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Nutritional Risk Factors, Microbiota and Parkinson's Disease: What Is the Current Evidence?
Boulos C, Yaghi N, El Hayeck R, Heraoui GN, Fakhoury-Sayegh N.
Nutrients. 2019 Aug 14;11(8). pii: E1896. doi: 10.3390/nu11081896. Review.
PMID: 31416163
[pdf availed from Pubmed site.]
Abstract
Parkinson's disease (PD) is a frequent neurodegenerative disease among elderly people. Genetic and underlying environmental factors seem to be involved in the pathogenesis of PD related to degeneration of dopaminergic neurons in the striatum. In previous experimental researches oxidative stress, mitochondrial dysfunction, homocysteine, and neuroinflammation have been reported as potential mechanisms. Among environmental factors, nutrition is one of the most investigated areas as it is a potentially modifiable factor. The purpose of this review is to provide current knowledge regarding the relation between diet and PD risk. We performed a comprehensive review including the most relevant studies from the year 2000 onwards including prospective studies, nested case-control studies, and meta-analysis. Among dietary factors we focused on specific nutrients and food groups, alcoholic beverages, uric acid, and dietary patterns. Furthermore, we included studies on microbiota as recent findings have shown a possible impact on neurodegeneration. As a conclusion, there are still many controversies regarding the relationship between PD and diet which, beside methodological differences among studies, may be due to underlying genetic and gender-specific factors. However, some evidence exists regarding a potential protective effect of uric acid, poly-unsaturated fatty acids, coffee, and tea but mainly in men, whereas dairy products, particularly milk, might increase PD risk through contaminant mediated effect.
KEYWORDS:
Parkinson’s disease; dietary factors; neurodegenerative diseases

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Daidzein and genistein have differential effects in decreasing whole body bone mineral density but had no effect on hip and spine density in premenopausal women: A 2-year randomized, double-blind, placebo-controlled study.
Nayeem F, Chen NW, Nagamani M, Anderson KE, Lu LW.
Nutr Res. 2019 Jul 3;68:70-81. doi: 10.1016/j.nutres.2019.06.007. [Epub ahead of print]
PMID: 31421395
Abstract
Soy isoflavones are potentially beneficial phytoestrogens, but their tissue-selective effects in women are poorly understood. We tested the hypothesis that soy isoflavones affect bone mineral density (BMD), which may be influenced by individual differences in isoflavone metabolism and serum calcium levels. Ninety-nine healthy premenopausal women were randomized to isoflavones (136.6 mg aglycone equivalence) and 98 to placebo for 5 days per week for up to 2 years. BMD, serum calcium, and urinary excretion of daidzein and genistein were measured before and during treatment. In 129 adherent subjects, we found that isoflavone exposure, determined by urinary excretion levels, but not by dose assignment, interacted with serum calcium in affecting whole body BMD, but not hip and spine BMD. The regression coefficient was -0.042 for genistein excretion (GE) and 0.091 for the interaction between GE and serum calcium (all P < .05). Daidzein excretion had similar but marginal effect. Genistein significantly decreased whole body BMD only at low normal serum calcium levels but increased whole body BMD at higher serum calcium levels. Comparing maximum to minimum GE, mean changes in whole body BMD were +0.033 and -0.113 g/cm2 at serum calcium levels of 10 and 8.15 mg/dL, respectively. These associations were not evident by intention-to-treat analysis, which could not model for inter-individual differences in isoflavone metabolism. In summary, soy isoflavones decrease whole body BMD only when serum calcium is low. Isoflavones are dietary substances that may influence calcium homeostasis by releasing calcium from bone while sparing the common fracture risk sites hip and spine.
KEYWORDS:
Bone metabolism; Calcium homeostasis; Daidzein; Genistein; Hormone receptor modulators; Isoflavones

A Prospective Study of Dietary Meat Intake and Risk of Incident Chronic Kidney Disease.
Mirmiran P, Yuzbashian E, Aghayan M, Mahdavi M, Asghari G, Azizi F.
J Ren Nutr. 2019 Aug 14. pii: S1051-2276(19)30265-1. doi: 10.1053/j.jrn.2019.06.008. [Epub ahead of print]
PMID: 31422013
Abstract
OBJECTIVE:
The aim of the present study was to investigate the association of different meat intake and substitution of them with risk of incident chronic kidney disease (CKD).
METHODS:
At the baseline, habitual dietary intakes of 4881 participants of the Tehran Lipid and Glucose Study who were free of CKD were assessed by a valid and reliable food-frequency questionnaire. Logistic regression, adjusted for age, sex, smoking, total energy intake, triglycerides, body mass index, physical activity, hypertension, and diabetes, was used to assess the relationship between major protein sources of food (total red meat, unprocessed red meat, and processed red meat) and incident CKD. Odds ratios (ORs) and 95% confidence intervals (CIs) for the CKD were estimated for substituting one serving of total red meat with one serving of low-fat dairy, nuts, whole grains, and legumes.
RESULTS:
The mean ± standard deviation age of participants was 40.1 ± 12.8 years. After adjustment for confounders, compared with the lowest quartile of total red meat intake, OR of incident CKD in the highest quartile was 1.73 (95% CI: 1.33 to 2.24; P for trend <0.001) in the final model. OR for participants in the highest compared with that in the lowest quartile of processed red meat was 1.99 (95% CI: 2.54 to 2.56; P for trend <0.001). In the substitution analyses, replacing 1 serving of total red meat and processed meat with 1 serving of low-fat dairy, nuts, whole grains, and legumes was associated with a lower risk of incident CKD.
CONCLUSIONS:
Higher consumption of total red meat and processed meat was associated with increased risk of incident CKD. Furthermore, substitution of total red and processed meat in the diet with other sources of dietary protein was associated with lower CKD risk.

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Low 24-hour core body temperature as a thrifty metabolic trait driving catch-up fat during weight regain after caloric restriction.
Calonne J, Arsenijevic D, Scerri I, Miles-Chan JL, Montani JP, Dulloo AG.
Am J Physiol Endocrinol Metab. 2019 Aug 20. doi: 10.1152/ajpendo.00092.2019. [Epub ahead of print]
PMID: 31430205
Abstract
The recovery of body weight after substantial weight loss or growth retardation is often characterized by a disproportionately higher rate of fat mass vs lean mass recovery, with this phenomenon of 'preferential catch-up fat' being contributed by energy conservation (thrifty) metabolism. To test the hypothesis that a low core body temperature (Tc) constitutes a thrifty metabolic trait underlying the high metabolic efficiency driving catch-up fat, the Anipill® system - with the telemetry capsules implanted in the peritoneal cavity - was used for continuous monitoring of Tc for several weeks in a validated rat model of semistarvation-refeeding in which catch-up fat is driven solely by suppressed thermogenesis. In animals housed at 22°C, 24h Tc was reduced in response to semistarvation (-0.77°C, p<0.001), and remained significantly lower than in controls during the catch-up fat phase of refeeding (-0.27°C on average, p<0.001); the lower Tc during refeeding being more pronounced during the light phase than during the dark phase of the 24h cycle (-0.30°C vs -0.23°C, p<0.01), and with no between-group differences in locomotor activity. A lower 24h Tc in animal showing catch-up fat was also observed when the housing temperature was raised to 29°C (i.e. at thermoneutrality). The reduced energy cost of homeothermy in response to caloric restriction persists during weight recovery, and constitutes a thrifty metabolic trait that contributes to the high metabolic efficiency that underlies the rapid restoration of the body's fat stores during weight regain, with implications for obesity relapse after therapeutic slimming and the pathophysiology of catch-up growth.
KEYWORDS:
Thermogenesis; Thrifty phenotype; caloric restriction; catch-up growth; obesity

Longitudinal analysis of the impact of loneliness on cognitive function over a 20-year follow-up.
Wang H, Lee C, Hunter S, Fleming J, Brayne C; CC75C Study Collaboration.
Aging Ment Health. 2019 Aug 20:1-7. doi: 10.1080/13607863.2019.1655704. [Epub ahead of print]
PMID: 31429312
Abstract
Background: Loneliness and cognitive impairment are both commonly experienced by older old people, but evidence for the association between these has been inconsistent. Moreover, most evidence has been cross-sectional in nature and largely based on studies with relatively young later life age groups rather than 'the oldest old'. We aimed to test the potential impact of loneliness amongst older old people on their cognitive function over a 20-year period. Method: Data were drawn from wave 3 to wave 10 of the Cambridge City over-75s Cohort (CC75C) study. The impact of loneliness on transition between normal and impaired cognitive states was examined by multi-state modelling. The associations between loneliness changes and cognitive function decline were tested by using generalized estimating equation (GEE) with an independent working correlation structure. Missing data were imputed by using multiple imputation chained equations. Results: At wave 3, 713 participants were interviewed, of whom 657 (92%) had Mini-Mental State Examination (MMSE) assessments. Of individuals who had an MMSE score, approximately one quarter reported feeling lonely, and another 16% felt slightly lonely. The prevalence of feeling lonely or slightly lonely varied between waves. Results from multi-state modelling indicated that loneliness was not related to cognitive function transitions, and results from the GEE model showed that loneliness was not significantly associated with cognitive function decline after adjusting for cohort effects, follow-up time, sex, education, and interaction terms for sex, education and time. Conclusions: Loneliness did not exert long-term harmful effects on cognitive function in the oldest old.
KEYWORDS:
Loneliness; cognition; longitudinal analysis; older people

The Effect of Pharmaceutical Innovation on Longevity: Patient Level Evidence from the 1996-2002 Medical Expenditure Panel Survey and Linked Mortality Public-use Files.
Lichtenberg FR.
Forum Health Econ Policy. 2013 Jan 1;16(1):1-33. doi: 10.1515/fhep-2012-0032.
PMID: 31419866
Abstract
This study uses patient-level data to analyze the effect of technological change embodied in pharmaceuticals on the longevity of elderly Americans. Previous patient-level studies could not control for important patient attributes such as education, income, and race; they did not provide estimates of the effect of using newer drugs on life expectancy, or of the overall cost-effectiveness of new drugs relative to old drugs; and they were not based on nationally representative samples of individuals. Our data, primarily derived from the Medical Expenditure Panel Survey and the Linked Mortality Public-use Files, enable us to overcome those limitations. We investigate the effect of the vintage (year of U.S. Food and Drug Administration approval) of the prescription drugs used by an individual on his or her survival and medical expenditure, controlling for a number of demographic characteristics and indicators and determinants of health status. When we control only for age, sex, and interview year, we estimate that a 1-year increase in drug vintage increases life expectancy by 0.52%. Controlling for a much more extensive set of other attributes (the mean year the person started taking his or her medications, and dummy variables for activity limitations, race, education, family income as a percent of the poverty line, insurance coverage, Census region, body mass index, smoking, and more than 100 medical conditions) has virtually no effect on the estimate of the effect of drug vintage on life expectancy. Between 1996 and 2003, the mean vintage of prescription drugs increased by 6.6 years. This is estimated to have increased the life expectancy of elderly Americans by 0.41-0.47 years. This suggests that not less than two-thirds of the 0.6-year increase in the life expectancy of elderly Americans during 1996-2003 was due to the increase in drug vintage. The 1996-2003 increase in drug vintage is also estimated to have increased annual drug expenditure per elderly American by $207, and annual total medical expenditure per elderly American by $218. This implies that the incremental cost-effectiveness ratio (cost per life-year gained) of pharmaceutical innovation was about $12,900. This estimate of the cost per life-year gained from the use of newer drugs is a small fraction of leading economists' estimates of the value of (willingness to pay for) an additional year of life. It is also consistent with estimates from clinical trials.
KEYWORDS:
innovation; longevity; mortality; pharmaceuticals; prescription drugs

Platelet Indices and Risk of Death and Cardiovascular Events: Results from a Large Population-Based Cohort Study.
Patti G, Di Martino G, Ricci F, Renda G, Gallina S, Hamrefors V, Melander O, Sutton R, Engström G, De Caterina R, Fedorowski A.
Thromb Haemost. 2019 Aug 20. doi: 10.1055/s-0039-1694969. [Epub ahead of print]
PMID: 31430798
Abstract
Studies evaluating the relationship between platelet indices and cardiovascular (CV) outcomes yielded conflicting results. We assessed the incidence of adverse events according to baseline quintiles of platelet indices in the prospective cohort of the Malmö Diet and Cancer Study. A total of 30,314 individuals (age 57 ± 8 years) were followed for a median of 16 years (468,490 person-years). Outcome measures included all-cause death, CV death, myocardial infarction (MI), and ischemic stroke. The fifth quintile of platelet count (> 274.6 × 109/L) was associated with higher incidence of all-cause death (hazard ratio {HR} 1.20, 95% confidence interval [CI] 1.09-1.32, p < 0.001), CV death (HR 1.19, 95% CI 1.00-1.42; p = 0.044), MI (HR 1.32, 95% CI 1.12-1.54; p = 0.001), and ischemic stroke (HR 1.27, 95% CI 1.08-1.50, p = 0.004) compared with the first quintile (≤ 185 × 109/L), and also associated with a lower survival, regardless of previous history of MI (p for interaction = 0.58) or stroke (p for interaction = 0.42). In the highest quintile, history of stroke had a higher risk of CV death (HR 3.18, 95% CI 1.54-6.54) compared with no previous stroke (HR 1.12, 95% CI 0.96-1.31). The risk of MI and stroke was greatest in the fifth quintile, regardless of previous MI or previous stroke, respectively. The risk of all adverse events was similar across different quintiles of mean platelet volume. In conclusion, elevated platelet count is associated with higher mortality and risk of CV events, regardless of previous MI and stroke. Platelet count may thus be a useful marker for further stratification of CV risk, and especially of death.

Protective Effects of Dietary MUFAs Mediating Metabolites against Hypertension Risk in the Korean Genome and Epidemiology Study.
Lee H, Jang HB, Yoo MG, Chung KS, Lee HJ.
Nutrients. 2019 Aug 16;11(8). pii: E1928. doi: 10.3390/nu11081928.
PMID: 31426326
[pdf availed from PMID site.]
Abstract
BACKGROUND AND AIMS:
Metabolites related to dietary factors can be used to identify biological markers to prevent metabolic disease. However, most studies have been conducted in the United States and Europe, and those in the Asian region are limited. We investigated the effects of dietary monounsaturated fatty acids (MUFAs) and metabolites on new-onset hypertension in the Korean Genome and Epidemiology Study.
METHOD AND RESULTS:
A total of 1529 subjects without hypertension were divided into tertiles of dietary MUFAs intake. After a 4-year follow-up, 135 serum metabolites were measured using the AbsoluteIDQ p180 kit. During the 4-year follow-up period, 193 new-onset hypertension incidences were observed. The highest MUFAs intake group was inversely associated with the risk of hypertension compared with the lowest MUFAs intake group (odds ratio (OR) = 0.49, (95% confidence interval (CI) = 0.29-0.82)). Of the 135 metabolites, eight were significantly associated with MUFAs intake. Phosphatidylcholine-diacyl (PC aa) C 38:1 and hydroxysphingomyelin (SM OH) C 16:1 were associated with a decrease in hypertension risk (PC aa C 38:1, OR = 0.60 (95% CI = 0.37-0.96); SM OH C 16:1, OR = 0.42 (95% CI = 0.20-0.90)). The highest MUFAs intake group had a significantly decreased risk of hypertension, even considering PC aa C 38:1 and SM (OH) C 16:1 as a mediator.
CONCLUSION:
We confirmed that dietary MUFAs intake, and PC aa C 38:1 and SM (OH) C 16:1 had protective effects against hypertension. Furthermore, high MUFAs intake combined with PC aa C 38:1 and SM (OH) C 16:1 has the most significant effect on reducing the risk hypertension.
KEYWORDS:
hypertension; metabolites; monounsaturated fatty acid /MUFAs

Edited by AlPater

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Healthy diet and fiber intake are associated with decreased risk of incident symptomatic peripheral artery disease - A prospective cohort study.
Kulezic A, Bergwall S, Fatemi S, Sonestedt E, Zarrouk M, Gottsäter A, Acosta S.
Vasc Med. 2019 Aug 20:1358863X19867393. doi: 10.1177/1358863X19867393. [Epub ahead of print]
PMID: 31431146
Abstract
Peripheral artery disease (PAD) is caused by atherosclerosis and associated with an increased risk of leg amputation, cardiovascular disease, and death. A healthy diet has been shown to reduce the risk of cardiovascular events, but relationships between diet, fiber intake, and incidence of PAD are virtually unknown. The aim was to investigate the long-term impact of diet on the development of PAD among 26,010 middle-aged individuals in the prospective Malmö Diet and Cancer study (MDCS). Data on dietary intake were collected through a 7-day food diary combined with a food questionnaire and a 1-hour interview. Adherence to a recommended intake of six dietary components - saturated fat, polyunsaturated fat, fish and shellfish, fiber, fruit and vegetables, and sucrose - was scored (sum 0-6 points) to assess a diet quality index, adjusting for potential confounders. Cox regression analysis was used to estimate associations between diet variables and PAD incidence expressed in hazard ratios (HR) with 95% CI. During a median follow-up of 21.7 years, 1122 participants developed PAD. Diet score was associated with a reduced risk of PAD in multivariable analysis (p = 0.03). When mutually adjusting for all dietary variables, only adherence to recommended levels of fiber intake was associated with a reduced risk of incident PAD (HR 0.84; 95% CI 0.72-0.99). In this prospective, population-based study including 26,010 participants with over 20 years of follow-up, a healthy diet, especially a high intake of fiber, was associated with a reduced risk of PAD. Primary prevention programs directed against PAD should therefore include a fiber recommendation.
KEYWORDS:
atherosclerosis; diet; epidemiology; fiber; peripheral artery disease (PAD); prospective cohort study

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Tomato and Lycopene Consumption Is Inversely Associated with Total and Cause-Specific Mortality: A Population-based Cohort Study, on behalf of the International Lipid Expert Panel (ILEP).
Mazidi M, Katsiki N, George ES, Banach M.
Br J Nutr. 2019 Aug 22:1-21. doi: 10.1017/S0007114519002150. [Epub ahead of print]
PMID: 31434581
Abstract
No data exist on the associations of dietary tomato and lycopene consumption with total and cause-specific mortality. Using the National Health and Nutrition Examination Surveys (NHANES) 1999-2010, we evaluted the long-term impact of tomato and lycopene intake on total and cause-specific (coronary heart disease [CHD] and cerebrovascular disease) mortality. We also assessed the changes in cardio-metabolic risk factors according to tomato and lycopene intake. Vital status through December 31, 2011 was ascertained. Cox proportional hazard regression models (followed by propensity score-matching) were used to investigate the link between tomato and lycopene consumption total, CHD and cerebrovascular mortality. Among the 23,935 participants included (mean age = 47.6 years, 48.8% men), 3403 deaths occurred during 76.4 months of follow-up. Tomato intake was inversely associated with total (risk ratio (RR):0.86, 95% confidence interval (CI):0.81-0.92), CHD (0.76, 95%CI: 0.70-0.85) and cerebrovascular (0.70, 95%CI: 0.62-0.81) mortality. Similar inverse associations were found between lycopene consumption, total (0.76, 95%CI: 0.72-0.81), CHD (0.73, 95%CI: 0.65-0.83) and cerebrovascular (0.71, 95%CI: 0.65-0.78) mortality; these associations were independent of anthropometric, clinical and nutritional parameters. Age and obesity did not affect the associations of tomato and lycopene consumption with total, CHD and cerebrovascular mortality. C-reactive protein significantly moderated the link between lycopene and tomato intake with total, CHD and cerebrovascular mortality. Analysis of co-variance showed that participants with a higher tomato and lycopene consumption had a more cardio-protective profile compared with those with a lower intake. Our results highlighted the favorable effect of tomato and lycopene intake on total and cause-specific mortality as well as to cardio-metabolic risk factors. These findings should be taken into consideration for public health strategies.
KEYWORDS:
Cardio-metabolic; Cerebrovascular Disease; Coronary Heart Disease; Lycopene; Mortality; Tomato

Associations of dairy product consumption with mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Italy cohort.
Pala V, Sieri S, Chiodini P, Masala G, Palli D, Mattiello A, Panico S, Tumino R, Frasca G, Fasanelli F, Ricceri F, Agnoli C, Grioni S, Krogh V.
Am J Clin Nutr. 2019 Aug 21. pii: nqz183. doi: 10.1093/ajcn/nqz183. [Epub ahead of print]
PMID: 31435641
Abstract
BACKGROUND:
The relation of dairy product consumption to health and mortality is controversial.
OBJECTIVES:
We investigated associations of consumption of various dairy products with mortality in the Italian cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Italy study.
METHODS:
Dairy product consumption was assessed by validated semiquantitative FFQs. Multivariable Cox models stratified by center, age, and sex and adjusted for confounders estimated associations of milk (total, full fat, and reduced fat), yogurt, cheese, butter, and dairy calcium consumption with mortality for cancer, cardiovascular disease, and all causes. Nonlinearity was tested by restricted cubic spline regression.
RESULTS:
After a median follow-up of 14.9 y, 2468 deaths were identified in 45,009 participants: 59% from cancer and 19% from cardiovascular disease. No significant association of consumption of any dairy product with mortality was found in the fully adjusted models. A 25% reduction in risk of all-cause mortality was found for milk intake from 160 to 120 g/d (HR: 0.75; 95% CI: 0.61, 0.91) but not for the highest (>200 g/d) category of intake (HR: 0.95; 95% CI: 0.84, 1.08) compared with nonconsumption. Associations of full-fat and reduced-fat milk consumption with all-cause and cause-specific mortality were similar to those for milk as a whole.
CONCLUSIONS:
In this Italian cohort characterized by low to average milk consumption, we found no evidence of a dose-response association between milk consumption and mortality and also no association of consumption of other dairy products investigated with mortality.
KEYWORDS:
EPIC-Italy; cancer; cardiovascular disease; dairy product consumption; mortality

Dose-response associations between accelerometry measured physical activity and sedentary time and all cause mortality: systematic review and harmonised meta-analysis.
Ekelund U, Tarp J, Steene-Johannessen J, Hansen BH, Jefferis B, Fagerland MW, Whincup P, Diaz KM, Hooker SP, Chernofsky A, Larson MG, Spartano N, Vasan RS, Dohrn IM, Hagströmer M, Edwardson C, Yates T, Shiroma E, Anderssen SA, Lee IM.
BMJ. 2019 Aug 21;366:l4570. doi: 10.1136/bmj.l4570.
PMID: 31434697
https://www.bmj.com/content/bmj/366/bmj.l4570.full.pdf
Abstract
OBJECTIVE:
To examine the dose-response associations between accelerometer assessed total physical activity, different intensities of physical activity, and sedentary time and all cause mortality.
DESIGN:
Systematic review and harmonised meta-analysis.
DATA SOURCES:
PubMed, PsycINFO, Embase, Web of Science, Sport Discus from inception to 31 July 2018.
ELIGIBILITY CRITERIA:
Prospective cohort studies assessing physical activity and sedentary time by accelerometry and associations with all cause mortality and reported effect estimates as hazard ratios, odds ratios, or relative risks with 95% confidence intervals.
DATA EXTRACTION AND ANALYSIS:
Guidelines for meta-analyses and systematic reviews for observational studies and PRISMA guidelines were followed. Two authors independently screened the titles and abstracts. One author performed a full text review and another extracted the data. Two authors independently assessed the risk of bias. Individual level participant data were harmonised and analysed at study level. Data on physical activity were categorised by quarters at study level, and study specific associations with all cause mortality were analysed using Cox proportional hazards regression analyses. Study specific results were summarised using random effects meta-analysis.
MAIN OUTCOME MEASURE:
All cause mortality.
RESULTS:
39 studies were retrieved for full text review; 10 were eligible for inclusion, three were excluded owing to harmonisation challenges (eg, wrist placement of the accelerometer), and one study did not participate. Two additional studies with unpublished mortality data were also included. Thus, individual level data from eight studies (n=36 383; mean age 62.6 years; 72.8% women), with median follow-up of 5.8 years (range 3.0-14.5 years) and 2149 (5.9%) deaths were analysed. Any physical activity, regardless of intensity, was associated with lower risk of mortality, with a non-linear dose-response. Hazards ratios for mortality were 1.00 (referent) in the first quarter (least active), 0.48 (95% confidence interval 0.43 to 0.54) in the second quarter, 0.34 (0.26 to 0.45) in the third quarter, and 0.27 (0.23 to 0.32) in the fourth quarter (most active). Corresponding hazards ratios for light physical activity were 1.00, 0.60 (0.54 to 0.68), 0.44 (0.38 to 0.51), and 0.38 (0.28 to 0.51), and for moderate-to-vigorous physical activity were 1.00, 0.64 (0.55 to 0.74), 0.55 (0.40 to 0.74), and 0.52 (0.43 to 0.61). For sedentary time, hazards ratios were 1.00 (referent; least sedentary), 1.28 (1.09 to 1.51), 1.71 (1.36 to 2.15), and 2.63 (1.94 to 3.56).
CONCLUSION:
Higher levels of total physical activity, at any intensity, and less time spent sedentary, are associated with substantially reduced risk for premature mortality, with evidence of a non-linear dose-response pattern in middle aged and older adults.

Four-in-one pill prevents third of heart problems
By James Gallagher
Health and science correspondent, BBC News
23 August 2019
https://www.bbc.com/news/health-49434337
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Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran): a pragmatic, cluster-randomised trial
Gholamreza Roshandel, Masoud Khoshnia, Hossein Poustchi, Karla Hemming, et al.
Published:August 24, 2019DOI:https://doi.org/10.1016/S0140-6736(19)31791-X
Summary
Background
A fixed-dose combination therapy (polypill strategy) has been proposed as an approach to reduce the burden of cardiovascular disease, especially in low-income and middle-income countries (LMICs). The PolyIran study aimed to assess the effectiveness and safety of a four-component polypill including aspirin, atorvastatin, hydrochlorothiazide, and either enalapril or valsartan for primary and secondary prevention of cardiovascular disease.
Methods
The PolyIran study was a two-group, pragmatic, cluster-randomised trial nested within the Golestan Cohort Study (GCS), a cohort study with 50 045 participants aged 40–75 years from the Golestan province in Iran. Clusters (villages) were randomly allocated (1:1) to either a package of non-pharmacological preventive interventions alone (minimal care group) or together with a once-daily polypill tablet (polypill group). Randomisation was stratified by three districts (Gonbad, Aq-Qala, and Kalaleh), with the village as the unit of randomisation. We used a balanced randomisation algorithm, considering block sizes of 20 and balancing for cluster size or natural log of the cluster size (depending on the skewness within strata). Randomisation was done at a fixed point in time (Jan 18, 2011) by statisticians at the University of Birmingham (Birmingham, UK), independent of the local study team. The non-pharmacological preventive interventions (including educational training about healthy lifestyle—eg, healthy diet with low salt, sugar, and fat content, exercise, weight control, and abstinence from smoking and opium) were delivered by the PolyIran field visit team at months 3 and 6, and then every 6 months thereafter. Two formulations of polypill tablet were used in this study. Participants were first prescribed polypill one (hydrochlorothiazide 12·5 mg, aspirin 81 mg, atorvastatin 20 mg, and enalapril 5 mg). Participants who developed cough during follow-up were switched by a trained study physician to polypill two, which included valsartan 40 mg instead of enalapril 5 mg. Participants were followed up for 60 months. The primary outcome—occurrence of major cardiovascular events (including hospitalisation for acute coronary syndrome, fatal myocardial infarction, sudden death, heart failure, coronary artery revascularisation procedures, and non-fatal and fatal stroke)—was centrally assessed by the GCS follow-up team, who were masked to allocation status. We did intention-to-treat analyses by including all participants who met eligibility criteria in the two study groups. The trial was registered with ClinicalTrials.gov, number NCT01271985.
Findings
Between Feb 22, 2011, and April 15, 2013, we enrolled 6838 individuals into the study—3417 (in 116 clusters) in the minimal care group and 3421 (in 120 clusters) in the polypill group. 1761 (51·5%) of 3421 participants in the polypill group were women, as were 1679 (49·1%) of 3417 participants in the minimal care group. Median adherence to polypill tablets was 80·5% (IQR 48·5–92·2). During follow-up, 301 (8·8%) of 3417 participants in the minimal care group had major cardiovascular events compared with 202 (5·9%) of 3421 participants in the polypill group (adjusted hazard ratio {HR} 0·66, 95% CI 0·55–0·80). We found no statistically significant interaction with the presence (HR 0·61, 95% CI 0·49–0·75) or absence of pre-existing cardiovascular disease (0·80; 0·51–1·12; p interaction=0·19). When restricted to participants in the polypill group with high adherence, the reduction in the risk of major cardiovascular events was even greater compared with the minimal care group (adjusted HR 0·43, 95% CI 0·33–0·55). The frequency of adverse events was similar between the two study groups. 21 intracranial haemorrhages were reported during the 5 years of follow-up—ten participants in the polypill group and 11 participants in the minimal care group. There were 13 physician-confirmed diagnoses of upper gastrointestinal bleeding in the polypill group and nine in the minimal care group.
Interpretation
Use of polypill was effective in preventing major cardiovascular events. Medication adherence was high and adverse event numbers were low. The polypill strategy could be considered as an additional effective component in controlling cardiovascular diseases, especially in LMICs. 

Do We Really Need Another Time-Series Study of the PM2.5-Mortality Association?
Balmes JR.
N Engl J Med. 2019 Aug 22;381(8):774-776. doi: 10.1056/NEJMe1909053. No abstract available.
PMID: 31433927
https://www.nejm.org/doi/full/10.1056/NEJMe1909053?query=TOC
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Ambient Particulate Air Pollution and Daily Mortality in 652 Cities.
Liu C, Chen R, Sera F, Vicedo-Cabrera AM, Guo Y, Tong S, Coelho MSZS, Saldiva PHN, Lavigne E, Matus P, Valdes Ortega N, Osorio Garcia S, Pascal M, Stafoggia M, Scortichini M, Hashizume M, Honda Y, Hurtado-Díaz M, Cruz J, Nunes B, Teixeira JP, Kim H, Tobias A, Íñiguez C, Forsberg B, Åström C, Ragettli MS, Guo YL, Chen BY, Bell ML, Wright CY, Scovronick N, Garland RM, Milojevic A, Kyselý J, Urban A, Orru H, Indermitte E, Jaakkola JJK, Ryti NRI, Katsouyanni K, Analitis A, Zanobetti A, Schwartz J, Chen J, Wu T, Cohen A, Gasparrini A, Kan H.
N Engl J Med. 2019 Aug 22;381(8):705-715. doi: 10.1056/NEJMoa1817364.
PMID: 31433918
https://sci-hub.tw/10.1056/NEJMoa1817364
Abstract
BACKGROUND:
The systematic evaluation of the results of time-series studies of air pollution is challenged by differences in model specification and publication bias.
METHODS:
We evaluated the associations of inhalable particulate matter (PM) with an aerodynamic diameter of 10 μm or less (PM10) and fine PM with an aerodynamic diameter of 2.5 μm or less (PM2.5) with daily all-cause, cardiovascular, and respiratory mortality across multiple countries or regions. Daily data on mortality and air pollution were collected from 652 cities in 24 countries or regions. We used overdispersed generalized additive models with random-effects meta-analysis to investigate the associations. Two-pollutant models were fitted to test the robustness of the associations. Concentration-response curves from each city were pooled to allow global estimates to be derived.
RESULTS:
On average, an increase of 10 μg per cubic meter in the 2-day moving average of PM10 concentration, which represents the average over the current and previous day, was associated with increases of 0.44% (95% confidence interval [CI], 0.39 to 0.50) in daily all-cause mortality, 0.36% (95% CI, 0.30 to 0.43) in daily cardiovascular mortality, and 0.47% (95% CI, 0.35 to 0.58) in daily respiratory mortality. The corresponding increases in daily mortality for the same change in PM2.5 concentration were 0.68% (95% CI, 0.59 to 0.77), 0.55% (95% CI, 0.45 to 0.66), and 0.74% (95% CI, 0.53 to 0.95). These associations remained significant after adjustment for gaseous pollutants. Associations were stronger in locations with lower annual mean PM concentrations and higher annual mean temperatures. The pooled concentration-response curves showed a consistent increase in daily mortality with increasing PM concentration, with steeper slopes at lower PM concentrations.
CONCLUSIONS:
Our data show independent associations between short-term exposure to PM10 and PM2.5 and daily all-cause, cardiovascular, and respiratory mortality in more than 600 cities across the globe. These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies. (Funded by the National Natural Science Foundation of China and others.).

Edited by AlPater

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The effect of omega-3 and vitamin E on oxidative stress and inflammation: Systematic review and meta-analysis of randomized controlled trials.
Moosavian SP, Arab A, Mehrabani S, Moradi S, Nasirian M.
Int J Vitam Nutr Res. 2019 Aug 23:1-11. doi: 10.1024/0300-9831/a000599. [Epub ahead of print]
PMID: 31442100
Abstract
Background: Several studies have investigated the effect of omega-3 fatty acids and vitamin E on oxidative stress and inflammation, but their findings are inconsistent. The aim of this meta-analysis is to elucidate the overall effects of co-supplementation with omega-3 fatty acids and vitamin E on oxidative stress and inflammation. Methods: We searched titles, abstracts, and keywords of relevant articles indexed in PubMed, ISI, Scopus, and Google Scholar databases up to December 2018 to identify eligible RCT studies. Random effects model was used to estimate the pooled effect of co-supplementation with omega-3 fatty acids and vitamin E on oxidative stress and inflammation. Results: Overall, 7 RCTs with 504 participants were included in this meta-analysis. We found that co-supplementation with omega-3 fatty acids and vitamin E decreased hs-CRP (weighed mean difference (WMD) = -2.15 mg/L; 95% CI: -3.40, -0.91 mg/L; P < 0.001) concentrations and increased total antioxidant capacity (TAC) (WMD = 92.87 mmol/L; 95% CI: 31.97, 153.77 mmol/L; P = 0.03), and nitric oxide levels (NO) (WMD: 6.95 μmol/L; 95% CI: 3.86, 10.04, P < 0.001) compared with control group. Omega-3 fatty acids and vitamin E had no significant effect on malondialdehyde (MDA) (WMD: 1.54 mmol/L; 95% CI: -1.29, 4.36; P = 0.196), and glutathione (GSH) (WMD: 20.87 mmol/L; 95% CI: -20.04, 61.6, P = 0.31) levels. Conclusion: The present meta-analysis found that omega-3 fatty acids and vitamin E co-supplementation significantly decreased hs-CRP and increased NO and TAC, although it had no significant effect on MDA and GSH.
KEYWORDS:
Inflammation; Omega-3 fatty acids; Oxidative stress; Supplementation; Vitamin E

Effect of L-Arginine Supplementation on Lipid Profiles and Inflammatory Markers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Sepandi M, Abbaszadeh S, Qobady S, Taghdir M.
Pharmacol Res. 2019 Aug 20:104407. doi: 10.1016/j.phrs.2019.104407. [Epub ahead of print] Review.
PMID: 31442577
Abstract
Several studies have examined the effect of oral L-Arginine supplementation on lipid profiles and inflammatory markers. However, findings are inconsistent in this regard. Therefore, the aim of this study is to summarize and examine the effect of L-Arginine supplementation on lipid profiles and inflammatory markers in published randomized controlled trials (RCTs). We searched PubMed/Medline, SCOPUS, ISI web of science, and Google Scholar up to May 2019. The weighted mean difference (WMD) and 95% confidence interval (CI) as mean changes of lipid profiles and inflammatory markers between L-Arginine supplementation and control groups were calculated using a random effect model. Subgroup analysis was used to find potential sources of heterogeneity among studies. A total of 6282 RCTs were found, of which 17 were included in the present study. A meta-analysis of 13 trials which reported the data on triglyceride (TG) revealed a borderline significant effect of the L-Arginine on TG values (WMD = -6.03 mg/dl; 95% CI: -12, -0.07, P = 0.04). Compared with the Placebo groups, there was no significant effect on low-density lipoprotein cholesterol (LDL-c), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-c) after L-Arginine treatment. According to the results of the present systematic review and meta-analysis, L-Arginine does not significantly affect CRP and TNFα indices. This review of systematic review suggests that although L-Arginine supplementation significantly reduces TG levels, other lipid profiles and inflammatory indices might not be influential. Therefore, further RCTs are recommended to assess the effect of oral L-Arginine intake on other lipid and inflammation indices.
KEYWORDS:
Dyslipidemia; Inflammatory markers; L-Arginine; Meta-analysis; Systematic review

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Myocardial Dysfunction after Severe Food Restriction Is Linked to Changes in the Calcium-Handling Properties in Rats.
Deus AF, Silva VLD, de Souza SLB, Mota GAF, Sant'Ana PG, Vileigas DF, Lima-Leopoldo AP, Leopoldo AS, Campos DHS, de Tomasi LC, Padovani CR, Kolwicz SC Jr, Cicogna AC.
Nutrients. 2019 Aug 22;11(9). pii: E1985. doi: 10.3390/nu11091985.
PMID: 31443528
Abstract
Severe food restriction (FR) impairs cardiac performance, although the causative mechanisms remain elusive. Since proteins associated with calcium handling may contribute to cardiac dysfunction, this study aimed to evaluate whether severe FR results in alterations in the expression and activity of Ca2+-handling proteins that contribute to impaired myocardial performance. Male 60-day-old Wistar-Kyoto rats were fed a control or restricted diet (50% reduction in the food consumed by the control group) for 90 days. Body weight, body fat pads, adiposity index, as well as the weights of the soleus muscle and lung, were obtained. Cardiac remodeling was assessed by morphological measures. The myocardial contractile performance was analyzed in isolated papillary muscles during the administration of extracellular Ca2+ and in the absence or presence of a sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) specific blocker. The expression of Ca2+-handling regulatory proteins was analyzed via Western Blot. Severe FR resulted in a 50% decrease in body weight and adiposity measures. Cardiac morphometry was substantially altered, as heart weights were nearly twofold lower in FR rats. Papillary muscles isolated from FR hearts displayed mechanical dysfunction, including decreased developed tension and reduced contractility and relaxation. The administration of a SERCA2a blocker led to further decrements in contractile function in FR hearts, suggesting impaired SERCA2a activity. Moreover, the FR rats presented a lower expression of L-type Ca2+ channels. Therefore, myocardial dysfunction induced by severe food restriction is associated with changes in the calcium-handling properties in rats.
KEYWORDS:
L-type calcium channel; SERCA2a; calcium transient proteins; heart impairment; malnutrition; papillary muscle assay

Telomere length and aging-related outcomes in humans: A Mendelian randomization study in 261,000 older participants.
Kuo CL, Pilling LC, Kuchel GA, Ferrucci L, Melzer D.
Aging Cell. 2019 Aug 24:e13017. doi: 10.1111/acel.13017. [Epub ahead of print]
PMID: 31444995
Abstract
Inherited genetic variation influencing leukocyte telomere length provides a natural experiment for testing associations with health outcomes, more robust to confounding and reverse causation than observational studies. We tested associations between genetically determined telomere length and aging-related health outcomes in a large European ancestry older cohort. Data were from n = 379,758 UK Biobank participants aged 40-70, followed up for mean of 7.5 years (n = 261,837 participants aged 60 and older by end of follow-up). Thirteen variants strongly associated with longer telomere length in peripheral white blood cells were analyzed using Mendelian randomization methods with Egger plots to assess pleiotropy. Variants in TERC, TERT, NAF1, OBFC1, and RTEL1 were included, and estimates were per 250 base pairs increase in telomere length, approximately equivalent to the average change over a decade in the general white population. We highlighted associations with false discovery rate-adjusted p-values smaller than .05. Genetically determined longer telomere length was associated with lowered risk of coronary heart disease (CHD; OR = 0.95, 95% CI: 0.92-0.98) but raised risk of cancer (OR = 1.11, 95% CI: 1.06-1.16). Little evidence for associations were found with parental lifespan, centenarian status of parents, cognitive function, grip strength, sarcopenia, or falls. The results for those aged 60 and older were similar in younger or all participants. Genetically determined telomere length was associated with increased risk of cancer and reduced risk of CHD but little change in other age-related health outcomes. Telomere lengthening may offer little gain in later-life health status and face increasing cancer risks.
KEYWORDS:
TERT; UK Biobank; anti-aging; cellular senescence; centenarians; frailty; longevity; sarcopenia

Association between educational level and total and cause-specific mortality: a pooled analysis of over 694 000 individuals in the Asia Cohort Consortium.
Yang K, Zhang Y, Saito E, Rahman MS, Gupta PC, Sawada N, Tamakoshi A, Gao YT, Koh WP, Shu XO, Tsuji I, Sadakane A, Nagata C, You SL, Yuan JM, Shin MH, Chen Y, Pan WH, Pednekar MS, Tsugane S, Cai H, Xiang YB, Ozasa K, Tomata Y, Kanemura S, Sugawara Y, Wada K, Wang R, Ahn YO, Yoo KY, Ahsan H, Chia KS, Boffetta P, Kang D, Potter JD, Inoue M, Zheng W, Nan H.
BMJ Open. 2019 Aug 22;9(8):e026225. doi: 10.1136/bmjopen-2018-026225.
PMID: 31444178
https://bmjopen.bmj.com/content/bmjopen/9/8/e026225.full.pdf
Abstract
OBJECTIVE:
To study the association of educational level and risk of death from all causes, cardiovascular disease (CVD) and cancer among Asian populations.
DESIGN:
A pooled analysis of 15 population-based cohort studies.
SETTING AND PARTICIPANTS:
694 434 Asian individuals from 15 prospective cohorts within the Asia Cohort Consortium.
INTERVENTIONS:
None.
MAIN OUTCOME MEASURES:
HRs and 95% CIs for all-cause mortality, as well as for CVD-specific mortality and cancer-specific mortality.
RESULTS:
A total of 694 434 participants (mean age at baseline=53.2 years) were included in the analysis. During a mean follow-up period of 12.5 years, 103 023 deaths were observed, among which 33 939 were due to cancer and 34 645 were due to CVD. Higher educational levels were significantly associated with lower risk of death from all causes compared with a low educational level (≤primary education); HRs and 95% CIs for secondary education, trade/technical education and ≥university education were 0.88 (0.85 to 0.92), 0.81 (0.73 to 0.90) and 0.71 (0.63 to 0.80), respectively (ptrend=0.002). Similarly, HRs (95% CIs) were 0.93 (0.89 to 0.97), 0.86 (0.78 to 0.94) and 0.81 (0.73 to 0.89) for cancer death, and 0.88 (0.83 to 0.93), 0.77 (0.66 to 0.91) and 0.67 (0.58 to 0.77) for CVD death with increasing levels of education (both ptrend <0.01). The pattern of the association among East Asians and South Asians was similar compared with ≤primary education; HR (95% CI) for all-cause mortality associated with ≥university education was 0.72 (0.63 to 0.81) among 539 724 East Asians (Chinese, Japanese and Korean) and 0.61 (0.54 to 0.69) among 154 710 South Asians (Indians and Bangladeshis).
CONCLUSION:
Higher educational level was associated with substantially lower risk of death among Asian populations.
KEYWORDS:
Asia; cancer; cardiovascular; education; mortality

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Lean body mass accretion is elevated in response to dietary vitamin 😧 A dose-response study in female weanling rats.
Razaghi M, Djekic-Ivankovic M, Agellon S, Mak I, Lavery P, Weiler HA.
Nutr Res. 2019 Jul 30;68:92-100. doi: 10.1016/j.nutres.2019.07.004. [Epub ahead of print]
PMID: 31446331
Abstract
Vitamin D status positively relates to lean body mass in infants. This study tested the effect of vitamin D on body composition and growth-related hormones. It was hypothesized that low vitamin D status programs for higher fat mass accretion. Female weanling Sprague-Dawley rats (4 weeks; n = 6/diet) were randomized to AIN-93G diets with modified vitamin D contents for 8 weeks: group 1 (1 IU vitamin D3/g diet), group 2 (2 IU vitamin D3/g diet), and group 3 (4 IU vitamin D3/g diet). At week 0, 4, and 8 of study, measurements included: serum 25(OH)D3, IGF-1, IGFBP3, leptin, and whole body composition assessed with DXA. Differences among groups were tested using mixed model ANOVA with Tukey's post hoc t-tests. No differences were observed in baseline body composition and biomarkers, nor did body weight and food intake differ over the study. At week 8, serum 25(OH)D3 in group 3 was higher (P < .0001) compared to groups 1 and 2. At 8 weeks, lean mass (P < .05) and lean mass accretion (P < .05) were significantly higher in groups 2 and 3 compared to group 1. Serum IGF-1 concentration declined over time (P < .001) with smaller declines at week 8 in group 3 (P < .05). Serum IGFBP3 concentration was lower at week 4 in group 2 compared to groups 1 and 3. Serum leptin concentration and fat mass were not affected by diet. These results suggested that the achievement of higher vitamin D status may support a lean body phenotype without altering weight gain.

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[Editor's note: Amusingly, the two characters "D :" were converted into a frowny emoji by the forum software. --DP]

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The Effect of Magnesium Intake on Stroke Incidence: A Systematic Review and Meta-Analysis With Trial Sequential Analysis.
Zhao B, Hu L, Dong Y, Xu J, Wei Y, Yu D, Xu J, Zhang W.
Front Neurol. 2019 Aug 7;10:852. doi: 10.3389/fneur.2019.00852. eCollection 2019.
PMID: 31447767
Abstract
Background: The effect of magnesium on stroke has been consistently discussed less, and the results of previous studies have been contradictory. We reviewed the latest literature and quantified robust evidence of the association between magnesium intake and stroke risk. Methods: PubMed, EMBASE, the Cochrane Library, the Web of Science and ClinicalTrials.gov were searched through inception to January 15, 2019 for prospective cohort studies on magnesium intake and the incidence of stroke. Results: Fifteen studies with low bias involving 18 cohorts were entered into this study. The summary relative risk (RR) was significantly reduced by 11% for total stroke (RR: 0.89 [95% CI, 0.83-0.94]; P < 0.001) and by 12% for ischemic stroke (RR: 0.88 [95% CI, 0.81-0.95]; P = 0.001), comparing the highest magnesium intake category to the lowest. After adjusting for calcium intake, the inverse association still existed for total stroke (RR: 0.89 ([95% CI, 0.80-0.99]; P = 0.040). There was an inverse but non-significant association for hemorrhagic stroke, subarachnoid hemorrhage and intracerebral hemorrhage. The quantitative associations for total and ischemic stroke were robust. Importantly, high-risk females who had a body mass index (BMI) ≥25 kg/m2 and who were subjected to a ≥12 y follow-up exhibited a greater decrease in RRs as a result of magnesium intake. For each 100 mg/day increase in magnesium, the risk for total stroke was reduced by 2% and the risk for ischemic stroke was reduced by 2%. Conclusions: Increasing magnesium intake may be a crucial component of stroke prevention that acts in a dose-dependent manner. However, the conclusion is limited by the observational nature of the studies examined, and further randomized controlled trials are still needed.
KEYWORDS:
magnesium; meta-analysis; stroke; systematic review; trial sequential analysis

Our Food Is Killing Too Many of Us
Improvig American nutrition would make the biggest impact on our health care.
By Dariush Mozaffarian and Dan Glickman
Mr. Mozaffarian is dean of the Tufts Friedman School of Nutrition Science and Policy. Mr. Glickman was the secretary of agriculture from 1995 to 2001.
Aug. 26, 2019
https://www.nytimes.com/2019/08/26/opinion/food-nutrition-health-care.html
>>>>>>
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 Free PMC Article
https://jamanetwork.com/journals/jama/fullarticle/2608221
https://www.crsociety.org/topic/11801-als-papers-citations-and-possibly-links-and-excerpts-or-my-synopses/?page=7&tab=comments#comment-20898

https://www.bbc.com/news/av/business-49437287/why-are-people-in-the-usa-living-shorter-lives

Association of Animal and Plant Protein Intake With All-Cause and Cause-Specific Mortality.
Budhathoki S, Sawada N, Iwasaki M, Yamaji T, Goto A, Kotemori A, Ishihara J, Takachi R, Charvat H, Mizoue T, Iso H, Tsugane S; Japan Public Health Center–based Prospective Study Group.
JAMA Intern Med. 2019 Aug 26. doi: 10.1001/jamainternmed.2019.2806. [Epub ahead of print]
PMID: 31449285
Abstract
IMPORTANCE:
Epidemiological evidence regarding the long-term effects of higher dietary protein intake on mortality outcomes in the general population is not clear.
OBJECTIVE:
To evaluate the associations between animal and plant protein intake and all-cause and cause-specific mortality.
DESIGN, SETTING, AND PARTICIPANTS:
This prospective cohort study included 70 696 participants in the Japan Public Health Center-based Prospective Cohort who were aged 45 to 74 years and had no history of cancer, cerebrovascular disease, or ischemic heart disease at study baseline. Data were collected from January 1, 1995, through December 31, 1999, with follow-up completed December 31, 2016, during which 12 381 total deaths were documented. Dietary intake information was collected through a validated food frequency questionnaire and used to estimate protein intake in all participants. Participants were grouped into quintile categories based on their protein intake, expressed as a percentage of total energy. Data were analyzed from July 18, 2017, through April 10, 2019.
MAIN OUTCOMES AND MEASURES:
Hazard ratios (HRs) and 95% CIs for all-cause and cause-specific mortality were estimated using Cox proportional hazards regression models with adjustment for potential confounding factors.
RESULTS:
Among the 70 696 participants, 32 201 (45.5%) were men (mean [SD] age, 55.6 [7.6] years) and 38 495 (54.5%) were women (mean [SD] age, 55.8 [7.7] years). Intake of animal protein showed no clear association with total or cause-specific mortality. In contrast, intake of plant protein was associated with lower total mortality, with multivariable-adjusted HRs of 0.89 (95% CI, 0.83-0.95) for quintile 2; 0.88 (95% CI, 0.82-0.95) for quintile 3; 0.84 (95% CI, 0.77-0.92) for quintile 4; and 0.87 (95% CI, 0.78-0.96) for quintile 5, with quintile 1 as the reference category (P = .01 for trend). For cause-specific mortality, this association with plant protein intake was evident for cardiovascular disease (CVD)-related mortality (HRs, 0.84 [95% CI, 0.73-0.96] to 0.70 [95% CI, 0.59-0.83]; P = .002 for trend). Isocaloric substitution of 3% energy from plant protein for red meat protein was associated with lower total (HR, 0.66; 95% CI, 0.55-0.80), cancer-related (HR, 0.61; 95% CI, 0.45-0.82), and CVD-related (HR, 0.58; 95% CI, 0.39-0.86) mortality; substitution for processed meat protein was associated with lower total (HR, 0.54; 95% CI, 0.38-0.75) and cancer-related (HR, 0.50; 95% CI, 0.30-0.85) mortality.
CONCLUSIONS AND RELEVANCE:
In this large prospective study, higher plant protein intake was associated with lower total and CVD-related mortality. Although animal protein intake was not associated with mortality outcomes, replacement of red meat protein or processed meat protein with plant protein was associated with lower total, cancer-related, and CVD-related mortality.

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Effect of diet composition on insulin sensitivity in humans.
Adeva-Andany MM, González-Lucán M, Fernández-Fernández C, Carneiro-Freire N, Seco-Filgueira M, Pedre-Piñeiro AM.
Clin Nutr ESPEN. 2019 Oct;33:29-38. doi: 10.1016/j.clnesp.2019.05.014. Epub 2019 Jun 6. Review.
Abstract
Diet composition has a marked impact on the risk of developing type 2 diabetes and cardiovascular disease. Prospective studies show that dietary patterns with elevated amount of animal products and low quantity of vegetable food items raise the risk of these diseases. In healthy subjects, animal protein intake intensifies insulin resistance whereas plant-based foods enhance insulin sensitivity. Similar effects have been documented in patients with diabetes. Accordingly, pre-pregnancy intake of meat (processed and unprocessed) has been strongly associated with a higher risk of gestational diabetes whereas greater pre-pregnancy vegetable protein consumption is associated with a lower risk of gestational diabetes. Population groups that modify their traditional dietary habit increasing the amount of animal products while reducing plant-based foods experience a remarkable rise in the frequency of type 2 diabetes. The association of animal protein intake with insulin resistance is independent of body mass index. In obese individuals that consume high animal protein diets, insulin sensitivity does not improve following weight loss. Diets aimed to lose weight that encourage restriction of carbohydrates and elevated consumption of animal protein intensify insulin resistance increasing the risk of developing type 2 diabetes and cardiovascular disease. The effect of dietary components on insulin sensitivity may contribute to explain the striking impact of eating habits on the risk of type 2 diabetes and cardiovascular disease. Insulin resistance predisposes to type 2 diabetes in healthy subjects and deteriorates metabolic control in patients with diabetes. In nondiabetic and diabetic individuals, insulin resistance is a major cardiovascular risk factor.
KEYWORDS:
Animal protein; Body mass index; Cardiovascular risk; Diabetes; Dietary pattern; Insulin resistance; Insulin sensitivity; Vegetable proteinPMID: 31451269

Independent and joint effects of vascular and cardiometabolic risk factor pairs for risk of all-cause dementia: a prospective population-based study.
Shaaban CE, Jia Y, Chang CH, Ganguli M.
Int Psychogeriatr. 2019 Aug 28:1-12. doi: 10.1017/S1041610219001066. [Epub ahead of print]
PMID: 31455442
https://sci-hub.tw/https://www.cambridge.org/core/journals/international-psychogeriatrics/article/independent-and-joint-effects-of-vascular-and-cardiometabolic-risk-factor-pairs-for-risk-of-allcause-dementia-a-prospective-populationbased-study/4CF7C97BF67D8454F709FC1E3EB4BC8B
Abstract
OBJECTIVES:
To assess independent and joint effects of pairs of vascular and cardiometabolic risk factors (VCMRFs) in relation to risk of all-cause dementia.
DESIGN:
Population-based longitudinal cohort study of cognitive impairment. We used an algorithm to select pairs of VCMRFs and tested their joint effects in time-dependent Cox models. We used attributable proportions (AP) to measure the proportion of risk from interactions beyond any additive effect.
SETTING:
Economically depressed small-town population.
PARTICIPANTS:
Adults age 65+ years with up to 10 yearly study visits (N=1701, median (Q1, Q3) age, 78 (71.0, 83.0), 62.3% female, 94.9% white).
RESULTS:
Among 1701 participants free from prevalent dementia with at least one follow-up visit, 109 developed incident all-cause dementia. In pairings of APOE*4 with hypertension (HTN) and congestive heart failure (CHF), the variables contributed independently and additively to all-cause dementia risk. In pairings of APOE*4 with stroke and stroke with CHF, the variables demonstrated independent contributions to all-cause dementia risk; their joint effects showed excess detriment demonstrating synergistic interactions (joint HR [95% CI]: 28.33 [6.74, 119.01] and 50.30 [14.57, 173.57] respectively, fully adjusted models). Physical activity (PA) was independently associated with lower all-cause dementia risk when paired with APOE*4, stroke, and CHF in unadjusted models; these associations did not survive covariate adjustment. The joint effect of low PA and APOE*4 was associated with additively increased all-cause dementia risk (joint HR [95% CI]: 4.61 [2.07, 10.23], fully adjusted model).
CONCLUSIONS:
Reduction of VCMRFs, including low PA, could be valuable for dementia prevention, especially among APOE*4 carriers.
KEYWORDS:
Alzheimer‘s disease (AD); apolipoprotein E (APOE); cerebral vascular disease (CVD); dementia; epidemiology

Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial.
Burt LA, Billington EO, Rose MS, Raymond DA, Hanley DA, Boyd SK.
JAMA. 2019 Aug 27;322(8):736-745. doi: 10.1001/jama.2019.11889.
PMID: 31454046
Abstract
IMPORTANCE:
Few studies have assessed the effects of daily vitamin D doses at or above the tolerable upper intake level for 12 months or greater, yet 3% of US adults report vitamin D intakes of at least 4000 IU per day.
OBJECTIVE:
To assess the dose-dependent effect of vitamin D supplementation on volumetric bone mineral density (BMD) and strength.
DESIGN, SETTING, AND PARTICIPANTS:
Three-year, double-blind, randomized clinical trial conducted in a single center in Calgary, Canada, from August 2013 to December 2017, including 311 community-dwelling healthy adults without osteoporosis, aged 55 to 70 years, with baseline levels of 25-hydroxyvitamin D (25[OH]D) of 30 to 125 nmol/L.
INTERVENTIONS:
Daily doses of vitamin D3 for 3 years at 400 IU (n = 109), 4000 IU (n = 100), or 10 000 IU (n = 102). Calcium supplementation was provided to participants with dietary intake of less than 1200 mg per day.
MAIN OUTCOMES AND MEASURES:
Co-primary outcomes were total volumetric BMD at radius and tibia, assessed with high resolution peripheral quantitative computed tomography, and bone strength (failure load) at radius and tibia estimated by finite element analysis.
RESULTS:
Of 311 participants who were randomized (53% men; mean [SD] age, 62.2 [4.2] years), 287 (92%) completed the study. Baseline, 3-month, and 3-year levels of 25(OH)D were 76.3, 76.7, and 77.4 nmol/L for the 400-IU group; 81.3, 115.3, and 132.2 for the 4000-IU group; and 78.4, 188.0, and 144.4 for the 10 000-IU group. There were significant group × time interactions for volumetric BMD. At trial end, radial volumetric BMD was lower for the 4000 IU group (-3.9 mg HA/cm3 [95% CI, -6.5 to -1.3]) and 10 000 IU group (-7.5 mg HA/cm3 [95% CI, -10.1 to -5.0]) compared with the 400 IU group with mean percent change in volumetric BMD of -1.2% (400 IU group), -2.4% (4000 IU group), and -3.5% (10 000 IU group). Tibial volumetric BMD differences from the 400 IU group were -1.8 mg HA/cm3 (95% CI, -3.7 to 0.1) in the 4000 IU group and -4.1 mg HA/cm3 in the 10 000 IU group (95% CI, -6.0 to -2.2), with mean percent change values of -0.4% (400 IU), -1.0% (4000 IU), and -1.7% (10 000 IU). There were no significant differences for changes in failure load (radius, P = .06; tibia, P = .12).
CONCLUSIONS AND RELEVANCE:
Among healthy adults, treatment with vitamin D for 3 years at a dose of 4000 IU per day or 10 000 IU per day, compared with 400 IU per day, resulted in statistically significant lower radial BMD; tibial BMD was significantly lower only with the 10 000 IU per day dose. There were no significant differences in bone strength at either the radius or tibia. These findings do not support a benefit of high-dose vitamin D supplementation for bone health; further research would be needed to determine whether it is harmful.

Sex- and age-specific associations between cardiorespiratory fitness, CVD morbidity and all-cause mortality in in 266.109 adults.
Ekblom-Bak E, Ekblom B, Söderling J, Börjesson M, Blom V, Kallings LV, Hemmingsson E, Andersson G, Wallin P, Ekblom Ö.
Prev Med. 2019 Aug 24:105799. doi: 10.1016/j.ypmed.2019.105799. [Epub ahead of print]
PMID: 31454664
Abstract
The aim was to investigate sex- and age-specific associations between cardiorespiratory fitness, all-cause and cause-specific mortality, and cardiovascular disease (CVD) morbidity. 266.109 participants (47% women, 18-74 years) free from CVD, participating in occupational health service screenings in 1995-2015 were included. CRF was assessed as estimated maximal oxygen consumption (estVO2max) using a submaximal cycle test. Incident cases of first-time CVD event and death from any cause were ascertained through national registers. There were 4244 CVD events and 2750 cases of all-cause mortality during mean 7.6 years follow-up. Male gender, higher age and lower estVO2max were associated with higher all-cause mortality and CVD morbidity incidence rates. Risk reductions with increasing estVO2max were present in all age-groups of men and women. No obvious levelling off in risk was identified in the total cohort. However, women and older age-groups showed no further reduction in higher aggregated estVO2max levels. CVD specific mortality was more associated with estVO2max compared to tumor specific mortality. The risk for all-cause mortality and CVD morbidity decreased by 2.3% and 2.6% per increase in 1 ml·min-1·kg-1 with no significant sex-differences but more pronounced in the three lower estVO2max categories for all-cause mortality (9.1%, 3.8% and 3.3%, respectively). High compared to lower levels of estVO2max was not related to a significantly elevated mortality or morbidity. In this large cohort study, CVD morbidity and all-cause mortality were inversely related to estVO2max in both men and women of all age-groups. Increasing cardiorespiratory fitness is a clear public health priority.
KEYWORDS:
Aerobic capacity; Cancer; Cardiovascular disease; Population; Risk; VO(2)max

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The flight response impairs cytoprotective mechanisms by activating the insulin pathway.
De Rosa MJ, Veuthey T, Florman J, Grant J, Blanco MG, Andersen N, Donnelly J, Rayes D, Alkema MJ.
Nature. 2019 Aug 28. doi: 10.1038/s41586-019-1524-5. [Epub ahead of print]
PMID: 31462774
Abstract
An animal's stress response requires different adaptive strategies depending on the nature and duration of the stressor. Whereas acute stressors, such as predation, induce a rapid and energy-demanding fight-or-flight response, long-term environmental stressors induce the gradual and long-lasting activation of highly conserved cytoprotective processes1-3. In animals across the evolutionary spectrum, continued activation of the fight-or-flight response weakens the animal's resistance to environmental challenges4,5. However, the molecular and cellular mechanisms that regulate the trade-off between the flight response and long-term stressors are poorly understood. Here we show that repeated induction of the flight response in Caenorhabditis elegans shortens lifespan and inhibits conserved cytoprotective mechanisms. The flight response activates neurons that release tyramine, an invertebrate analogue of adrenaline and noradrenaline. Tyramine stimulates the insulin-IGF-1 signalling (IIS) pathway and precludes the induction of stress response genes by activating an adrenergic-like receptor in the intestine. By contrast, long-term environmental stressors, such as heat or oxidative stress, reduce tyramine release and thereby allow the induction of cytoprotective genes. These findings demonstrate that a neural stress hormone supplies a state-dependent neural switch between acute flight and long-term environmental stress responses and provides mechanistic insights into how the flight response impairs cellular defence systems and accelerates ageing.

High Versus low Dietary Protein Intake and Bone Health in Older Adults: a Systematic Review and Meta-Analysis.
Groenendijk I, den Boeft L, van Loon LJC, de Groot LCPGM.
Comput Struct Biotechnol J. 2019 Jul 22;17:1101-1112. doi: 10.1016/j.csbj.2019.07.005. eCollection 2019. Review.
PMID: 31462966
Abstract
Protein may play a beneficial role in the prevention of bone loss and in slowing down osteoporosis. The effect of dietary protein may be different in older adults compared to younger adults, since this population has a greater need for protein. The aim of this systematic review and meta-analysis was to investigate the impact of a dietary protein intake above the Recommended Dietary Allowance (RDA) of 0.8 g/kg body weight/day from any source on Bone Mineral Density (BMD)/Bone Mineral Content (BMC), bone turnover markers, and fracture risk in older adults compared to a lower dietary protein intake. A systematic search was conducted through October 2018 in 3 databases: CENTRAL, MEDLINE, and EMBASE. We included all prospective cohort studies and Randomized Controlled Trials (RCTs) among adults aged ≥65 years that examined the relation between protein intake on bone health outcomes. Two investigators independently conducted abstract and full-text screenings, data extractions, and risk of bias assessments. Authors were contacted for missing data. After screening of 523 records, twelve cohort studies and one RCT were included. Qualitative evaluation showed a positive trend between higher protein intakes and higher femoral neck and total hip BMD. Meta-analysis of four cohort studies showed that higher protein intakes resulted in a significant decrease in hip fractures (pooled hazard ratio: 0.89; 95% confidence interval: 0.84, 0.94). This systematic review supports that a protein intake above the current RDA may reduce hip fracture risk and may play a beneficial role in BMD maintenance and loss in older adults.
KEYWORDS:
Bone; Bone density; Fractures; Older adults; Protein

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Modulation of intestinal microbiota and immunometabolic parameters by caloric restriction and lactic acid bacteria.
Fabersani E, Russo M, Marquez A, Abeijón-Mukdsi C, Medina R, Gauffin-Cano P.
Food Res Int. 2019 Oct;124:188-199. doi: 10.1016/j.foodres.2018.06.014. Epub 2018 Jun 5. No abstract available.
PMID: 31466639
https://ri.conicet.gov.ar/bitstream/handle/11336/81533/CONICET_Digital_Nro.296876a4-c56a-466c-a89a-60855d7aabc0_G.pdf;jsessionid=49E183E042E94A3A5CD1DED798132D33?sequence=8
"4. Conclusions
The CRD had a significant effect on IM composition. In addition, the supplementation
of the CRD with specific LAB can modify the effects of this diet on the IM
composition. This study reports a bifidogenic effect associated with the CRD, which
was higher after the supplementation with L. fermentum CRL1446. Thereby, the CRD
supplemented with LAB could represent an effective treatment to promote the growth of
intestinal beneficial bacteria and improve the health of the host. L. fermentum CRL1446
and Lac. lactis CRL1434 could be potentially probiotic strains to improve the immuno-
metabolic alterations associated with obesity. While, L. casei CRL431 could be used in
cases of undernourishment, where this strain could improve the absorption of nutrients
and protection against infections, further the stimulation of the immune system."

Regulation of thermogenic capacity in brown and white adipocytes by the prebiotic high-esterified pectin and its postbiotic acetate.
García-Carrizo F, Cannon B, Nedergaard J, Picó C, Dols A, Rodríguez AM, Palou A.
Int J Obes (Lond). 2019 Aug 29. doi: 10.1038/s41366-019-0445-6. [Epub ahead of print]
PMID: 31467421
Abstract
OBJECTIVES:
High-esterified pectin (HEP) is a prebiotic able to modulate gut microbiota, associated with health-promoting metabolic effects in glucose and lipid metabolism and adipostatic hormone sensitivity. Possible effects regulating adaptive thermogenesis and energy waste are poorly known. Therefore, we aimed to study how physiological supplementation with HEP is able to affect microbiota, energy metabolism and adaptive thermogenic capacity, and to contribute to the healthier phenotype promoted by HEP supplementation, as previously shown. We also attempted to decipher some of the mechanisms involved in the HEP effects, including in vitro experiments.
SUBJECTS AND EXPERIMENTAL DESIGN:
We used a model of metabolic malprogramming consisting of the progeny of rats with mild calorie restriction during pregnancy, both under control diet and an obesogenic (high-sucrose) diet, supplemented with HEP, combined with in vitro experiments in primary cultured brown and white adipocytes treated with the postbiotic acetate.
RESULTS:
Our main findings suggest that chronic HEP supplementation induces markers of brown and white adipose tissue thermogenic capacity, accompanied by a decrease in energy efficiency, and prevention of weight gain under an obesogenic diet. We also show that HEP promotes an increase in beneficial bacteria in the gut and peripheral levels of acetate. Moreover, in vitro acetate can improve adipokine production, and increase thermogenic capacity and browning in brown and white adipocytes, respectively, which could be part of the protection mechanism against excess weight gain observed in vivo.
CONCLUSION:
HEP and acetate stand out as prebiotic/postbiotic active compounds able to modulate both brown-adipocyte metabolism and browning and protect against obesity.

Body mass index and the risk of disability retirement: a systematic review and meta-analysis.
Shiri R, Falah-Hassani K, Lallukka T.
Occup Environ Med. 2019 Aug 29. pii: oemed-2019-105876. doi: 10.1136/oemed-2019-105876. [Epub ahead of print] Review.
PMID: 31467042
Abstract
The aim of this study was to determine the associations of body mass index (BMI) with all-cause and cause-specific disability retirement. Literature searches were conducted in PubMed, Embase and Web of Science from their inception to May 2019. A total of 27 (25 prospective cohort and 2 nested case-control) studies consisting of 2 199 632 individuals qualified for a meta-analysis. Two reviewers independently assessed the methodological quality of the included studies. We used a random effects meta-analysis, assessed heterogeneity and publication bias, and performed sensitivity analyses. There were a large number of participants and the majority of studies were rated at low or moderate risk of bias. There was a J-shaped relationship between BMI and disability retirement. Underweight (hazard ratio (HR)/risk ratio (RR)=1.20, 95% CI 1.02 to 1.41), overweight (HR/RR=1.13, 95% CI 1.07 to 1.19) and obese individuals (HR/RR=1.52, 95% CI 1.36 to 1.71) were more commonly granted all-cause disability retirement than normal-weight individuals. Moreover, overweight increased the risk of disability retirement due to musculoskeletal disorders (HR/RR=1.26, 95% CI 1.15 to 1.39) and cardiovascular diseases (HR=1.73, 95% CI 1.24 to 2.41), and obesity increased the risk of disability retirement due to musculoskeletal disorders (HR/RR=1.66, 95% CI 1.42 to 1.94), mental disorders (HR=1.29, 95% CI 1.04 to 1.61) and cardiovascular diseases (HR=2.80, 95% CI 1.85 to 4.24). The association between excess body mass and all-cause disability retirement did not differ between men and women and was independent of selection bias, performance bias, confounding and adjustment for publication bias. Obesity markedly increases the risk of disability retirement due to musculoskeletal disorders, cardiovascular diseases and mental disorders. Since the prevalence of obesity is increasing globally, disease burden associated with excess body mass and disability retirement consequently are projected to increase.
KEYWORDS:
obesity; overweight; pension; retirement

Short-Term and Long-Term Blood Pressure Changes and the Risk of All-Cause and Cardiovascular Mortality.
Dai Y, Wang Y, Xie Y, Zheng J, Guo R, Sun Z, Xing L, Zhang X, Sun Y, Zheng L.
Biomed Res Int. 2019 Aug 6;2019:5274097. doi: 10.1155/2019/5274097. eCollection 2019.
PMID: 31467896
Abstract
BACKGROUND:
Few studies compared the effects of BP changes in short- and long-terms on all-cause mortality and CVD mortality.
METHODS:
We performed a 12.5-year follow-up study to examine the association between short- (2008 to 2010) and long-term [baseline (2004-2006) to 2010] BP changes and the risk of mortality (2010 to 2017) in the Fuxin prospective cohort study. The Cox proportional hazards model was used for this study, and the average BP was stratified according to the Seven Joint National Committee (JNC7).
RESULTS:
We identified 1496 (805 CVD deaths) and 2138 deaths (1222 CVD deaths) in short- and long-term study. Compared with BP maintainer, in short-term BP changes, for participants from normotension or prehypertension to hypertension, the hazards ratios (HRs) and 95% confidence intervals (CIs) of all-cause mortality were 1.948 (1.118-3.392) and 1.439 (1.218-1.700), respectively, while for participants from hypertension to prehypertension, the HRs (95% CIs) were 0.766 (0.638-0.899) for all-cause mortality and 0.729 (0.585-0.908) for CVD mortality, respectively. In long-term BP changes, for participants from normotension or prehypertension to hypertension, the HRs (95% CIs) of all-cause mortality were 1.738 (1.099-2.749) and 1.203 (1.023-1.414), and they were 2.351 (1.049-5.269) and 1.323 (1.047-1.672) for CVD mortality, respectively. In addition, the effects of short-term BP changes on all-cause and CVD mortality, measured as regression coefficients (β), were significantly greater than those in long-term change (all P<0.05).
CONCLUSIONS:
Our study emphasizes that short-term changes in BP have a greater impact on all-cause and CVD mortality than long-term changes and assess the cut-off value of the changes in blood pressure elevation.

The effects of lycopene supplement on the spermatogram and seminal oxidative stress in infertile men: A randomized, double-blind, placebo-controlled clinical trial.
Nouri M, Amani R, Nasr-Esfahani M, Tarrahi MJ.
Phytother Res. 2019 Aug 30. doi: 10.1002/ptr.6493. [Epub ahead of print]
PMID: 31468596
Abstract
Infertility is a major, worldwide problem that is affected, and mediated, by several factors, in particular, oxidative stress. Thus, the aim of this study was to evaluate the effect of lycopene supplementation on spermatogram and seminal oxidative stress. In this randomized, double-blind, placebo-controlled trial study, 44 infertile men with oligozoospermia were randomly divided into two groups: The experimental group was supplemented with 25 mg of lycopene, and the control group received placebo for 12 weeks. Anthropometric, physical activity and dietary assessment, semen analysis, total antioxidant capacity (TAC), malondialdehyde, and glutathione peroxidase were measured pre- and post-intervention. At the end of the study, there was a significant increase in total sperm count and concentration in the lycopene group, and the latter total count remained significant after adjustment (p < .05). Intragroup analysis showed a significant increase in ejaculate volume, total sperm count, concentration total motility, nonprogressive, and nonmotility in lycopene group (p < .05). The TAC changes, in both groups, remained significant after adjustment (p < .05). Also, within-group analysis showed a significant increase in TAC levels (p < .05). Lycopene supplement can improve sperm parameters and oxidative stress biomarkers in oligozoospermia infertile men; however, further studies with larger sample size and duration are required.
KEYWORDS:
infertile men; lycopene; oxidative stress; spermatogram

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The effect of short-term methionine restriction on glutathione synthetic capacity and antioxidant responses at the whole tissue and mitochondrial level in the rat liver.
Tamanna N, Kroeker K, Braun K, Banh S, Treberg JR.
Exp Gerontol. 2019 Aug 28:110712. doi: 10.1016/j.exger.2019.110712. [Epub ahead of print]
PMID: 31472257
Abstract
Dietary methionine restriction (MR) where methionine is the sole source of sulfur amino acid increases lifespan in diverse species. Methionine restricted rodents experience a decrease in glutathione (GSH), a major antioxidant, in several tissues, which is paradoxical to longevity interventions because tissues with low GSH might experience more oxidative damage. Liver plays a key role in GSH synthesis and here we examine how MR influences GSH metabolism in the liver. We also hypothesised that low GSH might be subsidized by compensatory pathway (s) in the liver. To investigate GSH synthesis and antioxidant responses, Fischer-344 rats were given either a MR diet or a control diet for 8 weeks. Based on γ-glutamylcysteine synthetase activity, GSH synthetic capacity did not respond to low dietary methionine availability. Tissue level protein and lipid oxidation markers do not support elevated oxidative damage, despite low GSH availability. Whole tissue and mitochondrial level responses to MR differed. Specifically, the activity of glutathione reductase and thioredoxin reductase increase in whole liver tissue which might offset the effects of declined GSH availability whereas mitochondrial GSH levels were unperturbed by MR. Moreover, enhanced proton leak in liver mitochondria by MR (4 week) presumably diminishes ROS production. Taken together, we suggest that the effect of low GSH in liver tissue is subsidized, at least in part, by increased antioxidant activity and possibly enhanced mitochondrial proton leak.
KEYWORDS:
Glutathione; Methionine restriction; Oxidative stress; Protein carbonyls; Proton leak; Thioredoxin

The effects of L-carnitine supplementation on serum lipids: A systematic review and meta-analysis of randomized controlled trials.
Reiner Ž, Fathizadeh H, Kolahdooz F, Milajerdi A, Chamani M, Amiani E, Asemi Z.
Curr Pharm Des. 2019 Aug 30. doi: 10.2174/1381612825666190830154336. [Epub ahead of print]
PMID: 31470778
Abstract
The findings of trials investigating the effects of carnitine administration on serum lipids are inconsistent. This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to summarize the existing evidence and find which the effects of carnitine supplementation on serum lipids are. <p> Methods: Two authors independently searched electronic databases including MEDLINE, EMBASE, Cochrane Library, and Web of Science from inception until February 2019, in order to find relevant RCTs. The quality of selected RCTs was evaluated using the Cochrane Collaboration risk of bias tool. Cochrane's Q test and I-square (I2) statistic were used to determine the heterogeneity across included trials. Weight mean difference (SMD) and 95% CI between two intervention groups were used to determine pooled effect sizes. <p> Results: Out of 686 potential papers selected based on keywords, 43 studies met the inclusion criteria and were eligible for the meta-analysis. The pooled results indicated that L-carnitine administration led to a significant decrease in triglycerides (WMD: -4.08; 95% CI: -7.59, -0.58), total cholesterol (WMD: -7.75; 95% CI: -11.23, -4.28) and LDL-cholesterol concentrations (WMD: -4.67; 95% CI: -7.03, -2.30), and a significant increase in HDL-cholesterol levels (WMD: 1.01; 95% CI: 0.28, 1.74). L-carnitine supplementation did not influence VLDL-cholesterol concentrations. <p> Conclusions: This meta-analysis demonstrated that carnitine administration significantly reduced triglycerides, total cholesterol and LDL-cholesterol levels, and significantly increased HDL-cholesterol levels, but did not affect VLDL-cholesterol levels.
KEYWORDS:
Carnitine; HDL-cholesterol levels; RCTs; VLDL-cholesterol levels; lipid profiles; meta-analysis; serum lipids

Associations between calcium and magnesium intake and the risk of incident gastric cancer, a prospective cohort analysis of the NIH-AARP Diet and Health Study.
Shah SC, Dai Q, Zhu X, Peek RM Jr, Smalley W, Roumie C, Shrubsole MJ.
Int J Cancer. 2019 Aug 31. doi: 10.1002/ijc.32659. [Epub ahead of print]
PMID: 31472027
Abstract
Gastric cancer remains a leading cause of cancer-related mortality. Identifying dietary and other modifiable disease determinants has important implications for risk attenuation in susceptible individuals. Our primary aim was to estimate the association between dietary and supplemental intakes of calcium and magnesium and the risk of incident gastric cancer. We conducted a prospective cohort analysis of the NIH-AARP Diet and Health Study. We used Cox proportional hazard modeling to estimate the association between calcium and magnesium intakes with risk of incident gastric adenocarcinoma (GA) overall and by anatomic location, noncardia (NCGA) and cardia (CGA). A total of 536,403 respondents (59% males, 41% females) were included for analysis, among whom 1,518 incident GAs (797 NCGA, 721 CGA) occurred. Increasing calcium intake was associated with lower risk of GA overall (p-trend = 0.05), driven primarily by the association with NCGA, where above median calcium intakes were associated with a 23% reduction in risk compared to the lowest quartile (p-trend = 0.05). This magnitude of NCGA risk reduction was greater among non-white races and Hispanics (HR 0.51, 95% CI: 0.24-1.07, p-trend = 0.04), current/former smokers (HR 0.58, 95% CI: 0.41-0.81), obese individuals (HR 0.54,95% CI: 0.31-0.96), and those with high NCGA risk scores (HR 0.50, 95% CI: 0.31-0.80). Among men only, increasing magnesium intake was associated with 22-27% reduced risk of NCGA (p-trend = 0.05), while for the cohort, dietary magnesium intake in the highest versus lowest quartile was associated with a 34% reduced risk of NCGA (HR 0.66, 95% CI: 0.48-0.90). These findings have important implications for risk factor modification and personalized prevention. Future investigations are needed not only to confirm our results, but to define mechanisms underlying these associations.
KEYWORDS:
digestive system neoplasm; environment and public health; epidemiology; gastric neoplasm

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Association between intake of fruits and vegetables by pesticide residue status and coronary heart disease risk.
Chiu YH, Sandoval-Insausti H, Ley SH, Bhupathiraju SN, Hauser R, Rimm EB, Manson JE, Sun Q, Chavarro JE.
Environ Int. 2019 Aug 29;132:105113. doi: 10.1016/j.envint.2019.105113. [Epub ahead of print]
PMID: 31473415
https://reader.elsevier.com/reader/sd/pii/S0160412019317829?token=788D561E38ED957F5F94AEB840BC1929D7333D278C4078CA99695D11A08FE8EB18D5911020B68E2858F1913B52D3102F
Abstract
BACKGROUND:
Fruit and vegetable (FV) intake is recommended for the prevention of coronary heart disease (CHD). FVs are also an important source of exposure to pesticide residues. Whether the relations of FV intake with CHD differ according to pesticide residue status is unknown.
OBJECTIVE:
To examine the associations of high- and low-pesticide-residue FVs with the risk of CHD.
METHODS:
We followed 145,789 women and 24,353 men free of cardiovascular disease and cancer (excluding non-melanoma skin cancer) at baseline and participating in three ongoing prospective cohorts: the Nurses' Health Study (NHS: 1998-2012), the NHS-II (1999-2013), and the Health Professionals Follow-up Study (HPFS: 1998-2012). FV intake was assessed via food frequency questionnaires. We categorized FVs as having high- or low-pesticide-residues using a validated method based on pesticide surveillance data from the US Department of Agriculture. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95%CI) of CHD in relation to high- and low-pesticide-residue FV intake.
RESULTS:
A total of 3707 incident CHD events were identified during 2,241,977 person-years of follow-up. In multivariable-adjusted models, a greater intake of low-pesticide-residue FVs was associated with a lower risk of CHD whereas high-pesticide-residue FV intake was unrelated to CHD risk. Specifically, compared with individuals consuming <1 serving/day of low-pesticide-residue FVs, those consuming ≥4 servings/day had 20% (95CI: 4%, 33%) lower risk of CHD. The corresponding HR (comparing ≥4 servings/day to <1 serving/day) for high-pesticide-residue FV intake and CHD was 0.97 (95%CI: 0.72, 1.30).
CONCLUSIONS:
Our data suggested exposure to pesticide residues through FV intake may modify some cardiovascular benefits of FV consumption. Further confirmation of these findings, especially using biomarkers for assessment of pesticide exposure, is needed.
KEYWORDS:
Coronary heart disease; Fruits and vegetables; Pesticide residues

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Anti-Osteoporotic Effect of Soy Isoflavones Intake on Low Bone Mineral Density Caused by Voluntary Exercise and Food Restriction in Mature Female Rats.
Yanaka K, Higuchi M, Ishimi Y.
J Nutr Sci Vitaminol (Tokyo). 2019;65(4):335-342. doi: 10.3177/jnsv.65.335.
PMID: 31474683
https://www.jstage.jst.go.jp/article/jnsv/65/4/65_335/_pdf
Abstract
Female athlete triad (FAT) is an interrelationship between menstrual dysfunction, low energy availability with or without eating disorder, and decreased bone mineral density (BMD) in female athletes. The purpose of this study was to investigate whether isoflavone intake can prevent bone loss caused by voluntary wheel running under energy-restricted condition. We used a female rat model of osteoporosis for female athletes established previously. Fourteen female Sprague-Dawley rats (8-wk old) were fed ad libitum and had free access to wheels throughout the study. At 18 wk of age, the rats were divided randomly into the following groups: 1) running control (RC), 2) running energy restriction (RR), and 3) running energy restriction and isoflavone-fed (RR+Iso) groups. The RR group was 30% dietary restricted. The RR+Iso group was 30% dietary restricted and fed the diet containing 0.5% isoflavone powder (Fujiflavone P40). The experimental period lasted 31 wk. At the end of this experiment, BMD of the proximal femur in the RR group was significantly lower than that in the RC group. However, the BMD in the RR+Iso group was not significantly different from that in the RC group. Moreover, the plasma estradiol (E2) level in the RR and RR+Iso groups was significantly lower than that in the RC group. These findings suggest that isoflavone intake inhibited bone loss when the E2 level was low in female mature rat model. Our findings may reveal the possible novel role of isoflavone in osteoporosis among female athletes.
KEYWORDS:
BFR; estradiol; female athlete; femur; osteoporosis

[Nut consumption and cognitive function: a systematic review].
Arias-Fernández L, López García E, Struijk EA, Rodríguez Artalejo F, Lana Pérez A.
Nutr Hosp. 2019 Sep 2. doi: 10.20960/nh.02566. [Epub ahead of print] Spanish.
PMID: 31475842
Abstract
Antioxidant-rich diet patterns could contribute to the prevention and treatment of early stages of dementia. Nuts have an appreciable antioxidant load and there is evidence of their positive effects on several chronic diseases incidence and death rates. Moreover, they are rich in polyunsaturated fatty acids, which might also play a positive role in neurogenesis. The aim of this systematic review was to summarize the evidence from studies related to the effects of nut consumption on cognitive function among adults. We conducted a systematic search of articles published in PubMed, Scopus and Web of Science. A total of 19 articles met the inclusion criteria (seven cross-sectional, four prospective cohorts and eight experimental); these were independently extracted and reviewed by two reviewers. The evidence from the cross-sectional and cohort studies was uncertain, due to the disparity of results and risk of bias. However, in most experimental studies a protective effect of nut consumption on some dimension of cognitive function was observed and the methodological quality of these studies was acceptable. In addition, the effects appear to be independent of nut type, amount of intake, age and baseline status of subjects. In summary, these results suggest that the inclusion of daily nut consumption in the healthy diet pattern of adults could have positive effects on their cognitive function. Nevertheless, more well-designed longitudinal and experimental studies are needed to provide strength to this suggestive evidence.

The longitudinal association between alcohol consumption and muscle strength: A population-based prospective study.
Cui Y, Huang C, Momma H, Sugiyama S, Niu K, Nagatomi R.
J Musculoskelet Neuronal Interact. 2019 Sep 1;19(3):294-299.
PMID: 31475936
Abstract
OBJECTIVES:
Studies have investigated the association between alcohol consumption and muscle mass and muscle disease. However, the relationship between alcohol consumption and muscle strength remains unclear. This study aimed to prospectively investigate the association between alcohol consumption and changes in muscle strength.
METHODS:
This study evaluated 326 Japanese men and women over a 2-year period, assessing alcohol consumption using a brief, self administered diet-history questionnaire. Muscle strength was assessed using a digital grip dynamometer.
RESULTS:
In a non-adjusted model, alcohol consumption was positively correlated with a decline in muscle strength (p for trend = 0.002). After adjusting model 1 for age, sex, and body mass index, adjusting model 2 for health status and fully adjusting model 3, there was a significant positive association between alcohol consumption and a decline in muscle strength, and this association showed no change over the 2-year period (p for trend = 0.006).
CONCLUSION:
In this Japanese population, high alcohol consumption was associated with a greater decline in muscle strength. Future studies are needed to ascertain whether this relationship is present in other populations.
KEYWORDS:
Alcohol Consumption; Drinking Habits; Japanese Adults; Muscle Strength; Prospective Study

Clinical Benefits of Antioxidative Supplement Twendee X for Mild Cognitive Impairment: A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Prospective Interventionalfd Study.
Tadokoro K, Morihara R, Ohta Y, Hishikawa N, Kawano S, Sasaki R, Matsumoto N, Nomura E, Nakano Y, Takahashi Y, Takemoto M, Yamashita T, Ueno S, Wakutani Y, Takao Y, Morimoto N, Kutoku Y, Sunada Y, Taomoto K, Manabe Y, Deguchi K, Higashi Y, Inufusa H, You F, Yoshikawa T, von Greiffenclau MM, Abe K.
J Alzheimers Dis. 2019 Aug 24. doi: 10.3233/JAD-190644. [Epub ahead of print]
PMID: 31476161
Abstract
Oxidative stress is part of the entire pathological process that underlies the development of Alzheimer's disease (AD), including the mild cognitive impairment (MCI) stage. Twendee X (TwX) is a supplement containing a strong antioxidative mix of eight antioxidants, which has been shown to have a clinical and therapeutic benefit in AD model mice. Here, we conducted a multicenter, randomized, double-blind, and placebo-controlled prospective interventional study to evaluate the efficacy of TwX in mitigating MCI. The primary outcomes were differences in Mini-Mental State Examination (MMSE) and Hasegawa Dementia Scale-revised (HDS-R) scores between baseline and six months for placebo and TwX groups. Seventy-eight subjects with MCI were randomized into placebo (n = 37) and TwX (n = 41) groups. MMSE scores at six months differed significantly between the TwX and placebo groups (p = 0.018), and HDS-R scores for the TwX group exhibited a significant improvement at six months relative to baseline (p = 0.025). The TwX group did not show any change in affective or activities of daily living scores at six months. The present study indicates that strong antioxidative supplement TwX is clinical beneficial for cognitive function in subjects with MCI.
Keywords
Dementia; dietary supplement; mild cognitive impairment; oxidative stress; randomized controlled trial

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Fish consumption and risk of incident dementia in elderly Japanese: The Ohsaki Cohort 2006 Study.
Tsurumaki N, Zhang S, Tomata Y, Abe S, Sugawara Y, Matsuyama S, Tsuji I.
Br J Nutr. 2019 Sep 3:1-29. doi: 10.1017/S0007114519002265. [Epub ahead of print]
PMID: 31477191
https://www.cambridge.org/core/services/aop-cambridge-core/content/view/185715D25CFEAD4FD78C434E226DB7F9/S0007114519002265a.pdf/div-class-title-fish-consumption-and-risk-of-incident-dementia-in-elderly-japanese-the-ohsaki-cohort-2006-study-div.pdf
Abstract
Fish harbor many types of nutrients that are beneficial for preventing cognitive decline. Therefore, habitual fish intake might contribute to a lower risk of incident dementia. However, few prospective cohort studies have investigated fish consumption in relation to incident dementia, and their findings have been inconsistent. To investigate the association between fish consumption and the risk of incident dementia, we collected data on the consumption of fish and other foods using a food frequency questionnaire in a baseline survey of individuals aged ≥65 y living in Ohsaki city, Japan. After 5.7 y of follow-up, the incidence of dementia was 1,118 (8.5%) among 13,102 participants. We then used a multivariate-adjusted Cox model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Compared to subjects with the lowest fish intake (Q1), the multivariate HRs were 0.90 (95% CI 0.74, 1.11) for Q2, 0.85 (95% CI 0.73, 0.99) for Q3, and 0.84 (95% CI 0.71, 0.997) for Q4 (Ptrend = 0.029). Such associations were also observed even after excluding participants who were diagnosed with dementia in the first 2 y of follow-up and those who had poorer cognitive function at baseline. In conclusion, an association was observed between higher fish consumption and a lower risk of incident dementia among healthy elderly people without disability. These findings suggest that habitual fish intake may be beneficial for the prevention of dementia.
KEYWORDS:
Dementia; Elderly; Fish; Japan; Prospective cohort study

Association between habitual yogurt consumption and newly diagnosed non-alcoholic fatty liver disease.
Zhang S, Fu J, Zhang Q, Liu L, Lu M, Meng G, Yao Z, Wu H, Xia Y, Bao X, Gu Y, Sun S, Wang X, Zhou M, Jia Q, Song K, Wu Y, Xiang H, Niu K.
Eur J Clin Nutr. 2019 Sep 2. doi: 10.1038/s41430-019-0497-7. [Epub ahead of print]
PMID: 31477797
Abstract
BACKGROUND/OBJECTIVES:
Many studies have suggested that probiotics may be applied as a therapeutic agent for non-alcoholic fatty liver disease (NAFLD). However, the effects of frequent yogurt consumption (as a natural probiotic source) on NAFLD remain poorly understood. This study was to examine the association of habitual yogurt consumption with newly diagnosed NAFLD in the general adult population.
SUBJECT/METHODS:
Overall, 24,389 adults were included in this cross-sectional study. Yogurt consumption was estimated by using a validated self-administered food frequency questionnaire. NAFLD was diagnosed by abdominal ultrasonography. We used logistic regression models to assess the association between yogurt consumption categories and newly diagnosed NAFLD.
RESULTS:
The multivariable odds ratios with 95% confidence interval of newly diagnosed NAFLD were 1.00 (0.88, 1.14) for 1 time/week, 0.91 (0.81, 1.02) for 2-3 times/week, and 0.86 (0.76, 0.98) for ≥4 times/week (P for trend = 0.01), compared with those who consumed <1 time/week yogurt. The inverse association was observed in a sensitivity analysis.
CONCLUSION:
Higher yogurt consumption was inversely associated with the prevalence of newly diagnosed NAFLD. These results are needed to be confirmed in randomized controlled trials or prospective studies.

Carbohydrate quantity and quality affect the risk of endometrial cancer: A systematic review and dose-response meta-analysis.
Sadeghi A, Sadeghian M, Nasiri M, Rahmani J, Khodadost M, Pirouzi A, Maleki V, Sadeghi O.
Clin Nutr. 2019 Aug 19. pii: S0261-5614(19)30313-9. doi: 10.1016/j.clnu.2019.08.001. [Epub ahead of print] Review.
PMID: 31477367
Abstract
BACKGROUND:
Data on the association of dietary intake of total carbohydrates as well as dietary glycemic index (GI) and glycemic load (GL) with risk of endometrial cancer are contradictory. Therefore, we conducted a systematic review and dose-response meta-analysis of observational studies to summarize available findings in this field.
METHODS:
The online databases were searched for relevant publications to May 2018 using relevant keywords.
RESULTS:
Overall, eight prospective cohort and five case-control studies with a total sample size of 734,765 individuals, aged ≥18 years, and 8466 cases of endometrial cancer were included. Although the overall association between dietary intake of total carbohydrates and risk of endometrial cancer was non-significant, we found a significant positive association in some subgroups of cohort studies including those with ≥10 years' duration of follow-up (combined effect size: 1.29, 95% CI: 1.09-1.53, P = 0.003) and studies with sample size of ≥50,000 participants (combined effect size: 1.24, 95% CI: 1.08-1.43, P = 0.002). In addition, a non-linear dose-response relationship was found in this regard after considering the estimates from cohort studies (Pnonlinearity = 0.002). Combining effect sizes from case-control studies showed a significant positive association between dietary GI and risk of endometrial cancer; such that a-10 unit increase in GI was associated with a 4% greater risk of endometrial cancer (combined effect size: 1.04, 95% CI: 1.02-1.05, P < 0.001). There was also a significant positive association between dietary GL and risk of endometrial cancer in some subgroups of cohort studies and also in non-linear dose-response analysis.
CONCLUSIONS:
Although the overall associations of dietary total carbohydrate intake, GI, and GL with risk of endometrial cancer were not significant, there were significant positive associations in some subgroups of the included studies, particularly those with high quality. There was also a dose-response association between dietary total carbohydrate intake, GI and GL, and risk of endometrial cancer.
KEYWORDS:
Carbohydrate; Diet; Endometrial neoplasms; Glycemic index; Glycemic load

Association Between Soft Drink Consumption and Mortality in 10 European Countries.
Mullee A, Romaguera D, Pearson-Stuttard J, Viallon V, Stepien M, Freisling H, Fagherazzi G, Mancini FR, Boutron-Ruault MC, Kühn T, Kaaks R, Boeing H, Aleksandrova K, Tjønneland A, Halkjær J, Overvad K, Weiderpass E, Skeie G, Parr CL, Quirós JR, Agudo A, Sánchez MJ, Amiano P, Cirera L, Ardanaz E, Khaw KT, Tong TYN, Schmidt JA, Trichopoulou A, Martimianaki G, Karakatsani A, Palli D, Agnoli C, Tumino R, Sacerdote C, Panico S, Bueno-de-Mesquita B, Verschuren WMM, Boer JMA, Vermeulen R, Ramne S, Sonestedt E, van Guelpen B, Holgersson PL, Tsilidis KK, Heath AK, Muller D, Riboli E, Gunter MJ, Murphy N.
JAMA Intern Med. 2019 Sep 3. doi: 10.1001/jamainternmed.2019.2478. [Epub ahead of print]
PMID: 31479109
Abstract
IMPORTANCE:
Soft drinks are frequently consumed, but whether this consumption is associated with mortality risk is unknown and has been understudied in European populations to date.
OBJECTIVE:
To examine the association between total, sugar-sweetened, and artificially sweetened soft drink consumption and subsequent total and cause-specific mortality.
DESIGN, SETTING, AND PARTICIPANTS:
This population-based cohort study involved participants (n = 451 743 of the full cohort) in the European Prospective Investigation into Cancer and Nutrition (EPIC), an ongoing, large multinational cohort of people from 10 European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom), with participants recruited between January 1, 1992, and December 31, 2000. Excluded participants were those who reported cancer, heart disease, stroke, or diabetes at baseline; those with implausible dietary intake data; and those with missing soft drink consumption or follow-up information. Data analyses were performed from February 1, 2018, to October 1, 2018.
EXPOSURE:
Consumption of total, sugar-sweetened, and artificially sweetened soft drinks.
MAIN OUTCOMES AND MEASURES:
Total mortality and cause-specific mortality. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional hazards regression models adjusted for other mortality risk factors.
RESULTS:
In total, 521 330 individuals were enrolled. Of this total, 451 743 (86.7%) were included in the study, with a mean (SD) age of 50.8 (9.8) years and with 321 081 women (71.1%). During a mean (range) follow-up of 16.4 (11.1 in Greece to 19.2 in France) years, 41 693 deaths occurred. Higher all-cause mortality was found among participants who consumed 2 or more glasses per day (vs consumers of <1 glass per month) of total soft drinks (hazard ratio {HR}, 1.17; 95% CI, 1.11-1.22; P < .001), sugar-sweetened soft drinks (HR, 1.08; 95% CI, 1.01-1.16; P = .004), and artificially sweetened soft drinks (HR, 1.26; 95% CI, 1.16-1.35; P < .001). Positive associations were also observed between artificially sweetened soft drinks and deaths from circulatory diseases (≥2 glasses per day vs <1 glass per month; HR, 1.52; 95% CI, 1.30-1.78; P < .001) and between sugar-sweetened soft drinks and deaths from digestive diseases (≥1 glass per day vs <1 glass per month; HR, 1.59; 95% CI, 1.24-2.05; P < .001).
CONCLUSIONS AND RELEVANCE:
This study found that consumption of total, sugar-sweetened, and artificially sweetened soft drinks was positively associated with all-cause deaths in this large European cohort; the results are supportive of public health campaigns aimed at limiting the consumption of soft drinks.

Edited by AlPater

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Coffee intake protects against symptomatic gallstone disease in the general population: a Mendelian randomization study.
Nordestgaard AT, Stender S, Nordestgaard BG, Tybjaerg-Hansen A.
J Intern Med. 2019 Sep 4. doi: 10.1111/joim.12970. [Epub ahead of print]
PMID: 31486166
Abstract
BACKGROUND AND OBJECTIVES:
Coffee intake is associated with low risk of symptomatic gallstone disease (GSD). We tested the hypothesis that high coffee intake causally protects against symptomatic GSD using a Mendelian randomization design.
METHODS:
First, we tested whether high coffee intake was associated with low risk of GSD in 104 493 individuals from the general population. Mean follow-up was 8 years (range: <1-13 years). Secondly, we tested whether two genetic variants near CYP1A1/A2 (rs2472297) and AHR (rs4410790), combined as an allele score, were associated with higher coffee intake measured as a continuous variable. Thirdly, we tested whether the allele score was associated with lower risk of GSD in 114 220 individuals including 7294 gallstone events. Mean follow-up was 38 years (range: <1-40 years).
RESULTS:
In observational analysis, those with coffee intake of >6 cups daily had 23% lower risk of GSD compared to individuals without coffee intake [hazard ratio (HR) = 0.77 (95% confidence interval: 0.61-0.94)]. In genetic analysis, there was a stepwise higher coffee intake of up to 41% (caffeine per day) in individuals with 4 (highest) versus 0 (lowest) coffee intake alleles (P for trend = 3 x 10-178) and a corresponding stepwise lower risk of GSD up to 19%[HR = 0.81 (0.69-0.96)]. The estimated observational odds ratio for GSD for a one cup per day higher coffee intake was 0.97 (0.96-0.98), equal to 3% lower risk. The corresponding genetic odds ratio was 0.89 (0.83-0.95), equal to 11% lower risk.
CONCLUSION:
High coffee intake is associated observationally with low risk of GSD, and with genetic evidence to support a causal relationship.

Mushroom consumption and incident risk of prostate cancer in Japan: A pooled analysis of the Miyagi Cohort Study and the Ohsaki Cohort Study.
Zhang S, Sugawara Y, Chen S, Beelman RB, Tsuduki T, Tomata Y, Matsuyama S, Tsuji I.
Int J Cancer. 2019 Sep 4. doi: 10.1002/ijc.32591. [Epub ahead of print]
PMID: 31486077
Abstract
In vivo and in vitro evidence has shown that mushrooms have the potential to prevent prostate cancer. However, the relationship between mushroom consumption and incident prostate cancer in humans has never been investigated. In the present study, a total of 36,499 men, aged 40-79 years, who participated in the Miyagi Cohort Study in 1990 and in the Ohsaki Cohort Study in 1994 were followed for a median of 13.2 years. Data on mushroom consumption (categorized as <1, 1-2 and ≥3 times/week) was collected using a validated food frequency questionnaire. Cox proportional hazards regression analysis was used to estimate multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for prostate cancer incidence. During 574,397 person-years of follow-up, 1,204 (3.3%) cases of prostate cancer were identified. Compared to participants with mushroom consumption <1 time/week, frequent mushroom intake was associated with a decreased risk of prostate cancer (1-2 times/week: HRs [95% CIs] = 0.92 [0.81, 1.05]; ≥3 times/week: HRs [95% CIs] = 0.83 [0.70, 0.98]; p-trend = 0.023). This inverse relationship was especially obvious among participants aged ≥50 years and did not differ by clinical stage of cancer and intake of vegetables, fruit, meat and dairy products. The present study showed an inverse relationship between mushroom consumption and incident prostate cancer among middle-aged and elderly Japanese men, suggesting that habitual mushroom intake might help to prevent prostate cancer.
KEYWORDS:
Japan; cohort study; human; mushroom; prostate cancer

Risks of ischaemic heart disease and stroke in meat eaters, fish eaters, and vegetarians over 18 years of follow-up: results from the prospective EPIC-Oxford study.
Tong TYN, Appleby PN, Bradbury KE, Perez-Cornago A, Travis RC, Clarke R, Key TJ.
BMJ. 2019 Sep 4;366:l4897. doi: 10.1136/bmj.l4897.
PMID: 31484644
https://www.bmj.com/content/bmj/366/bmj.l4897.full.pdf
Abstract
OBJECTIVE:
To examine the associations of vegetarianism with risks of ischaemic heart disease and stroke.
DESIGN:
Prospective cohort study.
SETTING:
The EPIC-Oxford study, a cohort in the United Kingdom with a large proportion of non-meat eaters, recruited across the country between 1993 and 2001.
PARTICIPANTS:
48 188 participants with no history of ischaemic heart disease, stroke, or angina (or cardiovascular disease) were classified into three distinct diet groups: meat eaters (participants who consumed meat, regardless of whether they consumed fish, dairy, or eggs; n=24 428), fish eaters (consumed fish but no meat; n=7506), and vegetarians including vegans (n=16 254), based on dietary information collected at baseline, and subsequently around 2010 (n=28 364).
MAIN OUTCOME MEASURES:
Incident cases of ischaemic heart disease and stroke (including ischaemic and haemorrhagic types) identified through record linkage until 2016.
RESULTS:
Over 18.1 years of follow-up, 2820 cases of ischaemic heart disease and 1072 cases of total stroke (519 ischaemic stroke and 300 haemorrhagic stroke) were recorded. After adjusting for sociodemographic and lifestyle confounders, fish eaters and vegetarians had 13% (hazard ratio 0.87, 95% confidence interval 0.77 to 0.99) and 22% (0.78, 0.70 to 0.87) lower rates of ischaemic heart disease than meat eaters, respectively (P<0.001 for heterogeneity). This difference was equivalent to 10 fewer cases of ischaemic heart disease (95% confidence interval 6.7 to 13.1 fewer) in vegetarians than in meat eaters per 1000 population over 10 years. The associations for ischaemic heart disease were partly attenuated after adjustment for self reported high blood cholesterol, high blood pressure, diabetes, and body mass index (hazard ratio 0.90, 95% confidence interval 0.81 to 1.00 in vegetarians with all adjustments). By contrast, vegetarians had 20% higher rates of total stroke (hazard ratio 1.20, 95% confidence interval 1.02 to 1.40) than meat eaters, equivalent to three more cases of total stroke (95% confidence interval 0.8 to 5.4 more) per 1000 population over 10 years, mostly due to a higher rate of haemorrhagic stroke. The associations for stroke did not attenuate after further adjustment of disease risk factors.
CONCLUSIONS:
In this prospective cohort in the UK, fish eaters and vegetarians had lower rates of ischaemic heart disease than meat eaters, although vegetarians had higher rates of haemorrhagic and total stroke.

Comparison of glycemic improvement between intermittent calorie restriction and continuous calorie restriction in diabetic mice.
Wei S, Zhao J, Bai M, Li C, Zhang L, Chen Y.
Nutr Metab (Lond). 2019 Aug 28;16:60. doi: 10.1186/s12986-019-0388-x. eCollection 2019.
PMID: 31485253
https://nutritionandmetabolism.biomedcentral.com/track/pdf/10.1186/s12986-019-0388-x
Abstract
BACKGROUND:
Calorie restriction (CR) has been well proved to be a powerful tool to improve metabolic health associated with aging; and many types of CR have been proposed. Intermittent CR has become a trend in recent years due to its better compliance than continuous CR every day. However, there are few studies that directly compare the interventional activity of intermittent CR vs continuous CR in metabolic disorders such as diabetes.
METHODS:
In this study, we analyzed two protocols of intermittent CR with the calorie-matched continuous CR in two diabetic mouse models including db/db and streptozotocin-treated mice. Intermittent CR was carried out by a fasting-mimicking diet (FMD, with 30% calorie intake of the control per day) for 2 days or 5 days (i.e., 2-5 or 5-9 regimes followed by free eating for 5 or 9 days respectively).
RESULTS:
In the two diabetic mouse models, both intermittent CR and continuous CR significantly reduced fasting blood glucose level and improved insulin sensitivity. However, intermittent CR performed significantly better than continuous CR in improving glycemic control and insulin sensitivity in db/db mice. In addition, intermittent CR improved the glucose homeostasis of the db/db mice without causing loss of body weight. Analyses with the pancreatic islets reveal that intermittent CR profoundly elevated the number of insulin-positive cells in both diabetic mouse models.
CONCLUSIONS:
Our study indicated that both intermittent CR and continuous CR can lower fasting blood glucose level in the diabetic mice, while intermittent CR is better than the latter in improving glucose homeostasis in db/db mice.
KEYWORDS:
Calorie restriction; Diabetes; Fasting-mimicking diet; Insulin sensitivity; Intermittent fasting

Suboptimal hydration remodels metabolism, promotes degenerative diseases, and shortens life.
Allen MD, Springer DA, Burg MB, Boehm M, Dmitrieva NI.
JCI Insight. 2019 Sep 5;4(17). pii: 130949. doi: 10.1172/jci.insight.130949.
PMID: 31484829
https://insight.jci.org/articles/view/130949
Abstract
With increased life expectancy worldwide, there is an urgent need for improving preventive measures that delay the development of age-related degenerative diseases. Here, we report evidence from mouse and human studies that this goal can be achieved by maintaining optimal hydration throughout life. We demonstrate that restricting the amount of drinking water shortens mouse lifespan with no major warning signs up to 14 months of life, followed by sharp deterioration. Mechanistically, water restriction yields stable metabolism remodeling toward metabolic water production with greater food intake and energy expenditure, an elevation of markers of inflammation and coagulation, accelerated decline of neuromuscular coordination, renal glomerular injury, and the development of cardiac fibrosis. In humans, analysis of data from the Atherosclerosis Risk in Communities (ARIC) study revealed that hydration level, assessed at middle age by serum sodium concentration, is associated with markers of coagulation and inflammation and predicts the development of many age-related degenerative diseases 24 years later. The analysis estimates that improving hydration throughout life may greatly decrease the prevalence of degenerative diseases, with the most profound effect on dementia, heart failure (HF), and chronic lung disease (CLD), translating to the development of these diseases in 3 million fewer people in the United States alone.
KEYWORDS:
Aging; Epidemiology

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Effect of Short-Term Increase in Meal Frequency on Glucose Metabolism in Individuals with Normal Glucose Tolerance or Impaired Fasting Glucose: A Randomized Crossover Clinical Trial.
Hibi M, Hari S, Yamaguchi T, Mitsui Y, Kondo S, Katashima M.
Nutrients. 2019 Sep 6;11(9). pii: E2126. doi: 10.3390/nu11092126.
PMID: 31489910
[Free from PMID abastract.]
Abstract
Effects of meal frequency on blood glucose levels and glucose metabolism were evaluated over 3 days in adult males with normal glucose tolerance (NGT, n = 9) or impaired fasting glucose (IFG, n = 9) in a randomized, crossover comparison study. Subjects were provided with an isocaloric diet 3 times daily (3M) or 9 times daily (9M). Blood glucose was monitored on Day 3 using a continuous glucose monitoring system, and subjects underwent a 75-g oral glucose tolerance test (OGTT) on Day 4. Daytime maximum blood glucose, glucose range, duration of glucose ≥180 mg/dL, and nighttime maximum glucose were significantly lower in the NGT/9M condition than in the NGT/3M condition. Similar findings were observed in the IFG subjects, with a lower daytime and nighttime maximum glucose and glucose range, and a significantly higher daytime minimum glucose in the 9M condition than in the 3M condition. The OGTT results did not differ significantly between NGT/3M and NGT/9M conditions. In contrast, the incremental area under the curve tended to be lower and the maximum plasma glucose concentration was significantly lower in the IFG/9M condition than in the IFG/3M condition. In IFG subjects, the 9M condition significantly improved glucose metabolism compared with the 3M condition. Higher meal frequency may increase glucagon-like peptide 1 secretion and improve insulin secretion.
KEYWORDS:
CGMS; GLP-1; glucose; insulin; meal frequency

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Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study.
Yusuf S, Joseph P, Rangarajan S, Islam S, Mente A, Hystad P, Brauer M, Kutty VR, Gupta R, Wielgosz A, AlHabib KF, Dans A, Lopez-Jaramillo P, Avezum A, Lanas F, Oguz A, Kruger IM, Diaz R, Yusoff K, Mony P, Chifamba J, Yeates K, Kelishadi R, Yusufali A, Khatib R, Rahman O, Zatonska K, Iqbal R, Wei L, Bo H, Rosengren A, Kaur M, Mohan V, Lear SA, Teo KK, Leong D, O'Donnell M, McKee M, Dagenais G.
Lancet. 2019 Sep 2. pii: S0140-6736(19)32008-2. doi: 10.1016/S0140-6736(19)32008-2. [Epub ahead of print]
PMID: 31492503
Abstract
BACKGROUND:
Global estimates of the effect of common modifiable risk factors on cardiovascular disease and mortality are largely based on data from separate studies, using different methodologies. The Prospective Urban Rural Epidemiology (PURE) study overcomes these limitations by using similar methods to prospectively measure the effect of modifiable risk factors on cardiovascular disease and mortality across 21 countries (spanning five continents) grouped by different economic levels.
METHODS:
In this multinational, prospective cohort study, we examined associations for 14 potentially modifiable risk factors with mortality and cardiovascular disease in 155 722 participants without a prior history of cardiovascular disease from 21 high-income, middle-income, or low-income countries (HICs, MICs, or LICs). The primary outcomes for this paper were composites of cardiovascular disease events (defined as cardiovascular death, myocardial infarction, stroke, and heart failure) and mortality. We describe the prevalence, hazard ratios (HRs), and population-attributable fractions (PAFs) for cardiovascular disease and mortality associated with a cluster of behavioural factors (ie, tobacco use, alcohol, diet, physical activity, and sodium intake), metabolic factors (ie, lipids, blood pressure, diabetes, obesity), socioeconomic and psychosocial factors (ie, education, symptoms of depression), grip strength, and household and ambient pollution. Associations between risk factors and the outcomes were established using multivariable Cox frailty models and using PAFs for the entire cohort, and also by countries grouped by income level. Associations are presented as HRs and PAFs with 95% CIs.
FINDINGS:
Between Jan 6, 2005, and Dec 4, 2016, 155 722 participants were enrolled and followed up for measurement of risk factors. 17 249 (11·1%) participants were from HICs, 102 680 (65·9%) were from MICs, and 35 793 (23·0%) from LICs. Approximately 70% of cardiovascular disease cases and deaths in the overall study population were attributed to modifiable risk factors. Metabolic factors were the predominant risk factors for cardiovascular disease (41·2% of the PAF), with hypertension being the largest (22·3% of the PAF). As a cluster, behavioural risk factors contributed most to deaths (26·3% of the PAF), although the single largest risk factor was a low education level (12·5% of the PAF). Ambient air pollution was associated with 13·9% of the PAF for cardiovascular disease, although different statistical methods were used for this analysis. In MICs and LICs, household air pollution, poor diet, low education, and low grip strength had stronger effects on cardiovascular disease or mortality than in HICs.
INTERPRETATION:
Most cardiovascular disease cases and deaths can be attributed to a small number of common, modifiable risk factors. While some factors have extensive global effects (eg, hypertension and education), others (eg, household air pollution and poor diet) vary by a country's economic level. Health policies should focus on risk factors that have the greatest effects on averting cardiovascular disease and death globally, with additional emphasis on risk factors of greatest importance in specific groups of countries.

Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): a prospective cohort study.
Dagenais GR, Leong DP, Rangarajan S, Lanas F, Lopez-Jaramillo P, Gupta R, Diaz R, Avezum A, Oliveira GBF, Wielgosz A, Parambath SR, Mony P, Alhabib KF, Temizhan A, Ismail N, Chifamba J, Yeates K, Khatib R, Rahman O, Zatonska K, Kazmi K, Wei L, Zhu J, Rosengren A, Vijayakumar K, Kaur M, Mohan V, Yusufali A, Kelishadi R, Teo KK, Joseph P, Yusuf S.
Lancet. 2019 Sep 2. pii: S0140-6736(19)32007-0. doi: 10.1016/S0140-6736(19)32007-0. [Epub ahead of print]
PMID: 31492501
Abstract
BACKGROUND:
To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches.
METHODS:
The PURE study is a prospective, population-based cohort study of individuals aged 35-70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years.
FINDINGS:
This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years (IQR 8·5-10·9). During follow-up, 11 307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs (vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs.
INTERPRETATION:
Among adults aged 35-70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care.

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The association between bilateral maximum occlusal force and all-cause mortality among community-dwelling older adults: The Tsurugaya project.
Ohi T, Komiyama T, Miyoshi Y, Murakami T, Tsuboi A, Tomata Y, Tsuji I, Watanabe M, Hattori Y.
J Prosthodont Res. 2019 Sep 4. pii: S1883-1958(19)30055-6. doi: 10.1016/j.jpor.2019.08.005. [Epub ahead of print]
PMID: 31494054
Abstract
PURPOSE:
This study aimed to investigate the relationship between the bilateral maximum occlusal force (MOF) of full dental arches and all-cause mortality in a group of community-dwelling older males and females in Japan.
METHODS:
This 13-year prospective cohort study was conducted among 815 older adults (395 male and 420 female) aged 70 years or over (mean age ± standard deviation: 75.1 ± 4.5 years). Bilateral MOF in the intercuspal position was recorded with horseshoe-shaped pressure-sensitive film. Participants were grouped by gender into tertiles according to MOF. Demographic variables, chronicity, comorbidity, physical status, cognitive and psychological status, social functioning, and blood chemistry data were also assessed. Information regarding all-cause mortality and migration was obtained from the Sendai Municipal Authority. Cox proportional hazard modeling was performed to assess all-cause mortality during the follow-up period.
RESULTS:
In total, 159 male and 109 female participants died over a median 12.9-year follow-up period, and the cumulative mortality significantly increased with lower MOF in both males and females. The multivariate Cox proportional hazard model demonstrated a significant increase in the risk of all-cause mortality associated with lower tertiles of MOF, relative to the upper tertile in males (hazard ratio: 1.62; 95% confidence interval: 1.05-2.51) and females (hazard ratio: 1.94; 95% confidence interval: 1.10-3.56).
CONCLUSIONS:
There was a significant and independent association of bilateral MOF with all-cause mortality in community-dwelling elderly males and females in Japan. These findings suggested that maintenance of oral functioning contributes to general health.
KEYWORDS:
Cohort study; Elderly; Mortality; Occlusal force; Oral health

Effects of Zinc Supplementation on Cardiometabolic Risk Factors: a Systematic Review and Meta-analysis of Randomized Controlled Trials.
Khazdouz M, Djalalinia S, Sarrafi Zadeh S, Hasani M, Shidfar F, Ataie-Jafari A, Asayesh H, Zarei M, Gorabi AM, Noroozi M, Qorbani M.
Biol Trace Elem Res. 2019 Sep 7. doi: 10.1007/s12011-019-01870-9. [Epub ahead of print]
PMID: 31494808
Abstract
The prevalence of cardiometabolic risk factors has been increasing worldwide. The results of reported studies on the effects of zinc supplementation on cardiometabolic risk factors are unequivocal. This systematic review and meta-analysis of randomized controlled trials was conducted to evaluate the effects of zinc supplementation on cardiometabolic risk factors. A systematic search was conducted through international databases (PubMed/Medline, Institute of Scientific Information, and Scopus) until December 2018 to include all randomized controlled trials (RCT), quasi-RCT, and controlled clinical trials which assessed the effect of zinc supplementation on cardiometabolic risk factors including lipid profile, glycemic indices, blood pressure, and anthropometric indices. Random- or fixed-effects meta-analysis method was used to estimate the standardized mean difference (SMD) and 95% confidence interval (CI). A total of 20 studies were included in the meta-analysis, which included a total of 1141 participants in the intervention group. Meta-analysis showed that zinc supplementation significantly decreased plasma levels of triglyceride (SMD - 0.66, 95% CI - 1.27, - 0.06), very-low-density lipoprotein (SMD - 1.59, 95% CI - 2.86, - 0.31), and total cholesterol (SMD - 0.65, 95% CI - 1.15, - 0.15). Similarly, zinc supplementation significantly decreased fasting blood glucose (SMD - 0.52, 95% CI - 0.96, - 0.07) and HbA1c (SMD - 0.64, 95% CI - 1.27, - 0.02). The effects of zinc supplementation on blood pressure and anthropometric indices were not statistically significant (P > 0.05). Zinc supplements had beneficial effects on glycemic indices and lipid profile. Thus, it appeared that zinc supplementation might be associated with a decrease in cardiometabolic risk factors contributing to a reduction in risk of atherosclerosis.
KEYWORDS:
Cardiometabolic risk factors; Meta-analysis; Metabolic syndrome; Systematic review; Zinc supplementation

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The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta-review of meta-analyses of randomized controlled trials.
Firth J, Teasdale SB, Allott K, Siskind D, Marx W, Cotter J, Veronese N, Schuch F, Smith L, Solmi M, Carvalho AF, Vancampfort D, Berk M, Stubbs B, Sarris J.
World Psychiatry. 2019 Oct;18(3):308-324. doi: 10.1002/wps.20672.
PMID: 31496103
Abstract
The role of nutrition in mental health is becoming increasingly acknowledged. Along with dietary intake, nutrition can also be obtained from "nutrient supplements", such as polyunsaturated fatty acids (PUFAs), vitamins, minerals, antioxidants, amino acids and pre/probiotic supplements. Recently, a large number of meta-analyses have emerged examining nutrient supplements in the treatment of mental disorders. To produce a meta-review of this top-tier evidence, we identified, synthesized and appraised all meta-analyses of randomized controlled trials (RCTs) reporting on the efficacy and safety of nutrient supplements in common and severe mental disorders. Our systematic search identified 33 meta-analyses of placebo-controlled RCTs, with primary analyses including outcome data from 10,951 individuals. The strongest evidence was found for PUFAs (particularly as eicosapentaenoic acid) as an adjunctive treatment for depression. More nascent evidence suggested that PUFAs may also be beneficial for attention-deficit/hyperactivity disorder, whereas there was no evidence for schizophrenia. Folate-based supplements were widely researched as adjunctive treatments for depression and schizophrenia, with positive effects from RCTs of high-dose methylfolate in major depressive disorder. There was emergent evidence for N-acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia. All nutrient supplements had good safety profiles, with no evidence of serious adverse effects or contraindications with psychiatric medications. In conclusion, clinicians should be informed of the nutrient supplements with established efficacy for certain conditions (such as eicosapentaenoic acid in depression), but also made aware of those currently lacking evidentiary support. Future research should aim to determine which individuals may benefit most from evidence-based supplements, to further elucidate the underlying mechanisms.
KEYWORDS:
N-acetylcysteine; Nutrient supplements; adjunctive treatment; attention-deficit/hyperactivity disorder; depression; eicosapentaenoic acid; methylfolate; omega-3; polyunsaturated fatty acids; schizophrenia; vitamin D

Time-Restricted Feeding Improves Glucose Tolerance in Rats, but Only When in Line With the Circadian Timing System.
de Goede P, Foppen E, Ritsema WIGR, Korpel NL, Yi CX, Kalsbeek A.
Front Endocrinol (Lausanne). 2019 Aug 21;10:554. doi: 10.3389/fendo.2019.00554. eCollection 2019.
PMID: 31496992
https://www.frontiersin.org/articles/10.3389/fendo.2019.00554/full
Abstract
Epidemiological studies indicate that shift-workers have an increased risk of type 2 diabetes mellitus (T2DM). Glucose tolerance and insulin sensitivity both are dependent on the circadian timing system (i.e., the time-of-day) and fasting duration, in rodents as well as humans. Therefore, question is whether manipulation of the circadian timing system, for example by changing the timing of feeding and fasting, is a potential preventive treatment for T2DM. Time-restricted feeding (TRF) is well-known to have profound effects on various metabolic measures, including glucose metabolism. However, experiments that directly measure the effects of TRF on glucose tolerance and/or insulin sensitivity at different time points throughout the 24 h cycle are lacking. Here we show, in rats, that TRF in line with the circadian timing system (i.e., feeding during the active phase) improves glucose tolerance during intravenous glucose tolerance tests (ivGTT) in the active phase, as lower insulin levels were observed with similar levels of glucose clearance. However, this was not the case during the inactive phase in which more insulin was released but only a slightly faster glucose clearance was observed. Contrasting, TRF out of sync with the circadian timing system (i.e., feeding during the inactive phase) worsened glucose tolerance, although only marginally, likely because of adaptation to the 4 week TRF regimen. Our results show that TRF can improve glucose metabolism, but strict adherence to the time-restricted feeding period is necessary, as outside the regular eating hours glucose tolerance is worsened.
KEYWORDS:
Type 2 diabetes mellitus (T2DM); feeding behavior; insulin sensitivity; intravenous glucose tolerance test (ivGTT); metabolism; shift-work

Different dietary fibre sources and risks of colorectal cancer and adenoma: a dose-response meta-analysis of prospective studies.
Oh H, Kim H, Lee DH, Lee A, Giovannucci EL, Kang SS, Keum N.
Br J Nutr. 2019 Jul 2:1-11. doi: 10.1017/S0007114519001454. [Epub ahead of print]
PMID: 31495339
Abstract
Dietary fibre is believed to provide important health benefits including protection from colorectal cancer. However, the evidence on the relationships with different dietary fibre sources is mixed and little is known about which fibre source provides the greatest benefits. We conducted a dose-response meta-analysis of prospective cohorts to summarise the relationships of different fibre sources with colorectal cancer and adenoma risks. Analyses were restricted to publications that reported all fibre sources (cereals, vegetables, fruits, legumes) to increase comparability between results. PubMed and Embase were searched through August 2018 to identify relevant studies. The summary relative risks (RR) and 95 % CI were estimated using a random-effects model. This analysis included a total of ten prospective studies. The summary RR of colorectal cancer associated with each 10 g/d increase in fibre intake were 0·91 (95 % CI 0·82, 1·00; I2 = 0 %) for cereal fibre, 0·95 (95 % CI 0·87, 1·03, I2 = 0 %) for vegetable fibre, 0·91 (95 % CI 0·78, 1·06, I2 = 43 %) for fruit fibre and 0·84 (95 % CI 0·63, 1·13, I2 = 45 %) for legume fibre. For cereal fibre, the association with colorectal cancer risk remained statistically significant after adjustment for folate intake (RR 0·89, 95 % CI 0·80, 0·99, I2 = 2 %). For vegetable and fruit fibres, the dose-response curve suggested evidence of non-linearity. All fibre sources were inversely associated with incident adenoma (per 10 g/d increase: RR 0·81 (95 % CI 0·54, 1·21) cereals, 0·84 (95 % CI 0·71, 0·98) for vegetables, 0·78 (95 % CI 0·65, 0·93) for fruits) but not associated with recurrent adenoma. Our data suggest that, although all fibre sources may provide some benefits, the evidence for colorectal cancer prevention is strongest for fibre from cereals/grains.
KEYWORDS:
Colorectal adenoma; Colorectal cancer; Fibre; Meta-analyses

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Concentrations of Circulating Phylloquinone, but Not Cerebral Menaquinone-4, Are Positively Correlated with a Wide Range of Cognitive Measures: Exploratory Findings in Centenarians.
Tanprasertsuk J, Ferland G, Johnson MA, Poon LW, Scott TM, Barbey AK, Barger K, Wang XD, Johnson EJ.
J Nutr. 2019 Aug 28. pii: nxz200. doi: 10.1093/jn/nxz200. [Epub ahead of print]
PMID: 31504672
Abstract
BACKGROUND:
Vitamin K (VK) exists in the form of phylloquinone (PK) and menaquinones (MKs). Roles of VK on cognitive health in the elderly are emerging, but there is limited evidence on VK uptake and metabolism in human brain.
OBJECTIVES:
The primary objective of this study was to characterize VK distribution in brains of an elderly population with varied cognitive function. In addition, associations among circulating (a biomarker of VK intake) and cerebral VK concentrations and cognition were investigated.
METHODS:
Serum or plasma (n = 27) and brain samples from the frontal cortex (FC; n = 46) and the temporal cortex (TC; n = 33) were acquired from 48 decedents (aged 98-107 y; 25 demented and 23 nondemented) enrolled in the Georgia Centenarian Study. Both circulating and brain VK concentrations were measured using HPLC with fluorescence detection. Cognitive assessment was performed within 1 y prior to mortality. Partial correlations between serum/plasma or cerebral VK concentrations and cognitive function were performed, adjusting for covariates and separating by dementia and antithrombotic use.
RESULTS:
MK-4 was the predominant vitamer in both FC (mean ± SD = 4.92 ± 2.31 pmol/g, ≥89.15% ± 5.09% of total VK) and TC (4.60 ± 2.11 pmol/g, ≥89.71% ± 4.43% of total VK) regardless of cognitive status. Antithrombotic users had 34.0% and 53.9% lower MK-4 concentrations in FC (P < 0.05) and TC (P < 0.001), respectively. Circulating PK was not correlated with cerebral MK-4 or total VK concentrations. Circulating PK concentrations were significantly associated with a wide range of cognitive measures in nondemented centenarians (P < 0.05). In contrast, cerebral MK-4 concentrations were not associated with cognitive performance, either before or after exclusion of antithrombotic users.
CONCLUSIONS:
Circulating VK concentrations are not related to cerebral MK-4 concentrations in centenarians. Cerebral MK-4 concentrations are tightly regulated over a range of VK intakes and cognitive function. Circulating PK may reflect intake of VK-rich foods containing other dietary components beneficial to cognitive health. Further investigation of VK uptake and metabolism in the brain is warranted.
KEYWORDS:
cognition; menaquinone; older adults; phylloquinone; vitamin K
>>>>>>>>>
Nutrients. 2018 May 24;10(6). pii: E666. doi: 10.3390/nu10060666.
Vitamin K Antagonists and Cognitive Decline in Older Adults: A 24-Month Follow-Up.
Brangier A, Ferland G, Rolland Y, Gautier J, Féart C, Annweiler C.
Abstract
Vitamin K participates in brain physiology. This study aimed to determine whether using vitamin K antagonists (VKAs), which interfere with the vitamin K cycle, were (i) cross-sectionally associated with altered cognitive performance, and (ii) independent predictors of cognitive changes in older adults over 24 months. Information was collected on the use of VKAs (i.e., warfarin, acenocoumarol, and fluindione) among 378 geriatric outpatients (mean, 82.3 ± 5.6 years; 60.1% female). Global cognitive performance and executive functions were assessed with Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) scores, respectively, at baseline and after 12 and 24 months of follow-up. Age, gender, body mass index, mean arterial pressure, disability, gait speed, comorbidities, atrial fibrillation, stroke, carotid artery stenosis, leukoaraiosis grade on computed tomography (CT) scan, psychoactive drugs, antidementia drugs, blood-thinning drugs (i.e., anticoagulants other than VKAs, antiplatelet medications), serum creatinine levels, and vitamin B12 concentrations were considered as potential confounders. Using VKAs was associated with lower (i.e., worse) FAB score at baseline (adjusted β = -2.1, p = 0.026), and with a decrease in FAB score after 24 months (adjusted β = -203.6%, p = 0.010), but not after 12 months (p = 0.659). Using VKAs was not associated with any change in MMSE score at baseline (p = 0.655), after 12 months (p = 0.603), or after 24 months (p = 0.201). In conclusion, we found more severe executive dysfunction at baseline and incident executive decline over 24 months among geriatric patients using VKAs, when compared with their counterparts.
KEYWORDS:
cognition; executive functions; older adults; vitamin K; vitamin K antagonist
PMID: 29794977 PMCID: PMC6024671

Is bullying victimisation in childhood associated with mental health in old age?
Hu B.
J Gerontol B Psychol Sci Soc Sci. 2019 Sep 5. pii: gbz115. doi: 10.1093/geronb/gbz115. [Epub ahead of print]
PMID: 31504923
Abstract
OBJECTIVE:
This study investigates the relationship between bullying victimization in childhood and mental health in old age.
METHODS:
The study uses data from a nationally representative sample of 9,208 older people aged 60 and over collected through the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2014 and 2015.
RESULTS:
Older people who were bullied in childhood have more severe depressive symptoms and are more likely to be dissatisfied with life than those without the experience of bullying victimization. The negative impacts remain significant after childhood confounders (15 types of familial adversities), four groups of contemporary confounders (demographic, health, social support and socioeconomic factors), and community-level unobserved heterogeneity are all controlled for. The negative impacts of bullying victimization on mental health are attenuated among people in very old age, which confirms the socioemotional selectivity theory.
DISCUSSION:
The consequences of bullying victimization for mental health are comparable to, or even greater than those of familial adversities and contemporary risk factors. The factors threatening mental health vary considerably for older people in different age groups. Effective anti-bullying schemes in childhood and personalized support in later life can make a substantial contribution to healthy aging.
KEYWORDS:
Life-course perspective; depressive symptoms; healthy aging; life satisfaction; socioemotional selectivity theory

Polypharmacy and Kidney Function in Community-Dwelling Adults Age 60 Years and Older: A Prospective Observational Study.
Ernst R, Fischer K, de Godoi Rezende Costa Molino C, Orav EJ, Theiler R, Meyer U, Fischler M, Gagesch M, Ambühl PM, Freystätter G, Egli A, Bischoff-Ferrari HA.
J Am Med Dir Assoc. 2019 Sep 6. pii: S1525-8610(19)30559-6. doi: 10.1016/j.jamda.2019.07.007. [Epub ahead of print]
PMID: 31501003
Abstract
OBJECTIVES:
Information on the impact of polypharmacy on kidney function in older adults is limited. We prospectively investigated the association between intake of total number of drugs or nonsteroidal anti-inflammatory drugs (NSAIDs) and kidney function.
DESIGN:
Our study is a prospective observational analysis of the 2-year Zurich Multiple Endpoint Vitamin D Trial in Knee Osteoarthritis Patients.
SETTING AND PARTICIPANTS:
Of the 273 participants of the original trial, 270 participants (mean age 70.3 ± 6.4 years, 53% women) were included in this observational analysis.
METHODS:
The associations between (1) total number of drugs (or NSAIDs) at baseline or (2) cumulative number of drugs (or NASAIDs) repeatedly measured over 24 months and kidney function repeatedly measured over 24 months as estimated glomerular filtration rate (eGFR) were investigated using multivariable-adjusted repeated-measures analysis.
RESULTS:
Per drug at baseline, kidney function decreased by 0.64 mL/min/1.73 m2 eGFR (Beta = -0.64; 95% CI -1.19 to -0.08; P = .024) over 24 months. With every additional drug taken cumulatively over 24 months, kidney function decreased by 0.39 mL/min/1.73 m2 eGFR (Beta = -0.39; 95% CI -0.63 to -0.15; P = .002). In a high-risk subgroup, per NSAID taken cumulatively over 24 months, kidney function declined by 1.21 mL/min/1.73 m2 eGFR (Beta = -1.21; 95% CI -2.35 to -0.07; P = .021).
CONCLUSIONS AND IMPLICATIONS:
For every additional drug prescribed among older adults, our study supports an independent and immediate harmful impact on kidney function. This negative impact seems to be about 3 times greater for NSAIDs compared with an additional average drug.
KEYWORDS:
Polypharmacy; cumulative drug intake; eGFR; kidney function; nonsteroidal anti-inflammatory drugs (NSAIDS); older adults; prospective analysis

Dried Fruit Intake and Cancer: A Systematic Review of Observational Studies.
Mossine VV, Mawhinney TP, Giovannucci EL.
Adv Nutr. 2019 Aug 26. pii: nmz085. doi: 10.1093/advances/nmz085. [Epub ahead of print]
PMID: 31504082
Abstract
Insufficient intake of total fruits and vegetables is linked to an increased cancer risk, but the relation is not understood for dried fruits. Dried fruits are generally perceived, by both consumers and researchers, as a less attractive but shelf-stable equivalent to fresh fruits and constitute a small but significant proportion of modern diets. Chemical compositions of raw and dried fruits, however, may differ substantially. Several clinical and laboratory intervention studies have reported the protective effects of dehydrated fruits against the progression of some cancers and the modulating effects of dried fruits on common cancer risk factors. In this systematic review, we identified, summarized, and critically evaluated 9 prospective cohort and 7 case-control studies that examined the relations between traditional dried fruit (raisins, prunes, dates) consumption and cancer risk in humans. Prospective cohort studies determined that significant reductions in relative risk of precancerous colorectal polyps, incidence of prostate cancer, or mortality from pancreatic cancer, by, respectively, 24%, 49%, and 65%, were associated with 3-5 or more servings of dried fruits per week. Selected case-control studies revealed inverse associations between dried fruit intake and risk of cancer as well. The reported associations were comparable to or stronger than those observed for total or raw fruits. Although the small number and high heterogeneity impede meta-analysis of these studies, we conclude that currently available data provide some initial evidence that consumption of dried fruits may be associated with a lower cancer incidence or mortality in populations. The data suggest that higher intake of raisins and other dried fruits may be important in the prevention of cancers of the digestive system. Because only a limited number of health outcome and dried fruit intake relations have been evaluated in prospective studies to date, reanalyzing existing high-quality epidemiological data may expand the knowledge base.
KEYWORDS:
cancer risk; date palm fruits; epidemiology; nutrition; prunes; raisins

Effects of soy isoflavones on cognitive function: a systematic review and meta-analysis of randomized controlled trials.
Cui C, Birru RL, Snitz BE, Ihara M, Kakuta C, Lopresti BJ, Aizenstein HJ, Lopez OL, Mathis CA, Miyamoto Y, Kuller LH, Sekikawa A.
Nutr Rev. 2019 Sep 4. pii: nuz050. doi: 10.1093/nutrit/nuz050. [Epub ahead of print]
PMID: 31504836
Abstract
CONTEXT:
The results of preclinical and observational studies support the beneficial effect of soy isoflavones on cognition.
OBJECTIVE:
This review aimed to evaluate the effects of soy isoflavones on cognition in adults.
DATA SOURCES:
The PUBMED, EMBASE, Ovid Medline, Cochrane Library, and clinicaltrials.gov databases were searched.
STUDY SELECTION:
Two researchers independently screened 1955 records, using the PICOS criteria: participants were adults; intervention was dietary sources with soy isoflavones or isolated soy isoflavones; comparator was any comparator; outcome was cognitive function; study type was randomized controlled trials (RCTs). A third researcher was consulted to resolve any discrepancies. Sixteen RCTs were included and their quality assessed.
DATA EXTRACTION:
Information on study design, characteristics of participants, and outcomes was extracted. PRISMA guidelines were followed.
DATA ANALYSIS:
A random-effects meta-analysis was used to pool estimates across studies. In the 16 RCTs (1386 participants, mean age = 60 y), soy isoflavones were found to improve overall cognitive function (standardized mean difference [SMD], 0.19; 95% confidence interval [CI], 0.07-0.32) and memory (SMD, 0.15; 95%CI, 0.03-0.26).
CONCLUSION:
The results showed that soy isoflavones may improve cognitive function in adults.
SYSTEMATIC REVIEW REGISTRATION:
PROSPERO registration no. CRD42018082070.
KEYWORDS:
cognition; isoflavones; meta-analysis

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Prenatal Exposure to Acetaminophen and the Risk of Attention-Deficit/Hyperactivity Disorder: A Nationwide Study in Taiwan.
Chen MH, Pan TL, Wang PW, Hsu JW, Huang KL, Su TP, Li CT, Lin WC, Tsai SJ, Chen TJ, Bai YM.
J Clin Psychiatry. 2019 Sep 10;80(5). pii: 18m12612. doi: 10.4088/JCP.18m12612.
PMID: 31509360
Abstract
BACKGROUND:
Studies have suggested that a significant association exists between prenatal exposure to acetaminophen and the offspring's attention-deficit/hyperactivity disorder (ADHD) risk. However, this association has largely been unexplored among the Asian population, generally, and the Taiwanese population, specifically.
METHODS:
In our study, 950 study pairs (children with ADHD [ICD-9-CM code: 314] and their mothers) and 3,800 control pairs (children without ADHD and their mothers) matched by demographic characteristics were identified between 1998 and 2008 from the Taiwan Longitudinal Health Insurance Database. Maternal use of acetaminophen was assessed in the first trimester, second trimester, and third trimester of pregnancy and over the period from 3 months before pregnancy to the date of last menstrual cycle.
RESULTS:
Logistic regression analysis with adjustments for demographic data, gestational infections, comorbid perinatal conditions, and maternal mental health disorders indicated that exposure to acetaminophen in the second trimester (odds ratio [OR] = 1.19; 95% CI, 1.00-1.40), both the first and second trimesters (OR = 1.28; 95% CI, 1.00-1.64), or in any trimester (OR = 1.20; 95% CI, 1.01-1.42) was associated with an increased risk of ADHD in offspring. Sensitivity analysis excluding gestational infections and maternal mental health disorders confirmed this association (OR = 1.33; 95% CI, 1.04-1.69).
CONCLUSION:
Prenatal exposure to acetaminophen was associated with an increased risk of ADHD in offspring, regardless of gestational infections and maternal mental health disorders. Additional studies are necessary to clarify the underlying mechanisms by which prenatal exposure to acetaminophen leads to neurodevelopmental risks.

L-TRUST: Long-term risk of cancer in patients under statins therapy. A systematic review and meta-analysis.
Craveiro NS, Silva Lopes B, Tomás L, Fraga Almeida S, Palma H, Afreixo V, Costa Matos L.
Pharmacoepidemiol Drug Saf. 2019 Sep 11. doi: 10.1002/pds.4895. [Epub ahead of print] Review.
PMID: 31509302
Abstract
INTRODUCTION:
Statins are widely prescribed drugs with established efficacy in primary and secondary prevention of cardiovascular events. Although they are mostly well tolerated, several authors have been emphasizing that the statins' safety profile is not totally clarified especially when considering risk of cancer in patients with long-term exposure to statins. This meta-analysis was aimed at evaluating the risk of cancer in patients with prolonged exposure to statins.
METHODS:
Medline, Cochrane library, and clinicaltrials.gov were searched in order to identify studies with a minimum average follow-up of 10 years of exposure to statins and a cancer-related outcome reported. Relative risk (RR) of the primary outcomes and the combined effect was presented using a random-effects model. In the selected randomized control trials (RCT), statin exposure was compared with placebo, and in the selected observational studies, it was compared with no exposure to statins.
RESULTS:
We retrieved 1627 studies, of which 15 full-papers were included for final review, five RCT, two cohort studies (CSs), and eight case-control studies (CCs), representing a total of 358 544 patients. Five RCT, two cohort studies (CSs), and eight case-control studies (CCs). No significant differences were found regarding risk of cancer occurrence (RR = 1.08, 0.96-1.21) or cancer mortality (RR = 0.91, 0.80-1.04) due to long-term statin exposure. Regarding all-cause mortality, a protective effect was found (RR = 0.93, 0.90-0.97).
CONCLUSIONS:
According to available and published evidence, statins are not associated with an increased risk of cancer after prolonged exposure. These findings strengthen the role of statins in the primary and secondary prevention of cardiovascular events.
KEYWORDS:
cancer; drug Safety; pharmacoepidemiology; statins

Acute Fasting Does Not Induce Cognitive Impairment in Mice.
Zheng H, Ton H, Yang L, Liufu N, Dong Y, Zhang Y, Xie Z.
Front Neurosci. 2019 Aug 26;13:896. doi: 10.3389/fnins.2019.00896. eCollection 2019.
PMID: 31507368
[Free pdf from PMID site.]
Preoperative baseline cognitive impairment is associated with postoperative neurocognitive disorder (PND). Fasting, and more generally, calorie restriction has been shown to exert controversial effects in clinical settings and various animal models of neurological disorders. Every patient needs acute fasting before anesthesia and surgery. However, the impact of acute fasting on cognitive function remain largely unknown. We, therefore, set out to determine whether acute fasting can induce neurotoxicity and neurobehavioral deficits in rodents. In the present system establishment study, a mouse model of acute fasting was established. The effects of the acute fasting on natural and learned behavior were evaluated in the buried food test, open field test and the Y maze test. The expression of c-Fos, the marker of neuronal activation, and caspase-3 activation, the marker of cellular apoptosis, were measured with immunohistochemistry. We found that the 9 h acute fasting increased the latency to eat food in the buried food test. The acute fasting also selectively increased the total distance and decreased the freezing time in open field test, and increased the duration in the novel arm in the Y maze test. Besides, the immunohistochemical study showed that the fasting significantly increased the c-Fos level in the hippocampus and various sub-cortical areas, including paraventricular thalamus (PVT), dorsomedial hypothalamus (DMH), lateral hypothalamus (LH), and basal amygdala (BMA). However, the acute fasting did not induce apoptosis, demonstrating by no appearance of caspase-3 activation in the corresponding brain areas. These data showed that acute fasting did not cause cellular apoptosis and cognitive impairment in the mice. Instead, the acute fasting increased the neuronal activity, enhanced the ambulatory activity and improved the spatial recognition memory in the mice. These findings will promote more research in the established system to further determine the effects of perioperative factors on the postoperative neurocognitive function and the underlying mechanisms.
KEYWORDS:
acute fasting; cellular apoptosis; cognitive impairment; mice; neural activation

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Body composition in anorexia nervosa: Meta-analysis and meta-regression of cross-sectional and longitudinal studies.
Hübel C, Yilmaz Z, Schaumberg KE, Breithaupt L, Hunjan A, Horne E, García-González J, O'Reilly PF, Bulik CM, Breen G.
Int J Eat Disord. 2019 Sep 12. doi: 10.1002/eat.23158. [Epub ahead of print] Review.
PMID: 31512774
https://onlinelibrary.wiley.com/doi/epdf/10.1002/eat.23158
Abstract
OBJECTIVE:
Clinically, anorexia nervosa (AN) presents with altered body composition. We quantified these alterations and evaluated their relationships with metabolites and hormones in patients with AN longitudinally.
METHOD:
In accordance with PRISMA guidelines, we conducted 94 meta-analyses on 62 samples published during 1996-2019, comparing up to 2,319 pretreatment, posttreatment, and weight-recovered female patients with AN with up to 1,879 controls. Primary outcomes were fat mass, fat-free mass, body fat percentage, and their regional distribution. Secondary outcomes were bone mineral density, metabolites, and hormones. Meta-regressions examined relationships among those measures and moderators.
RESULTS:
Pretreatment female patients with AN evidenced 50% lower fat mass (mean difference [MD]: -8.80 kg, 95% CI: -9.81, -7.79, Q = 1.01 × 10-63 ) and 4.98 kg (95% CI: -5.85, -4.12, Q = 1.99 × 10-28 ) lower fat-free mass, with fat mass preferentially stored in the trunk region during early weight restoration (4.2%, 95% CI: -2.1, -6.2, Q = 2.30 × 10-4 ). While the majority of traits returned to levels seen in healthy controls after weight restoration, fat-free mass (MD: -1.27 kg, 95% CI: -1.79, -0.75, Q = 5.49 × 10-6 ) and bone mineral density (MD: -0.10 kg, 95% CI: -0.18, -0.03, Q = 0.01) remained significantly altered.
DISCUSSION:
Body composition is markedly altered in AN, warranting research into these phenotypes as clinical risk or relapse predictors. Notably, the long-term altered levels of fat-free mass and bone mineral density suggest that these parameters should be investigated as potential AN trait markers.
KEYWORDS:
BIA; DXA; binge-eating/purging; bioelectrical impedance analysis; body fat percentage; bone; dual-energy X-ray absorptiometry; estradiol; fat-free mass; insulin; lean mass; long-term follow-up; restricting; thyroid; weight restoration

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Effects of Full-Fat and Fermented Dairy Products on Cardiometabolic Disease: Food Is More Than the Sum of Its Parts.
Astrup A, Geiker NRW, Magkos F.
Adv Nutr. 2019 Sep 1;10(5):924S-930S. doi: 10.1093/advances/nmz069.
PMID: 31518411
https://sci-hub.tw/10.1093/advances/nmz069
Abstract
Current dietary recommendations to limit consumption of saturated fat are largely based on early nutrition studies demonstrating a direct link between dietary saturated fat, elevated blood cholesterol levels, and increased risk of cardiovascular disease. As full-fat dairy products are rich in saturated fat, these dietary guidelines recommend consumption of fat-free or low-fat dairy products in place of full-fat dairy. However, dairy products vary greatly in both their nutrient content and their bioactive ingredients, and research increasingly highlights the importance of focusing on whole foods (i.e., the food matrix) as opposed to single nutrients, such as saturated fat. In fact, the weight of evidence from recent large and well-controlled studies, systematic reviews, and meta-analyses of both observational studies and randomized controlled trials indicates that full-fat dairy products, particularly yogurt and cheese, do not exert the detrimental effects on insulin sensitivity, blood lipid profile, and blood pressure as previously predicted on the basis of their sodium and saturated fat contents; they do not increase cardiometabolic disease risk and may in fact protect against cardiovascular disease and type 2 diabetes. Although more research is warranted to adjust for possible confounding factors and to better understand the mechanisms of action of dairy products on health outcomes, it becomes increasingly clear that the recommendation to restrict dietary saturated fat to reduce risk of cardiometabolic disease is getting outdated. Therefore, the suggestion to restrict or eliminate full-fat dairy from the diet may not be the optimal strategy for reducing cardiometabolic disease risk and should be re-evaluated in light of recent evidence.
KEYWORDS:
cardiovascular disease; dairy; saturated fat; type 2 diabetes; yogurt

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