypertension; stroke


Dietary intake and peripheral arterial disease incidence in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study.

Ogilvie RP, Lutsey PL, Heiss G, Folsom AR, Steffen LM.

Am J Clin Nutr. 2017 Mar;105(3):651-659. doi: 10.3945/ajcn.116.137497.

PMID: 28077376



Background: Peripheral arterial disease (PAD) is a costly source of morbidity and mortality among older persons in the United States. Dietary intake plays a role in the development of atherosclerotic cardiovascular disease; however, few studies have examined the relation of food intake or dietary patterns with PAD.Objective: We examined the relation between habitual dietary intake at midlife and incident PAD over ∼20 y of follow-up.Design: Among 14,082 participants enrolled in the ARIC (Atherosclerosis Risk in Communities) Study initially free of PAD, dietary intake was assessed at baseline in 1987-1989 by using a modified Harvard food-frequency questionnaire. Food groups were created, and principal components analysis was used to develop "healthy" and "Western" dietary patterns; both were categorized into quintiles or quartiles. Incident PAD was determined by an ankle-brachial index <0.9 assessed at 2 subsequent examinations and hospital discharge codes through 2012. Multivariate-adjusted Cox proportional hazards regression was used.Results: During a mean follow-up of 19.9 y, 1569 participants developed incident PAD. In models adjusted for demographic characteristics, behaviors, and food groups, the HRs (95% CIs) for incident PAD increased across quintiles of meat consumption [quintile 1: reference, quintile 2: 1.38 (1.16, 1.65), quintile 3: 1.38 (1.16, 1.65), quintile 4: 1.45 (1.20, 1.74), quintile 5: 1.66 (1.36, 2.03); P-trend <0.001]. Compared with those who drank no alcohol, those who had 1-6 drinks/wk had a lower risk of incident PAD [0.78 (0.68, 0.89)]. For coffee, ≥4 cups/d compared with none was inversely associated with incident PAD [quintile 5 compared with quintile 1: 0.84 (0.75, 1.00); P-trend = 0.014]. There was no association between other food groups or patterns and incident PAD.Conclusions: In this prospective cohort study, greater meat consumption was associated with a higher risk, and moderate alcohol consumption was associated with a lower risk of incident PAD. Whether these associations are causal remains to be seen.


alcohol; cardiovascular disease; dietary patterns; food groups; meat; peripheral arterial disease


Dietary protein is associated with musculoskeletal health independently of dietary pattern: the Framingham Third Generation Study.

Mangano KM, Sahni S, Kiel DP, Tucker KL, Dufour AB, Hannan MT.

Am J Clin Nutr. 2017 Mar;105(3):714-722. doi: 10.3945/ajcn.116.136762.

PMID: 28179224



Background: Above-average dietary protein, as a single nutrient, improves musculoskeletal health. Evaluating the link between dietary protein and musculoskeletal health from a whole-diet perspective is important, as dietary guidelines focus on dietary patterns.Objective: We examined the prospective association of novel dietary protein food clusters (derived from established dietary pattern techniques) with appendicular lean mass (ALM), quadriceps strength (QS), and bone mineral density (BMD) in 2986 men and women, aged 19-72 y, from the Framingham Third Generation Study.Design: Total protein intake was estimated by food-frequency questionnaire in 2002-2005. A cluster analysis was used to classify participants into mutually exclusive groups, which were determined by using the percentage of contribution of food intake to overall protein intake. General linear modeling was used to 1) estimate the association between protein intake (grams per day) and BMD, ALM, appendicular lean mass normalized for height (ALM/ht2), and QS (2008-2011) and to 2) calculate adjusted least-squares mean outcomes across quartiles of protein (grams per day) and protein food clusters.Results: The mean ± SD age of subjects was 40 ± 9 y; 82% of participants met the Recommended Daily Allowance (0.8 g · kg body weight-1 · d-1). The following 6 dietary protein food clusters were identified: fast food and full-fat dairy, fish, red meat, chicken, low-fat milk, and legumes. BMD was not different across quartiles of protein intake (P-trend range = 0.32-0.82); but significant positive trends were observed for ALM, ALM/ht2 (P < 0.001), and QS (P = 0.0028). Individuals in the lowest quartile of total protein intake (quartile 1) had significantly lower ALM, ALM/ht2, and QS than did those in the higher quartiles of intake (quartiles 2-4; (P ranges = 0.0001-0.003, 0.0007-0.003, and 0.009-0.05, respectively). However, there were no associations between protein clusters and any musculoskeletal outcome in adjusted models.Conclusions: In a protein-replete cohort of adults, dietary protein is associated with ALM and QS but not with BMD. In this study, dietary protein food patterns do not provide further insight into beneficial protein effects on muscle outcomes.


bone mineral density; dietary patterns; dietary protein; muscle mass; muscle strength


Total and subtypes of dietary fat intake and risk of type 2 diabetes mellitus in the Prevención con Dieta Mediterránea (PREDIMED) study.

Guasch-Ferré M, Becerra-Tomás N, Ruiz-Canela M, Corella D, Schröder H, Estruch R, Ros E, Arós F, Gómez-Gracia E, Fiol M, Serra-Majem L, Lapetra J, Basora J, Martín-Calvo N, Portoles O, Fitó M, Hu FB, Forga L, Salas-Salvadó J.

Am J Clin Nutr. 2017 Mar;105(3):723-735. doi: 10.3945/ajcn.116.142034.

PMID: 28202478



Background: The associations between dietary fat and cardiovascular disease have been evaluated in several studies, but less is known about their influence on the risk of diabetes.Objective: We examined the associations between total fat, subtypes of dietary fat, and food sources rich in saturated fatty acids and the incidence of type 2 diabetes (T2D).Design: A prospective cohort analysis of 3349 individuals who were free of diabetes at baseline but were at high cardiovascular risk from the PREvención con DIeta MEDiterránea (PREDIMED) study was conducted. Detailed dietary information was assessed at baseline and yearly during the follow-up using a food frequency questionnaire. Multivariable Cox proportional hazards models were used to estimate T2D HRs and 95% CIs according to baseline and yearly updated fat intake.Results: We documented 266 incident cases during 4.3 y of follow-up. Baseline saturated and animal fat intake was not associated with the risk of T2D. After multivariable adjustment, participants in the highest quartile of updated intake of saturated and animal fat had a higher risk of diabetes than the lowest quartile (HR: 2.19; 95% CI: 1.28, 3.73; and P-trend = 0.01 compared with HR: 2.00; 95% CI: 1.29, 3.09; and P-trend < 0.01, respectively). In both the Mediterranean diet and control groups, participants in the highest quartile of updated animal fat intake had an ∼2-fold higher risk of T2D than their counterparts in the lowest quartile. The consumption of 1 serving of butter and cheese was associated with a higher risk of diabetes, whereas whole-fat yogurt intake was associated with a lower risk.Conclusions: In a Mediterranean trial focused on dietary fat interventions, baseline intake of saturated and animal fat was not associated with T2D incidence, but the yearly updated intake of saturated and animal fat was associated with a higher risk of T2D. Cheese and butter intake was associated with a higher risk of T2D, whereas whole-fat yogurt intake was associated with a lower risk of T2D.


PREDIMED study; dietary fat; fat subtypes; monounsaturated fat; saturated fat; type 2 diabetes; ω-3 fatty acids


Influence of temperate, subtropical, and tropical fruit consumption on risk of type 2 diabetes in an Asian population.

Alperet DJ, Butler LM, Koh WP, Yuan JM, van Dam RM.

Am J Clin Nutr. 2017 Mar;105(3):736-745. doi: 10.3945/ajcn.116.147090.

PMID: 28179225



Background: Findings on the relation between fruit consumption and the risk of type 2 diabetes mellitus (T2DM) have been inconsistent.Objectives: We examined whether the consumption of total, temperate, subtropical, and tropical fruit is associated with T2DM risk and whether differences in the carbohydrate quality of fruit influence T2DM risk in Asians.Design: We included 45,411 participants in the Singapore Chinese Health Study who were 45-74 y old and had no diabetes, cancer, or cardiovascular disease at recruitment (1993-1998). Fruit intake was assessed with the use of a validated food-frequency questionnaire. Physician-diagnosed incident T2DM cases were reported at follow-up 1 (1999-2004) and follow-up 2 (2006-2010) interviews. Cox proportional hazards regression was used to estimate HRs and 95% CIs of diabetes risk.Results: In 494,741 person-years of follow-up, 5207 participants developed T2DM. After adjustment for lifestyle and dietary risk factors, high total fruit consumption was not consistently associated with lower T2DM risk [men: HR of 1.33 (95% CI: 1.04, 1.71) for ≥3 servings/d compared with <1 serving/wk (P-trend = 0.17); women: HR of 0.88 (95% CI: 0.71, 1.11) (P-trend = 0.008); P-interaction = 0.003]. The direct association in men was observed for higher-glycemic index (GI) fruit [hr: 1.51 (95% CI: 1.22, 1.86) for ≥1 serving/d compared with rarely consumed; P-trend = 0.001] but not for lower or moderate GI fruit. In women, the consumption of temperate fruit, but not of subtropical or tropical fruit, was associated with lower T2DM risk [hr: 0.79 (95% CI: 0.67, 0.92) for ≥1 serving/d compared with rarely; P-trend = 0.006].Conclusions: The consumption of temperate fruit, such as apples, was associated with a lower risk of T2DM in women, whereas the consumption of higher-GI fruit, such as bananas, was associated with higher risk in men. The impact of fruit consumption on the risk of diabetes may differ by the type of fruit, which may reflect differences in the glycemic impact or phytochemical content.


fruit; glycemic index; subtropical; temperate; tropical; type 2 diabetes mellitus


Probiotics (<i>Lactobacillus gasseri</i> KS-13, <i>Bifidobacterium bifidum</i> G9-1, and <i>Bifidobacterium longum</i> MM-2) improve rhinoconjunctivitis-specific quality of life in individuals with seasonal allergies: a double-blind, placebo-controlled, randomized trial.

Dennis-Wall JC, Culpepper T, Nieves C Jr, Rowe CC, Burns AM, Rusch CT, Federico A, Ukhanova M, Waugh S, Mai V, Christman MC, Langkamp-Henken B.

Am J Clin Nutr. 2017 Mar;105(3):758-767. doi: 10.3945/ajcn.116.140012.

PMID: 28228426 Free Article




Background: Rhinoconjunctivitis-specific quality of life is often reduced during seasonal allergies. The Mini Rhinoconjunctivitis Quality of Life Questionnaire (MRQLQ) is a validated tool used to measure quality of life in people experiencing allergies (0 = not troubled to 6 = extremely troubled). Probiotics may improve quality of life during allergy season by increasing the percentage of regulatory T cells (Tregs) and inducing tolerance.Objective: The objective of this study was to determine whether consuming Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and B. longum MM-2 compared with placebo would result in beneficial effects on MRQLQ scores throughout allergy season in individuals who typically experience seasonal allergies. Secondary outcomes included changes in immune markers as part of a potential mechanism for changes in MRQLQ scores.Design: In this double-blind, placebo-controlled, parallel, randomized clinical trial, 173 participants (mean ± SEM: age 27 ± 1 y) who self-identified as having seasonal allergies received either a probiotic (2 capsules/d, 1.5 billion colony-forming units/capsule) or placebo during spring allergy season for 8 wk. MRQLQ scores were collected weekly throughout the study. Fasting blood samples were taken from a subgroup (placebo, n = 37; probiotic, n = 35) at baseline and week 6 (predicted peak of pollen) to determine serum immunoglobulin (Ig) E concentrations and Treg percentages.Results: The probiotic group reported an improvement in the MRQLQ global score from baseline to pollen peak (-0.68 ± 0.13) when compared with the placebo group (-0.19 ± 0.14; P = 0.0092). Both serum total IgE and the percentage of Tregs increased from baseline to week 6, but changes were not different between groups.Conclusions: This combination probiotic improved rhinoconjunctivitis-specific quality of life during allergy season for healthy individuals with self-reported seasonal allergies; however, the associated mechanism is still unclear.


Bifidobacterium bifidum; Bifidobacterium longum; Lactobacillus gasseri; allergic rhinitis; healthy adults; probiotics; quality of life; seasonal allergies


[The below paper is pdf-availed.]

Fear of Life Extension

James S. Goodwin

J Gerontol A Biol Sci Med Sci (2017) 72 (3): 353-354. DOI: https://doi.org/10.1093/gerona/glw340

Published: 18 January 2017


In about the year 2000, a commandment came down from the very heights of the Geriatric Olympus: “Thou Shalt Not Study Life Extension. Nay, nor shall thou speak wistfully of such a prospect. For it is written that life extension scares the bejesus out of the gods of policy.” The fear haunting policy makers is that medical progress will result in longer lives without better health—the specter of millions of empty shells in wheelchairs populating ever-expanding nursing homes. Ever since this commandment, the ruling concept has been “quality, not quantity.” We don’t want to live longer—just better. This concept ignores two realities:

[1. We do want to live longer.

2. At a population level, it’s impossible to live longer without living better. Conversely, living better means living longer.]

At one level, these realities are too obvious to require explanation. However, policy gods work at the level of abstract concepts, and strange...

[things can happen when abstractions are substituted for actual experience.

We do want to live longer. As any clinician knows, those with serious chronic illnesses not only cling to life but for the most part enjoy it and are grateful for the opportunity. Even in places with easy access to un-messy and legally sanctioned suicide, there are not that many takers.

And it is virtually impossible to separate quality from quantity in human life. Measures that reduce disease also increase longevity, and vice versa. There are rare examples where quality and quantity might diverge—perhaps chemotherapy and radiation for glioblastoma multiforme is one—but I challenge clinicians to come up with common examples. Aggressive end of life care does not increase quantity. Palliative care does not shorten life and in some trials even extends it (1–3).

Thirty years ago, there were serious articles by various experts about how the (then) continued increase in life expectancy would lead to an epidemic of Alzheimer’s and thence to a need for more nursing homes, more wheelchairs, more of everything unpleasant and costly. But that was silly. People live longer because they are healthier, not because some magic pill or machine keeps decrepit, barely functioning organisms alive.

The commandment outlawing enthusiasm for life extension requires groups like Espeland and colleagues (4) to start their articles with statements about wanting only to improve quality, not quantity of life.

Other than that minor quibble (stimulating my preceding and ongoing rant), Espeland and his colleagues have made a fine contribution to the literature on the feasibility of designing clinical trials that target the aging process per se, rather than a specific condition or complaint. They list several possible outcomes other than mortality that might be employed, such as active life expectancy and activities of daily living. They then rigorously explore the potential for using “incident multi morbidity” as an outcome.

What makes their work outstanding is their pragmatic approach. They test their constructs using data from three longitudinal studies, providing estimates of incident new chronic diseases, or new families of chronic diseases, that can be used in sample size calculations. Their preliminary analyses suggest that such trials are feasible, with good power to detect a 20% reduction in new chronic morbidity over 4–6 years with one to two thousand total participants. In other words, it should not take a huge bite out of the NIA budget to address this issue. This well-reasoned article should move such studies closer to reality.

There are potential limitations in moving from a hard outcome, mortality, to a somewhat fuzzier one, morbidity. Espeland and colleagues implicitly or explicitly recognize these limitations, which influenced their approach. First, mortality is dichotomous and objective. In contrast, multi morbidity is an abstract concept that must be operationalized to be used. Errors or variability can occur at each step in translating an abstract concept to a measurable entity. Multi morbidity is usually operationalized as having two or more conditions from a list of diseases. But some diseases are not really morbid, or even diseases. They are asymptomatic conditions, defined by a number produced by a machine. They are important risk factors for serious subsequent disease. Thus, a diagnosis of hypertension, osteoporosis or lipid disorders is important, but these conditions do not of themselves cause symptoms, or suffering, or increase “burden of disease.” Many studies investigating multi morbidity seem unaware of this distinction. Espeland and colleagues implicitly acknowledge this distinction by using hypertension and lipid disorders as selection criteria to identify appropriate participants in an intervention trial, rather than as outcomes of that trial.

Espeland and colleagues also wisely elected not to explore disability–free survival as an outcome. There is something distasteful about the quest for a world free of disability. All humans have disabilities: we cannot fly, nor breathe underwater, for example. Some of us also cannot walk well. Such individuals seem to do OK with the appropriate accommodations. However, if one uses the lens of “successful aging” and values only disability-free survival, those with disabilities can be viewed as failures.

It is reasonable to assume that some pill or treatment may indeed delay the onset of multi morbidity. It is certainly worth examining. Any successful treatment will also increase longevity, a prospect not to be feared.]


4. Mark A. Espeland; Eileen M. Crimmins; Brandon R. Grossardt; Jill P. Crandall; Jonathan A. L. Gelfond; Tamara B. Harris; Stephen B. Kritchevsky; JoAnn E. Manson; Jennifer G. Robinson; Walter A. Rocca; Marinella Temprosa; Fridtjof Thomas; Robert Wallace; Nir Barzilai; for the Multimorbidity Clinical Trials Consortium

Clinical trials targeting aging and age-related multimorbidity.

J Gerontol A Biol Sci Med Sci (2017) 72 (3): 355-361. doi:10.1093/gerona/glw220




There is growing interest in identifying interventions that may increase health span by targeting biological processes underlying aging. The design of efficient and rigorous clinical trials to assess these interventions requires careful consideration of eligibility criteria, outcomes, sample size, and monitoring plans.


Experienced geriatrics researchers and clinical trialists collaborated to provide advice on clinical trial design.


Outcomes based on the accumulation and incidence of age-related chronic diseases are attractive for clinical trials targeting aging. Accumulation and incidence rates of multimorbidity outcomes were developed by selecting at-risk subsets of individuals from three large cohort studies of older individuals. These provide representative benchmark data for decisions on eligibility, duration, and assessment protocols. Monitoring rules should be sensitive to targeting aging-related, rather than disease-specific, outcomes.


Clinical trials targeting aging are feasible, but require careful design consideration and monitoring rules.

Keywords: Clinical trial design, Geroscience, Chronic diseases

Edited by AlPater
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Effect of Alpha-Fetoprotein on Lifespan of Old Mice.

Krut'ko VN, Dontsov VI, Khalyavkin AV.

Biochemistry (Mosc). 2016 Dec;81(12):1477-1479. doi: 10.1134/S0006297916120087.

PMID: 28259124



Alpha-fetoprotein (AFP) is one of the best-known embryo-specific proteins. It is used to diagnose fetal abnormalities and tumors of the gastrointestinal tract and liver. AFP has pronounced immunotropic and detoxifying effect and a direct apoptotic effect on tumor cells. The treatment of mice at the oldest age in our experiments with AFP dramatically increased the survival and markedly increased the relative weight of immunotropic organs, apparently due to the general effect of AFP in improving functions of tissues and detoxifying actions. It also improved appearance and the relative weight of internal organs with a reduced age of autoaggression.


[The below paper is not pdf-availed.]

The cost and mortality of hip fractures in centenarians.

Moore J, Carmody O, Carey B, Harty JA, Reidy D.

Ir J Med Sci. 2017 Mar 4. doi: 10.1007/s11845-017-1589-9. [Epub ahead of print]

PMID: 28260154



Centenarians are the fastest rising age group in Ireland. Hip fractures most commonly affect older adults and are associated with significant morbidity and mortality, as well as the financial cost of healthcare resources. Despite this, very little is known regarding hip fractures in centenarians. The aim of this study was to investigate our experience with hip fractures in this group and to record the cost of treating these fractures to identify both the social and economic impact these injuries impose on the health system.


The study was a retrospective data review at a major trauma centre. Nine proximal femoral fractures from June 2010-2016 were identified through a stepwise analysis of theatre data and patient notes. Time of death was recorded directly from patient records or by contacting the patient's general practitioner. With the assistance of the hospital finance department, individual inpatient costs were calculated using length of stay, theatre time and implant costs.


Over the 7-year period we examined nine patients over 100 years of age were managed operatively for hip fractures with an average inpatient cost of €14,898. The mean age at the time of fracture was 101 years and 7 months. Eight of the patients were female and there was one male. Our inpatient, 30-day and 1-year mortality rate were 22, 22, and 71%.


The 1-year mortality rate of any person aged 100 years or older is thought to be 67% for men and 59% for women. This suggests that the 1-year mortality rate of 71% in this current study is only slightly worse than the usual life expectancy of a person older than 100 years of age. Our data suggest that the extreme elderly should be offered operative management.


100; Centenarian; Elderly; Health economics; Hip fracture; Savings


Is It Possible to Prove the Existence of an Aging Program by Quantitative Analysis of Mortality Dynamics?

Shilovsky GA, Putyatina TS, Lysenkov SN, Ashapkin VV, Luchkina OS, Markov AV, Skulachev VP.

Biochemistry (Mosc). 2016 Dec;81(12):1461-1476. doi: 10.1134/S0006297916120075. Review.

PMID: 28259123



Accumulation of various types of lesions in the course of aging increases an organism's vulnerability and results in a monotonous elevation of mortality rate, irrespective of the position of a species on the evolutionary tree. Stroustrup et al. (Nature, 530, 103-107) [1] showed in 2016 that in the nematode Caenorhabditis elegans, longevity-altering factors (e.g. oxidative stress, temperature, or diet) do not change the shape of the survival curve, but either stretch or shrink it along the time axis, which the authors attributed to the existence of an "aging program". Modification of the accelerated failure time model by Stroustrup et al. uses temporal scaling as a basic approach for distinguishing between quantitative and qualitative changes in aging dynamics. Thus we analyzed data on the effects of various longevity-increasing genetic manipulations in flies, worms, and mice and used several models to choose a theory that would best fit the experimental results. The possibility to identify the moment of switch from a mortality-governing pathway to some other pathways might be useful for testing geroprotective drugs. In this work, we discuss this and other aspects of temporal scaling.


Mediterranean diet adherence and risk of postmenopausal breast cancer: results of a cohort study and meta-analysis.

van den Brandt PA, Schulpen M.

Int J Cancer. 2017 Mar 5. doi: 10.1002/ijc.30654. [Epub ahead of print]

PMID: 28260236



The Mediterranean Diet (MD) has been associated with reduced mortality and risk of cardiovascular diseases, but there is only limited evidence on cancer. We investigated the relationship between adherence to MD and risk of postmenopausal breast cancer (and estrogen/progesterone receptor subtypes, ER/PR). In the Netherlands Cohort Study, 62,573 women aged 55-69 years provided information on dietary and lifestyle habits in 1986. Follow-up for cancer incidence until 2007 (20.3 years) consisted of record linkages with the Netherlands Cancer Registry and the Dutch Pathology Registry PALGA. Adherence to MD was estimated through the alternate Mediterranean Diet Score excluding alcohol. Multivariate case-cohort analyses were based on 2,321 incident breast cancer cases and 1,665 subcohort members with complete data on diet and potential confounders. We also conducted meta-analyses of our results with those of other published cohort studies. We found a statistically significant inverse association between MD adherence and risk of ER negative (ER-) breast cancer, with a hazard ratio of 0.60 (95% Confidence Interval, 0.39-0.93) for high versus low MD adherence (ptrend  = 0.032). MD adherence showed only nonsignificant weak inverse associations with ER positive (ER+) or total breast cancer risk. In meta-analyses, summary HRs for high versus low MD adherence were 0.94 for total postmenopausal breast cancer, 0.98 for ER+, 0.73 for ER- and 0.77 for ER - PR- breast cancer. Our findings support an inverse association between MD adherence and, particularly, receptor negative breast cancer. This may have important implications for prevention because of the poorer prognosis of these breast cancer subtypes.


Mediterranean diet; breast cancer; cohort study


Efficacy and Blood Plasmalogen Changes by Oral Administration of Plasmalogen in Patients with Mild Alzheimer's Disease and Mild Cognitive Impairment: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial.

Fujino T, Yamada T, Asada T, Tsuboi Y, Wakana C, Mawatari S, Kono S.

EBioMedicine. 2017 Feb 24. pii: S2352-3964(17)30071-3. doi: 10.1016/j.ebiom.2017.02.012. [Epub ahead of print]

PMID: 28259590





Plasmalogens (Pls) reportedly decreased in postmortem brain and in the blood of patients with Alzheimer's disease (AD). Recently we showed that intraperitoneal administration of Pls improved cognitive function in experimental animals. In the present trial, we tested the efficacy of oral administration of scallop-derived purified Pls with respect to cognitive function and blood Pls changes in patients with mild AD and mild cognitive impairment (MCI).


The study was a multicenter, randomized, double-blind, placebo-controlled trial of 24weeks. Participants were 328 patients aged 60 to 85years who had 20 to 27 points in Mini Mental State Examination-Japanese (MMSE-J) score and five or less points in Geriatric Depression Scale-Short Version-Japanese (GDS-S-J). They were randomized to receive either 1mg/day of Pls purified from scallop or placebo. The patients and study physicians were masked to the assignment. The primary outcome was MMSE-J. The secondary outcomes included Wechsler Memory Scale-Revised (WMS-R), GDS-S-J and concentration of phosphatidyl ethanolamine plasmalogens (PlsPE) in erythrocyte membrane and plasma. This trial is registered with the University Hospital Medical Information Network, number UMIN000014945.


Of 328 patients enrolled, 276 patients completed the trial (140 in the treatment group and 136 in the placebo group). In an intention-to-treat analysis including both mild AD (20≤MMSE-J≤23) and MCI (24≤MMSE-J≤27), no significant difference was shown between the treatment and placebo groups in the primary and secondary outcomes, with no severe adverse events in either group. In mild AD patients, WMS-R improved significantly in the treatment group, and the between group difference was nearly significant (P=0.067). In a subgroup analysis of mild AD patients, WMS-R significantly improved among females and those aged below 77years in the treatment group, and the between-group differences were statistically significant in females (P=0.017) and in those aged below 77years (P=0.029). Patients with mild AD showed a significantly greater decrease in plasma PlsPE in the placebo group than in the treatment group.


Oral administration of scallop-derived purified Pls may improve cognitive functions of mild AD.


Alzheimer's disease; Cognitive function; Mild cognitive impairment; Plasmalogen; Scallop


Physical Activity on the Weekend: Can It Wait Until Then?

Arem H, DiPietro L.

JAMA Intern Med. 2017 Jan 9. doi: 10.1001/jamainternmed.2016.8050. [Epub ahead of print] No abstract available.

PMID: 28097293



Exercising as "weekend warrior" still yields mortality benefit, study finds.

Wise J.

BMJ. 2017 Jan 9;356:j126. doi: 10.1136/bmj.j126. No abstract available.

PMID: 28073747



Association of "Weekend Warrior" and Other Leisure Time Physical Activity Patterns With Risks for All-Cause, Cardiovascular Disease, and Cancer Mortality.

O'Donovan G, Lee IM, Hamer M, Stamatakis E.

JAMA Intern Med. 2017 Jan 9. doi: 10.1001/jamainternmed.2016.8014. [Epub ahead of print]

PMID: 28097313




More research is required to clarify the association between physical activity and health in "weekend warriors" who perform all their exercise in 1 or 2 sessions per week.


To investigate associations between the weekend warrior and other physical activity patterns and the risks for all-cause, cardiovascular disease (CVD), and cancer mortality.


This pooled analysis of household-based surveillance studies included 11 cohorts of respondents to the Health Survey for England and Scottish Health Survey with prospective linkage to mortality records. Respondents 40 years or older were included in the analysis. Data were collected from 1994 to 2012 and analyzed in 2016.


Self-reported leisure time physical activity, with activity patterns defined as inactive (reporting no moderate- or vigorous-intensity activities), insufficiently active (reporting <150 min/wk in moderate-intensity and <75 min/wk in vigorous-intensity activities), weekend warrior (reporting ≥150 min/wk in moderate-intensity or ≥75 min/wk in vigorous-intensity activities from 1 or 2 sessions), and regularly active (reporting ≥150 min/wk in moderate-intensity or ≥75 min/wk in vigorous-intensity activities from ≥3 sessions). The insufficiently active participants were also characterized by physical activity frequency.


All-cause, CVD, and cancer mortality ascertained from death certificates.


Among the 63 591 adult respondents (45.9% male; 44.1% female; mean [sD] age, 58.6 [11.9] years), 8802 deaths from all causes, 2780 deaths from CVD, and 2526 from cancer occurred during 561 159 person-years of follow-up. Compared with the inactive participants, the hazard ratio (HR) for all-cause mortality was 0.66 (95% CI, 0.62-0.72) in insufficiently active participants who reported 1 to 2 sessions per week, 0.70 (95% CI, 0.60-0.82) in weekend warrior participants, and 0.65 (95% CI, 0.58-0.73) in regularly active participants. Compared with the inactive participants, the HR for CVD mortality was 0.60 (95% CI, 0.52-0.69) in insufficiently active participants who reported 1 or 2 sessions per week, 0.60 (95% CI, 0.45-0.82) in weekend warrior participants, and 0.59 (95% CI, 0.48-0.73) in regularly active participants. Compared with the inactive participants, the HR for cancer mortality was 0.83 (95% CI, 0.73-0.94) in insufficiently active participants who reported 1 or 2 sessions per week, 0.82 (95% CI, 0.63-1.06) in weekend warrior participants, and 0.79 (95% CI, 0.66-0.94) in regularly active participants.


Weekend warrior and other leisure time physical activity patterns characterized by 1 or 2 sessions per week may be sufficient to reduce all-cause, CVD, and cancer mortality risks regardless of adherence to prevailing physical activity guidelines.


[The first below paper is pdf-aviled.]

Toward a Healthier Patient Voice: More Independence, Less Industry Funding.

Moynihan R, Bero L.

JAMA Intern Med. 2017 Jan 17. doi: 10.1001/jamainternmed.2016.9179. [Epub ahead of print] No abstract available.

PMID: 28114596

Industry funding strengthens and extends the much-needed patient voice in health care, but at what cost? During the recent EpiPen scandal, the manufacturer-sponsored advocacy groups were largely silent about price gouging.1 Last year a drug company–funded “patient advocacy” campaign called “Even the Score” helped win regulatory approval for the thrice-rejected controversial female sex drug flibanserin.2 And not only does the National Osteoporosis Foundation accept funds from industry, mandatory transparency rules reveal that a majority of the medical leadership received a total of over $450 000 in payments in 2015, including for research projects.3,4 Patient advocacy groups play an increasingly powerful role in health care, sponsoring research, producing or promoting guidelines, driving media coverage, influencing regulatory decisions, promoting certain interventions, and shaping the way we think about disease. Just as the industry funding of clinical trials has been associated with more favorable findings,5 patient groups also face risks of bias when accepting money from companies seeking to expand markets for their new tests and treatments.

A survey by Rose and colleagues6 in this issue of JAMA Internal Medicine offers valuable and timely data on entanglement between patient advocacy organizations and for-profit companies. Two-thirds of groups reported receiving some industry funding, 1 in 10 reporting half their funding was from industry—defined in this study as any for-profit companies. Among groups accepting industry funding, the median amount was $50 000, with approximately 10% taking over $1 million annually—almost half of that from pharmaceutical and device companies. With rare candor, a small proportion of groups perceived “pressure to conform its positions to the interests of corporate donors or partners.” A minor limitation is the lack of disaggregation in the analysis of smaller organizations and the much larger influential groups—like the American Diabetes Association mentioned by Rose and colleagues6—that simultaneously accept corporate support and fund much medical research.

The study by Rose et al6 could not address the question of whether industry funding was associated with any bias, though the authors do raise concerns about the independence of groups receiving large amounts of money. While there is ample evidence across medicine more generally showing that funding has the potential to bias research, education, and practice,5,7 there are limited data on the possibility of similar associations between industry funding and advocacy group positions or activities. However, a small new study investigating this association by Lin and colleagues,8 also published in this issue of JAMA Internal Medicine, offers worrying findings. The team analyzed submissions from 158 organizations that commented on a draft guideline to address concerns about sharp increases in the use of opioids for chronic, noncancer pain, examining both their comments and funding sources. While most of the professional and patient groups supported the new Centers for Disease Control and Prevention (CDC) draft guidelines, including groups funded by opioid manufacturers, opposition was much more common among groups with funding from the manufacturers when compared with those with no industry funding: 38% vs 6%. In addition, the study found that of the 45 groups receiving funding from manufacturers, none disclosed this funding in comments to the CDC.

In light of the building evidence about funding source association with bias in medicine generally, it is easy to argue that advocacy groups should be totally free of such conflicts of interest. With the EpiPen saga, reports suggest it was the genuinely grass roots advocacy—not funded by industry—that helped bring the world’s attention to the excessive price hike.1 With flibanserin, groups without industry links, like the National Women’s Health Network, refused to support the company-sponsored “Even the Score” campaign to get the drug approved, due to concerns about its lack of meaningful benefits and serious, potentially fatal, harms.2 And while the National Osteoporosis Foundation continues to promote the idea of a widespread “disease,” others point to concern about the condition’s overdiagnosis and overtreatment, and call to reframe low bone mineral density as a risk factor rather than a disease.9

It is indisputable that industry and its tests and treatments are vital components of the health care system, bringing the benefits of extending human life and ameliorating suffering, and that many advocacy groups are motivated by good intentions. On the flip side, there is no doubt that industry funding can distort the patient voice. For the individual groups, the influence of a company sponsor is often invisible. Rarely does it lead to a clumsy intervention to change a group’s public position, but rather creates a routine awareness among sponsored groups that one doesn’t bite the hand that feeds it. Sometimes though the strings attached to funding are clear, with groups such as the Arthritis Foundation explicitly offering its sponsors “direct marketing” to over half a million constituents and “promotional tie-ins” with “educational initiatives” like National Arthritis Month and World Arthritis Day.10

At the system level, the aggregation of this influence raises substantial concerns. The results of the study by Rose and colleagues6 reveal that thousands of patient advocacy groups in the United States, including many that are wealthy and powerful, are reliant on support from the pharmaceutical and/or device industries. And these long shadows of corporate influence extend well beyond the nation’s borders, with impacts felt within health care systems globally. So much industry support for patient groups means certain perspectives and strategies are disproportionately supported. The very way we all think about disease—and the best ways to research, define, prevent, and treat it—is being subtly distorted because so many of the ostensibly independent players, including patient advocacy groups, are largely singing tunes acceptable to companies seeking to maximize markets for drugs and devices.

In our view this new work6,8 demonstrates an urgent need for patient advocacy organizations to explicitly focus much more on representing the interests of patients and citizens, rather than serving—inadvertently or otherwise—the interests of their industry sponsors. It also has key implications for broader reform. To ensure a healthier patient voice in medical research, education, policy, and practice, sponsored groups that want to be seen as independent and credible need to decrease their industry sponsorship and ultimately disentangle, gaining in authority what they lose in resources. In the meantime we need much greater transparency about industry funding, including prominently displayed disclosures of dollar amounts and proportions of total funding on group websites, as well as addition of patient advocacy groups to the Open Payments program established by the Sunshine Act (https://www.ama-assn.org/practice-management/physician-financial-transparency-reports-sunshine-act), which would mean mandatory disclosure of funding by sponsors. Finally, and perhaps most important, decisionmakers everywhere, including government agencies and others responsible for forging research agendas, setting health care standards, and regulating and paying for new technologies, should seek out and engage with genuinely independent patient and citizen voices, entirely free of the distorting impacts of industry funding, to help shape the future of health care.


Patient Advocacy Organizations, Industry Funding, and Conflicts of Interest.

Rose SL, Highland J, Karafa MT, Joffe S.

JAMA Intern Med. 2017 Jan 17. doi: 10.1001/jamainternmed.2016.8443. [Epub ahead of print]

PMID: 28114624




Patient advocacy organizations (PAOs) are influential health care stakeholders that provide direct counseling and education for patients, engage in policy advocacy, and shape research agendas. Many PAOs report having financial relationships with for-profit industry, yet little is known about the nature of these relationships.


To describe the nature of industry funding and partnerships between PAOs and for-profit companies in the United States.


A survey was conducted from September 1, 2013, to June 30, 2014, of a nationally representative random sample of 439 PAO leaders, representing 5.6% of 7865 PAOs identified in the United States. Survey questions addressed the nature of their activities, their financial relationships with industry, and the perceived effectiveness of their conflict of interest policies.


Amount and sources of revenue as well as organizational experiences with and policies regarding financial conflict of interest.


Of the 439 surveys mailed to PAO leaders, 289 (65.8%) were returned with at least 80% of the questions answered. The PAOs varied widely in terms of size, funding, activities, and disease focus. The median total revenue among responding organizations was $299 140 (interquartile range, $70 000-$1 200 000). A total of 165 of 245 PAOs (67.3%) reported receiving industry funding, with 19 of 160 PAOs (11.9%) receiving more than half of their funding from industry. Among the subset of PAOs that received industry funding, the median amount was $50 000 (interquartile range, $15 000-$200 000); the median proportion of industry support derived from the pharmaceutical, device, and/or biotechnology sectors was 45% (interquartile range, 0%-100%). A total of 220 of 269 respondents (81.8%) indicated that conflicts of interest are very or moderately relevant to PAOs, and 94 of 171 (55.0%) believed that their organizations' conflict of interest policies were very good. A total of 22 of 285 PAO leaders (7.7%) perceived pressure to conform their positions to the interests of corporate donors.


Patient advocacy organizations engage in wide-ranging health activities. Although most PAOs receive modest funding from industry, a minority receive substantial industry support, raising added concerns about independence. Many respondents report a need to improve their conflict of interest policies to help maintain public trust.


Conflict of Interest in Seminal Hepatitis C Virus and Cholesterol Management Guidelines.

Jefferson AA, Pearson SD.

JAMA Intern Med. 2017 Jan 17. doi: 10.1001/jamainternmed.2016.8439. [Epub ahead of print]

PMID: 28114439




Little is known regarding whether Institute of Medicine (IOM) standards for managing conflicts of interest (COI) have been met in the development of recent important clinical guidelines.


To evaluate adherence to the IOM standards for limits on commercial COI, guideline development, and evaluation of evidence by the 2013 American College of Cardiology and American Heart Association cholesterol management guideline and the 2014 American Association for the Study of Liver Diseases and Infectious Diseases Society of America hepatitis C virus management guideline.


This study was a retrospective document review of the June 2014 print version of the cholesterol guideline and the final September 2015 print version of the hepatitis C virus guideline. Each guideline was assessed for adherence to the IOM standards for commercial COI published in the 2011 special report Clinical Practice Guidelines We Can Trust.


The IOM standards call for no commercial COI among guideline committee chairs and cochairs and for less than 50% of committee members to have commercial COI. Guideline and contemporaneous article disclosure statements were used to evaluate adherence to these standards. Each guideline was also reviewed for adherence to other IOM standards for guideline development and evidence review.


Among the 16 cholesterol guideline committee members, 7 (44%) disclosed commercial COI, all 7 reported industry-sponsored research, and 6 (38%) also reported consultancy. Of 3 guideline chairs and cochairs, 1 (33%) disclosed commercial COI. Review of contemporaneous articles identified additional commercial COI. Among the 29 hepatitis C virus guideline committee members, 21 (72%) reported commercial COI. Eighteen (62%) disclosed industry-sponsored research, 10 (34%) served on advisory boards, 5 (17%) served on data safety monitoring boards, 3 (10%) were consultants, and 3 (10%) reported other honoraria. Of 6 guideline cochairs, 4 (67%) disclosed commercial COI. All 4 disclosed additional COI in other publications that were not listed in their guideline disclosures. Contemporaneous literature review revealed an additional cochair with commercial COI. Of the 9 IOM guideline development and evidence standards, the cholesterol guideline met 5 (56%), and the hepatitis C virus guideline met them all.


Neither the cholesterol guideline nor the hepatitis C virus guideline fully met the IOM standards for commercial COI management, and discordance between committee leader guideline disclosures and those in contemporaneous articles was common. Adherence to additional IOM standards for guideline development and evidence review was mixed. Adoption of consistent COI frameworks across specialty societies may help ensure that clinical guidelines are developed in a transparent and trustworthy manner.

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Induction of lipogenesis in white fat during cold exposure in mice: link to lean phenotype.

Flachs P, Adamcova K, Zouhar P, Marques C, Janovska P, Viegas I, Jones JG, Bardova K, Svobodova M, Hansikova J, Kuda O, Rossmeisl M, Liisberg U, Borkowska AG, Kristiansen K, Madsen L, Kopecky J.

Int J Obes (Lond). 2017 Jan 17. doi: 10.1038/ijo.2016.228. [Epub ahead of print]

PMID: 28008171



Futile substrate cycling based on lipolytic release of fatty acids (FA) from intracellular triacylglycerols (TAG) and their re-esterification (TAG/FA cycling), as well as de novo FA synthesis (de novo lipogenesis (DNL)), represent the core energy-consuming biochemical activities of white adipose tissue (WAT). We aimed to characterize their roles in cold-induced thermogenesis and energy homeostasis.


Male obesity-resistant A/J and obesity-prone C57BL/6J mice maintained at 30 °C were exposed to 6 °C for 2 or 7 days. In epididymal WAT (eWAT), TAG synthesis and DNL were determined using in vivo 2H incorporation from 2H2O into tissue TAG and nuclear magnetic resonance spectroscopy. Quantitative real-time-PCR and/or immunohistochemistry and western blotting were used to determine the expression of selected genes and proteins in WAT and liver.


The mass of WAT depots declined during cold exposure (CE). Plasma levels of TAG and non-esterified FA were decreased by day 2 but tended to normalize by day 7 of CE. TAG synthesis (reflecting TAG/FA cycle activity) gradually increased during CE. DNL decreased by day 2 of CE but increased several fold over the control values by day 7. Expression of genes involved in lipolysis, glyceroneogenesis, FA re-esterification, FA oxidation and mitochondrial biogenesis in eWAT was induced during CE. All these changes were more pronounced in obesity-resistant A/J than in B6 mice and occurred in the absence of uncoupling protein 1 in eWAT. Expression of markers of glyceroneogenesis in eWAT correlated negatively with hepatic FA synthesis by day 7 in both strains. Leptin and fibroblast growth factor 21 plasma levels were differentially affected by CE in the two mouse strains.


Our results indicate integrated involvement of (i) TAG/FA cycling and DNL in WAT, and (ii) hepatic very-low-density lipoprotein-TAG synthesis in the control of blood lipid levels and provision of FA fuels for thermogenesis in cold. They suggest that lipogenesis in WAT contributes to a lean phenotype.


Metabolic dysfunction following weight cycling in male mice.

Schofield SE, Parkinson JR, Henley AB, Sahuri-Arisoylu M, Sanchez-Canon GJ, Bell JD.

Int J Obes (Lond). 2017 Jan 17. doi: 10.1038/ijo.2016.193. [Epub ahead of print]

PMID: 27840414



Combatting overweight or obesity can lead to large fluctuations in an individual's body weight, often referred to as weight cycling or 'yo-yo' dieting. Current evidence regarding the potentially damaging effects of these changes is conflicting.


Here, we assess the metabolic effects of weight cycling in a murine model, comprising three dietary switches to normal or high-fat diets at 6 week intervals; male C57BL/6 mice were fed either a control © or high-fat (F) diet for 6 weeks (n=140/group). C and F groups were then either maintained on their initial diet (CC and FF, respectively) or switched to a high-fat (CF) or control (FC) diet (n=35/group). For the final 6 week interval, CC and CF groups were returned to the control diet (CCC and CFC groups), while FC and FF groups were placed on a high-fat diet (FCF and FFF) (n=28/group).


For the majority of metabolic outcomes changes aligned with dietary switches; however, assessment of neuropeptides and receptors involved in appetite regulation and reward signalling pathways reveal variable patterns of expression. Furthermore, we demonstrate that multiple cycling events leads to a significant increase in internal fat deposition, even when compared with animals maintained on a high-fat diet (internal fat: FCF: 7.4±0.2 g vs FFF: 5.6±0.2 g; P<0.01).


Increased internal adipose tissue is strongly linked to the development of metabolic syndrome associated conditions such as type 2 diabetes, cardiovascular disease and hypertension. Although further work will be required to elucidate the mechanisms underlying the neuronal control of energy homoeostasis, these studies provide a causative link between weight cycling and adverse health.


Patterned feeding induces neuroendocrine, behavioral and genetic changes that promote palatable food intake.

Sirohi S, Van Cleef A, Davis JF.

Int J Obes (Lond). 2017 Jan 31. doi: 10.1038/ijo.2016.235. [Epub ahead of print]

PMID: 28025575



Selection of a healthy diet is the cornerstone for treating obesity and metabolic disease. Unfortunately, the majority of diets fail leading to weight regain and in some cases, pathological feeding behavior. We hypothesize that alternating bouts of caloric overconsumption and caloric restriction, behavioral manifestations of dieting induce neuroendocrine, behavioral and genetic changes that promote future bouts of palatable food intake.


To test this hypothesis, we subjected male Long-Evans rats to a high-fat diet (HFD) feeding paradigm that induced a pattern of caloric overconsumption and caloric restriction. Under these conditions we measured operant responding for sucrose, pre-meal ghrelin secretion, the effects of peripheral ghrelin blockade on patterned feeding, HFD intake in an aversive environment and mRNA expression of the ghrelin receptor, orexin, orexin-1 and 2 receptors, and FTO in the medial prefrontal cortex, lateral hypothalamus and ventral tegmental area.


Rats subjected to this feeding regimen displayed increased ghrelin levels prior to HFD exposure and blockade of this response attenuated patterned feeding behavior. In addition, patterned feeding promoted enhanced motivation for sucrose, diminished extinction of this response and increased HFD intake in an aversive environment. The neuroendocrine and behavioral changes correlated with increased hypothalamic expression of the ghrelin receptor and FTO.


Collectively, these data indicate that patterns of feeding that include caloric overconsumption and caloric restriction induce neuroendocrine and neurobiological changes that signify an enhanced drive for palatable food.


Effects of aspartame-, monk fruit-, stevia- and sucrose-sweetened beverages on postprandial glucose, insulin and energy intake.

Tey SL, Salleh NB, Henry J, Forde CG.

Int J Obes (Lond). 2017 Jan 10. doi: 10.1038/ijo.2016.225. [Epub ahead of print]

PMID: 27956737



Substituting sweeteners with non-nutritive sweeteners (NNS) may aid in glycaemic control and body weight management. Limited studies have investigated energy compensation, glycaemic and insulinaemic responses to artificial and natural NNS.


This study compared the effects of consuming NNS (artificial versus natural) and sucrose (65 g) on energy intake, blood glucose and insulin responses.


Thirty healthy male subjects took part in this randomised, crossover study with four treatments: aspartame-, monk fruit-, stevia- and sucrose-sweetened beverages. On each test day, participants were asked to consume a standardised breakfast in the morning, and they were provided with test beverage as a preload in mid-morning and ad libitum lunch was provided an hour after test beverage consumption. Blood glucose and insulin concentrations were measured every 15 min within the first hour of preload consumption and every 30 min for the subsequent 2 h. Participants left the study site 3 h after preload consumption and completed a food diary for the rest of the day.


Ad libitum lunch intake was significantly higher for the NNS treatments compared with sucrose (P=0.010). The energy 'saved' from replacing sucrose with NNS was fully compensated for at subsequent meals; hence, no difference in total daily energy intake was found between the treatments (P=0.831). The sucrose-sweetened beverage led to large spikes in blood glucose and insulin responses within the first hour, whereas these responses were higher for all three NNS beverages following the test lunch. Thus, there were no differences in total area under the curve (AUC) for glucose (P=0.960) and insulin (P=0.216) over 3 h between the four test beverages.


The consumption of calorie-free beverages sweetened with artificial and natural NNS have minimal influences on total daily energy intake, postprandial glucose and insulin compared with a sucrose-sweetened beverage.


Sirtuin 1 regulates cardiac electrical activity by deacetylating the cardiac sodium channel.

Vikram A, Lewarchik CM, Yoon JY, Naqvi A, Kumar S, Morgan GM, Jacobs JS, Li Q, Kim YR, Kassan M, Liu J, Gabani M, Kumar A, Mehdi H, Zhu X, Guan X, Kutschke W, Zhang X, Boudreau RL, Dai S, Matasic DS, Jung SB, Margulies KB, Kumar V, Bachschmid MM, London B, Irani K.

Nat Med. 2017 Feb 13. doi: 10.1038/nm.4284. [Epub ahead of print]

PMID: 28191886


The voltage-gated cardiac Na+ channel (Nav1.5), encoded by the SCN5A gene, conducts the inward depolarizing cardiac Na+ current (INa) and is vital for normal cardiac electrical activity. Inherited loss-of-function mutations in SCN5A lead to defects in the generation and conduction of the cardiac electrical impulse and are associated with various arrhythmia phenotypes. Here we show that sirtuin 1 deacetylase (Sirt1) deacetylates Nav1.5 at lysine 1479 (K1479) and stimulates INa via lysine-deacetylation-mediated trafficking of Nav1.5 to the plasma membrane. Cardiac Sirt1 deficiency in mice induces hyperacetylation of K1479 in Nav1.5, decreases expression of Nav1.5 on the cardiomyocyte membrane, reduces INa and leads to cardiac conduction abnormalities and premature death owing to arrhythmia. The arrhythmic phenotype of cardiac-Sirt1-deficient mice recapitulated human cardiac arrhythmias resulting from loss of function of Nav1.5. Increased Sirt1 activity or expression results in decreased lysine acetylation of Nav1.5, which promotes the trafficking of Nav1.5 to the plasma membrane and stimulation of INa. As compared to wild-type Nav1.5, Nav1.5 with K1479 mutated to a nonacetylatable residue increases peak INa and is not regulated by Sirt1, whereas Nav1.5 with K1479 mutated to mimic acetylation decreases INa. Nav1.5 is hyperacetylated on K1479 in the hearts of patients with cardiomyopathy and clinical conduction disease. Thus, Sirt1, by deacetylating Nav1.5, plays an essential part in the regulation of INa and cardiac electrical activity.


α5 nicotinic receptors link smoking to schizophrenia

Nat Med. 2017 Jan 23. pp277 - 278

Xin-an Liu and Paul J Kenny



A new study shows that nicotinic receptors activate a particular type of interneuron in the prefrontal cortex. Deficits in this relationship give rise to behavioral abnormalities similar to those associated with schizophrenia, which can be ameliorated by nicotine.


Nicotine reverses hypofrontality in animal models of addiction and schizophrenia.

Koukouli F, Rooy M, Tziotis D, Sailor KA, O'Neill HC, Levenga J, Witte M, Nilges M, Changeux JP, Hoeffer CA, Stitzel JA, Gutkin BS, DiGregorio DA, Maskos U.

Nat Med. 2017 Jan 23. doi: 10.1038/nm.4274. [Epub ahead of print]

PMID: 28112735


The prefrontal cortex (PFC) underlies higher cognitive processes that are modulated by nicotinic acetylcholine receptor (nAChR) activation by cholinergic inputs. PFC spontaneous default activity is altered in neuropsychiatric disorders, including schizophrenia-a disorder that can be accompanied by heavy smoking. Recently, genome-wide association studies (GWAS) identified single-nucleotide polymorphisms (SNPs) in the human CHRNA5 gene, encoding the α5 nAChR subunit, that increase the risks for both smoking and schizophrenia. Mice with altered nAChR gene function exhibit PFC-dependent behavioral deficits, but it is unknown how the corresponding human polymorphisms alter the cellular and circuit mechanisms underlying behavior. Here we show that mice expressing a human α5 SNP exhibit neurocognitive behavioral deficits in social interaction and sensorimotor gating tasks. Two-photon calcium imaging in awake mouse models showed that nicotine can differentially influence PFC pyramidal cell activity by nAChR modulation of layer II/III hierarchical inhibitory circuits. In α5-SNP-expressing and α5-knockout mice, lower activity of vasoactive intestinal polypeptide (VIP) interneurons resulted in an increased somatostatin (SOM) interneuron inhibitory drive over layer II/III pyramidal neurons. The decreased activity observed in α5-SNP-expressing mice resembles the hypofrontality observed in patients with psychiatric disorders, including schizophrenia and addiction. Chronic nicotine administration reversed this hypofrontality, suggesting that administration of nicotine may represent a therapeutic strategy for the treatment of schizophrenia, and a physiological basis for the tendency of patients with schizophrenia to self-medicate by smoking.


Aging and Veterinary Care of Cats, Dogs, and Horses through the Records of Three University Veterinary Hospitals.

Cozzi B, Ballarin C, Mantovani R, Rota A.

Front Vet Sci. 2017 Feb 14;4:14. doi: 10.3389/fvets.2017.00014.

PMID: 28261586



The present article examines over 63,000 medical records belonging to the Veterinary Hospitals of the Universities of Bologna, Torino, and Padova, all in Northern Italy, and relative to dogs (approximately 50,000), cats (approximately 12,000), and companion horses (slightly less than 1,000). The animals of the three species were divided into age classes and categorized per sex into males, females, and neutered individuals. The mean age at visit and the effects of age classes and category (analyzed via ANOVA) are presented and discussed. The data indicate that many animals are presented to the hospitals either in the early phases of their life (presumably for vaccination and, in cats and dogs, gonadectomy) or in the advanced age (over 10 years in dogs, over 15 years in cats, and over 17 years in horses). The records of very old individuals of the three species are also reported. On the whole, the results suggest that a growing population of mature to old domestic carnivores or companion horses reaches ages that were considered exceptional only a few years ago. The data also testify an evolution in the animal-owner relationship and a renewed respect for the value of life in companion domestic mammals.


aging; animal gerontology; animal hospital; animal life span; cat; dog; horse


Coronary Artery Bypass Graft Surgery and Dementia Risk in the Cardiovascular Health Study.

Kuźma E, Airdrie J, Littlejohns TJ, Lourida I, Thompson-Coon J, Lang IA, Scrobotovici M, Thacker EL, Fitzpatrick A, Kuller LH, Lopez OL, Longstreth WT Jr, Ukoumunne OC, Llewellyn DJ.

Alzheimer Dis Assoc Disord. 2017 Mar 3. doi: 10.1097/WAD.0000000000000191. [Epub ahead of print]

PMID: 28263191




The association between history of coronary artery bypass graft surgery (CABG) and dementia risk remains unclear.


We conducted a prospective cohort analysis using data on 3155 elderly adults free from prevalent dementia from the US population-based Cardiovascular Health Study (CHS) with adjudicated incident all-cause dementia, Alzheimer disease (AD), vascular dementia (VaD), and mixed dementia.


In the CHS, the hazard ratio (HR) for all-cause dementia was 1.93 [95% confidence interval (CI), 1.36-2.74] for those with CABG history compared with those with no CABG history after adjustment for potential confounders. Similar HRs were observed for AD (HR=1.71; 95% CI, 0.98-2.98), VaD (HR=1.42; 95% CI, 0.56-3.65), and mixed dementia (HR=2.73; 95% CI, 1.55-4.80). The same pattern of results was observed when these CHS findings were pooled with a prior prospective study, the pooled HRs were 1.96 (95% CI, 1.42-2.69) for all-cause dementia, 1.71 (95% CI, 1.04-2.79) for AD and 2.20 (95% CI, 0.78-6.19) for VaD.


Our results suggest CABG history is associated with long-term dementia risk. Further investigation is warranted to examine the causal mechanisms which may explain this relationship or whether the association reflects differences in coronary artery disease severity.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.



Maria M. CorradaEmail the author Maria M. Corrada, Farah Mozaffar, Marcella A. Evans, Szofia S. Bullain, Ron Brookmeyer, Claudia H. Kawas


DOI: http://dx.doi.org/10.1016/j.jalz.2016.06.447



Hazard Ratios of Developing All-Cause Dementia in Relation to Vascular Diseases in the Oldest-Old: The 90+ Study


Vascular Disease===Prevalence N (%)===Univariable Analyses===Multivariable Analysis

- - ===Hazard Ratio (95% CI) p-value===Hazard Ratio (95% CI) p-value


Congestive heart failure 55 (10) 2.15 (1.43-3.25) <0.001 2.23 (1.47-3.39) <0.001

Heart valve disease 38 (7) 1.72 (1.08-2.73) 0.02 1.60 (0.96-2.67) 0.07

Stroke 53 (10) 1.72 (1.14-2.59) 0.01 1.68 (1.10-2.57) 0.02

Diabetes 33 (6) 1.53 (0.85-2.75) 0.16 - -

Myocardial infarction 65 (12) 1.32 (0.88-2.00) 0.18 -

Transient ischemic attack 83 (15) 1.29 (0.89 -1.87) 0.17 - -

Arrhythmia 150 (27) 1.20 (0.89 -1.63) 0.22 - -

Coronary artery disease 80 (15) 0.90 (0.59 -1.39) 0.64 - -

High cholesterol 190 (36) 0.78 (0.58-1.05) 0.10 - -

Hypertension 321 (58) 0.73 (0.56 -0.95) 0.02 0.74 (0.57-0.98) 0.04


Soft drink consumption and gestational diabetes risk in the SUN project.

Donazar-Ezcurra M, Lopez-Del Burgo C, Martinez-Gonzalez MA, Basterra-Gortari FJ, de Irala J, Bes-Rastrollo M.

Clin Nutr. 2017 Feb 20. pii: S0261-5614(17)30055-9. doi: 10.1016/j.clnu.2017.02.005. [Epub ahead of print]

PMID: 28262323




Gestational diabetes mellitus (GDM) prevalence is increasing worldwide. To the best of our knowledge the specific evaluation of soft drink consumption as a risk factor for developing GDM has only been conducted in the Nurses' Health Study II.


To investigate the incidence of GDM according to soft drink consumption in the SUN project.


The "Seguimiento Universidad de Navarra" (SUN) project is a prospective and dynamic cohort which included data of 3396 women who notified at least one pregnancy between December 1999 and March 2012. A validated 136-item semi-quantitative food frequency questionnaire was used to assess soft drink consumption. Four categories of sugar-sweetened soft drink (SSSD) and diet soft drink (DSD) consumption (servings) were established: rarely or never (<1/month), low (1-3/month), intermediate (>3/month and ≤1/week) and high (≥2/week). Potential confounders were adjusted through non-conditional logistic regression models.


During the follow-up, we identified 172 incident cases of GDM. After adjusting for age, baseline body mass index, family history of diabetes, smoking, total energy intake, physical activity, parity, fast-food consumption, adherence to Mediterranean dietary pattern, alcohol intake, multiple pregnancy, cardiovascular disease/hypertension at baseline, fiber intake, following special diet and snacking, SSSD consumption was significantly associated with an increased risk of incident GDM, with multivariable adjusted odds ratios (OR) of 2.03 (95% confidence interval [CI]: 1.25-3.31) and 1.67 (95% CI: 1.01-2.77) for the highest and intermediate categories, respectively, versus the lowest category (p for linear trend: 0.006). Conversely, DSD consumption was not associated with GDM incidence (adjusted OR: 0.82; 95% CI: 0.52-1.31) for the highest versus the lowest category (p for linear trend: 0.258). Additional sensitivity analyses did not change the results.


Higher consumption of SSSDs before pregnancy was an independent risk factor for GDM, however, no association was observed between DSD consumption and GDM risk.

Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.


Cohort; Diet soft drinks; Gestational diabetes mellitus risk; Pre-pregnancy dietary pattern; Sugar-sweetened soft drinks; Western-style dietary pattern


Chronic alcohol consumption decreases brown adipose tissue mass and disrupts thermoregulation: a possible role for altered retinoid signaling.

Blaner WS, Gao MA, Jiang H, Dalmer TR, Hu XJ, Ginsberg HN, Clugston RD.

Sci Rep. 2017 Mar 6;7:43474. doi: 10.1038/srep43474.

PMID: 28262768



Retinoic acid, an active metabolite of dietary vitamin A, acts as a ligand for nuclear receptor transcription factors with more than 500 known target genes. It is becoming increasingly clear that alcohol has a significant impact on cellular retinoic acid metabolism, with resultant effects on its function. Here, we test the hypothesis that chronic alcohol consumption impairs retinoic acid signaling in brown adipose tissue (BAT), leading to impaired BAT function and thermoregulation. All studies were conducted in age-matched, male mice consuming alcohol-containing liquid diets. Alcohol's effect on BAT was assessed by histology, qPCR, HPLC, LC/MS and measures of core body temperature. Our data show that chronic alcohol consumption decreases BAT mass, with a resultant effect on thermoregulation. Follow-up mechanistic studies reveal a decreased triglyceride content in BAT, as well as impaired retinoic acid homeostasis, associated with decreased BAT levels of retinoic acid in alcohol-consuming mice. Our work highlights a hitherto uncharacterized effect of alcohol on BAT function, with possible implications for thermoregulation and energy metabolism in drinkers. Our data indicate that alcohol's effects on brown adipose tissue may be mediated through altered retinoic acid signaling.


Dietary isoflavone intake and all-cause mortality in breast cancer survivors: The Breast Cancer Family Registry.

Zhang FF, Haslam DE, Terry MB, Knight JA, Andrulis IL, Daly MB, Buys SS, John EM.

Cancer. 2017 Mar 6. doi: 10.1002/cncr.30615. [Epub ahead of print]

PMID: 28263368




Soy foods possess both antiestrogenic and estrogen-like properties. It remains controversial whether women diagnosed with breast cancer should be advised to eat more or less soy foods, especially for those who receive hormone therapies as part of cancer treatment.


The association of dietary intake of isoflavone, the major phytoestrogen in soy, with all-cause mortality was examined in 6235 women with breast cancer enrolled in the Breast Cancer Family Registry. Dietary intake was assessed using a Food Frequency Questionnaire developed for the Hawaii-Los Angeles Multiethnic Cohort among 5178 women who reported prediagnosis diet and 1664 women who reported postdiagnosis diet. Cox proportional-hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).


During a median follow-up of 113 months (approximately 9.4 years), 1224 deaths were documented. A 21% decrease was observed in all-cause mortality for women who had the highest versus lowest quartile of dietary isoflavone intake (≥1.5 vs < 0.3 mg daily: HR, 0.79; 95% confidence interval CI, 0.64-0.97; Ptrend  = .01). Lower mortality associated with higher intake was limited to women who had tumors that were negative for hormone receptors (HR, 0.49; 95% CI, 0.29-0.83; Ptrend  = .005) and those who did not receive hormone therapy for their breast cancer (HR, 0.68; 95% CI, 0.51-0.91; Ptrend  = .02). Interactions, however, did not reach statistical significance.


In this large, ethnically diverse cohort of women with breast cancer living in North America, a higher dietary intake of isoflavone was associated with reduced all-cause mortality.

[see editorial on pages 0000-000, this issue.] Cancer 2017.


breast cancer; breast cancer survivors; isoflavone; mortality; soy; survival


Soy foods, isoflavones, and breast cancer.

Kucuk O.

Cancer. 2017 Mar 6. doi: 10.1002/cncr.30614. [Epub ahead of print] No abstract available.

PMID: 28263364


Recent data from Asia and North America indicate that soy foods may decrease the risk of breast cancer and improve the results of treatment in patients with breast cancer. Studying soy foods and isoflavones promises to be an exceptionally fertile area for a wide range of cancer researchers.

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The efficacy of the modified Atkins diet in North Sea Progressive Myoclonus Epilepsy: an observational prospective open-label study.

van Egmond ME, Weijenberg A, van Rijn ME, Elting JW, Gelauff JM, Zutt R, Sival DA, Lambrechts RA, Tijssen MA, Brouwer OF, de Koning TJ.

Orphanet J Rare Dis. 2017 Mar 7;12(1):45. doi: 10.1186/s13023-017-0595-3.

PMID: 28264719




North Sea Progressive Myoclonus Epilepsy is a rare and severe disorder caused by mutations in the GOSR2 gene. It is clinically characterized by progressive myoclonus, seizures, early-onset ataxia and areflexia. As in other progressive myoclonus epilepsies, the efficacy of antiepileptic drugs is disappointingly limited in North Sea Progressive Myoclonus Epilepsy. The ketogenic diet and the less restrictive modified Atkins diet have been proven to be effective in other drug-resistant epilepsy syndromes, including those with myoclonic seizures. Our aim was to evaluate the efficacy of the modified Atkins diet in patients with North Sea Progressive Myoclonus Epilepsy.


Four North Sea Progressive Myoclonus Epilepsy patients (aged 7-20 years) participated in an observational, prospective, open-label study on the efficacy of the modified Atkins diet. Several clinical parameters were assessed at baseline and again after participants had been on the diet for 3 months. The primary outcome measure was health-related quality of life, with seizure frequency and blinded rated myoclonus severity as secondary outcome measures. Ketosis was achieved within 2 weeks and all patients completed the 3 months on the modified Atkins diet. The diet was well tolerated by all four patients. Health-related quality of life improved considerably in one patient and showed sustained improvement during long-term follow-up, despite the progressive nature of the disorder. Health-related quality of life remained broadly unchanged in the other three patients and they did not continue the diet. Seizure frequency remained stable and blinded rating of their myoclonus showed improvement, albeit modest, in all patients.


This observational, prospective study shows that some North Sea Progressive Myoclonus Epilepsy patients may benefit from the modified Atkins diet with sustained health-related quality of life improvement. Not all our patients continued on the diet, but nonetheless we show that the modified Atkins diet might be considered as a possible treatment in this devastating disorder.


Epilepsy; GOSR2 gene; Ketogenic diet; Modified Atkins diet; Myoclonus; North Sea Progressive Myoclonus Epilepsy; Quality of life; Treatment


Effects on Health Outcomes of a Mediterranean Diet With No Restriction on Fat Intake: A Systematic Review and Meta-analysis.

Bloomfield HE, Koeller E, Greer N, MacDonald R, Kane R, Wilt TJ.

Ann Intern Med. 2016 Oct 4;165(7):491-500. doi: 10.7326/M16-0361.

PMID: 27428849




Mediterranean diets may be healthier than typical Western diets.


To summarize the literature comparing a Mediterranean diet with unrestricted fat intake with other diets regarding their effects on health outcomes in adults.


Ovid MEDLINE, CINAHL, and the Cochrane Library from 1990 through April 2016.


Controlled trials of 100 or more persons followed for at least 1 year for mortality, cardiovascular, hypertension, diabetes, and adherence outcomes, as well as cohort studies for cancer outcomes.


Data extracted by 1 investigator was verified by another. Two reviewers assessed risk of bias and strength of evidence.


Two primary prevention trials found no difference in all-cause mortality between diet groups. One large primary prevention trial found that a Mediterranean diet resulted in a lower incidence of major cardiovascular events (hazard ratio {HR}, 0.71 [95% CI, 0.56 to 0.90]), breast cancer (HR, 0.43 [CI, 0.21 to 0.88]), and diabetes (HR, 0.70 [CI, 0.54 to 0.92]). Pooled analyses of primary prevention cohort studies showed that compared with the lowest quantile, the highest quantile of adherence to a Mediterranean diet was associated with a reduction in total cancer mortality (risk ratio [RR], 0.86 [CI, 0.82 to 0.91]; 13 studies) and in the incidence of total (RR, 0.96 [CI, 0.95 to 0.97]; 3 studies) and colorectal (RR, 0.91 [CI, 0.84 to 0.98; 9 studies]) cancer. Of 3 secondary prevention studies reporting cardiovascular outcomes, 1 found a lower risk for recurrent myocardial infarction and cardiovascular death with the Mediterranean diet. There was inconsistent, minimal, or no evidence pertaining to any other outcome, including adherence, hypertension, cognitive function, kidney disease, rheumatoid arthritis, and quality of life.


Few trials; medium risk-of-bias ratings for many studies; low or insufficient strength of evidence for outcomes; heterogeneous diet definitions and components.


Limited evidence suggests that a Mediterranean diet with no restriction on fat intake may reduce the incidence of cardiovascular events, breast cancer, and type 2 diabetes mellitus but may not affect all-cause mortality.


Effects on Health Outcomes of a Mediterranean Diet With No Restriction on Fat Intake.

Martínez-González MA, Estruch R, Corella D, Ros E, Fitó M, Schwingshackl L, Salas-Salvadó J.

Ann Intern Med. 2017 Mar 7;166(5):378. doi: 10.7326/L16-0589. No abstract available.

PMID: 28265657


We are concerned by the statements on weak evidence of benefit of the traditional Mediterranean diet in Bloomfield and colleagues' systematic review (1). Rating the available evidence as limited is unfair. The quality and quantity of scientific evidence supporting the benefits of this diet are impressive and are lacking in other dietary patterns.

The PREDIMED (Prevención con Dieta Mediterránea) trial, a low-risk-of-bias study, was not designed to assess differences in all-cause mortality. The primary end point was cardiovascular disease—including myocardial infarction, stroke, and cardiovascular death, as stated in the protocol (2)—but not all-cause mortality. This is also the case in most cardiovascular trials, which are rarely powered for testing the effect on total mortality. The data and safety monitoring board recommended stopping the PREDIMED trial at 4.8 years for early evidence of benefit, although the planned duration was 6 years. The number of observed deaths was consequently even smaller than if the trial had been completed. Therefore, highlighting that no statistically significant results were observed for all-cause mortality is not fair. Doing so is even worse when these nonsignificant results are interpreted as evidence of equality and are placed as the first sentence in the Data Synthesis section of the abstract to support a conclusion of “no difference in all-cause mortality.” Dozens of adequately powered cohort studies already gave the correct conclusion: A strong inverse association exists between the Mediterranean diet and all-cause mortality (3, 4).

Why the authors included only cohort studies for cancer and rheumatoid arthritis but not other outcomes is unclear; they provided no rationale for this unusual decision. The whole available evidence should have been used. Why cohort studies for all-cause mortality, cardiovascular disease, and type 2 diabetes were discarded is difficult to understand. The conclusion that evidence is weak or limited is highly misleading given the consistent available scientific evidence (3, 4).

More important is the inappropriate and highly nonspecific definition of the Mediterranean diet (2 or more of 7 components) chosen by the authors. This definition is almost completely useless, because many studies meet at least 2 criteria but assess diets quite different from the traditional Mediterranean one. Some of these dietary patterns are also healthy, but they have little in common with the traditional Mediterranean diet (5). The criteria used for defining a Mediterranean diet in this systematic review are wrong and will only confuse readers. Such a peculiar definition of this diet should be avoided in the future.


Effects on Health Outcomes of a Mediterranean Diet With No Restriction on Fat Intake.

Papadaki A, Martinez JA.

Ann Intern Med. 2017 Mar 7;166(5):377-378. doi: 10.7326/L16-0590. No abstract available.

PMID: 28265658


Bloomfield and colleagues' systematic review (1) aims to examine the effect of a Mediterranean diet on various health outcomes. The authors mention the word “effect” throughout their article, which implies that only intervention studies were reviewed. This is not the case, because observational studies were also reviewed. According to the authors, “Observational studies were included if they assessed the association between 2 or more … [Mediterranean diet] components and any of our outcomes of interest.” As such, that they excluded not only observational studies examining the association between all Mediterranean diet components and health outcomes (which other systematic reviews of this diet have included [2]) but also those examining 2 or more components is surprising. For example, Fung and associates' 2008 trial (3) evaluating the role of a DASH (Dietary Approaches to Stop Hypertension)–style diet in coronary heart disease and stroke is a study of the latter that is not included in Bloomfield and colleagues' review.

The arbitrary definition of the Mediterranean diet used in this review also poses a major risk and makes the conclusions inappropriate. Granted, the food and nutrient components that the authors used to define the Mediterranean diet have been used before (4). However, consuming only 2 components of the ones listed does not make a diet Mediterranean. To our knowledge, all the Mediterranean scores and indices used so far in the literature have included 7 to 14 foods and/or nutrients (4), and a prespecified (or median) intake for each component usually needs to be met for a person to be considered adherent to this component. Adherence to the Mediterranean diet is then calculated by summing the adherence scores for each component; persons are then categorized as having high, moderate, or low adherence according to this overall score (4). The authors' definition does not comply with that of the traditional Mediterranean diet (4). Furthermore, adherence to the Mediterranean diet has never, to our knowledge, been assessed by having high adherence to only 2 (or 3 or 4) food components, even if those components are consumed in quantities considered to be in agreement with a “healthy” diet. Therefore, the authors' findings do not necessarily refer to the Mediterranean diet and should be viewed and used with this in mind.

Another issue to consider is the role of fat quality—not only quantity—that “Mediterranean” dietary patterns provide, as shown recently in menopausal women (5).


Effects on Health Outcomes of a Mediterranean Diet With No Restriction on Fat Intake.

Bloomfield HE, Greer N, Kane R, Wilt TJ.

Ann Intern Med. 2017 Mar 7;166(5):378-379. doi: 10.7326/L16-0617. No abstract available.

PMID: 28265659


Drs. Papadaki and Martinez's and Dr. Martínez-González and colleagues' comments both express concern about our definition of a Mediterranean diet. Any effort to review this field must confront the lack of a clear definition of what constitutes a Mediterranean diet. Our definition was a modified version of the one used in a recent Cochrane review (1). It required a minimum of 2 of 7 dietary components and no restriction on total fat intake. A key purpose of an intervention definition in a systematic review is to ensure that all relevant studies are included; we are confident that our definition, coupled with a search strategy that included the term “Mediterranean diet,” accomplished that goal. The letter authors did not identify any studies that were inappropriately included or excluded from our review on the basis of our diet definition. The article cited by Drs. Papadaki and Martinez (2) was not included because it was an observational study of cardiovascular outcomes, whereas only clinical trials were included for these outcomes.

Dr. Martínez-Gonzáles and colleagues object to our characterization of the evidence as “limited.” We used this terminology to reflect that no or only a few controlled trials were available for many of our outcomes of interest. Although there may be “dozens of adequately powered cohort studies,” cohort studies provide only limited evidence because of their inability to control for confounding. Our study design inclusion criteria differed for cardiovascular outcomes (clinical trials only) and cancer, rheumatoid arthritis, and cognitive impairment (clinical trials and cohort studies) on the basis of availability of published literature. Five clinical trials were available for cardiovascular outcomes; for cancer, rheumatoid arthritis, and cognitive impairment, only 1, none, and 2, respectively, were available.


Change in serum TSH levels within the reference range was associated with variation of future blood pressure: a 5-year follow-up study.

Jiang F, Liu A, Lai Y, Yu X, Li C, Han C, Zhang Y, Wang X, Wang Z, Bao S, Lv N, Jin M, Yang F, Fan Y, Jin T, Zhao W, Shan Z, Teng W.

J Hum Hypertens. 2016 Aug 25. doi: 10.1038/jhh.2016.59. [Epub ahead of print]

PMID: 27557892



Controversy exists on the relationship between serum thyrotropin (TSH) and blood pressure, and only a few prospective studies are available up to now. The study aimed to investigate the association between serum TSH within the reference range and blood pressure through a 5-year follow-up study. A total of 623 subjects with normal TSH were followed up for 5 years, including the measurement of demographic data, blood pressure, height, weight and serum TSH. Finally, 531 subjects were included in this prospective study. Body mass index (BMI), prevalence of hypertension, and systolic and diastolic blood pressure were all higher at follow-up than at baseline. Adjusted for age, gender, smoking status, BMI and homoeostasis model assessment of insulin resistance (HOMA-IR) at baseline, multiple linear regression analyses found no relationship between serum TSH at baseline and levels of blood pressure at follow-up, but the changes in serum TSH levels during follow-up was positively associated with the changes in systolic blood pressure (B=2.134, P<0.05), which became more significant in women but not significant in men. The change of systolic blood pressure in group of TSH increase >0.5 mIU l-1 was significantly higher than in group of TSH decrease >0.5 mIU l-1 within reference, after adjusting for age, gender, smoking status, BMI and HOMA-IR at baseline. This result became more significant in women, but no statistical significance was observed in men. Co-variation with serum TSH levels and blood pressure was observed during 5-year follow-up among people with normal TSH.


Perfect 24-h management of hypertension: clinical relevance and perspectives.

Kario K.

J Hum Hypertens. 2016 Sep 8. doi: 10.1038/jhh.2016.65. [Epub ahead of print] Review.

PMID: 27604658




Out-of-office blood pressure (BP) measured by home BP monitoring, or ambulatory BP monitoring, was demonstrated to be superior to office BP for the prediction of cardiovascular events. The J-HOP study of a nationwide Japanese cohort demonstrated that morning home BP is the best stroke predictor. In the prospective HONEST study of >21 000 hypertensives, on-treatment morning home BP was shown to be a strong predictor both of future coronary artery disease and stroke events. In subjects whose office BP was maintained at ⩾150 mm Hg, there was no increase in cardiovascular events when their morning systolic BP was well-controlled at <125 mm Hg. Since Asians show greater morning BP surges, it is particularly important for Asians to achieve 'perfect 24-hr BP control,' that is, the 24-h BP level, nocturnal BP dipping and BP variability including morning surge. The morning BP surge and the extremes of disrupted circadian rhythm (riser and extreme dipper patterns) are independent risks for stroke in hypertensives. A morning BP-guided approach is thus the first step toward perfect 24-h BP control, followed by the control of nocturnal hypertension. In the resonance hypothesis, the synergistic resonance of BP variability phenotypes would produce an extraordinary large 'dynamic BP surge' that can trigger a cardiovascular event, especially in high-risk patients with systemic hemodynamic atherothrombotic syndrome, a vicious cycle of exaggerated BP variability and vascular disease. In the future, information and communications technology and artificial intelligence technology with the innovation of wearable continuous surge BP monitoring will contribute to 'anticipation medicine' with the goal of zero cardiovascular events.


Leisure-time and commuting physical activity and high blood pressure: the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Treff C, Benseñor IM, Lotufo PA.

J Hum Hypertens. 2016 Oct 13. doi: 10.1038/jhh.2016.75. [Epub ahead of print]

PMID: 27734826




This study investigates the association between leisure-time physical activity and commuting-related physical activity and high blood pressure among participants in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Physical activity was assessed through application of the International Physical Activity Questionnaire, particularly the domains addressing leisure and transportation. We used the World Health Organization's definition (⩾150 min per week of moderate activities or 75 min per week of vigorous activities) to establish three categories: active, insufficiently active and inactive. Hypertension was defined as systolic/diastolic blood pressure of >140/90 mm Hg or use of antihypertensive medications. From a universe of 15 105 participants, we analysed 13 857 subjects without previous cardiovascular diseases. The association between physical activity and hypertension was obtained using Poisson regression with adjustment for age, race, education, income, body mass index, diabetes and sodium and alcohol intake. Men who were active during leisure time had a multivariate prevalence ratio (95% confidence interval) of 0.84 (0.77-0.92) for hypertension compared with inactive men. For women, the prevalence ratio of active vs inactive during leisure time was 0.86 (0.79-0.95). However, this protective effect of leisure-time physical activity was not observed among men and women with diabetes or obese women. The association found between commuting-related physical activity and hypertension was not detected among men, and the prevalence ratio for women who were active during commuting time compared with inactive women was 1.11 (1.01-1.21). In conclusion, leisure-time physical activity was protective against hypertension, and commuting-related physical activity was associated with high blood pressure among women.


A nutritional supplement containing lactoferrin stimulates the immune system, extends lifespan, and reduces amyloid <i>β</i> peptide toxicity in <i>Caenorhabditis elegans</i>.

Martorell P, Llopis S, Gonzalez N, Ramón D, Serrano G, Torrens A, Serrano JM, Navarro M, Genovés S.

Food Sci Nutr. 2016 Jul 28;5(2):255-265. doi: 10.1002/fsn3.388.

PMID: 28265360




Lactoferrin is a highly multifunctional glycoprotein involved in many physiological functions, including regulation of iron absorption and immune responses. Moreover, there is increasing evidence for neuroprotective effects of lactoferrin. We used Caenorhabditis elegans as a model to test the protective effects, both on phenotype and transcriptome, of a nutraceutical product based on lactoferrin liposomes. In a dose-dependent manner, the lactoferrin-based product protected against acute oxidative stress and extended lifespan of C. elegans N2. Furthermore, Paralysis of the transgenic C. elegans strain CL4176, caused by Aβ1-42 aggregates, was clearly ameliorated by treatment. Transcriptome analysis in treated nematodes indicated immune system stimulation, together with enhancement of processes involved in the oxidative stress response. The lactoferrin-based product also improved the protein homeostasis processes, cellular adhesion processes, and neurogenesis in the nematode. In summary, the tested product exerts protection against aging and neurodegeneration, modulating processes involved in oxidative stress response, protein homeostasis, synaptic function, and xenobiotic metabolism. This lactoferrin-based product is also able to stimulate the immune system, as well as improving reproductive status and energy metabolism. These findings suggest that oral supplementation with this lactoferrin-based product could improve the immune system and antioxidant capacity. Further studies to understand the molecular mechanisms related with neuronal function would be of interest.


Alzheimer's disease; Caenorhabditis elegans; immune system; lactoferrin; neuroprotection


Is There an Obesity Paradox for Outcomes in Atrial Fibrillation? A Systematic Review and Meta-Analysis of Non-Vitamin K Antagonist Oral Anticoagulant Trials.

Proietti M, Guiducci E, Cheli P, Lip GY.

Stroke. 2017 Mar 6. pii: STROKEAHA.116.015984. doi: 10.1161/STROKEAHA.116.015984. [Epub ahead of print]

PMID: 28265017




Obesity is a risk factor for all-cause and cardiovascular death but, despite this, an inverse relationship between overweight or obesity and a better cardiovascular prognosis in long-term follow-up studies has been observed; this phenomenon, described as obesity paradox, has also been found evident in atrial fibrillation cohorts.


We performed a systematic review on the relationship between body mass index and major adverse outcomes in atrial fibrillation patients. Moreover, we provided a meta-analysis of non-vitamin K antagonist oral anticoagulants (NOACs) trials.


An obesity paradox was found for cardiovascular death and all-cause death in the subgroup analyses of randomized trial cohorts; however, observational studies fail to show this relationship. From the meta-analysis of NOAC trials, a significant obesity paradox was found, with both overweight and obese patients reporting a lower risk for stroke/systemic embolic event (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.66-0.84 and OR, 0.62; 95% CI, 0.54-0.70, respectively). For major bleeding, only obese patients were at lower risk compared with normal weight patients (OR, 0.84; 95% CI, 0.72-0.98). A significant treatment effect of NOACs was found in normal weight patients, both for stroke/systemic embolic event (OR, 0.66; 95% CI, 0.56-0.78) and for major bleeding (OR, 0.72; 95% CI, 0.54-0.95). Major bleeding risk was lower in overweight patients treated with NOACs (OR, 0.84; 95% CI, 0.71-1.00).


There may be an obesity paradox in atrial fibrillation patients, particularly for all-cause and cardiovascular death outcomes. An obesity paradox was also evident for stroke/systemic embolic event outcome in NOAC trials, with a treatment effect favoring NOACs over warfarin for both efficacy and safety that was significant only for normal weight patients.


anticoagulants; atrial fibrillation; body weight; heart failure; obesity


Usefulness of Non-High-Density Lipoprotein Cholesterol as a Predictor of Cardiovascular Disease Mortality in Men in 22-Year Follow-Up.

Harari G, Green MS, Magid A, Zelber-Sagi S.

Am J Cardiol. 2017 Jan 25. pii: S0002-9149(17)30064-4. doi: 10.1016/j.amjcard.2017.01.008. [Epub ahead of print]

PMID: 28267961



Non-high-density lipoprotein cholesterol (non-HDL-C) may be equivalent or superior to low-density lipoprotein cholesterol (LDL-C) for prediction of cardiovascular disease (CVD) risk. However, studies comparing the predictive values of LDL-C and non-HDL-C for CVD and total mortality in a long-term follow-up yielded conflicting results. The Cardiovascular Occupational Risk Factor Determination in Israel Study (CORDIS) is a prospective cohort study of a young industrial population of workers with a long-term follow-up. The initial phase of the study was carried out in 1985-1999. Interviews and physical examinations were conducted, and fasting blood samples, including lipid panels, were undertaken. In 2007, after a 22-year follow-up period, the baseline data were merged with data on all-cause and CVD mortality obtained from the Israeli National Death Registry. A total of 4,832 men were included in the analysis with a mean age of 42.1 ± 12.1 years. Univariate analysis indicated a positive association between non-HDL-C and LDL-C levels and an increased risk for both all-cause and CVD mortality. Multiple regression analysis, following adjustment for potential confounders, resulted in attenuation of the association of both lipoproteins with total mortality. The adjusted association between non-HDL-C levels ≥190 mg/dl and CVD mortality remained significant (hazard ratio 1.80, 95% confidence interval 1.10 to 2.96), but the association of LDL-C with CVD mortality was attenuated (hazard ratio 1.53, 95% confidence interval 0.98 to 2.39). In conclusion, non-HDL-C may be a more potent predictor of CVD mortality than LDL-C levels.


Effect of 25% Sodium Reduction on Sales of a Top-Selling Bread in Remote Indigenous Australian Community Stores: A Controlled Intervention Trial.

McMahon E, Webster J, Brimblecombe J.

Nutrients. 2017 Feb 28;9(3). pii: E214. doi: 10.3390/nu9030214.

PMID: 28264485



Reducing sodium in the food supply is key to achieving population salt targets, but maintaining sales is important to ensuring commercial viability and maximising clinical impact. We investigated whether 25% sodium reduction in a top-selling bread affected sales in 26 remote Indigenous community stores. After a 23-week baseline period, 11 control stores received the regular-salt bread (400 mg Na/100 g) and 15 intervention stores received the reduced-salt version (300 mg Na/100 g) for 12-weeks. Sales data were collected to examine difference between groups in change from baseline to follow-up (effect size) in sales (primary outcome) or sodium density, analysed using a mixed model. There was no significant effect on market share (-0.31%; 95% CI -0.68, 0.07; p = 0.11) or weekly dollars ($58; -149, 266; p = 0.58). Sodium density of all purchases was not significantly reduced (-8 mg Na/MJ; -18, 2; p = 0.14), but 25% reduction across all bread could significantly reduce sodium (-12; -23, -1; p = 0.03). We found 25% salt reduction in a top-selling bread did not affect sales in remote Indigenous community stores. If achieved across all breads, estimated salt intake in remote Indigenous Australian communities would be reduced by approximately 15% of the magnitude needed to achieve population salt targets, which could lead to significant health gains at the population-level.


salt; Indigenous Australians; bread; population health; reformulation; sales; sodium


Attributing Death to Diet: Precision Counts.

Mueller NT, Appel LJ.

JAMA. 2017 Mar 7;317(9):908-909. doi: 10.1001/jama.2017.0946. No abstract available.

PMID: 28267836


A substantial body of evidence has implicated several aspects of diet with the occurrence of cardiometabolic disease (CMD)—heart disease, stroke, and type 2 diabetes. Dietary factors studied have included individual nutrients (macronutrients, micronutrients, minerals, vitamins, electrolytes, and phytochemicals), foods, and overall dietary patterns. It is generally accepted that a suboptimal diet is causally related to CMD, but scientists debate which factors are responsible and the relative importance of each factor given the challenges of isolating and estimating the potential effects of individual nutrients and foods, especially in observational studies. Another topic that is receiving considerably more attention is estimating the fraction of preventable deaths due to suboptimal diet and other factors. Policy makers, in particular, are eager to understand the total burden of CMD that may be attributable to suboptimal diet, given that modification of diet is a cornerstone of prevention policy.1


Association Between Dietary Factors and Mortality From Heart Disease, Stroke, and Type 2 Diabetes in the United States.

Micha R, Peñalvo JL, Cudhea F, Imamura F, Rehm CD, Mozaffarian D.

JAMA. 2017 Mar 7;317(9):912-924. doi: 10.1001/jama.2017.0947.

PMID: 28267855




In the United States, national associations of individual dietary factors with specific cardiometabolic diseases are not well established.


To estimate associations of intake of 10 specific dietary factors with mortality due to heart disease, stroke, and type 2 diabetes (cardiometabolic mortality) among US adults.


A comparative risk assessment model incorporated data and corresponding uncertainty on population demographics and dietary habits from National Health and Nutrition Examination Surveys (1999-2002: n = 8104; 2009-2012: n = 8516); estimated associations of diet and disease from meta-analyses of prospective studies and clinical trials with validity analyses to assess potential bias; and estimated disease-specific national mortality from the National Center for Health Statistics.


Consumption of 10 foods/nutrients associated with cardiometabolic diseases: fruits, vegetables, nuts/seeds, whole grains, unprocessed red meats, processed meats, sugar-sweetened beverages (SSBs), polyunsaturated fats, seafood omega-3 fats, and sodium.


Estimated absolute and percentage mortality due to heart disease, stroke, and type 2 diabetes in 2012. Disease-specific and demographic-specific (age, sex, race, and education) mortality and trends between 2002 and 2012 were also evaluated.


In 2012, 702 308 cardiometabolic deaths occurred in US adults, including 506 100 from heart disease (371 266 coronary heart disease, 35 019 hypertensive heart disease, and 99 815 other cardiovascular disease), 128 294 from stroke (16 125 ischemic, 32 591 hemorrhagic, and 79 578 other), and 67 914 from type 2 diabetes. Of these, an estimated 318 656 (95% uncertainty interval [uI], 306 064-329 755; 45.4%) cardiometabolic deaths per year were associated with suboptimal intakes-48.6% (95% UI, 46.2%-50.9%) of cardiometabolic deaths in men and 41.8% (95% UI, 39.3%-44.2%) in women; 64.2% (95% UI, 60.6%-67.9%) at younger ages (25-34 years) and 35.7% (95% UI, 33.1%-38.1%) at older ages (≥75 years); 53.1% (95% UI, 51.6%-54.8%) among blacks, 50.0% (95% UI, 48.2%-51.8%) among Hispanics, and 42.8% (95% UI, 40.9%-44.5%) among whites; and 46.8% (95% UI, 44.9%-48.7%) among lower-, 45.7% (95% UI, 44.2%-47.4%) among medium-, and 39.1% (95% UI, 37.2%-41.2%) among higher-educated individuals. The largest numbers of estimated diet-related cardiometabolic deaths were related to high sodium (66 508 deaths in 2012; 9.5% of all cardiometabolic deaths), low nuts/seeds (59 374; 8.5%), high processed meats (57 766; 8.2%), low seafood omega-3 fats (54 626; 7.8%), low vegetables (53 410; 7.6%), low fruits (52 547; 7.5%), and high SSBs (51 694; 7.4%). Between 2002 and 2012, population-adjusted US cardiometabolic deaths per year decreased by 26.5%. The greatest decline was associated with insufficient polyunsaturated fats (-20.8% relative change [95% UI, -18.5% to -22.8%]), nuts/seeds (-18.0% [95% UI, -14.6% to -21.0%]), and excess SSBs (-14.5% [95% UI, -12.0% to -16.9%]). The greatest increase was associated with unprocessed red meats (+14.4% [95% UI, 9.1%-19.5%]).


Dietary factors were estimated to be associated with a substantial proportion of deaths from heart disease, stroke, and type 2 diabetes. These results should help identify priorities, guide public health planning, and inform strategies to alter dietary habits and improve health.

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Dietary energy density and body weight changes after 3 years in the PREDIMED study.

Razquin C, Sanchez-Tainta A, Salas-Salvadó J, Buil-Cosiales P, Corella D, Fito M, Ros E, Estruch R, Arós F, Gómez-Gracia E, Fiol M, Lapetra J, Serra-Majem L, Pinto X, Schröder H, Tur J, Sorlí JV, Lamuela-Raventós RM, Bulló M, Bes-Rastrollo M, Martinez-Gonzalez MA; PREDIMED GROUP..

Int J Food Sci Nutr. 2017 Mar 6:1-8. doi: 10.1080/09637486.2017.1295028. [Epub ahead of print]

PMID: 28276290



The association of dietary energy density (ED) and overweight is not clear in the literature. Our aim was to study in 4259 of the PREDIMED trial whether an increase in dietary ED based on a higher adherence to a Mediterranean dietary pattern was associated with 3-year weight gain. A validated 137-item food-frequency questionnaire was administered. Multivariable-adjusted models were used to analyze the association between 3-year ED change and the subsequent 3-year body weight change. The most important weight reduction after 3-year follow-up was observed in the two lowest quintiles and the highest quintile of ED change. The highest ED increase was characterized by an increased intake of extra virgin olive oil (EVOO) and nuts and a decreased intake of other oils, vegetable and fruit consumption (p < .001). In conclusion, increased 3-year ED in the PREDIMED study, associated with a higher EVOO and nuts consumption, was not associated with weight gain.


Mediterranean dietary pattern; PREDIMED; body weight change; dietary energy density; extra-virgin olive oil; nuts


The Impact of Virgin Coconut Oil and High-Oleic Safflower Oil on Body Composition, Lipids, and Inflammatory Markers in Postmenopausal Women.

Harris M, Hutchins A, Fryda L.

J Med Food. 2017 Mar 9. doi: 10.1089/jmf.2016.0114. [Epub ahead of print]

PMID: 28277823



This randomized crossover study compared the impact of virgin coconut oil (VCO) to safflower oil (SO) on body composition and cardiovascular risk factors. Twelve postmenopausal women (58.8 ± 3.7 year) consumed 30 mL VCO or SO for 28 days, with a 28-day washout. Anthropometrics included body weight and hip and waist circumference. Fat percent for total body, android and gynoid, fat mass, and lean mass were measured using dual-energy X-ray absorptiometry. Women maintained their typical diet recording 28 days of food records during the study. Results were analyzed with SPSS v24 with significance at P ≤ .05. Comparisons are reported as paired t-test since no intervention sequence effect was observed. VCO significantly raised total cholesterol, TC (+18.2 ± 22.8 mg/dL), low-density lipoprotein (+13.5 ± 16.0 mg/dL), and high-density lipoprotein, HDL (+6.6 ± 7.5 mg/dL). SO did not significantly change lipid values. TC and HDL were significantly different between test oils. The TC/HDL ratio change showed a neutral effect of both VCO and SO. One person had adverse reactions to VCO and increased inflammation. VCO decreased IL-1β for each person who had a detected sample. The impact of VCO and SO on other cytokines varied on an individual basis. This was the first study evaluating the impact of VCO on body composition in Caucasian postmenopausal women living in the United States. Results are suggestive that individuals wishing to use coconut oil in their diets can do so safely, but more studies need to be conducted with larger sample sizes, diverse populations, and more specific clinical markers such as particle size.


adiposity; cholesterol; cytokines; fatty acid


The association of protein intake (amount and type) with ovarian antral follicle counts among infertile women: results from the EARTH prospective study cohort.

Souter I, Chiu YH, Batsis M, Afeiche MC, Williams PL, Hauser R, Chavarro JE; EARTH Study Team..

BJOG. 2017 Mar 9. doi: 10.1111/1471-0528.14630. [Epub ahead of print]

PMID: 28278351




To evaluate the association between protein intake (amount and type) and antral follicle count (AFC).


Prospective cohort.


Academic fertility center.


265 women undergoing fertility treatments at an academic fertility center and participating in an ongoing study on environment and reproductive health.


We measured AFC in ultrasonographic evaluation among women undergoing infertility treatments. Women completed a previously validated semi-quantitative food frequency questionnaire. We used Poisson regression to evaluate the relation between protein intake and AFC while adjusting for age, body mass index, race, smoking status, and total energy intake.


Antral follicle count.


Among 265 women (mean age: 35.0±3.9 years, 85% Caucasian), total protein intake (% energy) was unrelated to AFC. When protein from different food sources was considered separately, we found a negative association between dairy protein intake and AFC. The mean AFC was 14.4% (3.9%-23.7%) lower for women in the highest quintile of dairy protein intake than for women in the bottom quintile after adjusting for potential confounders (p-trend=0.04). This association was stronger among women who had never smoked (p-trend=0.002) but was not observed among previous smokers (p-trend=0.36). There were no associations between protein intake from either non-dairy animal or vegetable sources and AFC.


Higher dairy protein intake (≥ 5.24% of energy) was associated with lower antral follicle counts among women presenting for infertility treatment. These findings should be further investigated in prospective studies designed to also clarify the biology underlying the observed associations.


antral follicle count; dairy intake; female infertility; ovarian reserve; ovary; protein intake


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

Uric Acid and Left Ventricular Hypertrophy: A Potentially New Modifiable Target?

Kuwabara M, Sato Y, Kanbay M, Johnson RJ.

Am J Hypertens. 2017 Jan 17. pii: hpw195. doi: 10.1093/ajh/hpw195. [Epub ahead of print] No abstract available.

PMID: 28096149


Uric Acid and New Onset Left Ventricular Hypertrophy: Findings From the PAMELA Population.

Cuspidi C, Facchetti R, Bombelli M, Sala C, Tadic M, Grassi G, Mancia G.

Am J Hypertens. 2017 Jan 17. pii: hpw159. doi: 10.1093/ajh/hpw159. [Epub ahead of print]

PMID: 28096148





The association between serum uric acid (SUA) and left ventricular hypertrophy (LVH) is controversial and the ability of SUA in predicting incident LVH remains unsettled. Thus, we evaluated the relationship of SUA with new-onset echocardiographic LVH over a 10-year period in subjects of the general population enrolled in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study.


The study included 960 subjects with normal LV mass index (LVMI) at baseline echocardiographic evaluation and a readable echocardiogram at the end of follow-up. Cut-points for LVH were derived from reference values of the healthy fraction of the PAMELA population.


Over a 10-year period, 258 participants (26.9%) progressed to LVH. The incidence of new-onset LVH increased from the lowest (23%) to intermediate (25%) and the highest baseline SUA tertile (32%). After adjusting for confounders (not including body mass index (BMI)), each 1 mg/dl increase in SUA entailed a 26% higher risk of incident LVH. Adjusted odd ratio of LVH risk in the highest SUA tertile was 96% higher than in the lowest tertile (odds ratio (OR) = 1.966, 95% CI = 1.158-3.339, P = 0.0123). Correction for BMI reduced the magnitude and statistical significance of ORs.


The study shows that SUA is a predictor of long-term echocardiographic changes from normal LVMI to LVH in a community sample. Thus, life-style and pharmacologic measures aimed to reduce SUA levels may concur to preventing LVH development in the general population.


blood pressure; echocardiography; general population; hypertension; left ventricular hypertrophy; serum uric acid.


[The below paper is not pdf-availed.]

Alarming Prevalence of Emergency Hypertension Levels in the General Public Identified by a Hypertension Awareness Campaign.

Caligiuri SP, Austria JA, Pierce GN.

Am J Hypertens. 2017 Jan 5. pii: hpw136. doi: 10.1093/ajh/hpw136. [Epub ahead of print]

PMID: 28057629



Hypertension is a major cause of mortality and morbidity today. The "silent" nature of hypertension makes it critical to determine its prevalence and its severity in the general public and to identify strategies to identify people unaware of its presence. A mobile hypertension awareness campaign was created to: (i) determine the prevalence and types of hypertension in an urban North American center, (ii) increase hypertension awareness, and (iii) identify reasons for lack of therapy adherence.


Mobile clinics were provided at shopping malls, workplaces, hospitals, and community centres to measure blood pressure in the public. Blood pressure recordings were done on a voluntary basis.


Of 1097 participants, 50% presented with high blood pressure which was higher than expected. Of particular clinical significance, an unexpectedly large number of participants (2%) exhibited a hypertensive urgency/emergency. Most of these people were not adherent to medications (if their hypertension was detected previously), were unaware of their hypertensive state, and/or unwilling to acknowledge or ignored the clinical significance of the extremely high blood pressure readings. Reasons for lack of adherence included: denial, being unaware of health consequences, and proper management of hypertension.


A relatively large segment of an urban population lives unaware of severe emergency levels of hypertension. A public mobile hypertension clinic provides a valuable strategy for identifying hypertension in the general public and for knowledge translation of hypertension management.


blood pressure; drug adherence; emergency blood pressure; hypertension; incidence of hypertension.


'Get out of your comfort zone:' Interval training benefits extend to aging

U.S. study indicates mixing speeds of aerobic exercise is 'good from an aging perspective'

By Amina Zafar, CBC News Posted: Mar 09, 2017



Enhanced Protein Translation Underlies Improved Metabolic and Physical Adaptations to Different Exercise Training Modes in Young and Old Humans.

Robinson MM, Dasari S, Konopka AR, Johnson ML, Manjunatha S, Esponda RR, Carter RE, Lanza IR, Nair KS.

Cell Metab. 2017 Mar 7;25(3):581-592. doi: 10.1016/j.cmet.2017.02.009.

PMID: 28273480




The molecular transducers of benefits from different exercise modalities remain incompletely defined. Here we report that 12 weeks of high-intensity aerobic interval (HIIT), resistance (RT), and combined exercise training enhanced insulin sensitivity and lean mass, but only HIIT and combined training improved aerobic capacity and skeletal muscle mitochondrial respiration. HIIT revealed a more robust increase in gene transcripts than other exercise modalities, particularly in older adults, although little overlap with corresponding individual protein abundance was noted. HIIT reversed many age-related differences in the proteome, particularly of mitochondrial proteins in concert with increased mitochondrial protein synthesis. Both RT and HIIT enhanced proteins involved in translational machinery irrespective of age. Only small changes of methylation of DNA promoter regions were observed. We provide evidence for predominant exercise regulation at the translational level, enhancing translational capacity and proteome abundance to explain phenotypic gains in muscle mitochondrial function and hypertrophy in all ages.


aging; exercise; human; insulin clamp; interval; methylation; proteome; skeletal muscle; tracer; transcriptome


Sleep to Lower Elevated Blood Pressure: A Randomized Controlled Trial (SLEPT)

Emer R. McGrath Colin A. Espie Alice Power Andrew W. Murphy John Newell Caroline Kelly Niamh Duffy Patricia Gunning Irene Gibson Sophie Bostock Martin J. O’Donnell

Am J Hypertens (2017) 30 (3): 319-327. DOI: https://doi.org/10.1093/ajh/hpw132

Published: 19 January 2017 Article history





Impaired sleep quality is common and associated with an increased risk of cardiovascular disease (CVD), thought to be mediated through adverse effects on established vascular risk factors, particularly hypertension. We determined if a web-delivered sleep intervention (sleep–hygiene education, stimulus control, and cognitive behavioral therapy) reduces blood pressure compared to vascular risk factor education (standard care) alone.


Phase II randomized, blinded, controlled trial of 134 participants without CVD with mild sleep impairment and blood pressure 130–160/<110 mm Hg. The primary outcome was the difference in the mean change in 24-hour ambulatory systolic blood pressure (SBP) over 8 weeks between intervention and control groups. Secondary outcomes included measures of sleep quality and psychosocial health, namely Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI).


Participants in the sleep intervention group showed significantly greater improvements in sleep quality, including ISI [difference in mean improvement 2.8; 95% confidence interval (CI), 1.3–4.4], PSQI (1.1; 95% CI, 0.1–2.2), sleep condition indicator (0.8; 95% CI, 0.2–1.4), and psychosocial health, including BDI (2.0; 95% CI, 0.3–3.7) and BAI (1.4; 95% CI, 0.02–2.8). The mean improvement in 24-hour ambulatory SBP did not differ between the sleep intervention (0.9 mm Hg) and control (0.8 mm Hg) arms, (difference in mean improvement 0.1; 95% CI, −3.4 to 3.2).


A simple, low-cost, web-delivered sleep intervention is feasible and significantly improves sleep quality and measures of psychosocial health in individuals with mild sleep impairment but does not result in short-term improvements in blood pressure.

blood pressure, hypertension, primary prevention, risk factors, sleep.

Topic: hypertension blood pressure sleep arterial pressure, increased


Ambulatory Blood Pressure Characteristics and Long-Term Risk for Atrial Fibrillation.

Perkiömäki JS, Nortamo S, Ylitalo A, Kesäniemi A, Ukkola O, Huikuri HV.

Am J Hypertens. 2016 Nov 15. pii: hpw149. [Epub ahead of print]

PMID: 27852579




We hypothesized that elevated nighttime systolic ambulatory blood pressure (ABP) yields additional information compared with daytime systolic ABP for the long-term risk of atrial fibrillation (AF) and perhaps should be taken into account in treatment strategies for preventing the increasing burden of AF during aging.


A total of 903 subjects with or without hypertension aged 40 to 59 years, who were recruited to the Oulu Project Elucidating Risk of Atherosclerosis (OPERA) study, underwent ABP monitoring, thorough clinical examinations and laboratory tests.


After an average of 16.4 ± 3.6 years of follow-up, 91 (10%) of the study subjects had experienced a new-onset AF requiring a hospital emergency room or hospital visit. Of the components of baseline ABP, the nighttime mean systolic blood pressure had the strongest univariable association with the occurrence of AF (120.8 ± 15.9 vs. 116.4 ± 14.1 mm Hg, P = 0.006, in subjects with vs. without the occurrence AF). When the univariable predictors of AF, such as age, sex, body mass index, height, smoking history, alanine aminotransferase, uric acid, and fasting plasma glucose, were entered in the multivariable Cox hazards model, age (P < 0.001), and body mass index (P = 0.014) retained their significant predictive power. After adjustments in this clinical hazards model, the nighttime mean systolic blood pressure still predicted the occurrence of AF (hazards ratio = 1.07 per every 5 mm Hg increase, 95% confidence intervals = 1.004-1.15, P = 0.038).


Of the baseline ABP characteristics, the nighttime systolic blood pressure is a significant independent contributor to the long-term risk of new-onset AF requiring a hospital visit.


ambulatory blood pressure; atrial fibrillation; blood pressure; hypertension.


Neanderthal behaviour, diet, and disease inferred from ancient DNA in dental calculus.

Weyrich LS, Duchene S, Soubrier J, Arriola L, Llamas B, Breen J, Morris AG, Alt KW, Caramelli D, Dresely V, Farrell M, Farrer AG, Francken M, Gully N, Haak W, Hardy K, Harvati K, Held P, Holmes EC, Kaidonis J, Lalueza-Fox C, de la Rasilla M, Rosas A, Semal P, Soltysiak A, Townsend G, Usai D, Wahl J, Huson DH, Dobney K, Cooper A.

Nature. 2017 Mar 8. doi: 10.1038/nature21674. [Epub ahead of print]

PMID: 28273061



Recent genomic data have revealed multiple interactions between Neanderthals and modern humans, but there is currently little genetic evidence regarding Neanderthal behaviour, diet, or disease. Here we describe the shotgun-sequencing of ancient DNA from five specimens of Neanderthal calcified dental plaque (calculus) and the characterization of regional differences in Neanderthal ecology. At Spy cave, Belgium, Neanderthal diet was heavily meat based and included woolly rhinoceros and wild sheep (mouflon), characteristic of a steppe environment. In contrast, no meat was detected in the diet of Neanderthals from El Sidrón cave, Spain, and dietary components of mushrooms, pine nuts, and moss reflected forest gathering. Differences in diet were also linked to an overall shift in the oral bacterial community (microbiota) and suggested that meat consumption contributed to substantial variation within Neanderthal microbiota. Evidence for self-medication was detected in an El Sidrón Neanderthal with a dental abscess and a chronic gastrointestinal pathogen (Enterocytozoon bieneusi). Metagenomic data from this individual also contained a nearly complete genome of the archaeal commensal Methanobrevibacter oralis (10.2× depth of coverage)-the oldest draft microbial genome generated to date, at around 48,000 years old. DNA preserved within dental calculus represents a notable source of information about the behaviour and health of ancient hominin specimens, as well as a unique system that is useful for the study of long-term microbial evolution.


[The below paper is not pdf-availed.]

Significance to human health of carbamazepine detected in fruits and vegetables irrigated with recycled water.

Sheikh B.

Water Sci Technol. 2017 Mar;75(5):1059-1062. doi: 10.2166/wst.2016.585.

PMID: 28272035


The relevance and significance of the findings of chemicals of emerging concern at nanogram concentrations in recycled water is critically important for the consumers of these crops. The relevance and significance of these chemicals at these concentrations is placed in perspective in terms of the number of years of consumption necessary to accrue one acceptable daily intake every day, over a lifetime, specifically for carbamazepine. In this paper, the number of years is calculated and found to far exceed the maximum human life expectancy, even assuming that the individual consumes a mix of fruits and vegetables irrigated with recycled water throughout an 80-year life span, excluding other food crops free from carbamazepine.


Trends in premature mortality in the USA by sex, race, and ethnicity from 1999 to 2014: an analysis of death certificate data

Dr Meredith S Shiels, PhDa, , , Pavel Chernyavskiy, PhDa, William F Anderson, MDa, Ana F Best, PhDa, Emily A Haozous, PhDb, Patricia Hartge, ScDa, Philip S Rosenberg, PhDa, David Thomas, PhDc, Show more

doi: 10.1016/S0140-6736(17)30187-3




Reduction of premature mortality is a UN Sustainable Development Goal. Unlike other high-income countries, age-adjusted mortality in the USA plateaued in 2010 and increased slightly in 2015, possibly because of rising premature mortality. We aimed to analyse trends in mortality in the USA between 1999 and 2014 in people aged 25–64 years by age group, sex, and race and ethnicity, and to identify specific causes of death underlying the temporal trends.


For this analysis, we used cause-of-death and demographic data from death certificates from the US National Center for Health Statistics, and population estimates from the US Census Bureau. We estimated annual percentage changes in mortality using age-period-cohort models. Age-standardised excess deaths were estimated for 2000 to 2014 as observed deaths minus expected deaths (estimated from 1999 mortality rates).


Between 1999 and 2014, premature mortality increased in white individuals and in American Indians and Alaska Natives. Increases were highest in women and those aged 25–30 years. Among 30-year-olds, annual mortality increases were 2·3% (95% CI 2·1–2·4) for white women, 0·6% (0·5–0·7) for white men, and 4·3% (3·5–5·0) and 1·9% (1·3–2·5), respectively, for American Indian and Alaska Native women and men. These increases were mainly attributable to accidental deaths (primarily drug poisonings), chronic liver disease and cirrhosis, and suicide. Among individuals aged 25–49 years, an estimated 111 000 excess premature deaths occurred in white individuals and 6600 in American Indians and Alaska Natives during 2000–14. By contrast, premature mortality decreased substantially across all age groups in Hispanic individuals (up to 3·2% per year), black individuals (up to 3·9% per year), and Asians and Pacific Islanders (up to 2·6% per year), mainly because of declines in HIV, cancer, and heart disease deaths, resulting in an estimated 112 000 fewer deaths in Hispanic individuals, 311 000 fewer deaths in black individuals, and 34 000 fewer deaths in Asians and Pacific Islanders aged 25–64 years. During 2011–14, American Indians and Alaska Natives had the highest premature mortality, followed by black individuals.


Important public health successes, including HIV treatment and smoking cessation, have contributed to declining premature mortality in Hispanic individuals, black individuals, and Asians and Pacific Islanders. However, this progress has largely been negated in young and middle-aged (25–49 years) white individuals, and American Indians and Alaska Natives, primarily because of potentially avoidable causes such as drug poisonings, suicide, and chronic liver disease and cirrhosis. The magnitude of annual mortality increases in the USA is extremely unusual in high-income countries, and a rapid public health response is needed to avert further premature deaths.


Referred to by

Anna Zajacova, Jennifer Karas Montez

Macro-level perspective to reverse recent mortality increases

The Lancet, Volume 389, Issue 10073, 11–17 March 2017, Pages 991-992

doi: 10.1016/S0140-6736(17)30186-1



The Lancet

Premature deaths in the USA: repeal has no appeal

The Lancet, Volume 389, Issue 10067, 28 January–3 February 2017, Page 332

doi: 10.1016/S0140-6736(17)30196-4

Advances in treatment and access to care have seen premature deaths from HIV/AIDS and cancer decline dramatically for Americans. However, premature deaths from accidental causes—primarily drug overdoses, chronic liver disease, and suicide—have risen so precipitously that much of the good work on HIV/AIDS and cancer has been, in population terms, negated.

An Article by Meredith Shiels and colleagues in The Lancet today shows that between 1999 and 2014, white and native Americans aged 25–30 years have seen mortality rates rise steadily, an effect the authors call “extremely unusual”. While in Canada and England mortality rates continue a decline across the board, in the USA a 25-year-old white woman's death is now 3% more likely, while an American native or Alaskan native of the same age and gender faces a 5% increased risk of dying.

At root, addiction and suicide, two drivers in the mortality increase, could be addressed by better access to mental health and substance misuse counselling. The Mental Health Parity and Addiction Equity Act was enacted to equalise benefits for mental health care commensurate with other medical benefits, and expanded after the passage of the Affordable Care Act (ACA) to apply to individual health coverage plans. Although instrumental in improving parity for coverage of treatment for mental health, it is not perfect. Stigma around seeking treatment as well as rising costs and reduced provider and treatment facility capacity equates to profound gaps in care.

The potential repeal of the ACA, however, challenges those gains and threatens new hurdles. One risk is elimination of the pre-existing conditions clause, which prevents insurers from denying coverage on the grounds of previous illness. For people with mental health and substance misuse problems that are often recurrent and require substantial management, the inability to secure coverage can be life-threatening.

As Shiels and colleagues' Article underscores, such uncertainty comes at the worst possible time, when more Americans are vulnerable and the consequence is the most dire. We urge President Trump and his new administration to make tackling this surge in preventable deaths a priority, and to do so by retaining quality, affordable access to mental health care.


Impact of Physical Activity on Cognitive Decline, Dementia, and Its Subtypes: Meta-Analysis of Prospective Studies.

Guure CB, Ibrahim NA, Adam MB, Said SM.

Biomed Res Int. 2017;2017:9016924. doi: 10.1155/2017/9016924.

PMID: 28271072



The association of physical activity with dementia and its subtypes has remained controversial in the literature and has continued to be a subject of debate among researchers. A systematic review and meta-analysis of longitudinal studies on the relationship between physical activity and the risk of cognitive decline, all-cause dementia, Alzheimer's disease, and vascular dementia among nondemented subjects are considered. A comprehensive literature search in all available databases was conducted up until April 2016. Well-defined inclusion and exclusion criteria were developed with focus on prospective studies ≥ 12 months. The overall sample from all studies is 117410 with the highest follow-up of 28 years. The analyses are performed with both Bayesian parametric and nonparametric models. Our analysis reveals a protective effect for high physical activity on all-cause dementia, odds ratio of 0.79, 95% CI (0.69, 0.88), a higher and better protective effect for Alzheimer's disease, odds ratio of 0.62, 95% CI (0.49, 0.75), cognitive decline odds ratio of 0.67, 95% CI (0.55, 0.78), and a nonprotective effect for vascular dementia of 0.92, 95% CI (0.62, 1.30). Our findings suggest that physical activity is more protective against Alzheimer's disease than it is for all-cause dementia, vascular dementia, and cognitive decline.


Tooth Loss and Risk of Dementia in the Community: the Hisayama Study.

Takeuchi K, Ohara T, Furuta M, Takeshita T, Shibata Y, Hata J, Yoshida D, Yamashita Y, Ninomiya T.

J Am Geriatr Soc. 2017 Mar 8. doi: 10.1111/jgs.14791. [Epub ahead of print]

PMID: 28272750





To clarify the effect of tooth loss on development of all-cause dementia and its subtypes in an elderly Japanese population.


Prospective cohort study.


The Hisayama Study, Japan.


Community-dwelling Japanese adults without dementia aged 60 and older (N = 1,566) were followed for 5 years (2007-2012).


Participants were classified into four categories according to baseline number of remaining teeth (≥20, 10-19, 1-9, 0). The risk estimates of the effect of tooth loss on the development of all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were computed using a Cox proportional hazards model.


During follow-up, 180 (11.5%) subjects developed all-cause dementia; 127 (8.1%) had AD, and 42 (2.7%) had VaD. After adjusting for potential confounders, there was a tendency for the multivariable-adjusted hazard ratio of all-cause dementia to increase with decrease in number of remaining teeth (P for trend = .04). The risk of all-cause dementia was 1.62 times as great in subjects with 10 to 19 teeth, 1.81 times as great in those with one to nine teeth, and 1.63 times as great in those with no teeth as in those with 20 teeth or more. An inverse association was observed between number of remaining teeth and risk of AD (P for trend = .08), but no such association was observed with risk of VaD (P for trend = .20).


Tooth loss is associated with an increased risk of all-cause dementia and AD in the Japanese population.


Alzheimer's disease; epidemiology; oral health; prospective cohort study; vascular dementia


The effect of diurnal distribution of carbohydrates and fat on glycaemic control in humans: a randomized controlled trial.

Kessler K, Hornemann S, Petzke KJ, Kemper M, Kramer A, Pfeiffer AF, Pivovarova O, Rudovich N.

Sci Rep. 2017 Mar 8;7:44170. doi: 10.1038/srep44170.

PMID: 28272464



Diurnal carbohydrate and fat distribution modulates glycaemic control in rodents. In humans, the optimal timing of both macronutrients and its effects on glycaemic control after prolonged consumption are not studied in detail. In this cross-over trial, 29 non-obese men were randomized to two four-week diets: (1) carbohydrate-rich meals until 13.30 and fat-rich meals between 16.30 and 22.00 (HC/HF) versus (2) inverse sequence of meals (HF/HC). After each trial period two meal tolerance tests were performed, at 09.00 and 15.40, respectively, according to the previous intervention. On the HF/HC diet, whole-day glucose level was increased by 7.9% (p = 0.026) in subjects with impaired fasting glucose and/or impaired glucose tolerance (IFG/IGT, n = 11), and GLP-1 by 10.2% (p = 0.041) in normal glucose-tolerant subjects (NGT, n = 18). Diet effects on fasting GLP-1 (p = 0.009) and PYY (p = 0.034) levels were observed in IFG/IGT, but not in NGT. Afternoon decline of glucose tolerance was more pronounced in IFG/IGT and associated with a stronger decrease of postprandial GLP-1 and PYY levels, but not with changes of cortisol rhythm. In conclusion, the HF/HC diet shows an unfavourable effect on glycaemic control in IFG/IGT, but not in NGT subjects. Consequently, large, carbohydrate-rich dinners should be avoided, primarily by subjects with impaired glucose metabolism.

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Understanding the cognitive experience of death and the near-death experience

S. Parnia

QJM (2017) 110 (2): 67-69. DOI: https://doi.org/10.1093/qjmed/hcw185

Published: 01 November 2016


Transcendental mystical or spiritual experiences close to death have been described for millennia. However, following the birth of modern intensive care medicine four decades ago, the specific term ‘near-death experience’ (NDE) was coined.1 Current research indicates that, regardless of cultural background, adults and young children (<3 years) have described comparable experiences in association with death.1 These include: feelings of immense peace and love; a sensation of going through a tunnel; seeing a bright warm welcoming light that draws the person toward it; meeting a ‘being of light’; a feeling of entering a beautiful ‘heavenly’ domain; and encountering deceased relatives who are often perceived as greeting and welcoming the individual. A review of the person’s life from early childhood onward is another commonly reported experience,...

Topic: cardiac arrest, consciousness related finding, near-death experience


Why is the United States a sick country?

Donnelly SC.

QJM. 2017 Feb 1;110(2):57-58. doi: 10.1093/qjmed/hcx020. No abstract available.

PMID: 28204741





for decades, U.S. taxpayers have been lamenting the high cost of health care. Since the mid-1980s, Americans have had double-digit spending on health care. Despite this investment, Americans are less healthy than their European and Scandinavian counterparts across an array of health measures.


We sought to explore how inadequate attention to the social, behavioral, and environmental determinants of health may contribute to the American health care paradox of high health care spending and poor health outcomes.


Mixed methodsMethods: We report previous findings related from a 10-year analysis of national-level health and social service spending and health outcome data from the Organisation of Economic and Cooperation and Development (OECD). We also put forth case studies representing different socioeconomic strata to illustrate the relationship between health care and social service spending and health.


Although the U.S. spending more of its GDP on health care than any other country, it is not a high spender when one sums spending on both health care and social services. The U.S. however has the lowest ratio of our social service spending to health care spending in the OECD, and countries with lower ratios on average have worse health outcomes. Cases from diverse socioeconomic strata demonstrate how limited attention to the social determinants of health can result in extremely high health care costs and poor health outcomes.


Greater investment in addressing the social, behavioral, and environmental determinants of health may foster better health without accelerating health care costs in America.


The benefits and risks of consuming brewed tea: beware of toxic element contamination.

Schwalfenberg G, Genuis SJ, Rodushkin I.

J Toxicol. 2013;2013:370460. doi: 10.1155/2013/370460.

PMID: 24260033 Free PMC Article




Background. Increasing concern is evident about contamination of foodstuffs and natural health products. Methods. Common off-the-shelf varieties of black, green, white, and oolong teas sold in tea bags were used for analysis in this study. Toxic element testing was performed on 30 different teas by analyzing (i) tea leaves, (ii) tea steeped for 3-4 minutes, and (iii) tea steeped for 15-17 minutes. Results were compared to existing preferred endpoints. Results. All brewed teas contained lead with 73% of teas brewed for 3 minutes and 83% brewed for 15 minutes having lead levels considered unsafe for consumption during pregnancy and lactation. Aluminum levels were above recommended guidelines in 20% of brewed teas. No mercury was found at detectable levels in any brewed tea samples. Teas contained several beneficial elements such as magnesium, calcium, potassium, and phosphorus. Of trace minerals, only manganese levels were found to be excessive in some black teas. Conclusions. Toxic contamination by heavy metals was found in most of the teas sampled. Some tea samples are considered unsafe. There are no existing guidelines for routine testing or reporting of toxicant levels in "naturally" occurring products. Public health warnings or industry regulation might be indicated to protect consumer safety.


Nutrient sensing pathways as therapeutic targets for healthy ageing.

Aiello A, Accardi G, Candore G, Gambino CM, Mirisola M, Taormina G, Virruso C, Caruso C.

Expert Opin Ther Targets. 2017 Apr;21(4):371-380. doi: 10.1080/14728222.2017.1294684.

PMID: 28281903




In the present paper, the authors have discussed anti-aging strategies which aim to slow the aging process and to delay the onset of age-related diseases, focusing on nutrient sensing pathways (NSPs) as therapeutic targets. Indeed, several studies have already demonstrated that both in animal models and humans, dietary interventions might have a positive impact on the aging process through the modulation of these pathways. Areas covered: Achieving healthy aging is the main challenge of the twenty-first century because lifespan is increasing, but not in tandem with good health. The authors have illustrated different approaches that can act on NSPs, modulating the rate of the aging process. Expert opinion: Humanity's lasting dream is to reverse or, at least, postpone aging. In recent years, increasing attention has been devoted to anti-aging therapies. The subject is very popular among the general public, whose imagination runs wild with all the possible tools to delay aging and to gain immortality. Some approaches discussed in the present review should be able to substantially slow down the aging process, extending our productive, youthful lives, without frailty.


Aging; anti-aging approaches; dietary patterns; nutraceuticals; nutrient sensing pathways


Introduction to the special focus issue on the impact of diet on gut microbiota composition and function and future opportunities for nutritional modulation of the gut microbiome to improve human health.

Donovan SM.

Gut Microbes. 2017 Feb 28:1-7. doi: 10.1080/19490976.2017.1299309. [Epub ahead of print]

PMID: 28282253




Over the past decade, application of culture-independent, next generation DNA sequencing has dramatically enhanced our understanding of the composition of the gut microbiome and its association with human states of health and disease. Host genetics, age, and environmental factors such as where and who you live with, use of pre-, pro- and antibiotics, exercise and diet influence the short- and long-term composition of the microbiome. Dietary intake is a key determinant of microbiome composition and diversity and studies to date have linked long-term dietary patterns as well as short-term dietary interventions to the composition and diversity of the gut microbiome. The goal of this special focus issue was to review the role of diet in regulating the composition and function of the gut microbiota across the lifespan, from pregnancy to old age. Overall dietary patterns, as well as perturbations such as undernutrition and obesity, as well as the effects of dietary fiber/prebiotics and fat composition are explored.


diet; fat; fiber; microbiota; undernutrition


[The below paper is not pdf-availed.]

Mediterranean Diet and 10-year (2002-2012) Incidence of Diabetes and Cardiovascular Disease in Participants with Prediabetes: The ATTICA study.

Filippatos TD, Panagiotakos DB, Georgousopoulou EN, Pitaraki E, Kouli GM, Chrysohoou C, Tousoulis D, Stefanadis C, Pitsavos C; ATTICA Study Group..

Rev Diabet Stud. 2016 Winter;13(4):226-235. doi: 10.1900/RDS.2016.13.226.

PMID: 28278309



Prediabetes has been related to an increased risk of developing diabetes and cardiovascular disease (CVD).


The aim of the present study was to examine the effect of the Mediterranean diet on diabetes and CVD risk in subjects with impaired fasting glucose (IFG, i.e. fasting plasma glucose 100-125 mg/dl).


During 2001-2002, 3042 men and women (>18y) were enrolled for the study. The participants showed no clinical evidence of CVD or any other chronic disease, and were living in the greater Athens (Greece) area. In 2011 and 2012, the 10-year follow-up examinations were performed, including a working sample of n = 1875 participants without diabetes at baseline. Adherence to the Mediterranean diet at baseline evaluation was assessed using the MedDietScore (range 0-55).


The prediabetic subjects (n = 343) had a significantly higher incidence of diabetes (25% vs. 10%, p < 0.001) and CVD (17.8% vs. 12.3%, p = 0.007) compared with subjects with normal glucose values. A significant trend towards lower diabetes and CVD incidence was observed with medium and high adherence to the Mediterranean diet compared with low adherence (p < 0.001). High adherence to the Mediterranean diet (>35/55 score) was associated with lower 10-year incidence of diabetes and CVD. In multiple logistic regression models, participants with high levels of adherence to the Mediterranean diet were significantly less affected by diabetes and CVD than those with low adherence levels.


High adherence to the Mediterranean diet is associated with a low risk of developing diabetes and CVD in prediabetic subjects.


Effect of excess iodine intake on thyroid diseases in different populations: A systematic review and meta-analyses including observational studies.

Katagiri R, Yuan X, Kobayashi S, Sasaki S.

PLoS One. 2017 Mar 10;12(3):e0173722. doi: 10.1371/journal.pone.0173722.

PMID: 28282437





Although several reports concerning the association of iodine excess and thyroid disease have appeared, no systematic review of the association between iodine excess intake and thyroid diseases, especially hyperthyroidism and hypothyroidism, has yet been reported.


We conducted a systematic search of Ovid MEDLINE, PubMed, Cochrane Central Register of Controlled Trials databases, Ichushi-Web and CiNii database for intervention trials and observational studies. Search terms were constructed from related words for excess AND iodine intake or excretion AND thyroid hormones or diseases AND study designs. After considering the qualitative heterogeneity among studies, a meta-analysis was conducted and odds ratios and 95% confidence intervals (CI) were estimated in random-effects models. A protocol was registered with PROSPERO (No. CRD42015028081).


50 articles were included, including three intervention trials, six case-control studies, six follow-up studies and 35 cross-sectional studies. Three cross-sectional studies in adults included in meta-analysis. Odds ratio of overt and subclinical hypothyroidism between excess and adequate populations were 2.78 (CI:1.47 to 5.27) and 2.03 (CI:1.58 to 2.62) in adults, respectively. Source of excess iodine status was mainly iodized salt or water in included studies.


Although universal salt iodization has improved goiter rates, chronic exposure to excess iodine from water or poorly monitored salt are risk factors for hypothyroidism in free-living populations. Monitoring of both iodine concentration in salt as well as the iodine concentration in local drinking water are essential to preventing thyroid diseases. Hypothyroidism should be also carefully monitored in areas with excess iodine. Because of the low quality and limited number of included studies, further evidence and review are required.

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Profiles in emotional aging: does age matter?

Etxeberria I, Etxebarria I, Urdaneta E.

Aging Ment Health. 2017 Feb 17:1-9. doi: 10.1080/13607863.2017.1286450. [Epub ahead of print]

PMID: 28282728




The aim of this research project was to define emotional profiles in elderly people and to analyze the presence of each one in different age groups (from 65 to 74, 75 to 84, 85 to 94 and 95 to 104).


The sample group comprised 257 elderly people not suffering from cognitive impairment who were independent in the Basic and Instrumental Activities of Daily Living. The following emotional variables were analyzed: positive and negative affect, life satisfaction, loneliness, and regulation strategies.


Cluster analyses revealed three emotional profiles: 'dissatisfied' (elderly people with high levels of negative affect and loneliness who are unhappy with their lives and use problem solving to regulate their emotions), 'happy' (those with good levels of positive affect and life satisfaction, low levels of loneliness and negative affect and little use of passive strategies), and 'resilient' (those with low levels of positive and negative affect and medium levels of loneliness who are more or less satisfied with their lives and who use passive strategies to regulate their emotions). A relationship was observed between age and profile. Among the under 85s, the most common profile was 'happy', while among the over 85s, the most common profile was 'resilient.' The 'happy' profile was also observed in participants over the age of 85, although to a lesser extent. The prevalence of the 'dissatisfied' profile decreased with age.


These results highlight the fact that although age seems to be a key factor in determining profile, individual differences should not be overlooked, even among the oldest old.


Emotional profiles; centenarians; oldest old


[i did not know cod had that much iodine.]

Lean Fish Consumption Is Associated with Beneficial Changes in the Metabolic Syndrome Components: A 13-Year Follow-Up Study from the Norwegian Tromsø Study.

Tørris C, Molin M, Småstuen MC.

Nutrients. 2017 Mar 8;9(3). pii: E247. doi: 10.3390/nu9030247.

PMID: 28282859




Fish consumption may have beneficial effects on metabolic syndrome (MetS); however, limited information of such associations exists. This study investigated possible associations between fish consumption and changes in MetS components during a 13-year follow-up period.


The sample included participants (26-69 years) from the Tromsø Study 4 (1994-1995, n = 23,907) and Tromsø Study 6 (2007-2008, n = 12,981). Data were collected using questionnaires including food frequency questions, non-fasting blood samples, and physical examinations. MetS was defined using the Joint Interim Societies (JIS) definition, in which one point was given for each MetS criteria fulfilled (metabolic score). Longitudinal analyses were performed using Linear mixed models.


For both genders, lean fish consumption once a week or more was significantly associated with decreased future metabolic score, decreased triglycerides, and increased high-density lipoprotein (HDL)-cholesterol, whereas decreased waist circumference and blood pressure was identified only for men (age adjusted models). Fatty fish consumption was significantly associated with increased waist circumference for both genders and increased HDL-cholesterol levels in men. Conclusion: The results suggest that fatty and lean fish consumption may influence MetS differently and that lean fish consumption in particular seems to be associated with beneficial changes in the MetS components.


diet; fatty fish; fish consumption; insulin resistance; lean fish; metabolic syndrome; processed fish


Clinical and Metabolic Response to Vitamin D Supplementation in Endometrial Hyperplasia: a Randomized, Double-Blind, Placebo-Controlled Trial.

Tabassi Z, Bagheri S, Samimi M, Gilasi HR, Bahmani F, Chamani M, Asemi Z.

Horm Cancer. 2017 Mar 10. doi: 10.1007/s12672-017-0290-9. [Epub ahead of print]

PMID: 28283863



There was inconsistent evidence showing that vitamin D intake may be associated with reduced cancer risk due to optimized metabolic profile and reduced oxidative stress. However, we are not aware of any study evaluating the effects of vitamin D supplementation on clinical response and metabolic status of patients with endometrial hyperplasia (EH). This research was done to evaluate the effects of vitamin D supplementation on clinical response and metabolic status of patients with EH. This randomized, double-blind, placebo-controlled trial was conducted among 60 women diagnosed with EH. EH diagnosis was made based on specific diagnostic procedures of biopsy. Participants were randomly assigned into two groups to intake either 50,000 IU vitamin D3 supplements (n = 30) or placebo (n = 30) every 2 weeks for 12 weeks. After the 12-week intervention, compared with the placebo, vitamin D supplementation increased serum-25(OH) vitamin D levels (+12.0 ± 10.4 vs. +1.9 ± 7.1 ng/mL, P < 0.001). In addition, vitamin D administration was associated with significant decreases in fasting plasma glucose (FPG) (-1.6 ± 7.0 vs. +2.1 ± 6.1 mg/dL, P = 0.03), serum insulin levels (-0.8 ± 1.9 vs. +1.1 ± 3.5 μIU/mL, P = 0.01), homeostasis model of assessment-insulin resistance (HOMA-IR) (-0.2 ± 0.6 vs. +0.3 ± 0.8, P = 0.01), and a significant increase in the quantitative insulin sensitivity check index (QUICKI) (+0.003 ± 0.01 vs. -0.01 ± 0.02, P = 0.02) compared with the placebo. Additionally, a significant decrease in serum high-sensitivity C-reactive protein (hs-CRP) (-1.9 ± 2.8 vs. -0.003 ± 2.0 μg/mL, P = 0.003) and a significant rise in plasma total antioxidant capacity (TAC) values (+62.5 ± 53.5 vs. +7.5 ± 34.1 mmol/L, P < 0.001) were observed following supplementation with vitamin D compared with the placebo. In conclusion, vitamin D3 supplementation for 12 weeks among women with EH had beneficial effects on glucose metabolism, serum hs-CRP, and plasma TAC concentrations. In addition, vitamin D may have played an indirect role in reducing complications of EH due to its effect on improved glycemic control, hs-CRP, and TAC concentrations.

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Cystic fibrosis patients living 10 years longer in Canada than U.S.

Researchers identify differences in diet, health insurance and access to lung transplants

By Susan Noakes,

CBC News

Posted: Mar 13, 2017



Cognitive functioning of individuals aged 90 years and older without dementia: a systematic review.

Legdeur N, Binnekade TT, Otten RH, Badissi M, Scheltens P, Visser PJ, Maier AB.

Ageing Res Rev. 2017 Mar 8. pii: S1568-1637(16)30275-6. doi: 10.1016/j.arr.2017.02.006. [Epub ahead of print] Review.

PMID: 28284872




Reference values to define cognitive impairment in individuals aged 90 years and older are lacking. We systematically reviewed the literature to determine the level of cognitive functioning of individuals aged 90 years and older without dementia.


The search identified 3972 articles of which 20 articles were included in the review. We calculated mean cognitive test scores and cut-off scores for cognitive tests published in two or more articles.


The mean cognitive test scores (SD)/cut-off scores for individuals aged 90 years and older without dementia of the five most commonly used cognitive tests were: MMSE: 26.6 (2.6)/23.3 points, Digit Span forward: 5.9 (1.8)/3.6 digits, Digit Span backward: 4.4 (1.6)/2.4 digits, TMT-A: 85.8 (42.5)/140.2seconds and TMT-B: 220.3 (99.2)/347.3seconds.


We provided mean cognitive test scores and cut-off scores that will improve the diagnostic process of cognitive impairment in individuals aged 90 years and older.


cognitive functioning; cognitive impairment; healthy ageing; individuals aged 90 years and older; nonagenarians; reference values


Skipping breakfast reduces energy intake and physical activity in healthy women who are habitual breakfast eaters: A randomized crossover trial.

Yoshimura E, Hatamoto Y, Yonekura S, Tanaka H.

Physiol Behav. 2017 Mar 8. pii: S0031-9384(16)31165-9. doi: 10.1016/j.physbeh.2017.03.008. [Epub ahead of print]

PMID: 28284879



Many epidemiological studies indicate a positive relationship between skipping breakfast (SB) and obesity. However, it is unclear whether SB affects energy intake and physical activity during the day. The objective of the present study was to evaluate the acute effects of SB on energy intake and physical activity under free-living conditions. The present study used a randomized, crossover trial design comparing eating breakfast (EB) and SB days. Twenty lean, healthy women 21-25years old who were habitual breakfast eaters (≥5daysperweek) took part in this study. On EB days, participants were provided a standard breakfast (542kcal). The meals and physical activity after breakfast were under free-living conditions. The meals consisted of foods available at supermarkets, restaurants, and convenience stores. Dietary intake was evaluated by adding values from food labels. Physical activity was assessed using a tri-axial accelerometer. Energy intake at lunch was significantly increased after SB compared with EB (+131±188kcal; p=0.0057). Total energy intake per day was significantly lower after SB compared with EB (-262±428kcal, p=0.013). Physical activity energy expenditure was slightly lower after SB compared with EB (-41±75kcal in the morning, p=0.024; -56±129kcalperday, p=0.064). Step counts and time spent physically active over the whole day were not significantly different between conditions. Skipping breakfast reduced energy intake during the day and morning physical activity in healthy women who were habitual breakfast eaters. The decreased energy expenditure related to physical activity after SB did not exceed the decreased energy intake.

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Age-Related Changes in Locomotor Performance Reveal a Similar Pattern for Caenorhabditis elegans, Mus domesticus, Canis familiaris, Equus caballus, and Homo sapiens.

Marck A, Berthelot G, Foulonneau V, Marc A, Antero-Jacquemin J, Noirez P, Bronikowski AM, Morgan TJ, Garland T Jr, Carter PA, Hersen P, Di Meglio JM, Toussaint JF.

J Gerontol A Biol Sci Med Sci. 2016 Aug 13. pii: glw136. [Epub ahead of print]

PMID: 27522057




Locomotion is one of the major physiological functions for most animals. Previous studies have described aging mechanisms linked to locomotor performance among different species. However, the precise dynamics of these age-related changes, and their interactions with development and senescence, are largely unknown. Here, we use the same conceptual framework to describe locomotor performances in Caenorhabditis elegans, Mus domesticus, Canis familiaris, Equus caballus, and Homo sapiens We show that locomotion is a consistent biomarker of age-related changes, with an asymmetrical pattern throughout life, regardless of the type of effort or its duration. However, there is variation (i) among species for the same mode of locomotion, (ii) within species for different modes of locomotion, and (iii) among individuals of the same species for the same mode of locomotion. Age-related patterns are modulated by genetic (such as selective breeding) as well as environmental conditions (such as temperature). However, in all cases, the intersection of the rising developmental phase and the declining senescent phase reveals neither a sharp transition nor a plateau, but a smooth transition, emphasizing a crucial moment: the age at peak performance. This transition may define a specific target for future investigations on the dynamics of such biological interactions.


Aging; Comparative biology; Epidemiology; Exercise physiology; Senescence


Chlorogenic Acid Extends the Lifespan of Caenorhabditis elegans via Insulin/IGF-1 Signaling Pathway.

Zheng SQ, Huang XB, Xing TK, Ding AJ, Wu GS, Luo HR.

J Gerontol A Biol Sci Med Sci. 2016 Jul 4. pii: glw105. [Epub ahead of print]

PMID: 27378235



Coffee and tea, two of the most popular drinks around the world, share many in common from chemical components to beneficial effects on human health. One of their shared components, the polyphenols, most notably chlorogenic acid (CGA), was supposed to account for many of the beneficial effects on ameliorating diseases occurred accompanying people aging, such as the antioxidant effect and against diabetes and cardiovascular disease. CGA is also present in many traditional Chinese medicines. However, the mechanism of these effects was vague. The aging signaling pathways were conservative from yeast and worms to mammals. So, we tested if CGA had an effect on aging in Caenorhabditis elegans We found that CGA could extend the lifespan of C. elegans by up to 20.1%, delay the age-related decline of body movement, and improve stress resistance. We conducted genetic analysis with a series of worm mutants and found that CGA could extend the lifespan of the mutants of eat-2, glp-1, and isp-1, but not of daf-2, pdk-1, akt-1, akt-2, sgk-1, and clk-1 CGA could activate the FOXO transcription factors DAF-16, HSF-1, SKN-1, and HIF-1, but not SIR-2.1. Taken together, CGA might extend the lifespan of C. elegans mainly via DAF-16 in insulin/IGF-1 signaling pathway.


Caenorhabditis elegans; Chlorogenic acid; DAF-16/FOXO; Longevity; Stress resistance




Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake.

Nagano M, Shimizu K, Kondo R, Hayashi C, Sato D, Kitagawa K, Ohnuki K.

Biomed Res. 2010 Aug;31(4):231-7.

PMID: 20834180 Free Article



Hericium erinaceus, a well known edible mushroom, has numerous biological activities. Especially hericenones and erinacines isolated from its fruiting body stimulate nerve growth factor (NGF) synthesis, which expects H. erinaceus to have some effects on brain functions and autonomic nervous system. Herein, we investigated the clinical effects of H. erinaceus on menopause, depression, sleep quality and indefinite complaints, using the Kupperman Menopausal Index (KMI), the Center for Epidemiologic Studies Depression Scale (CES-D), the Pittsburgh Sleep Quality Index (PSQI), and the Indefinite Complaints Index (ICI). Thirty females were randomly assigned to either the H. erinaceus (HE) group or the placebo group and took HE cookies or placebo cookies for 4 weeks. Each of the CES-D and the ICI score after the HE intake was significantly lower than that before. In two terms of the ICI, "insentive" and "palpitatio", each of the mean score of the HE group was significantly lower than the placebo group. "Concentration", "irritating" and "anxious" tended to be lower than the placebo group. Our results show that HE intake has the possibility to reduce depression and anxiety and these results suggest a different mechanism from NGF-enhancing action of H. erinaceus.


Chemistry, Nutrition, and Health-Promoting Properties of Hericium erinaceus (Lion's Mane) Mushroom Fruiting Bodies and Mycelia and Their Bioactive Compounds.

Friedman M.

J Agric Food Chem. 2015 Aug 19;63(32):7108-23. doi: 10.1021/acs.jafc.5b02914. Review.

PMID: 26244378



The culinary and medicinal mushroom Hericium erinaceus is widely consumed in Asian countries, but apparently not in the United States, for its nutritional and health benefits. To stimulate broader interest in the reported beneficial properties, this overview surveys and consolidates the widely scattered literature on the chemistry (isolation and structural characterization) of polysaccharides and secondary metabolites such as erinacines, hericerins, hericenones, resorcinols, steroids, mono- and diterpenes, and volatile aroma compounds, nutritional composition, food and industrial uses, and exceptional nutritional and health-promoting aspects of H. erinaceus. The reported health-promoting properties of the mushroom fruit bodies, mycelia, and bioactive pure compounds include antibiotic, anticarcinogenic, antidiabetic, antifatigue, antihypertensive, antihyperlipodemic, antisenescence, cardioprotective, hepatoprotective, nephroprotective, and neuroprotective properties and improvement of anxiety, cognitive function, and depression. The described anti-inflammatory, antioxidative, and immunostimulating properties in cells, animals, and humans seem to be responsible for the multiple health-promoting properties. A wide range of research advances and techniques are described and evaluated. The collated information and suggestion for further research might facilitate and guide further studies to optimize the use of the whole mushrooms and about 70 characterized actual and potential bioactive secondary metabolites to help prevent or treat human chronic, cognitive, and neurological diseases.


Hericium erinaceus; anti-inflammatory effects; antioxidant capacity; bioactive compounds; cell, rodent, and human studies; erinaceolactones; erinacerins; erinacines; food processing; food use; fruit bodies; glycoproteins; health-promoting properties; immunostimulation; multifunctional health properties; mushrooms; mycelia; nutrients; phylogenetics; polysaccharides; research needs; resorcinols; sterols; volatile compounds


Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial.

Mori K, Inatomi S, Ouchi K, Azumi Y, Tuchida T.

Phytother Res. 2009 Mar;23(3):367-72. doi: 10.1002/ptr.2634.

PMID: 18844328



A double-blind, parallel-group, placebo-controlled trial was performed on 50- to 80-year-old Japanese men and women diagnosed with mild cognitive impairment in order to examine the efficacy of oral administration of Yamabushitake (Hericium erinaceus), an edible mushroom, for improving cognitive impairment, using a cognitive function scale based on the Revised Hasegawa Dementia Scale (HDS-R). After 2 weeks of preliminary examination, 30 subjects were randomized into two 15-person groups, one of which was given Yamabushitake and the other given a placebo. The subjects of the Yamabushitake group took four 250 mg tablets containing 96% of Yamabushitake dry powder three times a day for 16 weeks. After termination of the intake, the subjects were observed for the next 4 weeks. At weeks 8, 12 and 16 of the trial, the Yamabushitake group showed significantly increased scores on the cognitive function scale compared with the placebo group. The Yamabushitake group's scores increased with the duration of intake, but at week 4 after the termination of the 16 weeks intake, the scores decreased significantly. Laboratory tests showed no adverse effect of Yamabushitake. The results obtained in this study suggest that Yamabushitake is effective in improving mild cognitive impairment.

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Stirring the Pot: Can Dietary Modification Alleviate the Burden of CKD?

Snelson M, Clarke RE, Coughlan MT.

Nutrients. 2017 Mar 11;9(3). pii: E265. doi: 10.3390/nu9030265. Review.

PMID: 28287463



Diet is one of the largest modifiable risk factors for chronic kidney disease (CKD)-related death and disability. CKD is largely a progressive disease; however, it is increasingly appreciated that hallmarks of chronic kidney disease such as albuminuria can regress over time. The factors driving albuminuria resolution remain elusive. Since albuminuria is a strong risk factor for GFR loss, modifiable lifestyle factors that lead to an improvement in albuminuria would likely reduce the burden of CKD in high-risk individuals, such as patients with diabetes. Dietary therapy such as protein and sodium restriction has historically been used in the management of CKD. Evidence is emerging to indicate that other nutrients may influence kidney health, either through metabolic or haemodynamic pathways or via the modification of gut homeostasis. This review focuses on the role of diet in the pathogenesis and progression of CKD and discusses the latest findings related to the mechanisms of diet-induced kidney disease. It is possible that optimizing diet quality or restricting dietary intake could be harnessed as an adjunct therapy for CKD prevention or progression in susceptible individuals, thereby reducing the burden of CKD.


advanced glycation end products; albuminuria; cardiovascular disease; chronic kidney disease; diabetes; diet; inflammation



Arosio B, Ostan R, Mari D, Damanti S, Ronchetti F, Arcudi S, Scurti M, Franceschi C, Monti D.

Mech Ageing Dev. 2017 Mar 9. pii: S0047-6374(16)30245-7. doi: 10.1016/j.mad.2017.02.010. [Epub ahead of print] Review.

PMID: 28286214



Human life expectancy and the number of the oldest old are rapidly increasing worldwide. Advanced age is the main risk factor for dementia, representing one of the major causes of disability/dependency among older people with a strong impact on their families/caregivers. Centenarians have reached the extreme limits of human life escaping or delaying the major age-related diseases. Thus, these extraordinary individuals embody the best model to answer the crucial question if cognitive decline and dementia are progressive and unavoidable occurrences of increasing age. Despite a growing amount of data underlines the importance of cognitive function for quality of life and survival in old age, studies on centenarians have paid more attention to their physical condition rather than the assessment of their actual cognitive abilities. Accordingly, this work aims to summarize available data on the prevalence of dementia in centenarians and to critically address topics which can have a relevant impact on the cognitive assessment/status of the oldest old: i) lack of standardized tools for cognitive assessment; ii) criteria and threshold to establish the presence of dementia; iii) influence of birth cohort and education; iv) role of depression or positive attitude towards life; v) gender differences.


Centenarians; cognitive assessment; cognitive decline; dementia; depression; gender


Thyroid hormones in extreme longevity.

Garasto S, Montesanto A, Corsonello A, Lattanzio F, Fusco S, Passarino G, Giarritta VP, Corica F.

Mech Ageing Dev. 2017 Mar 9. pii: S0047-6374(16)30180-4. doi: 10.1016/j.mad.2017.03.002. [Epub ahead of print] Review.

PMID: 28286215



The aim of the present review was to summarize knowledge about thyroid hormones (THs) and longevity. Longevity is a complex multifactorial phenomenon on which specific biological pathways, including hormonal networks involved in the regulation of homeostasis and survival, exert a strong impact. THs are the key responsible for growth, metabolism rate and energy expenditure, and help in maintaining cognition, bone and cardiovascular health. THs production and metabolism are fine tuned, and may help the organism to cope with a variety of environmental challenges. Experimental evidence suggests that hypothyroid state may favor longevity by reducing metabolism rate, oxidative stress and cell senescence. Data from human studies involving healthy subjects and centenarians seem to confirm this view, but THs changes observed in older patients affected by chronic diseases cannot be always interpreted as a protective adaptive mechanism aimed at reducing catabolism and prolonging survival. Medications, selected chronic diseases and multi-morbidity can interfere with thyroid function, and their impact is still to be elucidated.

Copyright © 2017. Published by Elsevier B.V.


Age-related diseases; Aging; Centenarians; Longevity; Thyroid


Treatment of reactive hypoglycemia with the macrobiotic Ma-pi 2 diet as assessed by continuous glucose monitoring: The MAHYP randomized crossover trial.

Soare A, Khazrai YM, Fontana L, Del Toro R, Lazzaro MC, Di Rosa C, Buldo A, Fioriti E, Maddaloni E, Angeletti S, Di Mauro A, Gesuita R, Skrami E, Tuccinardi D, Fallucca S, Pianesi M, Pozzilli P.

Metabolism. 2017 Apr;69:148-156. doi: 10.1016/j.metabol.2017.01.023.

PMID: 28285645




Nutritional therapy is recommended for management of reactive hypoglycemia (RH), a condition characterized by hypoglycemia that occurs within four hours after a meal. The macrobiotic Ma-Pi 2 diet improves glycemic control in subjects with type 2 diabetes. We explored the effect of this diet on outcomes in non-diabetic individuals with RH.


Twelve subjects with RH were randomized to the Ma-Pi 2 diet for three days and a control diet for three days in a randomized crossover design. Subjects received snacks on two days out of each three-day period only, and were monitored using continuous glucose monitoring. The 24-h period was divided into daytime (08:00-22:30h [subdivided into 'daytime without snacks' and 'daytime with snacks']) and night-time (22:31-07:59h). The effects of the two diets on the number of RH events (blood glucose <70mg/dL [3.9mmol/L]) and the percentage distribution of glucose readings within each of 16 glycemic intervals from <40mg/dL (2.2mmol/L) to >180mg/dL (4.4mmol/L) were determined.


There were significantly fewer RH events on the Ma-Pi 2 diet than the control diet during daytime without snacks (-2.5 events; 95% CI: -7.5, 0.0; P=0.022) and daytime with snacks (-4.25 events; 95% CI: -7.5; -2.0; P=0.013) but no difference at night. The percentage of glucose readings in the interval 71-80mg/dL (3.9-4.4mmol/L) was significantly higher on the control diet during daytime with and without snacks (P=0.03 for both), while the percentage of glucose readings in the interval 91-100mg/dL (5.1-5.6mmol/L) was significantly higher on the Ma-Pi 2 diet during daytime without snacks (P=0.02).


The macrobiotic Ma-Pi 2 diet reduced blood glucose excursions during the day, thereby facilitating glycemic control in subjects with RH. The Ma-Pi 2 diet represents an effective nutritional tool for management of RH.


Continuous glucose monitoring; Macrobiotic Ma-pi 2 diet; Reactive hypoglycemia; Type-2 diabetes


Associations between dietary intakes of iron, copper and zinc with risk of type 2 diabetes mellitus: A large population-based prospective cohort study.

Eshak ES, Iso H, Maruyama K, Muraki I, Tamakoshi A.

Clin Nutr. 2017 Feb 28. pii: S0261-5614(17)30060-2. doi: 10.1016/j.clnu.2017.02.010. [Epub ahead of print]

PMID: 28285974




Abnormal homeostasis of iron, copper and zinc has been included in the pathogenesis of type 2 diabetes mellitus (T2DM). However, the evidence of associations between dietary intakes of these elements and T2DM is limited. We thought to examine the association between dietary intakes of iron, copper and zinc with risk of T2DM in Japanese population.


A prospective study encompassing 16,160 healthy Japanese men and women aged 40-65 years in whom the associations between dietary intakes of iron, copper and zinc, determined by a validated self-administered food frequency questionnaire, with risk of 5-year cumulative incidence of validated physician-diagnosed T2DM, were evaluated by logistic regression model.


We ascertained 396 self-reported new cases of diabetes within 5-year period. Dietary intakes of iron (total and nonheme but not heme iron) and copper were positively associated with risk of T2DM; the multivariable OR in the highest versus lowest quartiles of intakes were 1.32 (1.04, 1.70; P-trend = 0.03) and 1.55 (1.13, 2.02; P-trend = 0.003), respectively. These associations were more evident in the high risk group; older, overweight, smokers and those with family history of diabetes. The dietary intake of zinc was inversely associated with risk of T2DM; the multivariable OR was 0.64 (0.54, 1.00; P-trend = 0.003), and such association was evident among younger subjects (age 40-55 years) only.


Dietary intakes of iron and copper were associated with a higher risk, while dietary intake of zinc was associated with a reduced risk of T2DM in Japanese population.


Cohort study; Copper; Iron; Japanese; Type 2 diabetes mellitus; Zinc


Monounsaturated fatty acids might be key factors in the Mediterranean diet that suppress rheumatoid arthritis disease activity: The TOMORROW study.

Matsumoto Y, Sugioka Y, Tada M, Okano T, Mamoto K, Inui K, Habu D, Koike T.

Clin Nutr. 2017 Feb 21. pii: S0261-5614(17)30061-4. doi: 10.1016/j.clnu.2017.02.011. [Epub ahead of print]

PMID: 28285975




The Mediterranean diet is reportedly effective in suppressing disease activity in rheumatoid arthritis (RA), but the key elements responsible for this effect remain unknown. The presented study therefore aimed to identify such elements.


This study included 208 consecutive patients with RA (RA group) and 205 age- and sex-matched healthy volunteers (controls) from the prospective "TOMORROW" cohort study that has been ongoing since 2010 were included in this study. Food and nutrient intake was assessed using the brief self-administered diet history questionnaire (BDHQ), Mediterranean diet scores were calculated based on intake by controls and disease activity was determined from disease activity scores in 28 joints and erythrocyte sedimentation rates (DAS28-ESR).


Intake of monounsaturated fatty acids (MUFA) was significantly lower in the RA, than in the control group (P = 0.003) and the ratio of consumed monounsaturated to saturated fatty acid (MUFA/SFA) significantly differed within the RA group after being sub-classified according to DAS28-ESR. Moreover, DAS28-ESR significantly correlated with MUFA/SFA intake after age adjustment (R = -0.228, P < 0.01). Logistic regression analysis selected high MUFA intake as an independent predictor of remission in the RA group with borderline boundary significance (odds ratio, 1.97; 95% CI, 0.98-3.98; P = 0.057). Changes in DAS28-ESR between 2010 and 2011 significantly correlated with MUFA/SFA intake after age adjustment (R = 0.180, P = 0.01).


Daily MUFA intake, a component of the Mediterranean diet score, might suppress disease activity in RA patients.


Diet therapy; Disease activity; Inflammation; Mediterranean diet; Nutrition; Rheumatoid arthritis


Human aging, finite lives and the idealization of clocks.

Baars J.

Biogerontology. 2016 Oct 22. [Epub ahead of print]

PMID: 27771833



Aging and time are interconnected because aging is basically living seen in a temporal perspective. This makes 'time' an important concept in trying to explain aging. However, throughout modernity time has increasingly been identified as clock time: perfectly fit to measure 'age' as time since birth but failing to explain 'age' as an indicator of aging processes and even less adequate to grasp the lived time of human beings. Moreover, the clock as a cultural idol of instrumentalist perfection has led to approaching human aging in terms of maintenance and repair, inspiring a neglect and depreciation of human vulnerability. The instrumentalist culture of late modern society, including its health cure system, has difficulties to relate to the elusive but inevitable limitations of finite life. This tendency is supported by outspoken approaches in biogerontology indulging in perspectives of infinite human lives; a message that is eagerly consumed by the mass media. Moreover, as most people can be expected to survive into old age, thinking about finitude is easily postponed and reserved for those who are 'really old'. Instead of reducing aging to the opposite or mere continuation of vital adulthood, it should be seen as something with a potentially broad and deep significance: a process of learning to live a finite life.


Finitude; Philosophy of aging; Time; Vulnerability

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The role of transplanted visceral fat from the long-lived growth hormone receptor knockout mice on insulin signaling

Mohammed T. BennisAugusto SchneiderBerta VictoriaAndrew DoDenise S. WiesenbornLina SpinelAdam GesingJohn J. KopchickShadab A. SiddiqiMichal M. Masternak

First Online: 18 January 2017

DOI: 10.1007/s11357-017-9957-y

GeroScience (2017) 39: 51-9. doi:10.1007/s11357-017-9957-y



Growth hormone receptor knockout mice (GHRKO) are characterized by high insulin sensitivity and extended lifespan. Interestingly, the secretory activity of visceral fat in GHRKO mice is altered, stimulating whole body insulin sensitivity. In this study, we transplanted normal (N) mice with visceral fat pads from GHRKO or N mice to determine the role of visceral fat on the insulin signaling. We found that the transplant of visceral fat from GHRKO mice to N mice (N-GHRKO) improved whole body insulin sensitivity when comparing with sham-operated mice (N-S) and with mice that received visceral fat from N mice (N-N). This was associated with increased hepatic insulin sensitivity as observed by the increased phosphorylated insulin receptor and increased hepatic expression of Pparα and Pparγ. In conclusion, we demonstrated that visceral fat transplant from GHRKO mice into normal mice enhanced insulin sensitivity and glucose tolerance. These results further confirm the differential physiological role played by visceral adipose tissue from GH receptor deficient mice, indicating that the increase of this fat depot can be associated with beneficial effects on insulin signaling and longevity.


GHRKOGHRInsulin resistanceLongevityType 2 diabetes


The frailty index outperforms DNA methylation age and its derivatives as an indicator of biological age

Sangkyu Kim, Leann MyersJennifer WyckoffKatie E. CherryS. Michal Jazwinski

Open Access

First Online: 14 January 2017 DOI: 10.1007/s11357-017-9960-3

GeroScience (2017). pp 1–10 doi:10.1007/s11357-017-9960-3


The measurement of biological age as opposed to chronological age is important to allow the study of factors that are responsible for the heterogeneity in the decline in health and function ability among individuals during aging. Various measures of biological aging have been proposed. Frailty indices based on health deficits in diverse body systems have been well studied, and we have documented the use of a frailty index (FI34) composed of 34 health items, for measuring biological age. A different approach is based on leukocyte DNA methylation. It has been termed DNA methylation age, and derivatives of this metric called age acceleration difference and age acceleration residual have also been employed. Any useful measure of biological age must predict survival better than chronological age does. Meta-analyses indicate that age acceleration difference and age acceleration residual are significant predictors of mortality, qualifying them as indicators of biological age. In this article, we compared the measures based on DNA methylation with FI34. Using a well-studied cohort, we assessed the efficiency of these measures side by side in predicting mortality. In the presence of chronological age as a covariate, FI34 was a significant predictor of mortality, whereas none of the DNA methylation age-based metrics were. The outperformance of FI34 over DNA methylation age measures was apparent when FI34 and each of the DNA methylation age measures were used together as explanatory variables, along with chronological age: FI34 remained significant but the DNA methylation measures did not. These results indicate that FI34 is a robust predictor of biological age, while these DNA methylation measures are largely a statistical reflection of the passage of chronological time.


AgingBiological ageFrailtyDNA methylationMortality


Metabolic Effects of Inflammation on Vitamin A and Carotenoids in Humans and Animal Models

Lewis P Rubin, A Catharine Ross, Charles B Stephensen, Torsten Bohn, and Sherry A Tanumihardjo

Adv Nutr 2017; 8:197-212 doi:10.3945/an.116.014167



The association between inflammation and vitamin A (VA) metabolism and status assessment has been documented in multiple studies with animals and humans. The relation between inflammation and carotenoid status is less clear. Nonetheless, it is well known that carotenoids are associated with certain health benefits. Understanding these relations is key to improving health outcomes and mortality risk in infants and young children. Hyporetinolemia, i.e., low serum retinol concentrations, occurs during inflammation, and this can lead to the misdiagnosis of VA deficiency. On the other hand, inflammation causes impaired VA absorption and urinary losses that can precipitate VA deficiency in at-risk groups of children. Many epidemiologic studies have suggested that high dietary carotenoid intake and elevated plasma concentrations are correlated with a decreased risk of several chronic diseases; however, large-scale carotenoid supplementation trials have been unable to confirm the health benefits and in some cases resulted in controversial results. However, it has been documented that dietary carotenoids and retinoids play important roles in innate and acquired immunity and in the body’s response to inflammation. Although animal models have been useful in investigating retinoid effects on developmental immunity, it is more challenging to tease out the effects of carotenoids because of differences in the absorption, kinetics, and metabolism between humans and animal models. The current understanding of the relations between inflammation and retinoid and carotenoid metabolism and status are the topics of this review.


biomarkers cytokines infection retinol retinol-binding protein sequestration urinary loss


Magnitude and Timing of the Postprandial Inflammatory Response to a High-Fat Meal in Healthy Adults: A Systematic Review

Sam R Emerson, Stephanie P Kurti, Craig A Harms, Mark D Haub, Tonatiuh Melgarejo, Cindy Logan, and Sara K Rosenkranz

Adv Nutr 2017; 8:213-225 doi:10.3945/an.116.014431



Research findings over the past several decades have shown that inflammation is a prominent feature of many chronic diseases, with poor diet being one likely inflammatory stimulus. Specifically, a single high-fat meal (HFM) has been suggested to increase inflammation, although there is currently no consensus with regard to the specific changes in many of the proinflammatory markers that are frequently assessed after an HFM. The aim of this systematic review was to objectively describe the postprandial timing and magnitude of changes in 5 common inflammatory markers: interleukin (IL) 6, C-reactive protein (CRP), tumor necrosis factor (TNF) α, IL-1β, and IL-8. Ten relevant databases were searched, yielding 494 results, of which 47 articles met the pre-established inclusion criteria: 1) healthy men and women aged 18–60 y, 2) consuming a single HFM (≥30% fat, ≥500 kcal), and 3) assessing relevant inflammatory markers postmeal for ≥2 h. The only marker found to consistently change in the postprandial period was IL-6: on average, from a baseline of ∼1.4 pg/mL, it peaked at ∼2.9 pg/mL ∼6 h post-HFM (an average relative change of ∼100%). CRP, TNF-α, IL-1β, and IL-8 did not change significantly in 79% (23 of 29), 68% (19 of 28), 67% (2 of 3), and 75% (3 of 4) of included studies, respectively. We conclude that there is strong evidence that CRP and TNF-α are not responsive at the usual time scale observed in postprandial studies in healthy humans younger than age 60 y. However, future research should further investigate the role of IL-6 in the postprandial period, because it routinely increases even in healthy participants. We assert that the findings of this systematic review on markers of inflammation in the postprandial period will considerably aid in informing future research and advancing clinical knowledge.


cytokine interleukin C-reactive protein postmeal tumor necrosis factor


Effects of Dietary Flavonoids on Reverse Cholesterol Transport, HDL Metabolism, and HDL Function

Courtney L Millar, Quinn Duclos, and Christopher N Blesso

Adv Nutr 2017; 8:226-239 doi:10.3945/an.116.014050



Strong experimental evidence confirms that HDL directly alleviates atherosclerosis. HDL particles display diverse atheroprotective functions in reverse cholesterol transport (RCT), antioxidant, anti-inflammatory, and antiapoptotic processes. In certain inflammatory disease states, however, HDL particles may become dysfunctional and proatherogenic. Flavonoids show the potential to improve HDL function through their well-documented effects on cellular antioxidant status and inflammation. The aim of this review is to summarize the basic science and clinical research examining the effects of dietary flavonoids on RCT and HDL function. Based on preclinical studies that used cell culture and rodent models, it appears that many flavonoids (e.g., anthocyanidins, flavonols, and flavone subclasses) influence RCT and HDL function beyond simple HDL cholesterol concentration by regulating cellular cholesterol efflux from macrophages and hepatic paraoxonase 1 expression and activity. In clinical studies, dietary anthocyanin intake is associated with beneficial changes in serum biomarkers related to HDL function in a variety of human populations (e.g., in those who are hyperlipidemic, hypertensive, or diabetic), including increased HDL cholesterol concentration, as well as HDL antioxidant and cholesterol efflux capacities. However, clinical research on HDL functionality is lacking for some flavonoid subclasses (e.g., flavanols, flavones, flavanones, and isoflavones). Although there has been a tremendous effort to develop HDL-targeted drug therapies, more research is warranted on how the intake of foods or specific nutrients affects HDL function.


flavonoids HDL polyphenols anthocyanins atherosclerosis


Optimizing Protein Intake in Adults: Interpretation and Application of the Recommended Dietary Allowance Compared with the Acceptable Macronutrient Distribution Range

Robert R Wolfe, Amy M Cifelli, Georgia Kostas, and Il-Young Kim

Adv Nutr 2017; 8:266-275 doi:10.3945/an.116.013821




The adult RDA is defined as the average daily level of intake sufficient to meet the nutrient requirements of nearly all healthy people. The RDA for protein for adults ≥18 y of age (0.8 g/kg) has been essentially unchanged for >70 y. In practice, the RDA for protein was derived to estimate the minimum amount of protein that must be eaten to avoid a loss of body nitrogen. The Acceptable Macronutrient Distribution Range (AMDR) (10–35% of calories as protein) was developed to express dietary recommendations in the context of a complete diet. It is noteworthy that the lowest level of protein intake reflected in the AMDR is higher than that of the RDA. Furthermore, recent studies, particularly in older individuals, suggest specific health benefits at levels of protein intake that significantly exceed the RDA. Translation of protein intake recommendations for the general adult population into dietary guidance for individuals requires an understanding of the derivation and intended use of both the protein RDA and AMDR. The following discussion will describe limitations to the derivation and practical application of the RDA compared with the use of the AMDR to help maximize health benefits associated with higher protein intake by using flexible calories inherent in different dietary patterns.


protein nitrogen balance RDA AMDR dietary pattern



Jennifer C Kerns and Jean L Gutierrez

Adv Nutr 2017; 8:395-397 doi:10.3945/an.116.013979


"Because thiamin

must be obtained from the diet, is water soluble, and is not

stored in large amounts in the body, people who are thiamin

deficient (e.g., from calorie-restricted diets ..."

7. Vitamin B1 (thiamine) and dementia.

Gibson GE, Hirsch JA, Fonzetti P, Jordan BD, Cirio RT, Elder J.

Ann N Y Acad Sci. 2016 Mar;1367(1):21-30. doi: 10.1111/nyas.13031.

PMID: 26971083 Free PMC Article




The earliest and perhaps best example of an interaction between nutrition and dementia is related to thiamine (vitamin B1). Throughout the last century, research showed that thiamine deficiency is associated with neurological problems, including cognitive deficits and encephalopathy. Multiple similarities exist between classical thiamine deficiency and Alzheimer's disease (AD) in that both are associated with cognitive deficits and reductions in brain glucose metabolism. Thiamine-dependent enzymes are critical components of glucose metabolism that are reduced in the brains of AD patients and by thiamine decline, and a decrease in their levels could account for the reduction in glucose metabolism. In preclinical models, reduced thiamine can drive AD-like abnormalities, including memory deficits, neuritic plaques, and hyperphosphorylation of tau. Furthermore, excess thiamine diminishes AD-like pathologies. In addition to dietary deficits, drugs or other manipulations that interfere with thiamine absorption can cause thiamine deficiency. Elucidating the reasons why the brains of AD patients are functionally thiamine deficient and determining the effects of thiamine restoration may provide critical information to help treat patients with AD.


Alzheimer's disease; glucose metabolism; mitochondria; thiamine; vitamin B1

Edited by AlPater
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Rejuvenation by Therapeutic Elimination of Senescent Cells.

Krimpenfort P, Berns A.

Cell. 2017 Mar 23;169(1):3-5. doi: 10.1016/j.cell.2017.03.014.

PMID: 28340347



In this issue of Cell, Baar et al. show how FOXO4 protects senescent cell viability by keeping p53 sequestered in nuclear bodies, preventing it from inducing apoptosis. Disrupting this interaction with an all-D amino acid peptide (FOXO4-DRI) restores p53's apoptotic role and ameliorates the consequences of senescence-associated loss of tissue homeostasis.


Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging.

Baar MP, Brandt RM, Putavet DA, Klein JD, Derks KW, Bourgeois BR, Stryeck S, Rijksen Y, van Willigenburg H, Feijtel DA, van der Pluijm I, Essers J, van Cappellen WA, van IJcken WF, Houtsmuller AB, Pothof J, de Bruin RW, Madl T, Hoeijmakers JH, Campisi J, de Keizer PL.

Cell. 2017 Mar 23;169(1):132-147.e16. doi: 10.1016/j.cell.2017.02.031.

PMID: 28340339




The accumulation of irreparable cellular damage restricts healthspan after acute stress or natural aging. Senescent cells are thought to impair tissue function, and their genetic clearance can delay features of aging. Identifying how senescent cells avoid apoptosis allows for the prospective design of anti-senescence compounds to address whether homeostasis can also be restored. Here, we identify FOXO4 as a pivot in senescent cell viability. We designed a FOXO4 peptide that perturbs the FOXO4 interaction with p53. In senescent cells, this selectively causes p53 nuclear exclusion and cell-intrinsic apoptosis. Under conditions where it was well tolerated in vivo, this FOXO4 peptide neutralized doxorubicin-induced chemotoxicity. Moreover, it restored fitness, fur density, and renal function in both fast aging XpdTTD/TTD and naturally aged mice. Thus, therapeutic targeting of senescent cells is feasible under conditions where loss of health has already occurred, and in doing so tissue homeostasis can effectively be restored.


FOXO4; IL6; LMNB1; Senescence; TP53; aging; apoptosis; cell-penetrating peptide; chemotherapy; tissue homeostasis

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Theoretical and Biological Evaluation of the Link between Low Exercise Capacity and Disease Risk.

Koch LG, Britton SL.

Cold Spring Harb Perspect Med. 2017 Apr 7. pii: a029868. doi: 10.1101/cshperspect.a029868. [Epub ahead of print]

PMID: 28389512


Large-scale epidemiological studies show that low exercise capacity is the highest risk factor for all-cause morbidity and mortality relative to other conditions including diabetes, hypertension, and obesity. This led us to formulate the energy transfer hypothesis (ETH): Variation in capacity for energy transfer is the central mechanistic determinant of the divide between disease and health. As a test of this hypothesis, we predicted that two-way selective breeding of genetically heterogeneous rats for low and high intrinsic treadmill running capacity (a surrogate for energy transfer) would also produce rats that differ for disease risks. The lines are termed low-capacity runners (LCRs) and high-capacity runners (HCRs) and, after 36 generations of selection, they differ by more than eightfold in running capacity. Consistent with the ETH, the LCRs score high for developing disease risks, including metabolic syndrome, neurodegeneration, cognitive impairment, fatty liver disease, susceptibility to cancer, and reduced longevity. The HCRs are resistant to the development of these disease risks. Here we synthesize ideas on nonequilibrium thermodynamics and evolution from Ilya Prigogine, Hans Krebs, and Peter Mitchell to formulate theoretic explanations for the ETH. First, at every moment in time, the atoms and molecules of organisms are reorganizing to pursue avenues for energy transfer. Second, this continuous organization is navigating in a constantly changing environment such that "strategies" are perpetually in flux and do not leave a simple footprint (evolution). Third, as a consequence, human populations demonstrate a wide variation in capacity for energy transfer that mirrors mechanistically the divide between disease and health.


Hormetic efficacy of rutin to promote longevity in Drosophila melanogaster.

Chattopadhyay D, Chitnis A, Talekar A, Mulay P, Makkar M, James J, Thirumurugan K.

Biogerontology. 2017 Apr 7. doi: 10.1007/s10522-017-9700-1. [Epub ahead of print]

PMID: 28389882


Hormetins are compounds that mediate hormesis by being beneficial at low doses but detrimental at high doses. Recent studies have highlighted that many compounds that extended lifespan in model organisms did so by mediating hormesis. Rutin is a glycosylate conjugate of quercetin and rutinose and is abundant in citrus fruits and buckwheat seeds. Rutin possess ROS scavenging, anti-cancer, cardio-protective, skin-regenerative and neuro-protective properties. Drosophila melanogaster is an attractive model organism for longevity studies owing to its homology of organ and cellular-pathways with mammals. In this study, we aimed to understand the effect of rutin on extending longevity in Drosophila melanogaster. Male and female flies were administered with a range of rutin doses (100-800 µM) to analyse whether rutin mediated lifespan-extension by hormesis. Effect of rutin on physiological parameters like food intake, fecundity, climbing activity, development and resistance to various stresses was also studied. Lifespan assays showed that rutin at 200 and 400 µM significantly extended median lifespan in both male and female flies beyond which flies exhibited drastically reduced longevity. Increase in survival at 400 µM was associated with reduced food intake and fecundity. Flies exhibited improved climbing capability with both 200 and 400 µM rutin. Flies fed with 100 and 200 µM rutin exhibited enhanced survival upon exposure to oxidative stress with 400 µM rutin exhibiting no improvement in median lifespan following oxidative stress. Analysis of endogenous peroxide upon treatment with rutin (100-400 µM) with or without 5% H2O2 showed elevated levels of endogenous peroxide with 400 µM rutin whereas no increase in hydrogen peroxide level was observed with rutin at 100 and 200 µM. Finally, gene expression studies in male flies revealed that rutin treatment at 200 and/or 400 µM elevated transcript levels of dFoxO, MnSod, Cat, dTsc1, dTsc2, Thor, dAtg1, dAtg5 and dAtg7 and reduced transcript levels of dTor. Collectively, rutin at 200 and 400 µM improved longevity in flies; 200 µM rutin acted as a mild stressor to prolong lifespan in flies by mediating hormesis whereas 400 µM, being a high dose for best positive effects.


Drosophila melanogaster; Hormesis; Hormetin; Longevity; Rutin; Stress


Malnutrition is associated with increased mortality in older adults regardless of the cause of death.

Söderström L, Rosenblad A, Thors Adolfsson E, Bergkvist L.

Br J Nutr. 2017 Feb;117(4):532-540. doi: 10.1017/S0007114517000435. Epub 2017 Mar 14.

PMID: 28290264


Malnutrition predicts preterm death, but whether this is valid irrespective of the cause of death is unknown. The aim of the present study was to determine whether malnutrition is associated with cause-specific mortality in older adults. This cohort study was conducted in Sweden and included 1767 individuals aged ≥65 years admitted to hospital in 2008-2009. On the basis of the Mini Nutritional Assessment instrument, nutritional risk was assessed as well nourished (score 24-30), at risk of malnutrition (score 17-23·5) or malnourished (score <17). Cause of death was classified according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, into twenty different causes of death. Data were analysed using Cox proportional hazards regression models. At baseline, 55·1 % were at risk of malnutrition, and 9·4 % of the participants were malnourished. During a median follow-up of 5·1 years, 839 participants (47·5 %) died. The multiple Cox regression model identified significant associations (hazard ratio (HR)) between malnutrition and risk of malnutrition, respectively, and death due to neoplasms (HR 2·43 and 1·32); mental or behavioural disorders (HR 5·73 and 5·44); diseases of the nervous (HR 4·39 and 2·08), circulatory (HR 1·95 and 1·57) or respiratory system (HR 2·19 and 1·49); and symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified (HR 2·23 and 1·43). Malnutrition and risk of malnutrition are associated with increased mortality regardless of the cause of death, which emphasises the need for nutritional screening to identify older adults who may require nutritional support in order to avoid preterm death.


10th Revision; HR hazard ratio; ICD-10 International Statistical Classification of Diseases and Related Health Problems; MNA Mini Nutritional Assessment; Cause-specific mortality; Cohort studies; Malnutrition; Older adults; Survival analyses


Hb level, iron intake and mortality in Chinese adults: a 10-year follow-up study.

Shi Z, Zhen S, Zhou Y, Taylor AW.

Br J Nutr. 2017 Feb;117(4):572-581. doi: 10.1017/S000711451700040X.

PMID: 28382896


Anaemia is prevalent in developing countries and is commonly Fe deficiency related. We aimed to assess the association between Fe status, Fe intake and mortality among Chinese adults. We prospectively studied 8291 adults aged 20-98 years with a mean follow-up of 9·9 years. All participants were measured for Hb at baseline in 2002. Food intake, measured by 3-d weighed food record (n 2832), and fasting serum ferritin were measured. We documented 491 deaths (including 192 CVD and 165 cancer deaths) during 81 527 person-years of follow-up. There was a U-shaped association between Hb levels and all-cause mortality. Compared with the second quartile of Hb (121 g/l), the first (105) and fourth quartile (144) had hazard ratios (HR) of 2·29 (95 % CI 1·51, 3·48) and 2·31 (95 % CI 1·46, 3·64) for all-cause mortality in women. In men, compared with third quartile of Hb (143 g/l), first (122) and fourth quartiles (154) had 61 and 65 % increased risk of all-cause mortality. Anaemia was associated with an increased risk of all-cause and CVD mortality in men but not in women after adjusting for potential confounders. Low and high Fe intake as percentage of Chinese recommended nutrient intake (RNI) were positively associated with all-cause mortality in women but not in men. In women, across quartiles of relative Fe intake, HR for all-cause mortality were 2·55 (95 % CI 0·99, 6·57), 1·00, 3·12 (95 % CI 1·35, 7·18) and 2·78 (95 % CI 1·02, 7·58). Both low and high Hb levels are related to increased risk of all-cause mortality. Both low and high intake of Fe as percentage of RNI was positively associated with mortality in women.


CDC Centre for Disease Control and Prevention; CKD chronic kidney disease; HR hazard ratio; RNI recommended nutrient intake; Chinese adults; Cohort studies; Hb; Iron; Mortality


Longitudinal study of diet quality and change in asthma symptoms in adults, according to smoking status.

Li Z, Kesse-Guyot E, Dumas O, Garcia-Aymerich J, Leynaert B, Pison C, Le Moual N, Romieu I, Siroux V, Camargo CA, Nadif R, Varraso R.

Br J Nutr. 2017 Feb;117(4):562-571. doi: 10.1017/S0007114517000368.

PMID: 28382891


It has been hypothesised that increased asthma prevalence in westernised countries is associated with changes in lifestyle factors, including a poorer diet. However, little is known regarding the association between diet quality and asthma. In the diet-asthma association, the role of BMI as a potential mediator needs clarification; moreover, potential effect modification by non-diet sources of oxidants, such as smoking, merits investigation. We investigated the association between diet quality and change in asthma symptoms, as well as assessed effect modification by smoking, while accounting for BMI as a potential mediator. Using data from the French prospective Epidemiological study on the Genetics and Environment of Asthma study, we assessed diet quality using the Alternate Healthy Eating Index 2010 (AHEI-2010) at baseline and change in asthma symptoms (stable (reference), worsening, improved; mean follow-up time: 7 years). Mediation analysis was used to disentangle total and direct effects and the indirect effect mediated by BMI. The analyses included 969 adults (mean age 43 years; 49 % men; 42 % ever asthma). We observed a significant interaction between smoking and AHEI-2010 on change in asthma symptoms (P for interaction=0·04). Among never smokers (n 499), we observed a positive total effect (multivariable OR 1·39; 95 % CI 1·07, 1·80) and a positive direct effect (OR 1·41; 95 % CI 1·09, 1·80) of the AHEI-2010 (per ten-point increment) on improved symptoms. No indirect effect mediated through BMI was observed (OR 0·99; 95 % CI 0·91, 1·07). Among former and current smokers, all effects were statistically non-significant. Better diet quality was associated with improved asthma symptoms over time in never smokers, independently of BMI.


AHEI-2010 Alternate Healthy Eating Index 2010; EGEA Epidemiological study on the Genetics and Environment of Asthma; SU.VI.MAX SUpplémentation en VItamines et Minéraux AntioXydants; Asthma; BMI; Diet scores; Mediation analysis; Smoking


Synergistic attenuation of ovariectomy-induced bone loss by combined use of fish oil and 17β-oestradiol.

Jin Y, Lee M, Park Y.

Br J Nutr. 2017 Feb;117(4):479-489. doi: 10.1017/S0007114517000344. Epub 2017 Mar 14.

PMID: 28290259



Oestrogen and n-3 PUFA, especially EPA and DHA, have been reported to have beneficial effects on bone loss. Thus, the purpose of the present study was to investigate the synergistic bone-protective mechanism of combined treatments of EPA+DHA supplementation and oestrogen injection in ovariectomised rats. Rats were fed a modified American Institute of Nutrition-93G diet with 0 %, 1 % or 2 % n-3 PUFA (EPA+DHA) relative to the total energy intake for 12 weeks. Rats were surgically ovariectomised at week 8, and after a 1-week recovery period rats were injected with either 17β-oestradiol-3-benzoate (E2) or maize oil for the last 3 weeks. Combined use of n-3 PUFA and E2 synergistically increased femoral cortical bone volume, bone mineral content and the bone expression of runt-related transcription factor 2 (RUNX2), but decreased the bone expression of IL-1β. Both n-3 PUFA and E2 decreased the bone expressions of IL-7, TNF-α and PPAR-γ, and increased the bone expression of oestrogen receptor-α. n-3 PUFA in the presence of E2 and E2 alone significantly decreased the bone expressions of IL-1β and IL-6 and increased the bone expression of RUNX2. E2 significantly decreased the serum levels of bone turnover markers and the bone expression of receptor activator of NF-κB ligand, but decreased the bone expression of osteoprotegerin. The combined use of n-3 PUFA and E2 exerted synergistic bone-protective efficacy through up-regulation of RUNX2, an essential transcription factor for bone formation, as well as the suppression of bone-resorbing cytokine IL-1β.


n-3 PUFA; BMC bone mineral content; BV bone volume; E2 17β-oestradiol-3-benzoate; ER-α oestrogen receptor-α; OPG osteoprotegerin; OVX ovariectomised; RANKL receptor activator of NF-κB ligand; RUNX2 runt-related transcription factor 2; 17β-Oestradiol-3-benzoate; Bone loss; IL-1β ; Runt-related transcription factor 2


Vitamin B<sub>12</sub>, homocysteine and depressive symptoms: a longitudinal study among older adults.

Elstgeest LE, Brouwer IA, Penninx BW, van Schoor NM, Visser M.

Eur J Clin Nutr. 2017 Apr;71(4):468-475. doi: 10.1038/ejcn.2016.224. Epub 2017 Feb 1.

PMID: 28145420



The roles of vitamin B12 and homocysteine concentration in depression are not clear. We investigated cross-sectional and prospective associations of serum vitamin B12 and plasma homocysteine with depressive symptoms in Dutch older adults.


In the Longitudinal Aging Study Amsterdam (LASA), blood was collected in 1995/1996 among 1352 men and women aged ⩾65 years. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D) six times from 1995/1996 to 2011/2012. Multiple linear regression and mixed models were used to assess whether vitamin B12 and homocysteine were associated with severity at baseline and course of depressive symptoms over 16 years. Cox regression analyses were performed for the associations with incidence of depression (CES-D ⩾16 and/or antidepressant use). All analyses were adjusted for sociodemographic characteristics and lifestyle factors.


Vitamin B12 was neither cross-sectionally (n=1205) nor prospectively (n=1012) associated with depressive symptoms (adjusted β for CES-D over time, lowest versus highest quartile: -0.04 (95% confidence interval (CI): -0.15-0.06)). We also found no association with incident depression (n=853), except for a higher risk of depression over time in younger participants (aged 64.8-73.4 years; continuous vitamin B12, adjusted hazard ratio per s.d.: 1.38 (95% CI: 1.10-1.72)). For homocysteine, no associations were found, except for a lower risk of depression in younger participants.


Our study did not confirm earlier shown associations of serum vitamin B12 and plasma homocysteine with severity and course of depressive symptoms and incidence of depression in older adults. Further research into the influence of homocysteine metabolism on mental health is needed.


Tea consumption and its interactions with tobacco smoking and alcohol drinking on oral cancer in southeast China.

Chen F, He BC, Yan LJ, Liu FP, Huang JF, Hu ZJ, Lin Z, Zheng XY, Lin LS, Zhang ZF, Cai L.

Eur J Clin Nutr. 2017 Apr;71(4):481-485. doi: 10.1038/ejcn.2016.208. Epub 2017 Feb 8.

PMID: 28176772




Epidemiological results on the association between tea consumption and oral cancer remain controversial. We aimed to evaluate the exact relationship between tea consumption and oral cancer in Chinese population.


A large-scale case-control study was conducted on 586 oral cancer patients and 1024 controls frequency-matched by age and gender. Epidemiological data were collected through face-to-face interviews with a structure questionnaire. Unconditional logistic regression model was used to assess the effect of tea consumption on oral cancer stratified by smoking, alcohol drinking and demographics. Quantity of tea consumed (ml/day) was categorized into five subgroups based on quartiles and then its interactions was evaluated with tobacco smoking and alcohol drinking at each subgroup.


Tea consumption showed an inverse association with oral cancer for non-smokers or non-alcohol drinkers (the odds ratios (ORs) were 0.610 (95% confidence interval (CI): 0.425-0.876) and 0.686 (95% CI: 0.503-0.934), respectively). For smokers or alcohol drinkers, decreased risk was only observed in those who consumed >800 ml/day. Furthermore, oolong tea consumption was associated with decreased risk of oral cancer in smokers or alcohol drinkers but not in non-smokers or non-alcohol drinkers. Tea consumption combined with smoking or/and alcohol drinking had a greater risk than tea consumption alone, but the risk was roughly reduced from zero to Q4 (>800 ml/day). Additionally, when stratified by demographics, the protective effect of tea was especially evident in females, urban residents, normal body mass index population (18.5-23.9), farmers, office workers and those aged <60 years.


Tea consumption protects against oral cancer in non-smokers or non-alcohol drinkers, but this effect may be obscured in smokers or alcohol drinkers. Additionally, demographics may modify the association between tea consumption and oral cancer.


Criterion values for urine-specific gravity and urine color representing adequate water intake in healthy adults.

Perrier ET, Bottin JH, Vecchio M, Lemetais G.

Eur J Clin Nutr. 2017 Apr;71(4):561-563. doi: 10.1038/ejcn.2016.269. Epub 2017 Feb 1.

PMID: 28145416


Growing evidence suggests a distinction between water intake necessary for maintaining a euhydrated state, and water intake considered to be adequate from a perspective of long-term health. Previously, we have proposed that maintaining a 24-h urine osmolality (UOsm) of ⩽500 mOsm/kg is a desirable target for urine concentration to ensure sufficient urinary output to reduce renal health risk and circulating vasopressin. In clinical practice and field monitoring, the measurement of UOsm is not practical. In this analysis, we calculate criterion values for urine-specific gravity (USG) and urine color (UCol), two measures which have broad applicability in clinical and field settings. A receiver operating characteristic curve analysis performed on 817 urine samples demonstrates that a USG ⩾1.013 detects UOsm>500 mOsm/kg with very high accuracy (AUC 0.984), whereas a subject-assessed UCol⩾4 offers high sensitivity and moderate specificity (AUC 0.831) for detecting UOsm >500 m Osm/kg.


Intake of vitamin C, vitamin E, selenium, zinc and polyunsaturated fatty acids and upper respiratory tract infection-a prospective cohort study.

Raposo SE, Fondell E, Ström P, Bälter O, Bonn SE, Nyrén O, Plymoth A, Bälter K.

Eur J Clin Nutr. 2017 Apr;71(4):450-457. doi: 10.1038/ejcn.2016.261. Epub 2017 Jan 11.

PMID: 28074891




Antioxidants and polyunsaturated fatty acids (PUFAs) have a role in the human immune defense and may affect the susceptibility to upper respiratory tract infection (URTI). To examine dietary intake of vitamin C, vitamin E, selenium, zinc and PUFAs in relation to URTI incidence in a prospective cohort study.


A total of 1533 Swedish women and men aged 25-64 years were followed for nine months during 2011-2012. Information on dietary intake was assessed through a web-based food frequency questionnaire, and events of URTI were self-reported prospectively as they occurred. Cox proportional hazards regression was applied to obtain incidence rate ratios with 95% confidence intervals.


The mean number of URTI events was 0.9 among all participants, 1.0 among women and 0.7 among men. In women, the incidence rate ratios (95% confidence interval) for high compared with low intake were 0.69 (0.55-0.88) for vitamin C, 0.77 (0.62-0.96) for vitamin E, 0.57 (0.39-0.83) for docosahexaenoic acid (DHA) and 0.80 (0.65-0.99) for arachidonic acid (AA). No association was found for selenium or zinc among women. In men, an increased URTI incidence was seen with medium vitamin E intake (1.42 (1.09-1.85)) and high zinc intake (1.50 (1.04-2.16)). No association was found for vitamin C, selenium or PUFAs among men.


We found an inverse association of URTI incidence among women for vitamin C, vitamin E, DHA and AA intake and a positive association among men for vitamin E and zinc intake. The observed gender differences warrant further investigation.








Nevi, ambient ultraviolet radiation, and thyroid cancer risk: a French prospective study.

Mesrine S, Kvaskoff M, Bah T, Wald L, Clavel-Chapelon F, Boutron-Ruault MC.

Epidemiology. 2017 Apr 5. doi: 10.1097/EDE.0000000000000673. [Epub ahead of print]

PMID: 28383300



Incidence rates have increased considerably worldwide for both differentiated thyroid cancer and cutaneous melanoma, and two-way associations between these neoplasms have been described. Whether melanoma risk factors are associated with thyroid cancer risk remains unknown.


Using Cox regression modeling, we prospectively analyzed the relationship between self-reported pigmentary traits, baseline residential ultraviolet (UV) exposure, and thyroid cancer risk in 86,960 women from the E3N cohort, followed-up over 1990-2008 through biennial questionnaires. We assessed associations of pigmentary traits and UV exposure with personal history of benign thyroid diseases using logistic regression modeling. All statistical tests were two-sided.


In models adjusted for age and thyroid cancer risk factors, number of nevi was positively associated with thyroid cancer risk ("very many" vs. "none": Hazards Ratio (HR)=1.7, 95% Confidence Interval (CI)=1.0-2.8;Ptrend=0.01), independently of residential UV exposure or iodine intake. Risk was inversely associated with latitude and positively associated with mean daily UV level at baseline (HRs for the fourth vs. first quartile of latitude and spring/summer UVB level =0.7, 95% CI=0.5-0.9;Ptrend=0.03, and HR=1.9, 95% CI=1.4-2.7;Ptrend=0.02, respectively); associations were restricted to women with dietary iodine below the median intake. Number of nevi and UV level were also associated with personal histories of dysthyroidism and of goiter/nodules, although more weakly so.


Our results suggest that number of nevi and residential UV exposure are associated with the risks of thyroid cancer and benign conditions. They point to novel pathways in thyroid cancer or melanoma etiologies and warrant replication.


Weight History and All-Cause and Cause-Specific Mortality in Three Prospective Cohort Studies.

Yu E, Ley SH, Manson JE, Willett W, Satija A, Hu FB, Stokes A.

Ann Intern Med. 2017 Apr 4. doi: 10.7326/M16-1390. [Epub ahead of print]

PMID: 28384755




The relationship between body mass index (BMI) and mortality is controversial.


To investigate the relationship between maximum BMI over 16 years and subsequent mortality.


3 prospective cohort studies.


Nurses' Health Study I and II and Health Professionals Follow-Up Study.


225 072 men and women with 32 571 deaths observed over a mean of 12.3 years of follow-up.


Maximum BMI over 16 years of weight history and all-cause and cause-specific mortality.


Maximum BMIs in the overweight (25.0 to 29.9 kg/m2) (multivariate hazard ratio {HR}, 1.06 [95% CI, 1.03 to 1.08]), obese I (30.0 to 34.9 kg/m2) (HR, 1.24 [CI, 1.20 to 1.29]), and obese II (≥35.0 kg/m2) (HR, 1.73 [CI, 1.66 to 1.80]) categories were associated with increases in risk for all-cause death. The pattern of excess risk with a maximum BMI above normal weight was maintained across strata defined by smoking status, sex, and age, but the excess was greatest among those younger than 70 years and never-smokers. In contrast, a significant inverse association between overweight and mortality (HR, 0.96 [CI, 0.94 to 0.99]) was observed when BMI was defined using a single baseline measurement. Maximum overweight was also associated with increased cause-specific mortality, including death from cardiovascular disease and coronary heart disease.


Residual confounding and misclassification.


The paradoxical association between overweight and mortality is reversed in analyses incorporating weight history. Maximum BMI may be a useful metric to minimize reverse causation bias associated with a single baseline BMI assessment.


Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial.

Lappe J, Watson P, Travers-Gustafson D, Recker R, Garland C, Gorham E, Baggerly K, McDonnell SL.

JAMA. 2017 Mar 28;317(12):1234-1243. doi: 10.1001/jama.2017.2115.

PMID: 28350929




Evidence suggests that low vitamin D status may increase the risk of cancer.


To determine if dietary supplementation with vitamin D3 and calcium reduces the risk of cancer among older women.


A 4-year, double-blind, placebo-controlled, population-based randomized clinical trial in 31 rural counties (June 24, 2009, to August 26, 2015-the final date of follow-up). A total of 2303 healthy postmenopausal women 55 years or older were randomized, 1156 to the treatment group and 1147 to the placebo group. Duration of treatment was 4 years.


The treatment group (vitamin D3 + calcium group) received 2000 IU/d of vitamin D3 and 1500 mg/d of calcium; the placebo group received identical placebos.


The primary outcome was the incidence of all-type cancer (excluding nonmelanoma skin cancers), which was evaluated using Kaplan-Meier survival analysis and proportional hazards modeling.


Among 2303 randomized women (mean age, 65.2 years [sD, 7.0]; mean baseline serum 25-hydroxyvitamin D level, 32.8 ng/mL [sD, 10.5]), 2064 (90%) completed the study. At year 1, serum 25-hydroxyvitamin D levels were 43.9 ng/mL in the vitamin D3 + calcium group and 31.6 ng/mL in the placebo group. A new diagnosis of cancer was confirmed in 109 participants, 45 (3.89%) in the vitamin D3 + calcium group and 64 (5.58%) in the placebo group (difference, 1.69% [95% CI, -0.06% to 3.46%]; P = .06). Kaplan-Meier incidence over 4 years was 0.042 (95% CI, 0.032 to 0.056) in the vitamin D3 + calcium group and 0.060 (95% CI, 0.048 to 0.076) in the placebo group; P = .06. In unadjusted Cox proportional hazards regression, the hazard ratio was 0.70 (95% CI, 0.47 to 1.02). Adverse events potentially related to the study included renal calculi (16 participants in the vitamin D3 + calcium group and 10 in the placebo group), and elevated serum calcium levels (6 in the vitamin D3 + calcium group and 2 in the placebo group).


Among healthy postmenopausal older women with a mean baseline serum 25-hydroxyvitamin D level of 32.8 ng/mL, supplementation with vitamin D3 and calcium compared with placebo did not result in a significantly lower risk of all-type cancer at 4 years. Further research is necessary to assess the possible role of vitamin D in cancer prevention.


Comment in:

Vitamin D, Calcium, and Cancer: Approaching Daylight?

Manson JE, Bassuk SS, Buring JE.

JAMA. 2017 Mar 28;317(12):1217-1218. doi: 10.1001/jama.2017.2155. No abstract available.

PMID: 28350909



Dietary rapeseed/canola-oil supplementation reduces serum lipids and liver enzymes and alters postprandial inflammatory responses in adipose tissue compared to olive-oil supplementation in obese men.

Kruse M, von Loeffelholz C, Hoffmann D, Pohlmann A, Seltmann AC, Osterhoff M, Hornemann S, Pivovarova O, Rohn S, Jahreis G, Pfeiffer AF.

Mol Nutr Food Res. 2015 Mar;59(3):507-19. doi: 10.1002/mnfr.201400446. Epub 2014 Dec 22.

PMID: 25403327




Obesity is associated with hyperlipidemia, hepatic steatosis, and low-grade inflammation. Studies have shown that MUFA as well as PUFA have beneficial effects on blood lipids and the inflammatory state.


This study investigates the effects of a daily supplementation of either 50 g of rapeseed/canola (RA) or olive (OL) oil over 4 wk on serum lipids, serum liver enzymes, and inflammatory gene expression in subcutaneous (s. c.) adipose tissue in obese men. Consuming RA resulted in increased serum n-3 fatty acids and a reduction in total cholesterol, LDL cholesterol, and serum aspartate aminotransferase compared to OL. In s. c. adipose tissue, gene expression of the pro-inflammatory cytokine IL6 was reduced in RA compared to OL. However, after 4 h after a test meal, containing the appropriate oil, white bread, and 400 mL of liquid diet drink (835 kcal in total), gene expression of IL6, IL1B, and EMR1 (egf-like module containing Mucin-like hormone receptor-like 1) was increased in RA and of monocyte chemoattractant protein-1 (CCL2) in both RA and OL.


This demonstrates that consuming RA for 4 wk improves serum lipids, liver enzymes, and basal inflammation in s. c. adipose tissue, but it mediates an acute pro-inflammatory response in adipose tissue upon consuming a meal.


Inflammation; Obesity; Olive oil; Rapeseed oil; Serum lipids

" The oils used in this study were commercially

available, cold-pressed extra virgin OL and refined RA."


Race, Serum Potassium, and Associations With ESRD and Mortality.

Chen Y, Sang Y, Ballew SH, Tin A, Chang AR, Matsushita K, Coresh J, Kalantar-Zadeh K, Molnar MZ, Grams ME.

Am J Kidney Dis. 2017 Mar 28. pii: S0272-6386(17)30535-8. doi: 10.1053/j.ajkd.2017.01.044. [Epub ahead of print]

PMID: 28363732




Recent studies suggest that potassium levels may differ by race. The basis for these differences and whether associations between potassium levels and adverse outcomes differ by race are unknown.


Observational study.


Associations between race and potassium level and the interaction of race and potassium level with outcomes were investigated in the Racial and Cardiovascular Risk Anomalies in Chronic Kidney Disease (RCAV) Study, a cohort of US veterans (N=2,662,462). Associations between African ancestry and potassium level were investigated in African Americans in the Atherosclerosis Risk in Communities (ARIC) Study (N=3,450).


Race (African American vs non-African American and percent African ancestry) for cross-sectional analysis; serum potassium level for longitudinal analysis.


Potassium level for cross-sectional analysis; mortality and end-stage renal disease for longitudinal analysis.


The RCAV cohort was 18% African American (N=470,985). Potassium levels on average were 0.162mmol/L lower in African Americans compared with non-African Americans, with differences persisting after adjustment for demographics, comorbid conditions, and potassium-altering medication use. In the ARIC Study, higher African ancestry was related to lower potassium levels (-0.027mmol/L per each 10% African ancestry). In both race groups, higher and lower potassium levels were associated with mortality. Compared to potassium level of 4.2mmol/L, mortality risk associated with lower potassium levels was lower in African Americans versus non-African Americans, whereas mortality risk associated with higher levels was slightly greater. Risk relationships between potassium and end-stage renal disease were weaker, with no difference by race.


No data for potassium intake.


African Americans had slightly lower serum potassium levels than non-African Americans. Consistent associations between potassium levels and percent African ancestry may suggest a genetic component to these differences. Higher and lower serum potassium levels were associated with mortality in both racial groups.


African American; African ancestry; Race; end-stage renal disease (ESRD); genetic risk factor; hyperkalemia; hypokalemia; kidney disease; mortality; racial differences; serum potassium


Dietary and Lifestyle Risk Factors Associated with Incident Kidney Stones in Men and Women.

Ferraro PM, Taylor EN, Gambaro G, Curhan GC.

J Urol. 2017 Mar 29. pii: S0022-5347(17)43809-2. doi: 10.1016/j.juro.2017.03.124. [Epub ahead of print]

PMID: 28365271




Several dietary and lifestyle factors are associated with a higher risk of developing kidney stones. We estimated the population attributable fraction (PAF) and number needed to prevent (NNTP) for modifiable risk factors including body mass index (BMI), fluid intake, DASH-style diet, dietary calcium intake and intake of sugar-sweetened beverages.


We used data from the Health Professionals Follow-up Study (HPFS) and the Nurses' Health Studies (NHS) I and II cohorts. Information was obtained from validated questionnaires. Poisson regression models adjusted for potential confounders were used to estimate the association of each risk factor with development of incident kidney stones and to compute PAF and NNTP.


The study included 192,126 participants who contributed a total of 3,259,313 person-years of follow-up, during which 6,449 participants developed an incident kidney stone. All the modifiable risk factors were independently associated with incident stones in each of the cohorts. The PAF ranged from 4.4% for higher sugar-sweetened beverages intake to 26.0% for lower fluid intake; the PAF for all the five risk factors combined was 57.0% in HPFS, 55.2% in NHS I and 55.1% in NHS II. NNTP over 10 years ranged from 67 for lower fluid intake to 556 for lower dietary calcium intake.


Five modifiable risk factors accounted for more than 50% of incident kidney stones in three large prospective cohorts. Assuming a causal relation, our estimates suggest that preventive measures aimed at reducing those factors could substantially reduce the burden of kidney stones in the general population.


attributable fraction; cohort studies; nutrition; obesity; urolithiasis


Green tea and the risk of prostate cancer: A systematic review and meta-analysis.

Guo Y, Zhi F, Chen P, Zhao K, Xiang H, Mao Q, Wang X, Zhang X.

Medicine (Baltimore). 2017 Mar;96(13):e6426. doi: 10.1097/MD.0000000000006426. Review.

PMID: 28353571 Free Article


Prostate cancer (PCa) now remains the 2nd most frequently diagnosed cancer. In recent years, chemoprevention for PCa becomes a possible concept. Especially, many phytochemicals rich foods are suggested to lower the risk of cancer. Among these foods, green tea is considered as effective prevention for various cancers. However, clinical trials and previous meta-analyses on the relationship between green tea consumption and the risk of PCa have produced inconsistent outcomes. This study aims to determine the dose-response association of green tea intake with PCa risk and the preventive effect of green tea catechins on PCa risk. Seven observational studies and 3 randomized controlled trials were retrieved from Cochrane Library, PubMed, Sciencedirect Online, and hand searching. The STATA (version 12.0) was applied to analyze the data. The relative risks (RRs) and 95% confidence intervals were pooled by fixed or random effect modeling. Dose-response relations were evaluated with categories of green tea intake. Although there was no statistical significance in the comparison of the highest versus lowest category, there was a trend of reduced incidence of PCa with each 1 cup/day increase of green tea (P = 0.08). Our dose-response meta-analysis further demonstrated that higher green tea consumption was linearly associated with a reduced risk of PCa with more than 7 cups/day. In addition, green tea catechins were effective for preventing PCa with an RR of 0.38 (P = 0.02). In conclusion, our dose-response meta-analysis evaluated the association of green tea intake with PCa risk systematically and quantitatively. And this is the first meta-analysis of green tea catechins consumption and PCa incidence. Our novel data demonstrated that higher green tea consumption was linearly reduced PCa risk with more than 7 cups/day and green tea catechins were effective for preventing PCa. However, further studies are required to substantiate these conclusions.


Oral creatine supplements lower plasma homocysteine concentrations in humans.

Korzun WJ.

Clin Lab Sci. 2004 Spring;17(2):102-6.

PMID: 15168891



To determine if oral creatine supplements will lower the concentration of total plasma homocysteine (tHcy).


Apparently healthy volunteers, at least 19 years old, were recruited from the University of South Alabama and surrounding community. DESIGN/INTERVENTION/MAIN OUTCOME: Participants took multi-vitamins daily for four weeks, then were randomly divided into two groups. The control group © continued to take multi-vitamins daily for an additional four weeks. The experimental group (EX) took multivitamins plus an amount of creatine each day equal to twice their daily creatinine excretion, for the additional four weeks. Total plasma homocysteine concentrations were measured in all participants at the beginning and at the end of the second four week interval.


There were no statistically significant differences between the two groups in age, initial tHcy, serum folate, erythrocyte folate, serum vitamin B12, or creatinine excretion. After four weeks of creatine supplements, tHcy in EX changed by an average of -0.9 micromol/L (range: -1.8 to 0.0), compared to an average change of +0.2 micromol/L in C (range: -0.6 to 0.9) during the same four weeks. The difference in the changes in tHcy between the two groups was statistically significant (p < 0.01).


Creatine supplements may be an effective adjunct to vitamin supplements for lowering tHcy.


Does caffeine and alcohol intake before pregnancy predict the occurrence of spontaneous abortion?

Tolstrup JS, Kjaer SK, Munk C, Madsen LB, Ottesen B, Bergholt T, Grønbaek M.

Hum Reprod. 2003 Dec;18(12):2704-10.

PMID: 14645195



Consumption of caffeine and alcohol is suspected to affect pregnancy outcome. Use of both stimulants is widespread and even minor effects on fetal viability are of public health interest.


We performed a nested case-control study using prospective data from a population-based cohort comprising 11088 women aged 20-29 years. From this cohort, women who experienced either a spontaneous abortion (n = 303) or who gave birth (n = 1381) during follow-up [mean time: 2.1 years (range: 1.6-3.4)] were selected. Associations between self-reported exposures to caffeine and/or alcohol at enrolment and spontaneous abortion were analysed by means of logistic regression.


Compared with women with a pre-pregnancy intake of <75 mg caffeine per day, the adjusted odds ratio (95% confidence interval) for spontaneous abortion was 1.26 (0.77-2.06), 1.45 (0.87-2.41), 1.44 (0.87-2.37) and 1.72 (1.00-2.96) for a pre-pregnancy intake on 75-300, 301-500, 501-900 and >900 mg caffeine per day respectively (P = 0.05 for trend). A pre-pregnancy intake of alcohol was not a predictor for spontaneous abortion.


A high intake of caffeine prior to pregnancy seems to be associated with an increased risk of spontaneous abortion, whereas a low-to-moderate alcohol intake does not influence the risk.


A prospective study of dietary lactose and ovarian cancer.

Fairfield KM, Hunter DJ, Colditz GA, Fuchs CS, Cramer DW, Speizer FE, Willett WC, Hankinson SE.

Int J Cancer. 2004 Jun 10;110(2):271-7.

PMID: 15069693 Free Article



The milk sugar lactose is an hypothesized risk factor for epithelial ovarian cancer because of possible direct toxic effects of its metabolites on oocytes or by compensatory gonadotropin stimulation. Women are presently encouraged to consume dairy products as a source of calcium to prevent osteoporosis. The objective of our study was to prospectively assess lactose, milk and milk product consumption in relation to ovarian cancer risk among 80326 participants in the Nurses' Health Study who had no history of cancer other than nonmelanoma skin cancer. Participants in the Nurses' Health Study reported on known and suspected ovarian cancer risk factors in questionnaires mailed biennially from 1976 to 1996. Food frequency questionnaires were included in the years 1980, 1984, 1986 and 1990. Newly reported ovarian cancer was documented by review of medical records. During 16 years of follow-up (1980-1996), 301 cases of invasive epithelial ovarian cancer were confirmed. Pooled logistic regression was used to control for age, body mass index (kg/m(2)), caffeine intake, oral contraceptive use, smoking history, parity and tubal ligation. For all subtypes of invasive ovarian cancer combined, we observed a nonsignificant 40% greater risk for women in the highest category of lactose consumption compared to the lowest (multivariate relative risk (RR) 1.40, 95% confidence interval (CI), 0.98-2.01). We observed a 2-fold higher risk of the serous ovarian cancer subtype among those in the highest category of lactose consumption compared to the lowest (RR 2.07, 95% CI, 1.27-3.40). For each 11-gram increase in lactose consumption (the approximate amount in one glass of milk), we observed a 20% increase in risk of serous cancers (RR 1.20, 95% CI, 1.04-1.39). Skim and low-fat milk were the largest contributors to dietary lactose. Women who consumed one or more servings of skim or low-fat milk daily had a 32% higher risk of any ovarian cancer (RR 1.32, 95% CI, 0.97-1.82) and a 69% higher risk of serous ovarian cancer (RR 1.69, 95% CI, 1.12-2.56) compared to women consuming 3 or less servings monthly. Controlling for fat intake did not change our findings. Our findings provide some support for the hypothesis that lactose intake increases risk of epithelial ovarian cancer. However, the observed excess risk appeared limited to the serous subtype of ovarian cancer in our study.


Mono-unsaturated fatty acids link H3K4me3 modifiers to C. elegans lifespan.

Han S, Schroeder EA, Silva-García CG, Hebestreit K, Mair WB, Brunet A.

Nature. 2017 Apr 5. doi: 10.1038/nature21686. [Epub ahead of print]

PMID: 28379943


Chromatin and metabolic states both influence lifespan, but how they interact in lifespan regulation is largely unknown. The COMPASS chromatin complex, which trimethylates lysine 4 on histone H3 (H3K4me3), regulates lifespan in Caenorhabditis elegans. However, the mechanism by which H3K4me3 modifiers affect longevity, and whether this mechanism involves metabolic changes, remain unclear. Here we show that a deficiency in H3K4me3 methyltransferase, which extends lifespan, promotes fat accumulation in worms with a specific enrichment of mono-unsaturated fatty acids (MUFAs). This fat metabolism switch in H3K4me3 methyltransferase-deficient worms is mediated at least in part by the downregulation of germline targets, including S6 kinase, and by the activation of an intestinal transcriptional network that upregulates delta-9 fatty acid desaturases. Notably, the accumulation of MUFAs is necessary for the lifespan extension of H3K4me3 methyltransferase-deficient worms, and dietary MUFAs are sufficient to extend lifespan. Given the conservation of lipid metabolism, dietary or endogenous MUFAs could extend lifespan and healthspan in other species, including mammals.


New book explores 'Lagom' — the Swedish secret to a long life

Lagom, which means 'not too much and not too little', is the latest Scandinavian trend

By Brandie Weikle, CBC News Posted: Apr 09, 2017



Long-term residential road traffic noise and NO2 exposure in relation to risk of incident myocardial infarction - A Danish cohort study.

Roswall N, Raaschou-Nielsen O, Ketzel M, Gammelmark A, Overvad K, Olsen A, Sørensen M.

Environ Res. 2017 Mar 20;156:80-86. doi: 10.1016/j.envres.2017.03.019. [Epub ahead of print]

PMID: 28334645




Road traffic is a source of both air pollution and noise; two environmental hazards both found to increase the risk of ischemic heart disease. Given the high correlation between these pollutants, it is important to investigate combined effects, in relation to myocardial infarction (MI).


Among 50,744 middle-aged Danes enrolled into the Diet, Cancer and Health cohort from 1993 to 97, we identified 2403 cases of incident MI during a median follow-up of 14.5 years. Present and historical residential addresses from 1987 to 2011 were found in national registries, and traffic noise (Lden) and air pollution (NO2) were modelled for all addresses. Analyses were performed using Cox proportional hazard models.


Road traffic noise and NO2 were both individually associated with a higher risk of MI, with hazard ratios of 1.14 (1.07-1.21) and 1.08 (1.03-1.12) per inter-quartile range higher 10-year mean of road traffic noise and NO2, respectively. Mutual exposure adjustment reduced the association with 10-year NO2 exposure (1.02 (0.96-1.08)), whereas the association with road traffic noise remained: 1.12 (1.03-1.21). For fatal incident MI, the pattern was similar, but the associations for both pollutants were stronger. In analyses of tertiles across both pollutants, the strongest effects were seen for combined medium/high exposure, especially for fatal MI's.


Both road traffic noise and NO2 were associated with a higher risk of MI in single-pollutant models. In two-pollutant models, mainly noise was associated with MI. Combined exposure to both pollutants was associated with the highest risk.


Air pollution; Cohort study; Epidemiology; Myocardial infarction; Traffic noise


Multivitamin/mineral supplements: Rationale and safety.

Biesalski HK, Tinz J.

Nutrition. 2017 Apr;36:60-66. doi: 10.1016/j.nut.2016.06.003. Epub 2016 Jun 16. Review.

PMID: 28336109


Multivitamin/mineral supplements (MVMs) are widely used in many populations. MVMs, together with iron and folic acid, are recommended for pregnant women to improve birth outcome and to reduce low-birthweight and rates of miscarriage. However, MVM use is common in the general population as well. The aim of the present review was to evaluate the safety of long-term use of these supplements. To examine the safety of MVM use, we performed a literature search for randomized controlled studies involving supplementation with a combination of at least nine vitamins and three minerals at a maximum concentration of 100% of the Recommended Dietary Allowance. We found nine studies evaluating the use and efficacy of MVMs in pregnant women and healthy adults and six studies in the elderly where adverse effects were explicitly addressed. Only minor adverse events (e.g., unspecific gastrointestinal symptoms) were reported in all studies. In particular, there were no significant differences between treatment and placebo groups. MVM use within the range of the Dietary Reference Intake will not result in excess intake, even when including the effect of food and fortified food, and does not increase mortality. Taken together, these findings indicate that MVMs can be safe for long-term use (>10 y).


Long-term use; Minerals; Multivitamins; Randomized controlled trials; Safety; Supplements


Quantitative analysis of efficacy and associated factors of calcium intake on bone mineral density in postmenopausal women.

Wu J, Xu L, Lv Y, Dong L, Zheng Q, Li L.

Osteoporos Int. 2017 Mar 23. doi: 10.1007/s00198-017-3993-4. [Epub ahead of print]

PMID: 28337524


A model-based meta-analysis method was performed to quantitatively analyze the efficacy characteristics of calcium intake in BMD increase among postmenopausal women. We found that age and calcium intake dose were key factors affecting the efficiency and onset of BMD change, and daily 1200 mg calcium was suggested to be a beneficial dosage.


This paper aims to quantify the efficacy of calcium intake in preventing bone mineral density (BMD) decrease among postmenopausal women and to investigate the factors that may affect the efficacy.


Comprehensive literature search was conducted in PubMed and EMBASE from January 2016. Placebo-controlled or no-treatment controlled randomized trials focused on calcium intake for the management of osteoporosis in postmenopausal women were included. The clinical and demographic characteristics of participants and efficacy data, defined as the mean percentage change of spine BMD (L2-L4) at each observation time point compared with that of baseline, were extracted from the studies. Model-based meta-analysis (MBMA) was used to describe the time course of BMD change by calcium intake and identify the related factors.


This study includes 17 trials involving 2537 subjects. The results showed that a classic pharmacodynamic maximal effect (E max) model could describe the time course of BMD change by calcium intake. Using this model, we found that age and calcium intake dose were key factors affecting the efficiency and onset of BMD change. A 60-year-old woman administered with 800 mg/day calcium can achieve a maximum BMD increasing rate of 2.38%, and the time to reach 50% of this maximum (known as onset time) was 9.44 months. An increase of 0.0817% per year was noted in the maximal effect value for women aged between 50 and 83 years. For calcium dose interval from 250 to 2000 mg/day, the onset time was expressed as 9.44 × (dose/800)-1.33 months. Two-year calcium intake of 700, 1200, and 2000 mg/day resulted in a maximum efficacy of BMD of 68.0, 81.3, and 89.6%, respectively. This indicates that the final efficacy had already reached the plateau (>80% E max) under the 1200-mg/day dose.


Calcium intake can effectively postpone the tendency of BMD decrease in postmenopausal women. An increased calcium dose contributes to the shortening of the onset time. Considering the drug-acting rate and safety into account, menopausal women can be administered with a rational dose of 1200 mg/day to reduce bone loss.


Bone mineral density; Calcium intake; Postmenopausal women


Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality-a systematic review and dose-response meta-analysis of prospective studies.

Aune D, Giovannucci E, Boffetta P, Fadnes LT, Keum N, Norat T, Greenwood DC, Riboli E, Vatten LJ, Tonstad S.

Int J Epidemiol. 2017 Feb 22. doi: 10.1093/ije/dyw319. [Epub ahead of print]

PMID: 28338764




Questions remain about the strength and shape of the dose-response relationship between fruit and vegetable intake and risk of cardiovascular disease, cancer and mortality, and the effects of specific types of fruit and vegetables. We conducted a systematic review and meta-analysis to clarify these associations.


PubMed and Embase were searched up to 29 September 2016. Prospective studies of fruit and vegetable intake and cardiovascular disease, total cancer and all-cause mortality were included. Summary relative risks (RRs) were calculated using a random effects model, and the mortality burden globally was estimated; 95 studies (142 publications) were included.


For fruits and vegetables combined, the summary RR per 200 g/day was 0.92 [95% confidence interval (CI): 0.90-0.94, I 2  = 0%, n  = 15] for coronary heart disease, 0.84 (95% CI: 0.76-0.92, I 2  = 73%, n  = 10) for stroke, 0.92 (95% CI: 0.90-0.95, I 2  = 31%, n  = 13) for cardiovascular disease, 0.97 (95% CI: 0.95-0.99, I 2  = 49%, n  = 12) for total cancer and 0.90 (95% CI: 0.87-0.93, I 2  = 83%, n  = 15) for all-cause mortality. Similar associations were observed for fruits and vegetables separately. Reductions in risk were observed up to 800 g/day for all outcomes except cancer (600 g/day). Inverse associations were observed between the intake of apples and pears, citrus fruits, green leafy vegetables, cruciferous vegetables, and salads and cardiovascular disease and all-cause mortality, and between the intake of green-yellow vegetables and cruciferous vegetables and total cancer risk. An estimated 5.6 and 7.8 million premature deaths worldwide in 2013 may be attributable to a fruit and vegetable intake below 500 and 800 g/day, respectively, if the observed associations are causal.


Fruit and vegetable intakes were associated with reduced risk of cardiovascular disease, cancer and all-cause mortality. These results support public health recommendations to increase fruit and vegetable intake for the prevention of cardiovascular disease, cancer, and premature mortality.


Fruit and vegetables; all-cause mortality; cancer; cardiovascular disease; cohort; diet; global assessment; nutrition


Change in Body Weight from Age 20 Years Is a Powerful Determinant of the Metabolic Syndrome.

Lind L, Elmståhl S, Ärnlöv J.

Metab Syndr Relat Disord. 2017 Apr;15(3):112-117. doi: 10.1089/met.2016.0121. Epub 2017 Feb 16.

PMID: 28339342



Higher body weight is a well-known determinant of the metabolic syndrome (MetS) and its components. It is however less well studied how the change in weight from age 20 years to middle age or old age affects MetS development.


In the community-based EpiHealth (n = 19,000, age range 45 to 75 years, 56% females) and PIVUS (n = 1000, all aged 70 years, 50% females) studies, the participants were asked about their body weight at age 20 years. Data were collected to determine MetS prevalence (NCEP ATP III criteria).


In EpiHealth, the probability of having MetS increased fairly linearly with increasing weight from age 20 in the obese [odds ratios (OR) 1.04 per kg change in weight, 95% confidence interval (CI) 1.03-1.05, P < 0.0001], as well as in the overweight (OR 1.15, 95% CI 1.14-1.17, P < 0.0001) and normal-weight (OR 1.18, 95% CI 1.14-1.21, P < 0.0001), subjects after adjustment for age, sex, body mass index (BMI) at age 20, alcohol intake, smoking, education, and exercise habits. Also in the PIVUS study, the change in weight over 50 years was related to prevalent MetS (OR 1.08 per kg change in weight, 95% CI 1.06-1.10, P < 0.0001). In both studies, self-reported BMI at age 20 was related to prevalent MetS.


Self-reported weight gain from age 20 was strongly and independently associated with prevalent MetS both in middle age or old age. Interestingly, this relationship was not restricted only to obese subjects. Our data provide additional support for the importance of maintaining a stable weight throughout life.


body weight; epidemiology; longitudinal; metabolic syndrome; obesity

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Dietary acrylamide and cancer risk: an updated meta-analysis.

Pelucchi C, Bosetti C, Galeone C, La Vecchia C.

Int J Cancer. 2015 Jun 15;136(12):2912-22. doi: 10.1002/ijc.29339. Epub 2014 Nov 26. Review.

PMID: 25403648 Free Article




The debate on the potential carcinogenic effect of dietary acrylamide is open. In consideration of the recent findings from large prospective investigations, we conducted an updated meta-analysis on acrylamide intake and the risk of cancer at several sites. Up to July 2014, we identified 32 publications. We performed meta-analyses to calculate the summary relative risk (RR) of each cancer site for the highest versus lowest level of intake and for an increment of 10 µg/day of dietary acrylamide, through fixed-effects or random-effects models, depending on the heterogeneity test. Fourteen cancer sites could be examined. No meaningful associations were found for most cancers considered. The summary RRs for high versus low acrylamide intake were 0.87 for oral and pharyngeal, 1.14 for esophageal, 1.03 for stomach, 0.94 for colorectal, 0.93 for pancreatic, 1.10 for laryngeal, 0.88 for lung, 0.96 for breast, 1.06 for endometrial, 1.12 for ovarian, 1.00 for prostate, 0.93 for bladder and 1.13 for lymphoid malignancies. The RR was of borderline significance only for kidney cancer (RR = 1.20; 95% confidence interval, CI, 1.00-1.45). All the corresponding continuous estimates ranged between 0.95 and 1.03, and none of them was significant. Among never-smokers, borderline associations with dietary acrylamide emerged for endometrial (RR = 1.23; 95% CI, 1.00-1.51) and ovarian (RR = 1.39; 95% CI, 0.97-2.00) cancers. This systematic review and meta-analysis of epidemiological studies indicates that dietary acrylamide is not related to the risk of most common cancers. A modest association for kidney cancer, and for endometrial and ovarian cancers in never smokers only, cannot be excluded.


acrylamide; epidemiologic studies; meta-analysis; neoplasms; review


Interactions between dietary acrylamide intake and genes for ovarian cancer risk.

Hogervorst JG, van den Brandt PA, Godschalk RW, van Schooten FJ, Schouten LJ.

Eur J Epidemiol. 2017 Apr 8. doi: 10.1007/s10654-017-0244-0. [Epub ahead of print]

PMID: 28391539



Some epidemiological studies observed a positive association between dietary acrylamide intake and ovarian cancer risk but the causality needs to be substantiated. By analyzing gene-acrylamide interactions for ovarian cancer risk for the first time, we aimed to contribute to this. The prospective Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69 years. At baseline in 1986, a random subcohort of 2589 women was sampled from the total cohort for a case cohort analysis approach. Dietary acrylamide intake of subcohort members and ovarian cancer cases (n = 252, based on 20.3 years of follow-up) was assessed with a food frequency questionnaire. We selected single nucleotide polymorphisms (SNPs) in genes in acrylamide metabolism and in genes involved in the possible mechanisms of acrylamide-induced carcinogenesis (effects on sex steroid systems, oxidative stress and DNA damage). Genotyping was done on DNA from toenails through Agena's MassARRAY iPLEX platform. Multiplicative interaction between acrylamide intake and SNPs was assessed with Cox proportional hazards analysis. Among the results for 57 SNPs and 2 gene deletions, there were no statistically significant interactions between acrylamide and gene variants after adjustment for multiple testing. However, there were several nominally statistically significant interactions between acrylamide intake and SNPs in the HSD3B1/B2 gene cluster: (rs4659175 (p interaction = 0.04), rs10923823 (p interaction = 0.06) and its proxy rs7546652 (p interaction = 0.05), rs1047303 (p interaction = 0.005), and rs6428830 (p interaction = 0.05). Although in need of confirmation, results of this study suggest that acrylamide may cause ovarian cancer through effects on sex hormones.


Dietary acrylamide; Ovarian cancer; Prospective cohort; Single nucleotide polymorphism


"1 tsp salt = 6 g salt ≈ 2,400 mg sodium = 104 mmol sodium = 104 mEq sodium"

"Sodium reduction ... cholesterol increased 5.59 mg/dL (2.9%); triglyceride increased 7.04 mg/dL (6.3%)."

Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride.

Graudal NA, Hubeck-Graudal T, Jurgens G.

Cochrane Database Syst Rev. 2017 Apr 9;4:CD004022. doi: 10.1002/14651858.CD004022.pub4. [Epub ahead of print] Review.

PMID: 28391629




In spite of more than 100 years of investigations the question of whether a reduced sodium intake improves health is still unsolved.


To estimate the effects of low sodium intake versus high sodium intake on systolic and diastolic blood pressure (SBP and DBP), plasma or serum levels of renin, aldosterone, catecholamines, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides.


The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to March 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched the reference lists of relevant articles.


Studies randomising persons to low-sodium and high-sodium diets were included if they evaluated at least one of the above outcome parameters.


Two review authors independently collected data, which were analysed with Review Manager 5.3.


A total of 185 studies were included. The average sodium intake was reduced from 201 mmol/day (corresponding to high usual level) to 66 mmol/day (corresponding to the recommended level).The effect of sodium reduction on blood pressure (BP) was as follows: white people with normotension: SBP: mean difference (MD) -1.09 mmHg (95% confidence interval (CI): -1.63 to -0.56; P = 0.0001); 89 studies, 8569 participants; DBP: + 0.03 mmHg (MD 95% CI: -0.37 to 0.43; P = 0.89); 90 studies, 8833 participants. High-quality evidence. Black people with normotension: SBP: MD -4.02 mmHg (95% CI:-7.37 to -0.68; P = 0.002); seven studies, 506 participants; DBP: MD -2.01 mmHg (95% CI:-4.37 to 0.35; P = 0.09); seven studies, 506 participants. Moderate-quality evidence. Asian people with normotension: SBP: MD -0.72 mmHg (95% CI: -3.86 to 2.41; P = 0.65); DBP: MD -1.63 mmHg (95% CI:-3.35 to 0.08; P =0.06); three studies, 393 participants. Moderate-quality evidence.White people with hypertension: SBP: MD -5.51 mmHg (95% CI: -6.45 to -4.57; P < 0.00001); 84 studies, 5925 participants; DBP: MD -2.88 mmHg (95% CI: -3.44 to -2.32; P < 0.00001); 85 studies, 6001 participants. High-quality evidence. Black people with hypertension: SBP MD -6.64 mmHg (95% CI:-9.00 to -4.27; P = 0.00001); eight studies, 619 participants; DBP -2.91 mmHg (95% CI:-4.52, -1.30; P = 0.0004); eight studies, 619 participants. Moderate-quality evidence. Asian people with hypertension: SBP: MD -7.75 mmHg (95% CI:-11,44 to -4.07; P < 0.0001) nine studies, 501 participants; DBP: MD -2.68 mmHg (95% CI: -4.21 to -1.15; P = 0.0006). Moderate-quality evidence.In plasma or serum, there was a significant increase in renin (P < 0.00001), aldosterone (P < 0.00001), noradrenaline (P < 0.00001), adrenaline (P < 0.03), cholesterol (P < 0.0005) and triglyceride (P < 0.0006) with low sodium intake as compared with high sodium intake. All effects were stable in 125 study populations with a sodium intake below 250 mmol/day and a sodium reduction intervention of at least one week.


Sodium reduction from an average high usual sodium intake level (201 mmol/day) to an average level of 66 mmol/day, which is below the recommended upper level of 100 mmol/day (5.8 g salt), resulted in a decrease in SBP/DBP of 1/0 mmHg in white participants with normotension and a decrease in SBP/DBP of 5.5/2.9 mmHg in white participants with hypertension. A few studies showed that these effects in black and Asian populations were greater. The effects on hormones and lipids were similar in people with normotension and hypertension. Renin increased 1.60 ng/mL/hour (55%); aldosterone increased 97.81 pg/mL (127%); adrenalin increased 7.55 pg/mL (14%); noradrenalin increased 63.56 pg/mL: (27%); cholesterol increased 5.59 mg/dL (2.9%); triglyceride increased 7.04 mg/dL (6.3%).


Total volume and composition of fluid intake and mortality in older women: a cohort study.

Lim WH, Wong G, Lewis JR, Lok CE, Polkinghorne KR, Hodgson J, Lim EM, Prince RL.

BMJ Open. 2017 Mar 24;7(3):e011720. doi: 10.1136/bmjopen-2016-011720.

PMID: 28341683 Free Article





The health benefits of 'drinking at least 8 glasses of water a day" in healthy individuals are largely unproven. We aimed to examine the relationship between total fluid and the sources of fluid consumption, risk of rapid renal decline, cardiovascular disease (CVD) mortality and all-cause mortality in elderly women.


We conducted a longitudinal analysis of a population-based cohort study of 1055 women aged ≥70 years residing in Australia.


The associations between total daily fluid intake (defined as total volume of beverage excluding alcohol and milk) and the types of fluid (water, black tea, coffee, milk and other fluids) measured as cups per day and rapid renal decline, CVD and all-cause mortality were assessed using adjusted logistic and Cox regression analyses.


Over a follow-up period of 10 years, 70 (6.6%) experienced rapid renal decline and 362 (34.4%) died, of which 142 (13.5%) deaths were attributed to CVD. The median (IQR) intake of total fluid was 10.4 (8.5-12.5) cups per day, with water (median (IQR) 4 (2-6) cups per day) and black tea (median (IQR) 3 (1-4) cups per day) being the most frequent type of fluid consumed. Every cup per day higher intake of black tea was associated with adjusted HRs of 0.90 (95% CI 0.81 to 0.99) and 0.92 (95% CI 0.86 to 0.98) for CVD mortality and all-cause mortality, respectively. There were no associations between black tea intake and rapid renal decline, or between the quantity or type of other fluids, including water intake, and any clinical outcomes.


Habitual higher intake of black tea may potentially improve long-term health outcomes, independent of treating traditional CVD risk factors, but validation of our study findings is essential.


EPIDEMIOLOGY; elderly; fluid intake; mortality; tea


Comparison between the effect of 6 weeks of morning or evening aerobic exercise on appetite and anthropometric indices: a randomized controlled trial.

Alizadeh Z, Younespour S, Rajabian Tabesh M, Haghravan S.

Clin Obes. 2017 Mar 26. doi: 10.1111/cob.12187. [Epub ahead of print]

PMID: 28343364


Several studies have shown that exercise is directly related to c