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Marine n-3 fatty acids and CVD: new insights from recent follow-up studies and clinical supplementation trials.
Bork CS, Mortensen LT, Hjelmgaard K, Schmidt EB.
Proc Nutr Soc. 2020 Apr 1:1-7. doi: 10.1017/S0029665120006886. [Epub ahead of print]
PMID: 32234084
Marine n-3 PUFA exert beneficial effects that might inhibit atherosclerosis and reduce vascular disease. Previous studies have, however, reported conflicting results and here we have summarised the early history and the most recent findings from follow-up studies and randomised clinical trials investigating marine n-3 PUFA in relation to the risk of atherosclerotic CVD. Most follow-up studies have suggested that the intake of marine n-3 PUFA may be associated with a lower risk of CVD. Recent studies have also shown that it is important to focus on substitution issues and dietary patterns. Further, the use of gold standard biomarkers of fatty acid exposure such as adipose tissue should be encouraged. Findings from clinical supplemental trials have shown conflicting results and findings from previous meta-analyses and guidelines have generally not supported the use of fish oil supplements for the prevention of CVD. However, a recent meta-analysis including three recent large clinical trials with fish oil supplements reported a moderate beneficial effect on cardiovascular endpoints. Interestingly, results from a large clinical trial (REDUCE-IT) have suggested that supplementation with a high dose of purified EPA ethyl ester for 4⋅9 years significantly and markedly reduced the risk of cardiovascular events in patients with CVD and mild hypertriglyceridaemia; findings that need to be confirmed. While it seems appropriate to recommend consumption of fish, particular fatty fish for prevention of CVD, an effect of fish oil supplements is probably at best marginal perhaps apart from patients with hypertriglyceridaemia.
Atherosclerotic CVD; DHA; EPA; Marine n-3 PUFA

Effect of low-protein intake on all-cause mortality in subjects with an estimated glomerular filtration rate higher than 60 ml/min/1.73 m2 with or without albuminuria.
Lee CL, Liu WJ, Wang JS.
Int J Clin Pract. 2020 Apr 2. doi: 10.1111/ijcp.13505. [Epub ahead of print]
PMID: 32239620
We aimed to investigate the effect of a low-protein intake on all-cause mortality in subjects with an estimated glomerular filtration rate (eGFR) ≧ 60 ml/min/1.73 m2 with or without albuminuria using data from the National Health and Nutrition Examination Survey (NHANES).
We analyzed participants in the NHANES from 2003 to 2010. We excluded participants with an eGFR less than 60 ml/min/1.73 m2 from the analyses. Low-protein intake was defined as a protein intake of less than 0.8 g/kg/day. The Healthy Eating Index 2010 was used to assess diet quality. The vital status of all participants in the NHANES was determined by linking to the National Death Index through the end of 2011. The hazard ratios for the association of low-protein intake and mortality were determined using weighted Cox proportional hazards regression models.
A total of 7730 participants were included in the analyses. After a median follow-up of 4.7 years, 462 participants died. A low-protein intake was associated with a higher risk of mortality (hazard ratios 1.394, 95% CI 1.121-1.734, p=0.004) with adjustment for diet quality and relevant risk factors. The higher risk of mortality associated with a low-protein intake was consistent in subjects with or without albuminuria (p interaction 0.280).
A protein intake of less than 0.8 g/kg/day was associated with a higher risk of mortality in subjects with an eGFR ≧ 60 ml/min/1.73 m2 , irrespective of whether they had albuminuria.
Albuminuria; Low protein diet; Mortality

Dietary Intakes of Trace Elements and the Risk of Kidney Cancer: The Singapore Chinese Health Study.
Wang Y, Jafar TH, Jin A, Yuan JM, Koh WP.
Nutr Cancer. 2020 Apr 2:1-7. doi: 10.1080/01635581.2020.1743870. [Epub ahead of print]
PMID: 32238007
Background: Epidemiological studies have demonstrated separately that patients with kidney stone may have higher dietary intake of zinc and higher risk of developing kidney cancer. We prospectively assessed the associations of dietary zinc and other trace elements with kidney cancer risk for the first time.Methods: We used data from the prospective Singapore Chinese Health Study that recruited 63,257 adult Chinese residing in Singapore between 1993 and 1998. A validated food frequency questionnaire and the Singapore Food Composition Database was used to compute the values of intake for zinc, copper and manganese. We identified incident cancer cases via linkage with nationwide cancer registry, and used Cox proportional hazard models to compute hazard ratio (HR) and 95% confidence interval (CI) for the association with kidney cancer risk.Results: There were 229 incident kidney cancer cases after median follow-up of 20.1 years. Dietary zinc intake was positively associated with higher kidney cancer risk; the HR comparing the extreme quartiles of zinc intake was 1.74 (95% CI: 1.02-2.97; P-trend = 0.033). Conversely, intakes of copper and manganese were not associated with kidney cancer risk.Conclusions: The positive association between dietary zinc and risk of kidney cancer suggests that zinc may be implicated in renal carcinogenesis.

Changes in Nut Consumption and Subsequent Cardiovascular Disease Risk Among US Men and Women: 3 Large Prospective Cohort Studies.
Liu X, Guasch-Ferré M, Drouin-Chartier JP, Tobias DK, Bhupathiraju SN, Rexrode KM, Willett WC, Sun Q, Li Y.
J Am Heart Assoc. 2020 Apr 7;9(7):e013877. doi: 10.1161/JAHA.119.013877. Epub 2020 Apr 1.
PMID: 32233756
Background We aim to evaluate the association of within-individual changes in consumption of total and specific types of nuts and the subsequent risk of incident cardiovascular disease (CVD) in US men and women. Methods and Results We included 34 103 men from the HPFS (Health Professionals Follow-Up Study) (1986-2012), 77 815 women from the NHS (Nurses' Health Study) (1986-2012), and 80 737 women from the NHS II (1991-2013). We assessed nut consumption every 4 years using validated food frequency questionnaires. We used multivariable Cox proportional hazards regression models to examine the association between 4-year changes in nut consumption and risk of confirmed CVD end points in the subsequent 4 years. Per 0.5 serving/day increase in total nut consumption was associated with lower risk of CVD (relative risk [RR], 0.92; 95% CI, 0.86-0.98), coronary heart disease (RR, 0.94; 95% CI, 0.89-0.99), and stroke (RR, 0.89; 95% CI, 0.83-0.95). Compared with individuals who remained nonconsumers in a 4-year interval, those who had higher consumption of total nuts (≥0.5 servings/day) had a lower risk of CVD (RR, 0.75; 95% CI, 0.67-0.84), coronary heart disease (RR, 0.80; 95% CI, 0.69-0.93), and stroke (RR, 0.68; 95% CI, 0.57-0.82) in next 4 years. Individuals who decreased nut consumption by ≥0.50 servings/day had a higher risk of developing CVD (RR, 1.14; 95% CI, 0.99-1.32), coronary heart disease (RR, 1.06; 95% CI, 0.88-1.28), and stroke (RR, 1.28; 95% CI, 1.02-1.60) when compared with those who maintained their nut consumption. Conclusions Increasing total consumption of nuts and intake of individual types of nuts (eg, walnuts, other tree nuts, and peanuts) was associated with a subsequent lower risk of CVD. These data support the role of nut intake in the primary prevention of CVD.
cardiovascular disease; cohorts; nuts; peanuts; prevention; stroke

Effects of a Ketogenic Diet on Muscle Fatigue in Healthy, Young, Normal-Weight Women: A Randomized Controlled Feeding Trial.
Sjödin A, Hellström F, Sehlstedt E, Svensson M, Burén J.
Nutrients. 2020 Mar 30;12(4). pii: E955. doi: 10.3390/nu12040955.
PMID: 32235518
Ketogenic low-carbohydrate high-fat (LCHF) diets are increasingly popular in broad sections of the population. The main objective of this study was to evaluate the effects of a non-energy-restricted ketogenic LCHF diet on muscle fatigue in healthy, young, and normal-weight women. Twenty-four women were randomly allocated to a 4-week ketogenic LCHF diet followed by a 4-week control diet (a National Food Agency recommended diet), or the reverse sequence due to the crossover design. Treatment periods were separated by a 15 week washout period. Seventeen women completed the study and were included in the analyses. Treatment effects were evaluated using mixed models. The ketogenic LCHF diet had no effect on grip strength or time to fatigue, measured with handgrip test (day 24-26). However, cycling time to fatigue decreased with almost two minutes (-1.85 min 95% CI:[-2.30;-1.40]; p < 0.001) during incremental cycling (day 25-27), accommodated with higher ratings of perceived exertion using the Borg scale (p < 0.01). Participants' own diary notes revealed experiences of muscle fatigue during daily life activities, as well as during exercise. We conclude that in young and healthy women, a ketogenic LCHF diet has an unfavorable effect on muscle fatigue and might affect perceived exertion during daily life activities.
diet intervention; fat adaptation; female; food; low carbohydrate diet (LCD); nutrition; saturated fat; sports nutrition

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Systematic review and meta-analysis of the associations between body mass index, prostate cancer, advanced prostate cancer, and prostate-specific antigen.
Harrison S, Tilling K, Turner EL, Martin RM, Lennon R, Lane JA, Donovan JL, Hamdy FC, Neal DE, Bosch JLHR, Jones HE.
Cancer Causes Control. 2020 May;31(5):431-449. doi: 10.1007/s10552-020-01291-3. Epub 2020 Mar 11. Review.
PMID: 32162172
The relationship between body mass index (BMI) and prostate cancer remains unclear. However, there is an inverse association between BMI and prostate-specific antigen (PSA), used for prostate cancer screening. We conducted this review to estimate the associations between BMI and (1) prostate cancer, (2) advanced prostate cancer, and (3) PSA.
We searched PubMed and Embase for studies until 02 October 2017 and obtained individual participant data from four studies. In total, 78 studies were identified for the association between BMI and prostate cancer, 21 for BMI and advanced prostate cancer, and 35 for BMI and PSA. We performed random-effects meta-analysis of linear associations of log-PSA and prostate cancer with BMI and, to examine potential non-linearity, of associations between categories of BMI and each outcome.
In the meta-analyses with continuous BMI, a 5 kg/m2 increase in BMI was associated with a percentage change in PSA of - 5.88% (95% CI - 6.87 to - 4.87). Using BMI categories, compared to normal weight men the PSA levels of overweight men were 3.43% lower (95% CI - 5.57 to - 1.23), and obese men were 12.9% lower (95% CI - 15.2 to - 10.7). Prostate cancer and advanced prostate cancer analyses showed little or no evidence associations.
There is little or no evidence of an association between BMI and risk of prostate cancer or advanced prostate cancer, and strong evidence of an inverse and non-linear association between BMI and PSA. The association between BMI and prostate cancer is likely biased if missed diagnoses are not considered.

Trust, happiness and mortality: Findings from a prospective US population-based survey.
Miething A, Mewes J, Giordano GN.
Soc Sci Med. 2020 Jan 18;252:112809. doi: 10.1016/j.socscimed.2020.112809. [Epub ahead of print]
PMID: 32247108
There has been an abundance of research discussing the health implications of generalised trust and happiness over the past two decades. Both attitudes have been touted as independent predictors of morbidity and mortality, with strikingly similar trajectories and biological pathways being hypothesised. To date, however, neither trust nor happiness have been considered simultaneously as predictors of mortality. This study, therefore, aims to investigate the effects of generalised trust and happiness on all-cause and cause-specific mortality. The distinction between different causes of death (i.e. cardiovascular vs. cancer-related mortality) allowed us to assess if psychosocial mechanisms could account for associations between generalised trust, happiness and mortality. The study sample was derived from US General Social Survey data from 1978 to 2010 (response rates ranged from 70 to 82 per cent), and combined with death records from the National Death Index. The analytical sample comprised 23,933 individuals with 5382 validated deaths from all-cause mortality by 2014. Analyses were performed with Cox regression models and competing-risk models. In final models, generalised trust, but not happiness, showed robust and independent associations with all-cause mortality. Regarding cause-specific mortality, trust only showed a significant relationship with cardiovascular mortality. The distinct patterns of association between generalised trust and all-cause/cause-specific mortality suggest that their relationship could be being driven by cardiovascular mortality. In turn, this supports the feasibility of psychosocial pathways as possible biological mechanisms from distrust to mortality.
All-cause mortality; Cause-specific mortality; Competing-risk regression; Cox regression; Happiness; Psychosocial pathway; Trust; United States

Association of Coffee, Decaffeinated Coffee and Caffeine Intake from Coffee with Cognitive Performance in Older Adults: National Health and Nutrition Examination Survey (NHANES) 2011-2014.
Dong X, Li S, Sun J, Li Y, Zhang D.
Nutrients. 2020 Mar 20;12(3). pii: E840. doi: 10.3390/nu12030840.
PMID: 32245123
The aim of this study was to examine the association of coffee, caffeinated coffee, decaffeinated coffee and caffeine intake from coffee with cognitive performance in older adults. we used data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Coffee and caffeine intake were obtained through two 24-hour dietary recalls. Cognitive performance was evaluated by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test, Animal Fluency test and Digit Symbol Substitution Test (DSST). Binary logistic regression and restricted cubic spline models were applied to evaluate the association of coffee and caffeine intake with cognitive performance. A total of 2513 participants aged 60 years or older were included. In the fully adjusted model, compared to those reporting no coffee consumption, those who reported 266.4-495 (g/day) had a multivariate adjusted odd ratio (OR) with 95% confidence interval (CI) of 0.56(0.35-0.89) for DSST test score, compared to those reporting no caffeinated coffee consumption, those who reported ≥384.8 (g/day) had a multivariate-adjusted OR (95% CI) of 0.68(0.48-0.97) for DSST test score, compared to the lowest quartile of caffeine intake from coffee, the multivariate adjusted OR (95% CI) of the quartile (Q) three was 0.62(0.38-0.98) for the CERAD test score. L-shaped associations were apparent for coffee, caffeinated coffee and caffeine from coffee with the DSST test score and CERAD test score. No significant association was observed between decaffeinated coffee and different dimensions of cognitive performance. Our study suggests that coffee, caffeinated coffee and caffeine from coffee were associated with cognitive performance, while decaffeinated coffee was not associated with cognitive performance.
caffeine intake from coffee; cognitive performance; decaffeinated coffee; dose–response

Serologic markers of Chlamydia trachomatis and other sexually transmitted infections and subsequent ovarian cancer risk: Results from the EPIC cohort.
Idahl A, Cornet CL, Maldonado SG, Waterboer T, Bender N, Tjønneland A, Hansen L, Boutron-Ruault MC, Fournier A, Kvaskoff M, Boeing H, Trichopoulou A, Valanou E, Peppa E, Palli D, Agnoli C, Mattiello A, Tumino R, Sacerdote C, Onland-Moret NC, Gram IT, Weiderpass E, Quirós JR, Duell EJ, Sánchez MJ, Chirlaque MD, Barricarte A, Gil L, Brändstedt J, Riesbeck K, Lundin E, Khaw KT, Perez-Cornago A, Gunter MJ, Dossus L, Kaaks R, Fortner RT.
Int J Cancer. 2020 Apr 3. doi: 10.1002/ijc.32999. [Epub ahead of print] Review.
PMID: 32243586
A substantial proportion of epithelial ovarian cancer (EOC) arises in the fallopian tube and other epithelia of the upper genital tract; these epithelia may incur damage and neoplastic transformation following sexually transmitted infections (STI) and pelvic inflammatory disease. We investigated the hypothesis that past STI infection, particularly Chlamydia trachomatis, is associated with higher EOC risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort including 791 cases and 1,669 matched controls. Serum antibodies against C. trachomatis, Mycoplasma genitalium, herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) 16, 18 and 45 were assessed using multiplex fluorescent bead-based serology. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals [CI] comparing women with positive vs. negative serology. A total of 40% of the study population was seropositive to at least one STI. Positive serology to C. trachomatis Pgp3 antibodies was not associated with EOC risk overall, but with higher risk of the mucinous histotype (RR=2.30 [95% CI=1.22-4.32]). Positive serology for chlamydia heat shock protein 60 (cHSP60-1) was associated with higher risk of EOC overall (1.36 [1.13-1.64]) and with the serous subtype (1.44 [1.12-1.85]). None of the other evaluated STIs were associated with EOC risk overall; however, HSV-2 was associated with higher risk of endometrioid EOC (2.35 [1.24-4.43]). The findings of this study suggest a potential role of C. trachomatis in the carcinogenesis of serous and mucinous EOC, while HSV-2 might promote the development of endometrioid disease.

Effect of tomato consumption on fasting blood glucose and lipid profiles: A systematic review and meta-analysis of randomized controlled trials.
Li H, Chen A, Zhao L, Bhagavathula AS, Amirthalingam P, Rahmani J, Salehisahlabadi A, Abdulazeem HM, Adebayo O, Yin X.
Phytother Res. 2020 Apr 3. doi: 10.1002/ptr.6660. [Epub ahead of print] Review.
PMID: 32243013
Tomato (Solanum lycopersicum) phytochemicals, which include phytoene, phytofluene, beta-carotene, flavonoids, lycopene, and polyphenols, have been shown to improve the effects of fasting on plasma triglyceride (TG), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), total cholesterol (TC), and fasting blood sugar (FBS). The aim of this study was to systematically evaluate the effects of Tomato TC, TG, HDL, LDL, and FBS in humans. A systematic literature search was conducted in PubMed/MEDLINE, Web of sciences, and SCOPUS databases by two researchers for studies published until August of 2019 without language and time limitations. Results were combined with random effect models. Six studies were included in this meta-analysis. Combined results reveal a significant reduction in cholesterol (weighted mean difference [WMD]: -4.39 mg/dl, 95% CI: -7.09, -1.68, I2 = % 48, p heterogeneity: .05), TG (WMD: -3.94 mg/dl, 95% CI: -7.67, -0.21, I2 = % 90, p heterogeneity: .001), LDL levels (WMD: -2.09 mg/dl, 95% CI: -3.73, -0.81, I2 = % 78, p heterogeneity: .001), and increasing in HDL levels (WMD: 2.25 mg/dl, 95% CI: 0.41, 4.10, I2 = % 97, p heterogeneity: .001). Tomato was found to have a higher reduction effect on TG and LDL in younger participants. While pooled results indicate no significant effect on FBS levels (WMD: 0.59 mg/dl, 95% CI: -0.28, 1.46, I2 = % 95, p heterogeneity: .001). In conclusion, the results indicate a significant reduction in total cholesterol, TG, and LDL and increase in HDL levels that is caused by tomato consumption.
HDL; LDL; cholesterol; tomato; triglyceride

Association Between One-carbon Metabolism-related Vitamins and Risk of Breast Cancer: A Systematic Review and Meta-analysis of Prospective Studies.
Zeng J, Gu Y, Fu H, Liu C, Zou Y, Chang H.
Clin Breast Cancer. 2020 Mar 6. pii: S1526-8209(20)30047-1. doi: 10.1016/j.clbc.2020.02.012. [Epub ahead of print] Review.
PMID: 32241696
Epidemiologic studies focusing on the association between 1-carbon metabolism-related vitamins (ie, folate, vitamin B6, vitamin B2, vitamin B12) and breast cancer risk have reported inconsistent findings. We conducted a systematic search of the reported data and performed a meta-analysis of prospective case-control and cohort studies to derive a more precise evaluation. The PubMed and EMBASE databases were searched to identify eligible studies. A total of 27 studies involving 49,707 cases and 1,274,060 individuals were included in the meta-analysis. The results indicated that a high intake of folate, vitamin B6, and vitamin B2 might decrease the risk of breast cancer. The corresponding pooled relative risks (RRs) for the highest intake compared with the lowest were 0.93 (95% confidence interval [CI], 0.88-0.99; P = .018), 0.94 (95% CI, 0.89-1.00; P = .037) and 0.90 (95% CI, 0.82-0.99; P = .026). No significant association between vitamin B12 and breast cancer risk was found (RR, 0.99; 95% CI, 0.94-1.04; P = .604). Further study showed that folate and vitamin B6 might decrease the risk of estrogen receptor-negative (ER-)/progesterone receptor-negative (PR-) breast cancer but not ER+/PR+ breast cancer. The dose-response meta-analysis indicated a significant linearity relationship between folate intake and a reduced risk of ER-/PR- breast cancer. An increment of folate intake (100 μg/d) corresponded to a 7% deceased risk of ER-/PR- breast cancer (RR, 0.93; 95% CI, 0.89-0.98; P = .007). In conclusion, a high intake of 1-carbon metabolism-related vitamins might contribute to the prevention of breast cancer, especially ER-/PR- breast cancer.
Cancer prevention; Dietary intake; Folate; Pyridoxine; Riboflavin

Associations between calcium and magnesium intake and the risk of incident oesophageal cancer: an analysis of the NIH-AARP Diet and Health Study prospective cohort.
Shah SC, Dai Q, Zhu X, Peek RM Jr, Roumie C, Shrubsole MJ.
Br J Cancer. 2020 Apr 3. doi: 10.1038/s41416-020-0818-6. [Epub ahead of print]
PMID: 32242097
Risk reduction through dietary modifications is an adjunct strategy for prevention of oesophageal cancer, a leading cause of cancer-related mortality and morbidity worldwide. We aimed to estimate the association between calcium and magnesium intakes and incident oesophageal cancer (OC).
We conducted a retrospective analysis of the NIH-AARP Diet and Health Study prospective cohort. We used multivariable Cox proportional hazard modeling to estimate the association between total intakes and incident OC overall and by histology (oesophageal squamous cell carcinoma (OSCC) and adenocarcinoma (OAC)). Sensitivity and stratified analyses were performed.
Among 536,359 included respondents, 1414 incident OCs occurred over 6.5 million person-years follow-up time. Increasing dietary calcium intake was associated with an adjusted 32-41% lower risk of OSCC compared to the lowest quartile (p-trend 0.01). There was a positive association between increasing magnesium intake and OAC risk, but only among participants with low calcium:magnesium intake ratios (p-trend 0.04). There was a significant interaction with smoking status.
Based on a retrospective analysis of the NIH-AARP Diet and Health Study prospective cohort, dietary intakes of calcium and magnesium were significantly associated with risk of OSCC and, among certain participants, OAC, respectively. If validated, these findings could inform dietary modifications among at-risk individuals. Mechanistic investigations would provide additional insight.

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The Impact of BMI Categories on Metabolic Abnormality Development in Chinese Adults Who are Metabolically Healthy: A 7-Year Prospective Study.
Liu X, Zhang J, Wu J, Xu X, Tao L, Sun Y, Chen S, Han Y, Luo Y, Yang X, Guo X.
Diabetes Metab Syndr Obes. 2020 Mar 19;13:819-834. doi: 10.2147/DMSO.S237550. eCollection 2020.
PMID: 32256097
To determine what metabolic abnormalities develop frequently among metabolically healthy adults over time according to different baseline body mass index (BMI) categories.
A prospective cohort study was performed on 10,805 adults, who were metabolically healthy at the time of the 2008 survey. Participants were divided into four groups: metabolically healthy obese (MHO), metabolically healthy overweight (MHOW), metabolically healthy normal-weight (MHN), and metabolically healthy underweight (MHU). Modified Poisson regression models were used to evaluate the relationship of BMI with the development of metabolic abnormalities. Association rule mining was used to identify the most frequent abnormalities that developed over time.
Compared with the MHN group, the adjusted relative risks of the MHO group were 1.57 (95% CI: 1.09-2.27) and 2.08 (95% CI: 1.59-2.73) for developing elevated fasting glucose and elevated blood pressure, respectively, after adjusting for lifestyle behaviours and dietary factors. At the end of follow-up, 33 (19.1%) MHO subjects and 342 (16.6%) MHOW subjects had elevated blood pressure as the predominant metabolic syndrome component, whereas 236 (9.0%) MHU subjects had elevated plasma glucose. The results were similar after stratification by sex.
MHO and MHOW subjects developed elevated blood pressure most frequently, and MHU subjects developed elevated blood glucose most commonly, regardless of sex.
diabetes; hypertension; metabolic diseases; risk factors

25-Hydroxyvitamin D and Risk of Osteoporotic Fractures: Mendelian Randomization Analysis in 2 Large Population-Based Cohorts.
Çolak Y, Afzal S, Nordestgaard BG.
Clin Chem. 2020 Apr 7. pii: hvaa049. doi: 10.1093/clinchem/hvaa049. [Epub ahead of print]
PMID: 32255480
Whether low plasma 25-hydroxyvitamin D concentrations cause osteoporotic fractures is unclear. We tested the hypothesis that low plasma 25-hydroxyvitamin D concentrations are associated with increased risk of osteoporotic fractures using a Mendelian randomization analysis.
We genotyped 116 335 randomly chosen white Danish persons aged 20-100 years in 2 population-based cohort studies for plasma 25-hydroxyvitamin D decreasing genotypes in CYP2R1 (rs117913124 and rs12794714), DHCR7 (rs7944926 and rs11234027), GEMIN2 (rs2277458), and HAL (rs3819817); 35 833 had information on plasma 25-hydroxyvitamin D. We assessed risk of total, osteoporotic, and anatomically localized fractures from 1981 through 2017. Information on fractures and vital status was obtained from nationwide registries.
During up to 36 years of follow-up, we observed 17 820 total fractures, 10 861 osteoporotic fractures, and 3472 fractures of hip or femur. Compared with individuals with 25-hydroxyvitamin D ≥ 50nmol/L, multivariable adjusted hazard ratios (95% CIs) for total fractures were 1.03 (0.97-1.09) for individuals with 25-49.9 nmol/L, 1.19 (1.10-1.28) for individuals with 12.5-24.9 nmol/L, and 1.39 (1.21-1.60) for individuals with 25-hydroxyvitamin D < 12.5 nmol/L. Corresponding hazard ratios were 1.07 (1.00-1.15), 1.25 (1.13-1.37), and 1.49 (1.25-1.77) for osteoporotic fractures and 1.09 (0.98-1.22), 1.37 (1.18-1.57), and 1.41 (1.09-1.81) for fractures of hip or femur, respectively. Hazard ratios per 1 increase in vitamin D allele score, corresponding to 3.0% (approximately 1.6 nmol/L) lower 25-hydroxyvitamin D concentrations, were 0.99 (0.98-1.00) for total fractures, 0.99 (0.97-1.00) for osteoporotic fractures, and 0.98 (0.95-1.00) for fractures of hip or femur.
Low plasma 25-hydroxyvitamin D concentrations were associated with osteoporotic fractures; however, Mendelian randomization analysis provided no evidence supporting a causal role for vitamin D in the risk for osteoporotic fractures.
Bone; Calcium; Dietary Supplements; Endocrine System; Epidemiology; Fractures; Genetic Polymorphism; Metabolism; Osteoporosis; Vitamin D

Incidence and Risk of Pneumococcal Pneumonia in Adults with Distinct Underlying Medical Conditions: A Population-Based Study.
Vila-Corcoles A, Ochoa-Gondar O, Vila-Rovira A, Aragon M, Esteban-Julvez L, Chamorro N, Hospital I, Satue E, Blade J, de Diego C, Gomez-Bertomeu F, Raga X.
Lung. 2020 Apr 6. doi: 10.1007/s00408-020-00349-y. [Epub ahead of print]
PMID: 32253492
This study investigated the incidence of pneumococcal pneumonia requiring hospitalisation among middle-aged and older adults with and without specific underlying medical conditions, evaluating the influence of these conditions in the risk of developing pneumonia.
Population-based prospective cohort study included 2,025,730 individuals ≥ 50 years around Catalonia, Spain. The Catalonian information system for the development of research in primary care (SIDIAP) was used to establish baseline characteristics of the cohort (comorbidities and underlying medical conditions). Hospitalisations from pneumococcal pneumonia occurred among cohort members between 01/01/2015 and 31/12/2015 were collected from hospital discharge codes of 68 reference Catalonian hospitals. Cox regression was used to estimate the association between baseline conditions and the risk of developing pneumonia.
Global incidence rate (IR) of hospitalised pneumococcal pneumonia was 82.8 cases per 100,000 persons-year. Maximum IRs (per 100,000 persons-year) emerged among persons with haematological neoplasia (837.4), immunodeficiency (709.2), HIV infection (474.7), severe renal disease (407.5) and chronic pulmonary disease (305.7). In the multivariable analyses, apart from increasing age, HIV infection (hazard ratio{HR} 6.78), haematological neoplasia (HR 6.30), prior all-cause pneumonia (HR 5.27), immunodeficiency (HR 4.57) and chronic pulmonary disease (HR 2.89) were the conditions most strongly associated with an increasing risk. Pneumococcal vaccination did not emerge associated with a reduced risk in our study population (nor PPsV23 neither PCV13).
Old age, immunocompromising conditions and chronic pulmonary/respiratory disease are major risk factors for pneumococcal pneumonia in adults. Our data underline the need for better prevention strategies in these persons.
Adults; Incidence; Pneumococcal pneumonia; Risk factors; Streptococcus pneumonia

Associations of regular glucosamine use with all-cause and cause-specific mortality: a large prospective cohort study.
Li ZH, Gao X, Chung VC, Zhong WF, Fu Q, Lv YB, Wang ZH, Shen D, Zhang XR, Zhang PD, Li FR, Huang QM, Chen Q, Song WQ, Wu XB, Shi XM, Kraus VB, Yang X, Mao C.
Ann Rheum Dis. 2020 Apr 6. pii: annrheumdis-2020-217176. doi: 10.1136/annrheumdis-2020-217176. [Epub ahead of print]
PMID: 32253185
To evaluate the associations of regular glucosamine use with all-cause and cause-specific mortality in a large prospective cohort.
This population-based prospective cohort study included 495 077 women and men (mean (SD) age, 56.6 (8.1) years) from the UK Biobank study. Participants were recruited from 2006 to 2010 and were followed up through 2018. We evaluated all-cause mortality and mortality due to cardiovascular disease (CVD), cancer, respiratory and digestive disease. HRs and 95% CIs for all-cause and cause-specific mortality were calculated using Cox proportional hazards models with adjustment for potential confounding variables.
At baseline, 19.1% of the participants reported regular use of glucosamine supplements. During a median follow-up of 8.9 years (IQR 8.3-9.7 years), 19 882 all-cause deaths were recorded, including 3802 CVD deaths, 8090 cancer deaths, 3380 respiratory disease deaths and 1061 digestive disease deaths. In multivariable adjusted analyses, the HRs associated with glucosamine use were 0.85 (95% CI 0.82 to 0.89) for all-cause mortality, 0.82 (95% CI 0.74 to 0.90) for CVD mortality, 0.94 (95% CI 0.88 to 0.99) for cancer mortality, 0.73 (95% CI 0.66 to 0.81) for respiratory mortality and 0.74 (95% CI 0.62 to 0.90) for digestive mortality. The inverse associations of glucosamine use with all-cause mortality seemed to be somewhat stronger among current than non-current smokers (p for interaction=0.00080).
Regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases.
cardiovascular disease; epidemiology; outcomes research

Vitamin K2 alleviates insulin resistance in skeletal muscle by improving mitochondrial function via SIRT1 signaling.
Su X, Wang W, Fang C, Ni C, Zhou J, Wang X, Zhang L, Xu X, Cao R, Lang H, Wang F.
Antioxid Redox Signal. 2020 Apr 7. doi: 10.1089/ars.2019.7908. [Epub ahead of print]
PMID: 32253917
High-fat diet (HFD)-induced insulin resistance (IR) impairs skeletal muscle mitochondrial biogenesis and functions, adversely affecting human health and lifespan. Vitamin K2 (VK2) has a beneficial role in improving insulin sensitivity and glucose metabolism. However, the underlying molecular mechanisms of VK2 on insulin sensitivity have not been well established. We investigated VK2's modulation of mitochondrial function to protect against IR in mice and cell models.
VK2 supplementation could effectively ameliorate the development of IR by improving mitochondrial function in both HFD-fed mice and PA-exposed cells. We revealed for the first time that HFD-caused mitochondrial dysfunction could be reversed by VK2 treatment. VK2 enhanced the mitochondrial function by improving mitochondrial respiratory capacity, increasing mitochondrial biogenesis and the enzymatic activities of mitochondrial complexes through SIRT1 signaling. The benefits of VK2 were abrogated in C2C12 transfected with SIRT1 siRNA but not in C2C12 transfected with AMPK siRNA. VK2 and SRT1720, a specific agonist of SIRT1, had the same effect on improving mitochondrial function via SIRT1 signaling. Thus, SIRT1 is required for VK2 improvement skeletal muscle. Furthermore, the beneficial effects of VK2 and GGOH both contribute to inhibited IR in skeletal muscle via SIRT1.
These studies demonstrated a previously undiscovered mechanism by which VK2 alleviates IR in skeletal muscle by improving mitochondrial function via SIRT1.
Naturally occurring VK2 prevents IR by improving mitochondrial function through SIRT1 signaling. These results could provide a foundation to identify new VK2-based preventive and therapeutic strategies for IR.

Evaluation of the Association Between Gastric Acid Suppression and Risk of Intestinal Colonization With Multidrug-Resistant Microorganisms: A Systematic Review and Meta-analysis.
Willems RPJ, van Dijk K, Ket JCF, Vandenbroucke-Grauls CMJE.
JAMA Intern Med. 2020 Feb 24. doi: 10.1001/jamainternmed.2020.0009. [Epub ahead of print]
PMID: 32091544 Free PMC Article
Acid suppressants inhibit gastric acid secretion and disrupt the intestinal microbiome. Whether acid suppression increases the risk of colonization with multidrug-resistant microorganisms (MDROs) is unclear.
To systematically examine the association of use of acid suppressants with the risk of colonization with MDROs and to perform a meta-analysis of current evidence.
PubMed, Embase, the Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials were searched from database inception through July 8, 2019.
Study selection was performed independently by 2 authors (R.P.J.W. and C.M.J.E.V.-G.) on the basis of predefined selection criteria; conflicts were resolved by consensus or by an adjudicator (K.v.D.). Human observational studies (case control, cohort, and cross-sectional) and clinical trial designs were selected if they quantified the risk of MDRO colonization in users of acid suppressants in comparison with nonusers.
The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) recommendations were followed. Data were extracted independently by the same 2 authors, and adjudication was conducted when necessary. Risk of bias was assessed according to a modified Newcastle-Ottawa Scale. Pooled odds ratios (ORs) were estimated using random-effects models; heterogeneity was evaluated using the I2 method.
The primary outcome measure was intestinal colonization with MDROs of the Enterobacterales order (producing extended-spectrum β-lactamases, carbapenemases, or plasmid-mediated AmpC β-lactamases), vancomycin-resistant enterococci, methicillin-resistant or vancomycin-resistant Staphylococcus aureus, or multidrug-resistant Pseudomonas or Acinetobacter species.
A total of 26 observational studies including 29 382 patients (11 439 [38.9%] acid suppressant users) met the selection criteria. Primary meta-analysis of 12 studies including 22 305 patients that provided adjusted ORs showed that acid suppression increased the odds of intestinal carriage of MDROs of the Enterobacterales order and of vancomycin-resistant enterococci by roughly 75% (OR = 1.74; 95% CI, 1.40-2.16; I2 = 68%). The odds were concordant with the secondary pooled analysis of all 26 studies (OR = 1.70; 95% CI, 1.44-1.99; I2 = 54%). Heterogeneity was partially explained by variations in study setting and the type of acid suppression.
Acid suppression is associated with increased odds of MDRO colonization. Notwithstanding the limitations of observational studies, the association is plausible and is strengthened by controlling for confounders. In view of the global increase in antimicrobial resistance, stewardship to reduce unnecessary use of acid suppressants may help to prevent MDRO colonization.

Associations of Processed Meat, Unprocessed Red Meat, Poultry, or Fish Intake With Incident Cardiovascular Disease and All-Cause Mortality.
Zhong VW, Van Horn L, Greenland P, Carnethon MR, Ning H, Wilkins JT, Lloyd-Jones DM, Allen NB.
JAMA Intern Med. 2020 Feb 3. doi: 10.1001/jamainternmed.2019.6969. [Epub ahead of print]
PMID: 32011623
Although the associations between processed meat intake and cardiovascular disease (CVD) and all-cause mortality have been established, the associations of unprocessed red meat, poultry, or fish consumption with CVD and all-cause mortality are still uncertain.
To identify the associations of processed meat, unprocessed red meat, poultry, or fish intake with incident CVD and all-cause mortality.
This cohort study analyzed individual-level data of adult participants in 6 prospective cohort studies in the United States. Baseline diet data from 1985 to 2002 were collected. Participants were followed up until August 31, 2016. Data analyses were performed from March 25, 2019, to November 17, 2019.
Processed meat, unprocessed red meat, poultry, or fish intake as continuous variables.
Hazard ratio (HR) and 30-year absolute risk difference (ARD) for incident CVD (composite end point of coronary heart disease, stroke, heart failure, and CVD deaths) and all-cause mortality, based on each additional intake of 2 servings per week for monotonic associations or 2 vs 0 servings per week for nonmonotonic associations.
Among the 29 682 participants (mean [SD] age at baseline, 53.7 [15.7] years; 13 168 [44.4%] men; and 9101 [30.7%] self-identified as non-white), 6963 incident CVD events and 8875 all-cause deaths were adjudicated during a median (interquartile range) follow-up of 19.0 (14.1-23.7) years. The associations of processed meat, unprocessed red meat, poultry, or fish intake with incident CVD and all-cause mortality were monotonic (P for nonlinearity ≥ .25), except for the nonmonotonic association between processed meat intake and incident CVD (P for nonlinearity = .006). Intake of processed meat (adjusted HR, 1.07 [95% CI, 1.04-1.11]; adjusted ARD, 1.74% [95% CI, 0.85%-2.63%]), unprocessed red meat (adjusted HR, 1.03 [95% CI, 1.01-1.06]; adjusted ARD, 0.62% [95% CI, 0.07%-1.16%]), or poultry (adjusted HR, 1.04 [95% CI, 1.01-1.06]; adjusted ARD, 1.03% [95% CI, 0.36%-1.70%]) was significantly associated with incident CVD. Fish intake was not significantly associated with incident CVD (adjusted HR, 1.00 [95% CI, 0.98-1.02]; adjusted ARD, 0.12% [95% CI, -0.40% to 0.65%]). Intake of processed meat (adjusted HR, 1.03 [95% CI, 1.02-1.05]; adjusted ARD, 0.90% [95% CI, 0.43%-1.38%]) or unprocessed red meat (adjusted HR, 1.03 [95% CI, 1.01-1.05]; adjusted ARD, 0.76% [95% CI, 0.19%-1.33%]) was significantly associated with all-cause mortality. Intake of poultry (adjusted HR, 0.99 [95% CI, 0.97-1.02]; adjusted ARD, -0.28% [95% CI, -1.00% to 0.44%]) or fish (adjusted HR, 0.99 [95% CI, 0.97-1.01]; adjusted ARD, -0.34% [95% CI, -0.88% to 0.20%]) was not significantly associated with all-cause mortality.
These findings suggest that, among US adults, higher intake of processed meat, unprocessed red meat, or poultry, but not fish, was significantly associated with a small increased risk of incident CVD, whereas higher intake of processed meat or unprocessed red meat, but not poultry or fish, was significantly associated with a small increased risk of all-cause mortality. These findings have important public health implications and should warrant further investigations.

Fiber consumption and breast cancer incidence: A systematic review and meta-analysis of prospective studies.
Farvid MS, Spence ND, Holmes MD, Barnett JB.
Cancer. 2020 Apr 6. doi: 10.1002/cncr.32816. [Epub ahead of print]
PMID: 32249416
Associations between fiber intake and breast cancer risk have been evaluated in prospective studies, but overall, the evidence is inconsistent. The authors performed a systematic review and meta-analysis of prospective studies to investigate the relation between intake of total and types of fiber with breast cancer incidence.
The MEDLINE and Excerpta Medica dataBASE (EMBASE) databases were searched through July 2019 for prospective studies that reported on the association between fiber consumption and incident breast cancer. The pooled relative risk (RR) and 95% confidence intervals (95% CI) were estimated comparing the highest versus the lowest category of total and types of fiber consumption, using a random-effects meta-analysis.
The authors identified 17 cohort trials, 2 nested case-control trials, and 1 clinical trial. Total fiber consumption was associated with an 8% lower risk of breast cancer (comparing the highest versus the lowest category, pooled RR, 0.92; 95% CI, 0.88-0.95 [I2  = 12.6%]). Soluble fiber was found to be significantly inversely associated with risk of breast cancer (pooled RR, 0.90 [95% CI, 0.84-0.96; I2 = 12.6%]) and insoluble fiber was found to be suggestively inversely associated with risk of breast cancer (pooled RR, 0.93 [95% CI, 0.86-1.00; I2 = 33.4%]). Higher total fiber intake was associated with a lower risk of both premenopausal and postmenopausal breast cancers (pooled RR, 0.82 [95% CI, 0.67-0.99; I2  = 35.2%] and pooled RR, 0.91 [95% CI, 0.88-0.95; I2  = 0.0%], respectively). Furthermore, the authors observed a nonsignificant inverse association between intake of total fiber and risk of both estrogen and progesterone receptor-positive and estrogen and progesterone receptor-negative breast cancers.
A random-effects meta-analysis of prospective observational studies demonstrated that high total fiber consumption was associated with a reduced risk of breast cancer. This finding was consistent for soluble fiber as well as for women with premenopausal and postmenopausal breast cancer.
breast cancer; estrogen and progesterone receptor-positive and -negative tumors; fiber; meta-analysis; postmenopausal; premenopausal

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Number of natural teeth, denture use and mortality in Chinese elderly: a population-based prospective cohort study.
Yuan JQ, Lv YB, Kraus VB, Gao X, Yin ZX, Chen HS, Luo JS, Zeng Y, Mao C, Shi XM.
BMC Oral Health. 2020 Apr 10;20(1):100. doi: 10.1186/s12903-020-01084-9.
PMID: 32276615
The associations between the number of natural teeth/denture use and all-cause mortality remain unclear due to lake of investigation for the potential interaction between tooth loss and denture use and for the potential changes in these exposures over time in older adults. We undertake this study to evaluate the associations of the number of natural teeth and/or denture use with mortality in Chinese elderly.
This is a prospective cohort study of 36,283 older adults (median age: 90). The number of natural teeth and denture use were collected with structured questionnaire. We evaluated hazard ratios (HRs) and confidence intervals (CIs) using a Cox proportional hazards model adjusting for demographic factors, education, income, lifestyle factors, and comorbidities.
We documented 25,857 deaths during 145,947 person-years of observation. Compared to those with 20+ teeth, tooth loss was associated with a gradual increase in mortality, with an adjusted HR of 1.14 (95% CI, 1.06 to 1.23) for those with 10-19 teeth, 1.23 (95% CI, 1.15 to 1.31) for those with 1-9 teeth, and 1.35 (95% CI, 1.26 to 1.44) for those without natural teeth. Denture use was associated with lower risk of mortality (adjusted HR 0.81; 95% CI, 0.77 to 0.84). Subgroup analyses indicated that the benefit of denture use was greater in men than in women (P = 0.02) and tended to decrease with age (P < 0.001). The effects of denture use did not differ among various degrees of tooth loss (P = 0.17).
Tooth loss was associated with an increased risk of mortality in older adults. Denture use provided a protective effect against death for all degrees of tooth loss however, this effect appeared to be modified by sex and age.
Cohort study; Denture; Mortality; Tooth loss

Chocolate for breakfast prevents circadian desynchrony in experimental models of jet-lag and shift-work.
Escobar C, Espitia-Bautista E, Guzmán-Ruiz MA, Guerrero-Vargas NN, Hernández-Navarrete MÁ, Ángeles-Castellanos M, Morales-Pérez B, Buijs RM.
Sci Rep. 2020 Apr 10;10(1):6243. doi: 10.1038/s41598-020-63227-w.
PMID: 32277140
Night-workers, transcontinental travelers and individuals that regularly shift their sleep timing, suffer from circadian desynchrony and are at risk to develop metabolic disease, cancer, and mood disorders, among others. Experimental and clinical studies provide evidence that food intake restricted to the normal activity phase is a potent synchronizer for the circadian system and can prevent the detrimental metabolic effects associated with circadian disruption. As an alternative, we hypothesized that a timed piece of chocolate scheduled to the onset of the activity phase may be sufficient stimulus to synchronize circadian rhythms under conditions of shift-work or jet-lag. In Wistar rats, a daily piece of chocolate coupled to the onset of the active phase (breakfast) accelerated re-entrainment in a jet-lag model by setting the activity of the suprachiasmatic nucleus (SCN) to the new cycle. Furthermore, in a rat model of shift-work, a piece of chocolate for breakfast prevented circadian desynchrony, by increasing the amplitude of the day-night c-Fos activation in the SCN. Contrasting, chocolate for dinner prevented re-entrainment in the jet-lag condition and favored circadian desynchrony in the shift-work models. Moreover, chocolate for breakfast resulted in low body weight gain while chocolate for dinner boosted up body weight. Present data evidence the relevance of the timing of a highly caloric and palatable meal for circadian synchrony and metabolic function.

Adequate access to healthcare and added life expectancy among older adults in China.
Hao L, Xu X, Dupre ME, Guo A, Zhang X, Qiu L, Zhao Y, Gu D.
BMC Geriatr. 2020 Apr 9;20(1):129. doi: 10.1186/s12877-020-01524-9.
PMID: 32272883
Adequate access to healthcare is associated with lower risks of mortality at older ages. However, it is largely unknown how many more years of life can be attributed to having adequate access to healthcare compared with having inadequate access to healthcare.
A nationwide longitudinal survey of 27,794 older adults aged 65+ in mainland China from 2002 to 2014 was used for analysis. Multivariate hazard models and life table techniques were used to estimate differences in life expectancy associated with self-reported access to healthcare (adequate vs. inadequate). The findings were assessed after adjusting for a wide range of demographic factors, socioeconomic status, family/social support, health practices, and health conditions.
At age 65, adequate access to healthcare increased life expectancy by approximately 2.0-2.5 years in men and women and across urban-rural areas compared with those who reported inadequate access to healthcare. At age 85, the corresponding increase in life expectancy was 1.0-1.2 years. After adjustment for multiple confounding factors, the increase in life expectancy was reduced to approximately 1.1-1.5 years at age 65 and 0.6-0.8 years at age 85. In women, the net increase in life expectancy attributable to adequate access to healthcare was 6 and 8% at ages 65 and 85, respectively. In men, the net increases in life expectancy were generally greater (10 and 14%) and consistent after covariate adjustments. In contrast, the increase in life expectancy was slightly lower in rural areas (2.0 years at age 65 and 1.0 years at age 85) than in urban areas (2.1 years at age 65 and 1.1 years age 85) when no confounding factors were taken into account. However, the increase in life expectancy was greater in rural areas (1.0 years at age 65 and 0.6 years at age 85) than in urban areas (0.4 years at age 65 and 0.2 years at age 85) after accounting for socioeconomic and other factors.
Adequate access to healthcare was associated with longer life expectancy among older adults in China. These findings have important implications for efforts to improve access to healthcare among older populations in China.
Access to healthcare; China; Gender differences; Healthcare; Life expectancy; Medical care; Older adults; Oldest-old; Urban-rural differences

Habitual dietary fat intake and risk of muscle weakness and lower-extremity functional impairment in older adults: A prospective cohort study.
Arias-Fernández L, Struijk EA, Rodríguez-Artalejo F, Lopez-Garcia E, Lana A.
Clin Nutr. 2020 Mar 27. pii: S0261-5614(20)30135-7. doi: 10.1016/j.clnu.2020.03.018. [Epub ahead of print]
PMID: 32273201
Fatty acid supplementation increases muscle mass and function in older adults, but the effect of habitual dietary intake is uncertain. Therefore, the objective of this study was to examine the association between habitual dietary fat intake and risk of muscle weakness and lower-extremity functional impairment (LEFI) in older adults.
Prospective study with 1873 individuals aged ≥60 years from the Seniors-ENRICA cohort. In 2008-10 and 2012, a validated face-to-face diet history was used to record the one-year consumption of up to 880 foods. Then, fatty acids, other nutrients and energy intake were estimated using standard food composition tables. Means of intake between these years were calculated to represent cumulative consumption over the follow-up. Study participants were followed up through 2015 to assess incident muscle weakness (lowest quintile of grip strength) and incident LEFI (Short Physical Performance Battery score ≤6). Analyses were performed with Cox regression and adjusted for the main confounders, including other types of fatty acids.
Over a median follow-up of 5.2 years, 331 participants developed muscle weakness and 397 LEFI. Intake of saturated fatty acids (SFA) did not show an association with muscle weakness but was associated with higher risk of LEFI (multivariable hazard ratio (HR) for tertile 3 vs. tertile 1: 1.15; 95% confidence interval: 1.05-2.01; p-trend = 0.02). This association was mostly due to consumption of Spanish cold cuts and pastry and, to a lesser extent, dairy. Monounsaturated fatty acids (MUFA) intake was associated with lower risk of muscle weakness (HR t3 vs. t1: 0.73; 0.54-0.99; p trend = 0.04), and intake of n-3 polyunsaturated fatty acids (PUFA) was associated with reduced risk of both muscle weakness (0.70; 0.52-0.95; p-trend = 0.02) and LEFI (0.49; 0.35-0.68; p-trend <0.001). Olive oil and blue fish, the main sources of MUFA and PUFA, were also associated with lower risk of muscle weakness and LEFI.
Habitual intake of SFA was associated with increased risk of LEFI. By contrast, habitual intake of MUFA and PUFA were associated with lower risk of physical performance impairment.
Diet; Elderly; Fatty acids; Muscle strength; Physical function

Substitutions between potatoes and other vegetables and risk of ischemic stroke.
Hansen MD, Würtz AML, Hansen CP, Tjønneland A, Rimm EB, Johnsen SP, Schmidt EB, Overvad K, Jakobsen MU.
Eur J Nutr. 2020 Apr 9. doi: 10.1007/s00394-020-02237-w. [Epub ahead of print]
PMID: 32274553
Intake of vegetables has been associated with a lower risk of ischemic stroke in observational studies controlling for total energy intake. However, adjustment for energy intake introduces a substitution aspect, which affects the interpretation of the results. We investigated replacement of potatoes with other vegetables, substitutions between vegetable subgroups, and risk of ischemic stroke and ischemic stroke subtypes.
The Danish Diet, Cancer and Health cohort included 57,053 participants aged 50-64 years at recruitment in 1993-1997. Diet was assessed from a validated 192-item semi-quantitative food frequency questionnaire. We calculated hazard ratios (HR) with 95% confidence intervals (CI) for the incidence of ischemic stroke using Cox proportional hazard regression.
During 13.5 years of follow-up, 1879 cases of ischemic stroke were identified including 319 cases of large-artery atherosclerosis and 844 cases of small-vessel occlusion. The adjusted HR for total ischemic stroke associated with food substitutions of equal amounts (500 g/week) was 0.86 (95% CI 0.76, 0.97) for replacement of potatoes with fruiting vegetables and 0.92 (95% CI 0.84, 1.02) for replacement of potatoes with other root vegetables. The HR for replacing potatoes with the sum of other vegetables was 0.95 (95% CI 0.90, 1.00). Substitution of cabbage for either potatoes, fruiting vegetables or other root vegetables was associated with a statistically non-significant higher risk of ischemic stroke. The patterns of associations were similar for ischemic stroke subtypes and for equivalent substitutions using isocaloric amounts.
Replacing potatoes with fruiting vegetables was associated with a lower risk of ischemic stroke.
Cohort study; Diet; Ischemic stroke; Potatoes; Substitution models; Vegetables

Patterns of Cardiovascular Risk Factors in Old Age and Survival and Health Status at 90.
Odden MC, Rawlings AM, Arnold AM, Cushman M, Biggs ML, Psaty BM, Newman AB.
J Gerontol A Biol Sci Med Sci. 2020 Apr 8. pii: glaa043. doi: 10.1093/gerona/glaa043. [Epub ahead of print]
PMID: 32267489
The population age 90 years and older is the fastest growing segment of the U.S. population. Only recently is it possible to study the factors that portend survival to this age.
Among participants of the Cardiovascular Health Study, we studied the association of repeated measures of cardiovascular risk factors measured over 15-23 years of follow-up and not only survival to 90 years of age, but also healthy aging outcomes among the population who reached age 90. We included participants aged 67-75 years at baseline (n = 3,613/5,888) to control for birth cohort effects, and followed participants until death or age 90 (median follow-up = 14.7 years).
Higher systolic blood pressure was associated with a lower likelihood of survival to age 90, although this association was attenuated at older ages (p-value for interaction <.001) and crossed the null for measurements taken in participants' 80's. Higher levels of high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and body mass index (BMI) were associated with greater longevity. Among the survivors to age 90, those with worse cardiovascular profile (high blood pressure, LDL cholesterol, glucose, and BMI; low HDL cholesterol) had lower likelihood of remaining free of cardiovascular disease, cognitive impairment, and disability.
In summary, we observed paradoxical associations between some cardiovascular risk factors and survival to old age; whereas, among those who survive to very old age, these risk factors were associated with higher risk of adverse health outcomes.
Blood; Cardiovascular; Longevity; Nonagenarians; Successful aging

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Association between dietary tomato intake and the risk of hepatocellular carcinoma: the Singapore Chinese Health Study.
Thomas CE, Luu HN, Wang R, Adams-Haduch J, Jin A, Koh WP, Yuan JM.
Cancer Epidemiol Biomarkers Prev. 2020 Apr 13. pii: cebp.0051.2020. doi: 10.1158/1055-9965.EPI-20-0051. [Epub ahead of print]
PMID: 32284341
Intake of tomato and/or lycopene has been found to be associated with reduced risk of several cancer types, but there is no report on the association with risk of hepatocellular carcinoma (HCC).
The associations of tomato and lycopene consumption with risk of HCC were examined in the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese aged 45-74 years at enrollment from 1993 to 1998. Usual diet was assessed using a validated semi-quantitative food frequency questionnaire. Incident HCC cases were ascertained through linkage with the nationwide Singapore Cancer Registry. Cox proportional hazard regression models were used to estimate hazard ratio (HR) and its 95% confidence interval (CI) of HCC with the consumption of tomato and lycopene among all cohort participants, and unconditional logistic regression was used to assess the association by hepatitis B surface antigen (HBsAg) positivity in a case-control study nested in this cohort.
After a mean follow-up of 17.6 years, 561 incident HCC cases were identified. Higher tomato intake was associated with lower risk of HCC after adjustment for multiple potential confounders (Ptrend<0.001). Compared to the lowest quartile, HRs (95% CIs) of HCC for the 2nd, 3rd, and 4th quartile of tomato intake were 0.70 (0.56-0.88), 0.73 (0.58-0.92), and 0.63 (0.49-0.81). Among HBsAg-negative individuals, the inverse association remained (Ptrend=0.03). There was no association between lycopene intake and HCC risk (Ptrend = 0.54). 
Tomato intake may offer protection against the development of HCC, particularly among individuals without chronic infection with hepatitis B virus.

HDL-C is associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose-response fashion: a pooled analysis of 37 prospective cohort studies.
Zhong GC, Huang SQ, Peng Y, Wan L, Wu YQ, Hu TY, Hu JJ, Hao FB.
Eur J Prev Cardiol. 2020 Apr 14:2047487320914756. doi: 10.1177/2047487320914756. [Epub ahead of print] No abstract available.
PMID: 32283957
The association between high-density lipoprotein cholesterol (HDL-C) levels and mortality remains controversial. We aimed to investigate the potential dose–response associations between HDL-C levels and mortality from all causes, cardiovascular disease and cancer in the general population.
PubMed and Embase were searched through April 2019. Prospective cohort studies reporting risk estimates of HDL-C levels and mortality were included. Linear and non-linear dose–response analyses were conducted. A random-effects model was employed to calculate pooled hazard ratio.
Thirty-seven studies, involving 3,524,505 participants and more than 612,027 deaths, were included. HDL-C level was found to be associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose–response pattern, with the lowest risk observed at HDL-C levels of 54–58 mg/dL, 68–71 mg/dL and 64–68 mg/dL, respectively. Compared with HDL-C level of 56 mg/dL, the pooled hazard ratios for all-cause mortality were 1.03 (95% confidence interval (CI) 1.01, 1.05) and 1.10 (95% CI 1.09, 1.12) for each 10-mg/dL increase and decrease in HDL-C levels, respectively; furthermore, compared with the reference category, the pooled hazard ratios for all-cause mortality were 1.21 (95% CI 1.09, 1.36) and 1.36 (95% CI 1.21, 1.53) for the highest and the lowest categories of HDL-C levels, respectively. Similar results were obtained for cardiovascular and cancer mortality.
In the general population, HDL-C level is associated with mortality from all causes, cardiovascular disease and cancer in a J-shaped dose–response manner; both extremely high and low HDL-C levels are associated with an increased risk of mortality.
HDL-C, cancer, cardiovascular disease, mortality, dose–response

One-Carbon Metabolism-Related Micronutrients Intake and Risk for Hepatocellular Carcinoma: A Prospective Cohort Study.
Antwi SO, Petrick JL, Campbell PT, Norez DA, Stevens VL, Liao LM, Roberts LR, Patel T, McGlynn KA.
Int J Cancer. 2020 Apr 14. doi: 10.1002/ijc.33007. [Epub ahead of print]
PMID: 32285447
Deficient intake of micronutrients involved in one-carbon metabolism (e.g., choline, methionine, vitamin B12 , and folic acid) leads to hepatocellular carcinoma (HCC) development in rodents, but it is under-investigated in humans. We investigated the association between one-carbon metabolism-related micronutrient intake and HCC risk in a prospective cohort of 494,860 participants with 16 years of follow-up in the NIH-AARP study. Dietary intakes and supplement use were ascertained at baseline using a food-frequency questionnaire. Total intake (diet plus supplements) of the following one-carbon metabolism-related micronutrients were calculated: folate, methionine, and vitamins B2 (riboflavin), B3 (niacin), B6 , and B12 . These micronutrients were examined both individually and simultaneously, with adjustment for covariates. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over the 16-year follow-up period, 647 incident HCC cases were diagnosed. When examined individually, higher total vitamin B3 intake was associated with a lower HCC risk (HRQ5vsQ1 =0.60; 95%CI=0.42-0.85; Ptrend =0.008), and the association remained significant when all six micronutrients were examined simultaneously (HRQ5vsQ1 =0.32; 95%CI=0.18-0.55; Ptrend <0.0001). Among participants with >3 years of follow-up, higher total vitamin B3 intake was again associated with lower risk (HRQ5vsQ1 =0.37; 95%CI=0.20-0.68; Ptrend =0.001), whereas higher total vitamin B6 intake was associated with higher risk (HRQ5vsQ1 =2.04; 95%CI=1.02-4.07; Ptrend =0.04). Restricted cubic spline analyses showed a dose-response inverse association between total vitamin B3 intake and HCC risk, and dose-response positive association between total vitamin B6 intake and HCC risk. The study suggests that higher vitamin B3 intake is associated with lower HCC risk, whereas higher vitamin B6 intake is associated with increased risk.

Long-term treatment with spermidine increases health span of middle-aged Sprague-Dawley male rats.
Filfan M, Olaru A, Udristoiu I, Margaritescu C, Petcu E, Hermann DM, Popa-Wagner A.
Geroscience. 2020 Apr 13. doi: 10.1007/s11357-020-00173-5. [Epub ahead of print]
PMID: 32285289
Let alone calorie restriction, life span extension in higher organisms has proven to be difficult to achieve using simple drugs. Previous studies have shown that the polyamine spermidine increased the maximum life span in C. elegans and the median life span in mice. However, younger subjects (< 40 years of age) are infrequently prescribed nor self-medicating with antiaging drugs. Therefore, in the present study, we aimed at assessing the effect of long-term treatment with spermidine given in the drinking water on behavioral performance and longevity of male, middle-aged Sprague-Dawley rats. We report that spermidine given in the drinking water did not extend neither the median nor the maximum life span of the middle-aged male Sprague-Dawley rats. However, spermidine treatment had a beneficial effect on the body weight and the kidney tubules, liver, and heart morphology. Behaviorally, spermidine led to a reduction in anxiety and an increase in curiosity, as assessed by exploratory behavior. Moreover, long-term treatment with spermidine enhanced autophagy in the brain and led to a diminished expression of the inflammatory markers, Tgfb, CD11b, Fcgr1, Stat1, CR3, and GFAP mRNAs in several cortical region and hippocampus of the treated rats suggesting that one beneficial effect of the long-term treatment with spermidine is an attenuated proinflammatory state in the aged brain. Our results suggest that long-term treatment with spermidine increases health span of middle-aged rats by attenuating neuroinflammation and improving anxiety and exploratory behavior.
Autophagy; Behavior; Longevity; Middle-aged rats; Neuroinflammation; Spermidine

Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review.
Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB.
JAMA. 2020 Apr 13. doi: 10.1001/jama.2020.6019. [Epub ahead of print]
PMID: 32282022
The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection.
No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19.
The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.

Meat consumption, depressive symptomatology and cardiovascular disease incidence in apparently healthy men and women: highlights from the ATTICA cohort study (2002-2012).
Kouvari M, Panagiotakos DB, Chrysohoou C, Yannakoulia M, Georgousopoulou EN, Tousoulis D, Pitsavos C; ATTICA study Investigators.
Nutr Neurosci. 2020 Apr 11:1-10. doi: 10.1080/1028415X.2020.1750169. [Epub ahead of print]
PMID: 32281497
Objectives: To evaluate the association of meat consumption with prevalent depressive symptomatology and cardiovascular disease (CVD) incidence in apparently healthy individuals.Methods: ATTICA study was conducted during 2001-2012 including n = 1514 men and n = 1528 women (aged >18 years old) from the greater Athens area, Greece. At baseline, depressive symptomatology through Zung Self-Rating Depression Scale (range 20-80) and meat consumption (total meat, red, white and processed meat) through validated semi-quantitative food frequency questionnaire were assessed. Follow-up (2011-2012) was achieved in n = 2020 participants (n = 317 cases); n = 845 participants with complete psychological metrics were used for the primary analysis.Results: Ranking from 1st to 3rd total meat consumption (low to high) tertiles, participants assigned in 2nd tertile had the lowest depressive-symptomatology scoring (p<0.001). This trend was retained in multiadjusted logistic regression analysis; participants reporting moderate total and red meat consumption had ∼20% lower likelihood to be depressed (i.e. Zung scale<45) compared with their 1st tertile counterparts (Odds Ratio (OR)total meat 0.82, 95% Confidence Interval (95%CI) (0.60, 0.97) and ORred meat 0.79 95%CI (0.45, 0.96)). Non-linear associations were revealed; 2-3 serving/week total meat and 1-2 servings/week red meat presented the lowest odds of depressive symptomatology (all ps<0.05). These U-shape trends seemed to attenuate the aggravating effect of depressive symptomatology on CVD hard endpoints. All aforementioned associations were more evident in women (all ps for sex-related interaction<0.05).Discussion: The present findings generate the hypothesis that moderate total meat consumption and notably, red meat may be more beneficial to prevent depressed mood and in turn hard CVD endpoints.
Meat; depression; gender; heart disease; primary prevention; psychological health; red meat; women

Ca:Mg Ratio, APOE Cytosine Modifications, and Cognitive Function: Results from a Randomized Trial.
Zhu X, Borenstein AR, Zheng Y, Zhang W, Seidner DL, Ness R, Murff HJ, Li B, Shrubsole MJ, Yu C, Hou L, Dai Q.
J Alzheimers Dis. 2020 Apr 3. doi: 10.3233/JAD-191223. [Epub ahead of print]
PMID: 32280092
Deterioration of ionized calcium (Ca2+) handling in neurons could lead to neurodegenerative disease. Magnesium (Mg) antagonizes Ca during many physiologic activities, including energy metabolism and catalyzation of demethylation from 5-methylcytosine(5-mC) to 5-hydroxymethylcytosine(5-hmC).
To test the hypothesis that actively reducing the Ca:Mg intake ratio in the diet through Mg supplementation improves cognitive function, and to test whether this effect is partially mediated by modified cytosines in Apolipoprotein E (APOE).
This study is nested within the Personalized Prevention of Colorectal Cancer Trial (PPCCT), a double-blind 2×2 factorial randomized controlled trial, which enrolled 250 participants from Vanderbilt University Medical Center. Target doses for both Mg and placebo arms were personalized.
Among those aged > 65 years old who consumed a high Ca:Mg ratio diet, we found that reducing the Ca:Mg ratio to around 2.3 by personalized Mg supplementation significantly improved cognitive function by 9.1% (p = 0.03). We also found that reducing the Ca:Mg ratio significantly reduced 5-mC at the cg13496662 and cg06750524 sites only among those aged > 65 years old (p values = 0.02 and 0.03, respectively). Furthermore, the beneficial effect of reducing the Ca:Mg ratio on cognitive function in those aged over 65 years was partially mediated by reductions in 5-mC levels (i.e., cg13496662 and cg06750524) in APOE (p for indirect effect = 0.05).
Our findings suggest that, among those age 65 and over with a high dietary Ca:Mg ratio, optimal Mg status may improve cognitive function partially through modifications in APOE methylation. These findings, if confirmed, have significant implications for the prevention of cognitive aging and Alzheimer's disease.Clinical Trial Registry number and website: #100106 https://clinicaltrials.gov/ct2/show/NCT03265483.
APOE methylation; calcium; cognitive function; magnesium; mediation analysis; ratio

Artificial sweeteners impair endothelial vascular reactivity: Preliminary results in rodents.
Risdon S, Meyer G, Marziou A, Riva C, Roustit M, Walther G.
Nutr Metab Cardiovasc Dis. 2020 Feb 12. pii: S0939-4753(20)30047-8. doi: 10.1016/j.numecd.2020.01.014. [Epub ahead of print]
PMID: 32278610
Prospective epidemiological studies highlighted recently the link between artificial sweeteners (AS) consumption and the risk of developing cardiometabolic diseases. However, underlying mechanisms remain unknown. Thus, the aim of this preliminary study was to characterize, in a healthy rat population, the effect of chronic AS consumption on body composition and vascular function, an early marker for cardiovascular disease.
Healthy Wistar rats followed a 10-week standard diet including the consumption of water sweetened or not with a sucralose/acesulfame potassium solution at different concentrations: for moderate consumption at 1 and 2 mg.kg-1.day-1, respectively or high intake at 15 and 15 mg.kg-1.day-1 for both molecules (acceptable daily intake). Body fat composition has been evaluated and ex vivo aortic vasomotor function has been investigated with a pharmacological approach.
Both groups of AS-treated rats showed a significant increase in subcutaneous and perirenal adipose tissue mass storage, without changes in total body mass. However, rats that have consumed AS at Acceptable Daily Intake (ADI) concentration revealed a significant vascular endothelial dysfunction compared to other groups. These results are interesting because they will help to better explain the observed increase in cardiometabolic risk.
Artificial sweeteners; Endothelium; Metabolic disease; Vascular reactivity

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Familial Longevity is Associated with an Attenuated Thyroidal Response to Recombinant Human Thyroid Stimulating Hormone.
Zutinic A, Pijl H, Ballieux BE, Roelfsema F, Westendorp RGJ, Blauw GJ, van Heemst D.
J Clin Endocrinol Metab. 2020 Apr 18. pii: dgaa195. doi: 10.1210/clinem/dgaa195. [Epub ahead of print]
PMID: 32303766
Longevity is associated with higher circulating levels of thyroid stimulating hormone (TSH) in the absence of differences in circulating thyroid hormones (TH), as previously observed in F2 members of long-lived families (F2-LLS) and their partners (F2-Con). The mechanism underlying this observed difference remains unknown.
We hypothesized that the thyroid gland of members from long-lived families are less responsive to TSH stimulation, thereby requiring higher circulating TSH levels to maintain adequate TH levels.
We performed a case-control intervention study with a single intra-muscular (gluteal) injection with 0.1mg recombinant human TSH (rhTSH) in a subgroup of 14 F2-LLS and 15 similarly aged F2-Con. They were followed-up for 4 days. No serious adverse events were reported. For analyses, we compared time trajectories of TSH and TH, and the ratio of TH to TSH using area under the curve (AUC) calculations.
The AUC fT4/AUC TSH ratio was significantly lower in F2-LLS than in F2-Con (estimated mean (95%CI) 1.6 (1.2-1.9) and 2.2 (1.9-2.6), respectively, p=0.01). The AUC Tg/AUC TSH ratio was also lower in F2-LLS than in F2-Con (median (IQR) 2.1 (1.4-3.6) and 3.2 (2.7-7.4), respectively, p=0.04). We observed the same trend with the AUC fT3/AUC TSH ratio, although the difference was not statistically significant (estimated mean (95%CI) 0.6 (0.4-0.7) and 0.7 (0.6-0.8), respectively, p=0.07).
The present findings show that members of long-living families have a lower thyroid responsivity to TSH compared to their partners.
Thyroid; longevity; recombinant human TSH; responsivity

Effects of alternate-day fasting, time-restricted fasting and intermittent energy restriction DSS-induced on colitis and behavioral disorders.
Zhang X, Zou Q, Zhao B, Zhang J, Zhao W, Li Y, Liu R, Liu X, Liu Z.
Redox Biol. 2020 Apr 10;32:101535. doi: 10.1016/j.redox.2020.101535. [Epub ahead of print]
PMID: 32305005
Intermittent fasting (IF) has been reported to have beneficial effects on improving gut function via lowering gut inflammation and altering the gut microbiome diversity. In this study, we aimed to investigate the differential effects of three different common IF treatments, alternate day fasting (ADF), time-restricted fasting (TRF), and intermittent energy restriction (IER), on a dextran sodium sulfate (DSS)-induced colitis mouse model. The results indicated that TRF and IER, but not ADF improved the survival rates of the colitis mice. TRF and IER, but not ADF, reversed the colitis pathological development by improving the gut barrier integrity and colon length. Importantly, TRF and IER suppressed the inflammatory responses and oxidative stress in colon tissues. Interestingly, TRF and IER also attenuated colitis-related anxiety-like and obsessive-compulsive disorder behavior and alleviated the neuroinflammation and oxidative stress. TRF and IER also altered the gut microbiota composition, including the decrease of the enrichments of colitis-related microbes such as Shigella and Escherichia Coli, and increase of the enrichments of anti-inflammatory-related microbes. TRF and IER also improved the short chain fatty acid formation in colitis mice. In conclusion, the TRF and IER but not ADF exhibited the protective effects against colitis and related behavioral disorders, which could be partly explained by improving the gut microbiome compositions and preventing gut leak, and consequently suppressing the inflammation and oxidative damages in both colon and brain. The current research indicates that proper IF regimens could be effective strategies for nutritional intervention for the prevention and treatment of colitis.
Anxiety-like behavior; Colitis; Gut microbes; Inflammation; Intermittent fasting; Oxidative stress

Meat and fish intake and type 2 diabetes: dose-response meta-analysis of prospective cohort studies.
Yang X, Li Y, Wang C, Mao Z, Zhou W, Zhang L, Fan M, Cui S, Li L.
Diabetes Metab. 2020 Apr 14. pii: S1262-3636(20)30055-0. doi: 10.1016/j.diabet.2020.03.004. [Epub ahead of print] Review.
PMID: 32302686
This meta-analysis aimed to quantitatively examine the possible associations between total meat, red meat, processed meat, poultry and fish intakes and type 2 diabetes (T2D).
Relevant articles were identified in PubMed, Embase and Web of Science databases using a search time up to January 2019. Generalized least-squares trend estimations and restricted cubic spline regression models were used for analysis.
Twenty-eight articles were included in the analysis. When comparing the highest with the lowest category of meat intake, the summary relative risk of T2D was 1.33 (95% CI: 1.16-1.52) for total meat, 1.22 (95% CI: 1.16-1.28) for red meat, 1.25 (95% CI: 1.13-1.37) for processed meat, 1.00 (95% CI: 0.93-1.07) for poultry and 1.01 (95% CI: 0.93-1.10) for fish. In the dose-response analysis, each additional 100 g/day of total and red meat, and 50 g/day of processed meat, were found to be associated with a 36% (95% CI: 1.23-1.49), 31% (95% CI: 1.19-1.45) and 46% (95% CI: 1.26-1.69) increased risk of T2D, respectively. In addition, there was evidence of a non-linear dose-response association between processed meat and T2D (P = 0.004), with the risk increasing by 30% with increasing intakes up to 30 g/day.
Our meta-analysis has shown a linear dose-response relationship between total meat, red meat and processed meat intakes and T2D risk. In addition, a non-linear relationship of intake of processed meat with risk of T2D was detected.
Fish; Meat; Meta-analysis; Prospective; Type 2 diabetes

Associations between self-reported sleep characteristics and incident mild cognitive impairment: The Heinz Nixdorf Recall Cohort Study.
Brachem C, Winkler A, Tebrügge S, Weimar C, Erbel R, Jöckel KH, Stang A, Dragano N, Moebus S, Kowall B, Jokisch M.
Sci Rep. 2020 Apr 16;10(1):6542. doi: 10.1038/s41598-020-63511-9.
PMID: 32300149
Associations of sleep characteristics with mild cognitive impairment (MCI) have been examined in cross-sectional, but rarely in longitudinal studies. Incident MCI and sleep characteristics were assessed in 1,890 participants of the first and second follow-up of the Heinz Nixdorf Recall study, a population-based cohort study in Germany (age at first follow-up 50-80 years, mean follow-up 5.2 years). MCI was assessed with extensive cognitive tests. Sleep questionnaires including PSQI (Pittsburgh Sleep Quality Index) were used to assess sleep quality, sleep disturbances, time asleep, and time in bed. Relative risks (RR) of developing MCI when exposed to sleep characteristics were assessed in regression models adjusted for sociodemographic and cardiovascular risk factors. Poor sleep quality (PSQI > 5) (RR = 1.43, 95% CI: 1.12-1.82, fully adjusted, reference: PSQI ≤ 5) and difficulties initiating sleep (almost nightly versus never) (RR = 1.40, 0.94-2.08) were associated with incident MCI. For time in bed, the risk of MCI was increased for ≤ 5 hours (RR = 2.86, 1.24─6.60, reference:7 to <8 hours). In this longitudinal study with older participants, MCI risk was increased in persons with poor sleep quality, difficulties initiating sleep, and short time in bed.

Differential Effects of Long-Term Caloric Restriction and Dietary Protein Source on Bone and Marrow Fat of the Aging Rat.
Duque G, Al Saedi A, Rivas D, Miard S, Ferland G, Picard F, Gaudreau P.
J Gerontol A Biol Sci Med Sci. 2020 Apr 16. pii: glaa093. doi: 10.1093/gerona/glaa093. [Epub ahead of print]
PMID: 32298404
Long-term caloric restriction (CR) has been shown to be beneficial to various tissues and organs. In contrast, CR exerts differential effects on bone, which could be due in part to the nature of the protein regime utilized. Male Sprague Dawley rats (8-month-old) were subjected for 12 months to 40% CR in macronutrients and compared to rats fed ad libitum for the same period. Casein- and soy-fed groups were compared. There was a significant decrease in bone quality in both CR groups, which was independent of the source of protein in the diet. In contrast, the group fed soy protein ad libitum showed better bone quality and higher levels of bone formation compared to casein-fed animals. Notably, bone marrow adipocytes were not mobilized upon CR as demonstrated by an absence of change in adipocyte number and tissue expression of leptin. This study demonstrates that the negative effect of CR on bone quality could not be prevented by the most common protein regimes.
Caloric restriction; PPARγ; Sirt1; bone; marrow adipose tissue

Repeated measurements of serum urate and mortality: a prospective cohort study of 152,358 individuals over 8 years of follow-up.
Li S, Cui L, Cheng J, Shu R, Chen S, Nguyen US, Misra D, Wu S, Gao X.
Arthritis Res Ther. 2020 Apr 15;22(1):84. doi: 10.1186/s13075-020-02173-4.
PMID: 32295651
Longitudinal evidence on change of serum urate level with mortality risk is limited as prior studies have a measurement of serum urate at a single time point. Further, the combined effect of serum urate and systemic inflammation on mortality is unknown.
We conducted a prospective cohort study of 152,358 participants (122,045 men and 30,313 women) with repeated measurements of serum urate in 2006, 2008, 2010, and 2012 (107,751 participants had all four measurements of serum urate). We used the Cox proportional hazard model to examine the association between cumulative average and changes in serum urate with mortality. The combined effect of serum urate and systemic inflammation was determined by testing the interaction of serum urate and high-sensitive C-reactive protein (hs-CRP) in relation to mortality risk.
During a median follow-up of 8.7 (interquartile range 6.3-9.2) years, we identified 7564 all-cause deaths, 1763 CVD deaths, 1706 cancer deaths, and 1572 other deaths. We observed U-shaped relationships of cumulative average serum urate with all-cause mortality, cardiovascular mortality, and other mortalities. Compared with participants with stable serum urate, those with greater increases in serum urate had a 1.7-fold elevated mortality (hazard ratio (HR) = 1.66, 95% confidence interval (CI) = 1.49-1.84), and those with decreased serum urate had a 2-fold elevated mortality risk (HR = 2.14, 95% CI 1.93-2.37). Participants with both hyperuricemia and hs-CRP had 1.6 times higher mortality, compared with those with low serum urate and hs-CRP levels (HR = 1.56, 95% CI 1.37-1.76).
We observed a U-shaped relationship of long-term cumulative average serum urate with all-cause mortality, cardiovascular mortality, and other mortalities. Compared with participants with relatively stable serum urate levels, a greater increase or decrease in serum urate was associated with elevated mortality. Participants with both hyperuricemia and high systemic inflammation had the greatest mortality risk compared with those with low serum urate and low hs-CRP levels.
Mortality; Serum urate

A systematic review and meta-analysis: The Effectiveness of probiotics for viral gastroenteritis.
Ansari F, Pashazadeh F, Nourollahi E, Hajebrahimi S, Munn Z, Pourjafar H.
Curr Pharm Biotechnol. 2020 Apr 16. doi: 10.2174/1389201021666200416123931. [Epub ahead of print]
PMID: 32297578
Probiotics can be used for the treatment of viral gastroenteritis.
This systematic review is to evaluate the evidence regarding the effect of probiotics on human cases of viral gastroenteritis.
The objective of this review is to evaluate the effectiveness of probiotics versus placebo or standard treatment for viral gastroenteritis. A comprehensive search of Cochrane Library, EMBASE, MEDLINE via PubMed and Ovid databases, and unpublished studies (till 27 January 2018) was conducted followed by a process of study selection and critical appraisal by two independent reviewers. Randomized controlled trials assessing probiotic administration in human subjects infected with any species of gastroenteritis viruses were considered for inclusion. Only studies with a confirmed viral cause of infection were included. This study was developed using the JBI methodology for systematic reviews which is in accordance with the PRISMA guideline. Meta-analysis was conducted where feasible. Data were pooled using the inverse variance method with random effects models and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed by Cochran Q statistic and quantified by the I2 statistic. We included 17 RCTs, containing 3082 patients.
Probiotics can improve symptoms of viral gastroenteritis, including the duration of diarrhea (mean difference 0. 7 days, 95% CI 0.31 to 1.09 days, n = 740, ten trials) and duration of hospitalization (mean difference 0.76 days, 95% CI 0.61 to 0.92 days, n = 329, four trials).
The results of this review show that the administration of probiotics in patients with viral gastroenteritis should be considered.
Viral gastroenteritis; diarrhoea; enteric infections; gastritis; prebiotics; probiotics; virus shedding.

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Evenly Distributed Protein Intake over 3 Meals Augments Resistance Exercise-Induced Muscle Hypertrophy in Healthy Young Men.
Yasuda J, Tomita T, Arimitsu T, Fujita S.
J Nutr. 2020 Apr 22. pii: nxaa101. doi: 10.1093/jn/nxaa101. [Epub ahead of print]
PMID: 32321161
Although daily protein intake (PI) has been reported to be essential for regulating muscle mass, the distribution of daily PI in individuals is typically the lowest at breakfast and skewed toward dinner. Skewed protein intake patterns and inadequate PI at breakfast were reported to be negative factors for muscle maintenance.
This study examined whether a protein-enriched meal at breakfast is more effective for muscle accretion compared with the typical skewed PI pattern.
This 12-wk, parallel-group, randomized clinical trial included 26 men (means ± SEs; age: 20.8 ± 0.4 y; BMI: 21.8 ± 0.4 kg/m2). The "high breakfast" (HBR) group (n = 12) consumed a protein-enriched meal at breakfast providing a PI of 0.33 g/kg body weight (BW); their PI at lunch (0.46 g/kg BW) and dinner (0.48 g/kg BW) provided an adequate overall daily PI (1.30 g/kg BW/d). The "low breakfast" (LBR) group (n = 14) consumed 0.12 g protein/kg BW at breakfast; intakes at lunch (0.45 g/kg BW) and dinner (0.83 g/kg BW) yielded the same daily PI as in the HBR group. The participants performed supervised resistance training (RT) 3 times per week (75-80% 1-repetition maximum; 3 sets × 10 repetitions). DXA was used to measure the primary outcome variable, that is, total lean soft tissue mass (LTM).
The total LTM at baseline did not differ between the HBR (52.4 ± 1.3 kg) and LBR (53.4 ± 1.2 kg) groups. After the intervention, increases in total LTM were significant in both groups, with that in the HBR group (2.5 ± 0.3 kg) tending to be greater than that in the LBR group (1.8 ± 0.3 kg) (P = 0.06), with a large effect size (Cohen d = 0.795).
For RT-induced muscle hypertrophy in healthy young men, consuming a protein-enriched meal at breakfast and less protein at dinner while achieving an adequate overall PI is more effective than consuming more protein at dinner.This study was registered at University hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000037583 (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042763).
muscle hypertrophy; protein distribution; protein intake; resistance training; young subjects

How oro-sensory exposure and eating rate affect satiation and associated endocrine responses-a randomized trial.
Lasschuijt M, Mars M, de Graaf C, Smeets PAM.
Am J Clin Nutr. 2020 Apr 22. pii: nqaa067. doi: 10.1093/ajcn/nqaa067. [Epub ahead of print]
PMID: 32320002
Longer oral processing decreases food intake. This can be attributed to greater oro-sensory exposure (OSE) and a lower eating rate (ER). How these factors contribute to food intake, and the underlying physiological mechanisms, remain unclear.
We aimed to determine the independent and simultaneous effects of OSE and ER on satiation and associated endocrine responses.
Forty participants in study 1 [mean ± SD age: 24 ± 4 y; BMI (in kg/m2): 22 ± 2] and 20 in study 2 (mean ± SD age: 23 ± 3 y; BMI: 23 ± 2) participated in a 2 × 2 randomized trial. In both studies, participants ate chocolate custard with added caramel sauce (low OSE) or caramel fudge (high OSE) and with short (fast ER) or long breaks (slow ER) in between bites, until fullness. In study 2, endocrine responses were measured during the meal.
In study 1, participants ate (mean ± SEM) 42 ± 15 g less in the slow- than in the fast-ER condition, only within the high-OSE condition (P = 0.04). In study 2, participants ate 66 ± 21 g less in the high- than in the low-OSE condition and there were no intake differences between slow and fast ER (P = 0.35). Eight minutes after starting to eat, insulin concentrations increased by 42%-65% in all treatments compared with the control. At the end of the meal, insulin concentrations were 81% higher in the high-OSE, slow-ER than in the low-OSE, fast-ER condition (P = 0.049). Pancreatic polypeptide (PP) increased by 62%, 5 min after meal onset in the low-OSE, fast-ER condition (P = 0.005). Ghrelin concentrations did not change.
Greater OSE increases insulin responsiveness. In contrast, PP responses are stronger when OSE is reduced and ER is fast. Insulin and PP responses may mediate the independent effects of OSE and ER on food intake. These may be beneficial eating strategies, particularly for type 2 diabetic patients, to control food intake and maintain glucose homeostasis.This trial was registered at trialregister.nl as NL6544.
cephalic phase; eating behavior; eating rate; ghrelin; human; insulin; oro-sensory exposure; pancreatic polypeptide; satiation

Circadian regulation of mitochondrial uncoupling and lifespan.
Ulgherait M, Chen A, McAllister SF, Kim HX, Delventhal R, Wayne CR, Garcia CJ, Recinos Y, Oliva M, Canman JC, Picard M, Owusu-Ansah E, Shirasu-Hiza M.
Nat Commun. 2020 Apr 21;11(1):1927. doi: 10.1038/s41467-020-15617-x.
PMID: 32317636
Because old age is associated with defects in circadian rhythm, loss of circadian regulation is thought to be pathogenic and contribute to mortality. We show instead that loss of specific circadian clock components Period (Per) and Timeless (Tim) in male Drosophila significantly extends lifespan. This lifespan extension is not mediated by canonical diet-restriction longevity pathways but is due to altered cellular respiration via increased mitochondrial uncoupling. Lifespan extension of per mutants depends on mitochondrial uncoupling in the intestine. Moreover, upregulated uncoupling protein UCP4C in intestinal stem cells and enteroblasts is sufficient to extend lifespan and preserve proliferative homeostasis in the gut with age. Consistent with inducing a metabolic state that prevents overproliferation, mitochondrial uncoupling drugs also extend lifespan and inhibit intestinal stem cell overproliferation due to aging or even tumorigenesis. These results demonstrate that circadian-regulated intestinal mitochondrial uncoupling controls longevity in Drosophila and suggest a new potential anti-aging therapeutic target.

Determination of total purine and purine base content of 80 food products to aid nutritional therapy for gout and hyperuricemia.
Kaneko K, Takayanagi F, Fukuuchi T, Yamaoka N, Yasuda M, Mawatari KI, Fujimori S.
Nucleosides Nucleotides Nucleic Acids. 2020 Apr 20:1-9. doi: 10.1080/15257770.2020.1748197. [Epub ahead of print]
PMID: 32312146
The aim of this work is to facilitate the nutritional therapy of gout and hyperuricemia. In Japan, patients with gout or hyperuricemia are recommended to consume less than 400 mg of dietary purines per day. When receiving nutritional therapy for gout or hyperuricemia, purine-rich foods (>200 mg/100 g) should be eaten in even lower quantities. The purine content of foods reported in this study are as follows: noodles, 0.6-12.1 mg/100 g; bread, 4.4 mg/100 g; peas or seeds, 19.6-67.1 mg/100 g; dairy, 0.0-1.4 mg/100 g; Japanese vegetables, 0.9-47.1 mg/100 g; seasonings, 0.7-847.1 mg/100 g; meat or fish, 19.0-385.4 mg/100 g; fish milt, 375.4-559.8 mg/100 g; and supplements, 81.9-516.0 mg/100 g. Foods containing very large amounts of purine (>300 mg/100 g) included anchovy, cutlassfish (hairtail), cod milt, globefish milt, dried Chinese soup stock, dried yeast, a Euglena supplement, and a Lactobacillus supplement. When eating these high-purine food or supplements, the quantity taken at one meal should be limited, especially milt because they typically consumed amount of 20-30 g is equivalent to 75-168 mg total purines. This is 20%-40% of the recommended daily amount (400 mg/day) for patients with gout or hyperuricemia. Thus, these patients should restrict the amount of purine-rich foods they consume. Good dietary habits with a good balance of nutrients are recommended.
Gout; determination of purine; hyperuricemia; nutritional therapy; purine-rich food

Weight loss since early adulthood, later life risk of fracture hospitalizations, and bone mineral density: a prospective cohort study of 0.5 million Chinese adults.
Shen Z, Yu C, Guo Y, Bian Z, Wei Y, Du H, Yang L, Chen Y, Gao Y, Zhang X, Chen J, Chen Z, Lv J, Li L; China Kadoorie Biobank Collaborative Group.
Arch Osteoporos. 2020 Apr 19;15(1):60. doi: 10.1007/s11657-020-00734-3.
PMID: 32307596
In a Chinese population from both urban and rural areas, weight loss of ≥ 5 kg from early adulthood to midlife was associated with a higher risk of hip fracture and lower BMD in later life.
This study investigates the association of the long-term weight loss from young adulthood through the middle ages with the subsequent 10-year risk of hospitalized fracture and calcaneus bone mineral density (BMD).
China Kadoorie Biobank (CKB) was established during 2004-2008 in ten areas across China. Weight at age 25 years was self-reported at baseline, and weight at baseline and resurvey was measured by the calibrated equipment. Outcomes were hospitalized fracture during follow-up and calcaneus BMD measured at resurvey. Analysis for fracture risk included 411,812 participants who were free of fracture in the last 5 years before baseline, cancer, or stroke at any time before baseline. Analysis for BMD included 21,453 participants who participated in the resurvey of 2013-2014 with the same exclusion criteria as above.
The mean age was 50.8 at baseline and 58.4 at resurvey. Median weight change from age 25 to baseline was 4.4 kg, with 20.7% losing weight and 58.5% gaining weight. During a median follow-up of 10.1 years, we documented 13,065 cases of first diagnosed fracture hospitalizations, including 1222 hip fracture. Compared with participants whose weight was stable (± 2.4 kg), the adjusted hazard ratios (95% CIs) for those with weight loss of ≥ 5.0 kg from age 25 to baseline was 1.39 (1.17 to 1.66) for hip fracture. Weight loss was not associated with fracture risk at other sites. Those with weight loss from age 25 to resurvey had the lowest BMD measures, with β (95% CIs) of - 4.52 (- 5.08 to - 3.96) for broadband ultrasound attenuation (BUA), - 4.83 (- 6.98, - 2.67) for speed of sound (SOS), and - 4.36 (- 5.22, - 3.49) for stiffness index (SI).
Weight loss from early adulthood to midlife was associated with a higher risk of hip fracture and lower BMD in later life.
Bone mineral density; Fracture; Prospective cohort study; Weight loss

Association of types of dietary fats and all-cause and cause-specific mortality: A prospective cohort study and meta-analysis of prospective studies with 1,148,117 participants.
Mazidi M, Mikhailidis DP, Sattar N, Toth PP, Judd S, Blaha MJ, Hernandez AV, Penson PE, Banach M; International Lipid Expert Panel (ILEP) & Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group.
Clin Nutr. 2020 Apr 3. pii: S0261-5614(20)30146-1. doi: 10.1016/j.clnu.2020.03.028. [Epub ahead of print]
PMID: 32307197
Associations between dietary fats and mortality are unclear.
We evaluated the relationship between quartiles of total fat, mono-unsaturated (MUFA), polyunsaturated (PUFA) and saturated fatty acid (SFA) consumption, and all-cause, coronary heart disease (CHD), stroke, and type 2 diabetes (T2D)-associated mortality in 24,144 participants from the National Health and Nutrition Examination Surveys (NHANES) 1999-2010. We added our results to a meta-analysis based on searches until November 2018.
In fully adjusted Cox-proportional hazard models in our prospective study, there was an inverse association between total fat (HR: 0.90, 95% confidence interval 0.82, 0.99, Q4 vs Q1) and PUFA (0.81, 0.78-0.84) consumption and all-cause mortality, whereas SFA were associated with the increased mortality (1.08, 1.04-1.11). In the meta-analysis of 29 prospective cohorts (n = 1,148,117) we found a significant inverse association between total fat (0.89, 0.82-0.97), MUFA (0.93, 0.87-0.99) and PUFA (0.86, 0.80-0.93) consumption and all-cause mortality. No association was observed between total fat and CVD (0.92, 0.79-1.08) or CHD mortality (1.03 0.99-1.09). A significant association between SFA intake and CHD mortality (1.10, 1.01-1.20) was observed. Neither MUFA nor PUFA were associated with CVD or CHD mortality. Inverse associations were observed between MUFA (0.80, 0.67-0.96) and PUFA (0.84, 0.80-0.90) intakes and stroke mortality.
We showed differential associations of total fat, MUFA and PUFA with all-cause mortality, but not CVD or CHD mortalities. SFA was associated with higher all-cause mortality in NHANES and with CHD mortality in our meta-analysis. The type of fat intake appears to be associated with important health outcomes.
Coronary heart disease; Diabetes; Dietary fats; Meta-analysis; Mortality; Stroke

Long-term potassium intake and associated renal and cardiovascular outcomes in the clinical setting.
Olde Engberink RHG, van den Born BH, Peters-Sengers H, Vogt L; K+ onsortium.
Clin Nutr. 2020 Apr 1. pii: S0261-5614(20)30144-8. doi: 10.1016/j.clnu.2020.03.026. [Epub ahead of print]
PMID: 32307195
High potassium intake has been suggested to lower the risk for renal and cardiovascular outcome, but data are conflicting. This may be explained by the use of different methods for potassium intake assessment across studies. Also, most data are limited to the general population. We investigated the optimal potassium intake, as measured with multiple 24-h urine samples, in patients with a clinical indication for 24-h urine collection, for prevention of cardiorenal disease.
We performed a retrospective cohort study in 541 outpatient subjects with an estimated glomerular filtration rate >60 mL/min/1.73 m2 who had sampled a 24-h urine collection between 1998 and 1999, and had at least 1 additional collection during a 17-year follow-up. We assessed incidence of renal (i.e. renal replacement therapy, 60% decline in estimated glomerular filtration rate or death) and cardiovascular disease (i.e. cardiovascular event or death).
Average age of subjects was 47 years. Estimated mean potassium intake was 74 mmol/day and remained similar during follow-up. The highest tertile of estimated potassium intake was associated with a significant 76% reduction in renal outcome, and 73% decrease of cerebrovascular events, while no effect for overall cardiovascular outcome was found. A 20-mmol increase in potassium intake during follow-up was associated with a 24% reduction in renal outcome.
Our data demonstrate that high estimated potassium intake is associated with improved renal outcome and less cerebrovascular events in outpatient subjects with preserved kidney function.
Cardiovascular; Chronic kidney disease; Nutrition; Potassium; Urine

Omega-3, Omega-6, and Polyunsaturated Fat for Cognition: Systematic Review and Meta-analysis of Randomized Trials.
Brainard JS, Jimoh OF, Deane KHO, Biswas P, Donaldson D, Maas K, Abdelhamid AS, Hooper L; PUFAH group.
J Am Med Dir Assoc. 2020 Apr 15. pii: S1525-8610(20)30219-X. doi: 10.1016/j.jamda.2020.02.022. [Epub ahead of print] Review.
PMID: 32305302
Neurocognitive function may be influenced by polyunsaturated fat intake. Many older adults consume omega-3 supplements hoping to prevent cognitive decline. We assessed effects of increasing omega-3, omega-6, or total polyunsaturated fats on new neurocognitive illness and cognition.
We carried out a systematic review and meta-analysis of randomized controlled trials (RCTs) in adults, with duration ≥24 weeks, assessing effects of higher vs lower omega-3, omega-6, or total polyunsaturated fats and outcomes: new neurocognitive illness, newly impaired cognition, and/or continuous measures of cognition.
We searched MEDLINE, Embase, Cochrane CENTRAL, and trials registers (final update of ongoing trials December 2018). We duplicated screening, data extraction, and risk of bias assessment. Neurocognitive measures were grouped to enable random effects meta-analysis. GRADE assessment, sensitivity analyses, and subgrouping by dose, duration, type of intervention, and replacement were used to interrogate our findings.
Searches generated 37,810 hits, from which we included 38 RCTs (41 comparisons, 49,757 participants). Meta-analysis suggested no or very little effect of long-chain omega-3 on new neurocognitive illness [risk ratio (RR) 0.98, 95% confidence interval (CI) 0.87-1.10, 6 RCTs, 33,496 participants, I2 36%), new cognitive impairment (RR 0.99, 95% CI 0.92-1.06, 5 RCTs, 33,296 participants, I2 0%) or global cognition assessed using the Mini-Mental State Examination (MD 0.10, 95% CI 0.03-0.16, 13 RCTs, 14,851 participants, I2 0%), all moderate-quality evidence. Effects did not differ with sensitivity analyses, and we found no differential effects by dose, duration, intervention type, or replacement. Effects of increasing α-linolenic acid, omega-6, or total PUFA were unclear.
This extensive trial data set enabled assessment of effects on neurocognitive illness and cognitive decline not previously adequately assessed. Long-chain omega-3 probably has little or no effect on new neurocognitive outcomes or cognitive impairment.
Long-chain omega-3 supplements do not help older adults protect against cognitive decline.
Fatty acids, omega-3; cognition; dementia; fatty acids, omega-6; fatty acids, unsaturated; meta-analysis

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Association of Nongenetic Factors With Breast Cancer Risk in Genetically Predisposed Groups of Women in the UK Biobank Cohort.
Al Ajmi K, Lophatananon A, Mekli K, Ollier W, Muir KR.
JAMA Netw Open. 2020 Apr 1;3(4):e203760. doi: 10.1001/jamanetworkopen.2020.3760.
PMID: 32329772
The association between noninherited factors, including lifestyle factors, and the risk of breast cancer (BC) in women and the association between BC and genetic makeup are only partly characterized. A study using data on current genetic stratification may help in the characterization.

To examine the association between healthier lifestyle habits and BC risk in genetically predisposed groups.

Data from UK Biobank, a prospective cohort comprising 2728 patients with BC and 88 489 women without BC, were analyzed. The data set used for the analysis was closed on March 31, 2019. The analysis was restricted to postmenopausal white women. Classification of healthy lifestyle was based on Cancer Research UK guidance (healthy weight, regular exercise, no use of hormone replacement therapy for more than 5 years, no oral contraceptive use, and alcohol intake <3 times/wk). Three groups were established: favorable (≥4 healthy factors), intermediate (2-3 healthy factors), and unfavorable (≤1 healthy factor). The genetic contribution was estimated using the polygenic risk scores of 305 preselected single-nucleotide variations. Polygenic risk scores were categorized into 3 tertiles (low, intermediate, and high).

Cox proportional hazards regression was used to assess the hazard ratios (HRs) of the lifestyles and polygenic risk scores associated with a malignant neoplasm of the breast.

Mean (SD) age of the 2728 women with BC was 60.1 (5.5) years, and mean age of the 88 489 women serving as controls was 59.4 (4.9) years. The median follow-up time for the cohort was 10 years (maximum 13 years) (interquartile range, 9.44-10.82 years). Women with BC had a higher body mass index (relative risk [RR], 1.14; 95% CI, 1.05-1.23), performed less exercise (RR, 1.12; 95% CI, 1.01-1.25), used hormonal replacement therapy for longer than 5 years (RR, 1.23; 95% CI, 1.13-1.34), used more oral contraceptives (RR, 1.02; 95% CI, 0.93-1.12), and had greater alcohol intake (RR, 1.11; 95% CI, 1.03-1.19) compared with the controls. Overall, 20 657 women (23.3%) followed a favorable lifestyle, 60 195 women (68.0%) followed an intermediate lifestyle, and 7637 women (8.6%) followed an unfavorable lifestyle. The RR of the highest genetic risk group was 2.55 (95% CI, 2.28-2.84), and the RR of the most unfavorable lifestyle category was 1.44 (95% CI, 1.25-1.65). The association of lifestyle and BC within genetic subgroups showed lower HRs among women following a favorable lifestyle compared with intermediate and unfavorable lifestyles among all of the genetic groups: women with an unfavorable lifestyle had a higher risk of BC in the low genetic group (HR, 1.63; 95% CI, 1.13-2.34), intermediate genetic group (HR, 1.94; 95% CI, 1.46-2.58), and high genetic group (HR, 1.39; 95% CI, 1.11-1.74) compared with the reference group of favorable lifestyle. Intermediate lifestyle was also associated with a higher risk of BC among the low genetic group (HR, 1.40; 95% CI, 1.09-1.80) and the intermediate genetic group (HR, 1.37; 95% CI, 1.12-1.68).

In this cohort study of data on women in the UK Biobank, a healthier lifestyle with more exercise, healthy weight, low alcohol intake, no oral contraceptive use, and no or limited hormonal replacement therapy use appeared to be associated with a reduced level of risk for BC, even if the women were at higher genetic risk for BC.

Dietary Factors and Risks of Cardiovascular Diseases: An Umbrella Review.
Chareonrungrueangchai K, Wongkawinwoot K, Anothaisintawee T, Reutrakul S.
Nutrients. 2020 Apr 15;12(4). pii: E1088. doi: 10.3390/nu12041088. Review.
PMID: 32326404
Unhealthy diet is a significant risk factor for cardiovascular diseases (CVD). Therefore, this umbrella review aims to comprehensively review the effects of dietary factors, including dietary patterns, food groups, and nutrients on CVD risks. Medline and Scopus databases were searched through March 2020. Systematic reviews with meta-analyses (SRMA) of randomized controlled trials (RCTs) or observational studies measuring the effects of dietary factors on CVD risks were eligible. Fifty-four SRMAs, including 35 SRMAs of observational studies, 10 SRMAs of RCTs, and 9 SRMAs of combined RCT and observational studies, were included for review. Findings from the SRMAs of RCTs suggest the significant benefit of Mediterranean and high-quality diets for lowering CVD risk, with pooled risk ratios (RRs) ranging from 0.55 (95%CI: 0.39-0.76) to 0.64 (95%CI: 0.53-0.79) and 0.70 (95%CI: 0.57-0.87), respectively. For food nutrients, two SRMAs of RCTs found that high intake of n-3 polyunsaturated fatty acid (PUFA) significantly reduced CVD risks, with pooled RRs ranging from 0.89 (95%CI: 0.82, 0.98) to 0.90 (95%CI: 0.85-0.96), while evidence of efficacy of n-6 PUFA and combined n-3 and n-6 PUFA were inconsistent. Moreover, results from the SRMAs of RCTs did not find a significant benefit of a low-salt diet and low total fat intake for CVD prevention. For food groups, results from the SRMAs of cohort studies suggest that high intakes of legumes, nuts, and chocolate, as well as a vegetarian diet significantly reduced the risk of coronary heart disease, with pooled RRs of 0.90 (95%CI: 0.84-0.97), 0.68 (95%CI: 0.59-0.78), 0.90 (95%CI: 0.82-0.97), and 0.71 (95%CI: 0.57-0.87), respectively. Healthy dietary patterns had a significant benefit for CVD prevention. With the substitutional and synergistic interactions between different food groups and nutrients, dietary recommendations for CVD prevention should be focused more on healthy dietary patterns than single food groups or nutrients.
cardiovascular disease; dietary factor; umbrella review

Associations of Coffee and Tea Consumption With Survival to Age 90 Years Among Older Women.
Shadyab AH, Manson JE, Luo J, Haring B, Saquib N, Snetselaar LG, Chen JC, Groessl EJ, Wassertheil-Smoller S, Sun Y, Hale L, LeBoff MS, LaCroix AZ.
J Am Geriatr Soc. 2020 Apr 24. doi: 10.1111/jgs.16467. [Epub ahead of print]
PMID: 32329900
Coffee and tea are two of the most widely consumed beverages worldwide and have been associated with reduced risk of mortality in some studies. However, it is unknown whether consumption of these beverages is associated with survival to an advanced age.
To examine associations of coffee and tea consumption with survival to age 90 years.
Prospective cohort study among participants from the Women's Health Initiative, recruited during 1993 to 1998 and followed up until March 31, 2018.
The setting included 40 US clinical centers.
A racially and ethnically diverse cohort of 27,480 older women, aged 65 to 81 years at baseline.
Women were classified as having either survived to age 90 years or died before this age. Consumption of caffeinated and decaffeinated coffee and caffeinated tea was assessed at baseline and categorized as 0, 1, 2 to 3, or 4 or more cups/day. Associations of coffee and tea consumption with survival to age 90 years were examined using logistic regression models adjusted for sociodemographic characteristics, lifestyle behaviors, dietary quality, and chronic disease history.
A total of 14,659 (53.3%) women survived to age 90 years during follow-up. Caffeinated coffee, decaffeinated coffee, or caffeinated tea consumption was not significantly associated with survival to age 90 years after adjusting for confounders. Findings did not significantly vary by smoking, body mass index, or race/ethnicity.
No amount of coffee or tea consumption was associated with late-age survival among older women. These findings may be reassuring to older women who consume coffee and tea as part of their daily diets but do not support drinking these beverages to achieve longevity.
aging; coffee; diet; longevity; tea

AMPK activation by metformin promotes survival of dormant ER+ breast cancer cells.
Hampsch RA, Wells JD, Traphagen NA, McCleery CF, Fields JL, Shee K, Dillon LM, Pooler DB, Lewis LD, Demidenko E, Huang YH, Marotti JD, Goen AE, Kinlaw WB, Miller TW.
Clin Cancer Res. 2020 Apr 22. pii: clincanres.0269.2020. doi: 10.1158/1078-0432.CCR-20-0269. [Epub ahead of print]
PMID: 32321715
Despite adjuvant endocrine therapy for patients with estrogen receptor alpha (ER)-positive breast cancer, dormant residual disease can persist for years and eventually cause tumor recurrence. We sought to deduce mechanisms underlying the persistence of dormant cancer cells to identify therapeutic strategies.
Mimicking the aromatase inhibitor-induced depletion of estrogen levels used to treat patients, we developed preclinical models of dormancy in ER+ breast cancer induced by estrogen withdrawal in mice. We analyzed tumor xenografts and cultured cancer cells for molecular and cellular responses to estrogen withdrawal and drug treatments. Publicly available clinical breast tumor gene expression datasets were analyzed for responses to neoadjuvant endocrine therapy.
Dormant breast cancer cells exhibited upregulated 5' adenosine monophosphate-activated protein kinase (AMPK) levels and activity, and upregulated fatty acid oxidation. While the anti-diabetes AMPK-activating drug metformin slowed the estrogen-driven growth of cells and tumors, metformin promoted the persistence of estrogen-deprived cells and tumors through increased mitochondrial respiration driven by fatty acid oxidation. Pharmacologic or genetic inhibition of AMPK or fatty acid oxidation promoted clearance of dormant residual disease, while dietary fat increased tumor cell survival.
AMPK has context-dependent effects in cancer, cautioning against the widespread use of an AMPK activator across disease settings. The development of therapeutics targeting fat metabolism is warranted in ER+ breast cancer.

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Resistance training attenuates circulating FGF-21 and myostatin and improves insulin resistance in elderly men with and without type 2 diabetes mellitus: A randomized controlled clinical trial.
Shabkhiz F, Khalafi M, Rosenkranz S, Karimi P, Moghadami K.
Eur J Sport Sci. 2020 Apr 28:1-14. doi: 10.1080/17461391.2020.1762755. [Epub ahead of print]
PMID: 32345132
Fibroblast growth factor 21 (FGF-21) and myostatin have been proposed to be potential therapeutic target for insulin resistance in age-related metabolic disorders including type 2 diabetes (T2D). Moreover, despite the potential metabolic effect of resistance training on insulin resistance, aging, and T2D; the effect of this type of exercise training on FGF-21 and myostatin in elderly men with and without T2D are unknown. Forty-four elderly men were assigned to either the RT training (RT; without T2D: 12, with TD2 = 10) or the control group (C; without T2D: 12, with TD2 = 10). The RT group performed 12-wk resistance training intervention, 3 days/wk, 10 repetitions with 70% 1RM. At the baseline, the elderly men with T2D had a higher FGF-21 (p=0.002) and myostatin (p=0.02) concentrations and lower muscle strength (p=0.01) than the elderly men without T2D. RT resulted in significant decrease in FGF-21 and myostatin concentration and increase in muscle strength in both elderly men with and without T2D (P=0.001, for all) as well as decrease in HOMA-IR in only elderly men without T2D (P=0.001). There was no significant difference in the RT-induced FGF-21 reduction between elderly men with and without T2D (p=0.77, p=0.28, respectively), but, RT caused a larger reduction in circulating myostatin in elderly men without T2D than with T2D (P=0.007). Taken together, our results demonstrated that 12 weeks of RT induced an overall significant reduction of FGF-21 and myostatin in elderly men with and without T2D; with higher reduction of myostatin in elderly men without T2D.
Elderly; FGF-21; Myostatin; Resistance Training; Type 2 diabetes

Effect of Increased Daily Water Intake and Hydration on Health in Japanese Adults.
Nakamura Y, Watanabe H, Tanaka A, Yasui M, Nishihira J, Murayama N.
Nutrients. 2020 Apr 23;12(4). pii: E1191. doi: 10.3390/nu12041191.
PMID: 32340375
Increased hydration is recommended as healthy habit with several merits. However, supportive data are sparse. To assess the efficacy of increased daily water intake, we tested the effect of water supplementation on biomarkers in blood, urine, and saliva. Twenty-four healthy Japanese men and 31 healthy Japanese women with fasting blood glucose levels ranging from 90-125 mg/dL were included. An open-label, two-arm, randomized controlled trial was conducted for 12 weeks. Two additional 550 mL bottles of water on top of habitual fluid intake were consumed in the intervention group. The subjects drank one bottle of water (550 mL) within 2 h of waking, and one bottle (550 mL) 2 h before bedtime. Subjects increased mean fluid intake from 1.3 L/day to 2.0 L/day, without changes in total energy intake. Total body water rate increased with associated water supplementation. There were no significant changes in fasting blood glucose and arginine vasopressin levels, but systolic blood pressure was significantly decreased in the intervention group. Furthermore, water supplementation increased body temperature, reduced blood urea nitrogen concentration, and suppressed estimated glomerular filtration rate reduction. Additionally, existence of an intestinal microbiome correlated with decreased systolic blood pressure and increased body temperature. Habitual water supplementation after waking up and before bedtime in healthy subjects with slightly elevated fasting blood glucose levels is not effective in lowering these levels. However, it represents a safe and promising intervention with the potential for lowering blood pressure, increasing body temperature, diluting blood waste materials, and protecting kidney function. Thus, increasing daily water intake could provide several health benefits.
blood pressure; body temperature; hydration; microbiome; water intake

Associations of Coffee Consumption with the Circulating Level of Alanine Aminotransferase and Aspartate Aminotransferase. A Meta-Analysis of Observational Studies.
Ding J, Zhang Y.
J Am Coll Nutr. 2020 Apr 28:1-12. doi: 10.1080/07315724.2020.1755912. [Epub ahead of print]
PMID: 32343195
Background: The associations of coffee consumption with the circulating level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) remains controversial. We conducted a meta-analysis of observational studies to sum up the existing evidence about this matter.Methods: A comprehensive literature-search up to January 2020, using PubMed, Embase and Web of Science databases, was conducted to identify the relevant observational studies that examined the associations of coffee consumption with the circulating level of ALT and AST. The standard mean difference (SMD) for the level of ALT and AST, odds ratio (OR) for the elevated ALT and AST and their corresponding 95% CIs for the highest versus lowest categories of coffee intake were determined.Results: A total of 19 observational studies, which involved 222,067 individuals, were included in this meta-analysis. The combined SMD suggested that coffee consumption was associated with a lower level of ALT (SMD = -0.14, 95% CI: -0.22 to -0.06; p = 0.001) and AST (SMD = -0.17, 95% CI: -0.20 to -0.13; p < 0.001), respectively. Meanwhile, the overall multivariable adjusted OR showed that coffee consumption was inversely associated with the elevated ALT (OR = 0.69, 95% CI: 0.60 to 0.79; p < 0.001) and AST (OR = 0.62, 95% CI: 0.48 to 0.81; p < 0.001), respectively.Conclusion: The results of this meta-analysis suggest that coffee consumption is inversely associated with the circulating level of ALT and AST, and elevated ALT and AST. More randomized controlled trials are needed to elaborate the concerned issues.
Coffee consumption; alanine aminotransferase; aspartate aminotransferase; meta-analysis; observational studies

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Associations between consumption of dietary fibers and the risk of cardiovascular diseases, cancers, type 2 diabetes, and mortality in the prospective NutriNet-Santé cohort.
Partula V, Deschasaux M, Druesne-Pecollo N, Latino-Martel P, Desmetz E, Chazelas E, Kesse-Guyot E, Julia C, Fezeu LK, Galan P, Hercberg S, Mondot S, Lantz O, Quintana-Murci L, Albert ML, Duffy D; Milieu Intérieur Consortium, Srour B, Touvier M.
Am J Clin Nutr. 2020 May 5. pii: nqaa063. doi: 10.1093/ajcn/nqaa063. [Epub ahead of print]
PMID: 32369545
Mounting evidence, yet with varying levels of proof, suggests that dietary fibers (DFs) may exert a protective role against various chronic diseases, but this might depend on the DF type and source.
Our objectives were to assess the associations between the intake of DFs of different types [total (TDF), soluble (SF), insoluble (IF)] and from different sources (fruits, vegetables, whole grains, legumes, potatoes and tubers) and the risk of cardiovascular diseases (CVDs), cancer, type 2 diabetes (T2D), and mortality in the large-scale NutriNet-Santé prospective cohort (2009-2019).
Overall, 107,377 participants were included. Usual DF intake was estimated from validated repeated 24-h dietary records over the first 2 y following inclusion in the cohort. Associations between sex-specific quintiles of DF intake and the risk of chronic diseases and mortality were assessed using multiadjusted Cox proportional hazards models.
T2D risk was inversely associated with TDFs [HR for quintile 5 compared with quintile 1: 0.59 (95% CI: 0.42, 0.82), P-trend <0.001], SFs [HR: 0.77 (0.56, 1.08); P-trend = 0.02], and IFs [HR: 0.69 (0.50, 0.96); P-trend = 0.004]. SFs were associated with a decreased risk of CVD [HR: 0.80 (0.66, 0.98); P-trend = 0.01] and colorectal cancer [HR: 0.41 (0.21, 0.79); P-trend = 0.01]. IFs were inversely associated with mortality from cancer or CVDs [HR: 0.65 (0.45, 0.94); P-trend = 0.02]. TDF intake was associated with a decreased risk of breast cancer [HR:: 0.79 (0.54, 1.13); P-trend = 0.04]. DF intake from fruit was associated with the risk of several chronic diseases.
Our results suggest that DF intake, especially SFs and DFs from fruits, was inversely associated with the risk of several chronic diseases and with mortality. Further studies are needed, involving different types and sources of fiber. Meanwhile, more emphasis should be put on DFs in public health nutrition policies, as DF intake remains below the recommended levels in many countries.
cancers; cardiovascular diseases; dietary fibers; mortality; prospective cohort; type 2 diabetes

Polyphenols intervention is an effective strategy to ameliorate inflammatory bowel disease: a systematic review and meta-analysis.
Liu F, Li D, Wang X, Cui Y, Li X.
Int J Food Sci Nutr. 2020 May 5:1-12. doi: 10.1080/09637486.2020.1760220. [Epub ahead of print]
PMID: 32369394
Whether polyphenols could ameliorate inflammatory bowel disease (IBD) is still conflicting. To explore the efficacy of polyphenols as an adjuvant therapy for IBD, we conducted this systematic review and meta-analysis. Literature search was performed using PubMed, Web of Science, Scopus and Cochrane databases. Finally, 12 randomized controlled trials (RCTs) were included. In contrast to control group, curcumin treatment significantly improved clinical remission in intention-to-treat (ITT) (OR = 3.36, 95% CI: 1.09-10.37) and per-protocol (PP) analysis (OR = 5.13, 95% CI: 1.84-14.27). Meanwhile, curcumin could significantly ameliorate endoscopic remission (OR = 5.69, 95% CI: 1.28-25.27) and clinical response (OR = 4.69, 95% CI: 1.03-21.47) in PP analysis. Heterogeneity was present across the studies. In conclusions, polyphenols might be an effective adjuvant treatment for ameliorating IBD. Considering the relatively few studies included in our present study, further clinical trials are required to verify the effects of polyphenols on IBD.
Inflammatory bowel disease; RCT; meta-analysis; polyphenols

EPA is Cardioprotective in Male Rats Subjected to Sepsis, but ALA Is Not Beneficial.
Leger T, Jouve C, Hininger-Favier I, Rigaudiere JP, Capel F, Sapin V, Moreau C, Charrier A, Demaison L.
Antioxidants (Basel). 2020 Apr 29;9(5). pii: E371. doi: 10.3390/antiox9050371.
PMID: 32365668
It has been proven that dietary eicosapentaenoic acid (C20:5 n-3 or EPA) protects the heart against the deleterious effects of sepsis in female rats. We do not know if this is the case for male rodents. In this case, the efficiency of other n-3 polyunsaturated fatty acids (PUFAs) remains to be determined in both female and male rats. This study aimed at (i) determining whether dietary EPA is cardioprotective in septic male rats; (ii) evaluating the influence of dietary α-linolenic (C18:3 n-3 or ALA) on cardiac function during this pathology; and (iii) finding out the physiological and molecular mechanisms responsible for the observed effects. Sixty male rats were divided into three dietary groups. The animals were fed a diet deficient in n-3 PUFAs (DEF group), a diet enriched with ALA (ALA group) or a diet fortified with EPA (EPA group) for 6 weeks. Thereafter, each group was subdivided into 2 subgroups, one being subjected to cecal ligation and puncture (CLP) and the other undergoing a fictive surgery. Cardiac function was determined in vivo and ex vivo. Several parameters related to the inflammation process and oxidative stress were determined. Finally, the fatty acid compositions of circulating lipids and cardiac phospholipids were evaluated. The results of the ex vivo situation indicated that sepsis triggered cardiac damage in the DEF group. Conversely, the ex vivo data indicated that dietary ALA and EPA were cardioprotective by resolving the inflammation process and decreasing the oxidative stress. However, the measurements of the cardiac function in the in vivo situation modulated these conclusions. Indeed, in the in vivo situation, sepsis deteriorated cardiac mechanical activity in the ALA group. This was suspected to be due to a restricted coronary flow which was related to a lack of cyclooxygenase substrates in membrane phospholipids. Finally, only EPA proved to be beneficial in sepsis. Its action necessitates both resolution of inflammation and increased coronary perfusion. In that sense, dietary ALA, which does not allow the accumulation of vasodilator precursors in membrane lipids, cannot be protective during the pathology.
heart; inflammation; n-3 polyunsaturated fatty acids; oxidative stress; sepsis

Plant-sourced cooking oil consumption is associated with lower total mortality in a longitudinal nationwide cohort study.
Wu F, Mao L, Zhuang P, Chen X, Jiao J, Zhang Y.
Clin Nutr. 2020 Apr 2. pii: S0261-5614(20)30149-7. doi: 10.1016/j.clnu.2020.03.031. [Epub ahead of print]
PMID: 32359931
Evidence linking individual cooking oil consumption with total mortality is limited in China. The aim of this study was to examine the associations of intakes of plant-sourced and animal-sourced cooking oils with total mortality in a Chinese nationwide cohort.
We analyzed data from 14,305 adults aged ≥20 y at entry in the China Health and Nutrition Survey (CHNS). The 3-day 24-h dietary records were used to collect dietary information. Cox proportional hazards regression models were established to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause death.
Overall 1006 deaths were documented during a median of 14 years (199,091 person-years) of follow-up. Multivariate-adjusted HRs (95% CIs) of total mortality via comparing the highest tertile of cooking oil consumption with no consumption were 0.86 (0.70-1.06) for lard, 0.59 (0.47-0.74) for peanut oil, 0.71 (0.54-0.93) for soybean oil, 0.76 (0.61-0.94) for canola oil, 0.71 (0.50-0.99) for salad oil, and 0.59 (0.44-0.79) for other plant cooking oils. Replacing animal cooking oils with 1 tablespoon/d of total plant cooking oils or other plant cooking oils was related to 4% or 17% lower total mortality, respectively, while consumption of peanut oil or salad oil in replacement of animal cooking oils had a marginal inverse association with total mortality.
Intakes of plant-sourced cooking oils, including peanut oil, soybean oil, canola oil, salad oil, and other plant cooking oils and substituting plant cooking oils for animal cooking oils were associated with lower total mortality among general Chinese population (NCT03259321).
Animal-sourced cooking oils; China Health and Nutrition Survey; Nationwide cohort; Plant-sourced cooking oils; Total mortality

Maternal visceral adipose tissue during the first half of pregnancy predicts gestational diabetes at the time of delivery - a cohort study.
Rocha ADS, Bernardi JR, Matos S, Kretzer DC, Schöffel AC, Goldani MZ, de Azevedo Magalhães JA.
PLoS One. 2020 Apr 30;15(4):e0232155. doi: 10.1371/journal.pone.0232155. eCollection 2020.
PMID: 32353068
Gestational diabetes mellitus (GDM) is a common condition, often associated with high maternal and fetal morbidity. The use of new tools for early GDM screening can contribute to metabolic control to reduce maternal and fetal risk. This study aimed to ascertain whether maternal visceral adipose tissue (VAT) measurement by ultrasound during the first half of pregnancy can predict the occurrence of GDM during the third trimester.
A prospective cohort study of 133 pregnant women with gestational age ≤20 weeks in an outpatient setting. VAT depth was measured by ultrasound at the maternal periumbilical region. GDM status was obtained through hospital charts during hospitalization to delivery. A Receiver Operator Characteristic (ROC) curve was used to determine the optimum threshold to predict GDM.
According to the ROC curve, a 45mm threshold was identified as the best cut-off value, with 66% of accuracy to predict GDM. Crude and adjusted odds ratios (OR) for GDM were 13.4 (95%CI 2.9-61.1) and 8.9 (95%CI 1.9-42.2), respectively. A similar result was obtained among pre-gravid non-obese women, with crude and adjusted OR of 16.6 (95%CI 1.9-142.6) and 14.4 (95%CI 1.7-125.7), respectively. Among pre-gravid obese patients, a 45mm threshold did not reach statistical significance to predict GDM.
The high and significant OR found before and after adjustments provides additional evidence of a strong association between VAT and GDM. It appears that VAT measurement during the first half of pregnancy has great potential in identifying non-obese women at high risk for GDM. This evidence can assist obstetricians in correctly allocating resources among populations of pregnant women at risk, determined not only by pre-gravid body mass index (BMI).

Red Cell Distribution Width is Associated with Future Incidence of Abdominal Aortic Aneurysm in a Population-Based Cohort Study.
Xiao J, Borné Y, Gottsäter A, Pan J, Acosta S, Engström G.
Sci Rep. 2020 Apr 29;10(1):7230. doi: 10.1038/s41598-020-64331-7.
PMID: 32350354
Red cell distribution width (RDW) has been suggested to have a predictive potential for several cardiovascular diseases, but its association with abdominal aortic aneurysm (AAA) is unknown. We examined whether RDW is associated with the risk of AAA among 27,260 individuals from the population-based Malmö Diet and Cancer Study cohort. Data of baseline characteristics were collected during 1991-1996. Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for AAA across quartiles of RDW. During a median follow-up of 21.7 years, 491 subjects developed AAA. After adjustment for other confounding factors, participants in the highest quartile of RDW experienced 61% increased risk of AAA as compared to those with the lowest quartile (HR = 1.61, CI = 1.20, 2.12). RDW showed similar relationship with severe (i.e. ruptured or surgically repaired) AAA or non-severe AAA (adjusted HR 1.58 and 1.60, respectively). The observed association between RDW and AAA risk was significant in current smokers (adjusted HR = 1.68, CI = 1.18, 2.38) but not in former smokers (adjusted HR = 1.13, CI = 0.72, 1.79), or never-smokers (adjusted HR = 1.77, CI = 0.74, 4.22). Elevated RDW is associated with increased future incidence of AAA, however the causal and pathophysiological mechanisms remain to be explored.

Açaí (Euterpe oleracea Mart.) and juçara (Euterpe edulis Mart.) juices improved HDL-c levels and antioxidant defense of healthy adults in a 4-week randomized cross-over study.
de Liz S, Cardoso AL, Copetti CLK, Hinnig PF, Vieira FGK, da Silva EL, Schulz M, Fett R, Micke GA, Di Pietro PF.
Clin Nutr. 2020 Apr 11. pii: S0261-5614(20)30162-X. doi: 10.1016/j.clnu.2020.04.007. [Epub ahead of print]
PMID: 32349893
To evaluate the effects of moderate-term açaí and juçara juice intake on fasting glucose, lipid profile, and oxidative stress biomarkers in healthy subjects.
A randomized cross-over study was performed with 30 healthy adults. The subjects were assigned to drink 200 mL/day of açaí or juçara juice for four weeks with a 4-week washout period. Before and after each nutritional intervention, blood samples were obtained to evaluate the outcomes: fasting glucose, total cholesterol, triglycerides, high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), small, dense LDL-c (sd-LDL-c), total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), uric acid, and activity of the enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx).
After four weeks, açaí and juçara juices increased the concentrations of HDL-c by 7.7% and 11.4%, respectively (P < 0.05). In addition, açaí juice intake promoted significant increases in TAC (66.7%), CAT (275.1%), GPx (15.3%), and a decrease in OSI (55.7%) compared to baseline (P < 0.05 for all). Juçara juice intake significantly increased CAT activity (~15.0%) in relation to baseline. No significant intergroup differences were observed for any outcomes (P > 0.05).
The results indicated a positive impact of regular consumption of açaí and juçara juices on the HDL-c levels, as well as on the antioxidant enzyme activities, which may contribute to cardiovascular health.
Anthocyanins; Antioxidant activity; Cholesterol; Intervention study; Lipoproteins

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Bean, fruit, and vegetable fiber, but not cereal fiber are associated with reduced mortality in Japan.
Jenkins DJA, Srichaikul KK, Kendall CWC, Sievenpiper JL.
Am J Clin Nutr. 2020 May 1;111(5):941-943. doi: 10.1093/ajcn/nqaa045. No abstract available.
PMID: 32219427
Dietary fiber intake and total and cause-specific mortality: the Japan Public Health Center-based prospective study.
Katagiri R, Goto A, Sawada N, Yamaji T, Iwasaki M, Noda M, Iso H, Tsugane S.
Am J Clin Nutr. 2020 May 1;111(5):1027-1035. doi: 10.1093/ajcn/nqaa002.
PMID: 31990973
An inverse association has been shown between dietary fiber intake and several noncommunicable diseases. However, evidence of this effect remains unclear in the Asian population.
We examined the association between dietary fiber intake and all-cause and cause-specific mortality, as well as the association between fiber intake from dietary sources and all-cause mortality.
We conducted a large-scale population-based cohort study (Japan Public Health Center-based prospective study). A validated questionnaire with 138 food items was completed by 92,924 participants (42,754 men and 50,170 women) aged 45-74 y. Dietary fiber intake was calculated and divided into quintiles. HR and 95% CI of total and cause-specific mortality were reported.
During the mean follow-up of 16.8 y, 19,400 deaths were identified. In multivariable adjusted models, total, soluble, and insoluble fiber intakes were inversely associated with all-cause mortality. The HRs of total mortality in the highest quintile of total fiber intake compared with the lowest quintile were 0.77 (95% CI: 0.72, 0.82; Ptrend <0.0001) in men and 0.82 (95% CI: 0.76, 0.89; Ptrend <0.0001) in women. Increased quintiles of dietary fiber intake were significantly associated with decreased mortality due to total cardiovascular disease (CVD), respiratory disease, and injury in both men and women, whereas dietary fiber intake was inversely associated with cancer mortality in men but not women. Fiber from fruits, beans, and vegetables, but not from cereals, was inversely associated with total mortality.
In this large-scale prospective study with a long follow-up period, dietary fiber was inversely associated with all-cause mortality. Since intakes of dietary fiber, mainly from fruits, vegetables, and beans were associated with lower all-cause mortality, these food sources may be good options for people aiming to consume more fiber.
Asian population; beans; cohort study; dietary fiber intake; food source; fruits and vegetables; mortality; noncommunicable disease

Protection against renal ischemia and reperfusion injury by short-term time-restricted feeding involves the mitochondrial unfolded protein response.
Rojas-Morales P, León-Contreras JC, Granados-Pineda J, Hernandez-Pando R, Gonzaga G, Sánchez-Lozada LG, Osorio-Alonso H, Pedraza-Chaverri J, Tapia E.
Free Radic Biol Med. 2020 May 3. pii: S0891-5849(20)30565-7. doi: 10.1016/j.freeradbiomed.2020.04.025. [Epub ahead of print]
PMID: 32376457
Food restriction improves metabolic health and increases resistance to stress in experimental animals. However, most studies have focused on long-term dietary restriction protocols consisting of several weeks or months of limited food ingestion. Here it was investigated the impact of 2-h time-restricted feeding (TRF) for one week on stress resistance in a rat model of kidney injury induced by ischemia and reperfusion. At baseline, TRF reduced blood glucose, increased β-hydroxybutyrate and improved body composition in male Wistar rats. Importantly, implementing the one-week TRF schedule before ischemia significantly improved renal function, suppressed tubular injury, prevented the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and inhibited the development of interstitial fibrosis. These benefits were related to increased antioxidant protection, reduction in dynamin-related protein 1 (DRP1)-mediated mitochondrial fragmentation and modulation of the mitochondrial unfolded protein response (UPRmt). Specifically, preoperative TRF boosted the activation of the UPRmt in the acute phase after renal IR while promoted its resolution at the stage of fibrosis. Our study indicates that dietary preconditioning by short-term TRF improves the outcome of renal ischemia and reperfusion injury, and suggests that an optimal intervention that promotes kidney protection may not necessarily require adherence to restrictive diets for prolonged periods of time.
Ischemia and reperfusion; Mitochondrial unfolded protein response; Oxidative stress; Renal fibrosis; Time-restricted feeding

Effects of timing of moderate exercise in the evening on sleep and subsequent dietary intake in lean, young, healthy adults: randomized crossover study.
Saidi O, Davenne D, Lehorgne C, Duché P.
Eur J Appl Physiol. 2020 May 5. doi: 10.1007/s00421-020-04386-6. [Epub ahead of print]
PMID: 32372217
This work studied the acute effects in healthy adults of evening exercise timing on their quality of sleep and dietary intake over the following 12 h.
Sixteen men and women, (age: 22.3 ± 1.4 years; BMI: 20.8 ± 1.4 kg/m2, intermediate chronotype) took part in three randomized crossover sessions spread over three consecutive weeks: control session (CTL), 1 h exercise session at 6:30 pm (E6:30) and 1 h exercise session at 8:30 pm (E8:30), in which exercise finished 4 h and 2 h before habitual bedtime, respectively. Exercise was an outdoor run at 60% HRmaxth. Energy expenditure and sleep were ambulatories monitored by accelerometry under free-living condition. Ad-libitum dinner and breakfast were used to measure subsequent energy intake and proportion of that energy derived from each macronutrient.
Evening exercise did not disrupt sleep. Improvement in sleep quality compared to the control condition was observed only when exercise was performed 4 h before habitual bedtime (WASO: p < 0.01; SE: p < 0.02). Interestingly, our results give insight into differences in sleep parameters response to evening exercise between habitually poor and good sleepers mainly when it comes to sleep efficiency and wake after sleep onset (all p < 0.01). There was no difference in calorie intake from ad-libitum dinner and breakfast. However, an association between improvement in sleep efficiency from acute exercise and reduction of energy intake the following morning was found.
Early evening exercise could offer a useful alternative for achieving better sleep in healthy young adults especially when it comes to poor sleepers.
Accelerometry; Ad-libitum; College student; Energy balance; Sleep efficiency

The association of outdoor temperature with blood pressure, and its influence on future cardio-cerebrovascular disease risk in cold areas.
Yu B, Jin S, Wang C, Yan S, Zhou X, Cui X, Tang Z, Luan Q, Guo Y, Bian Z, Li L, Chen Z, Na L.
J Hypertens. 2020 Jun;38(6):1080-1089. doi: 10.1097/HJH.0000000000002387.
PMID: 32371798
To explore whether lower outdoor temperature increases cardio-cerebrovascular disease risk through regulating blood pressure and whether indoor heating in winter is beneficial to prevent cardio-cerebrovascular disease in cold areas.
We analyzed the data of 38 589 participants in Harbin from the China Kadoorie Biobank (CKB) during 2004-2008, with an average of 7.14-year follow-up. Linear regression analysis was performed to estimate the relationship between outdoor temperature and blood pressure. Cox regression analysis and logistic regression analysis were used to analyze the association of blood pressure with cardio-cerebrovascular event risk. Mediation analysis was performed to explore the role of blood pressure in the association between outdoor temperature and cardio-cerebrovascular events risk.
There was an increase of 6.7 mmHg in SBP and 2.1 mmHg in DBP for each 10 °C decrease in outdoor temperature when outdoor temperature was higher than 5 °C. There was an inverse association between outdoor temperature and cardio-cerebrovascular event morbidity. The increases in blood pressure and cardio-cerebrovascular event morbidity were attenuated in months when central heating was fully provided. Participants with hypertension have higher risks of cardio-cerebrovascular disease (hazard ratio 1.347; 95% CI 1.281--1.415), CVD (hazard ratio 1.347; 95% CI 1.282--1.416), MACE (hazard ratio 1.670; 95% CI 1.560--1.788) and stroke (hazard ratio 1.683; 95% CI 1.571--1.803). Mediation analysis demonstrated that the association between outdoor temperature and cardio-cerebrovascular events risk was potentially mediated by blood pressure.
Temperature-driven blood pressure potentially mediates the association between outdoor temperature and cardio-cerebrovascular events risk. Indoor heating in winter is probably beneficial to cardio-cerebrovascular disease prevention by inhibition of blood pressure increase.

Chronic effects and optimal dosage of strength training on SBP and DBP: a systematic review with meta-analysis.
Oliver-Martínez PA, Ramos-Campo DJ, Martínez-Aranda LM, Martínez-Rodríguez A, Rubio-Arias JÁ.
J Hypertens. 2020 May 4. doi: 10.1097/HJH.0000000000002459. [Epub ahead of print]
PMID: 32371773
Hypertension is a disease affecting a large part of the world's population that causes millions of deaths annually. Physical exercise is proposed as an alternative to pharmacologic therapies used to reduce blood pressure. The main objective was to compare the effect of different types of strength training in blood pressure, as well as to analyse several variables that can modify the effect of strength training not combined with medication in SBP and DBP (SBP-DBP).
The search was carried out in two scientific databases: PubMed and Web of Science. Articles were included following three criteria: analysing the chronic effect of strength training in blood pressure; the studies were conducted at least during 4 weeks; and the articles were published in English.
The analysis showed a significant decrease of blood pressure for all types of training. The effect on SBP was greater when training without medication was carried out with isometric exercises than when training was performed with dynamic exercises. Moreover, the effects were no longer significant when the duration of the training programme exceeded 20 weeks as well as when training frequency was lower than three times per week were found.
Strength training is effective in reducing both blood pressures (SBP-DBP). Training programmes, consisting of dynamic strength training without medication at a moderate intensity and with a frequency of three times per week, seem to be optimal in order to reduce blood pressure.

Effects of waist to height ratio, waist circumference, body mass index on the risk of chronic diseases, all-cause, cardiovascular and cancer mortality.
Lo K, Huang YQ, Shen G, Huang JY, Liu L, Yu YL, Chen CL, Feng YQ.
Postgrad Med J. 2020 May 5. pii: postgradmedj-2020-137542. doi: 10.1136/postgradmedj-2020-137542. [Epub ahead of print]
PMID: 32371408
Given the fat redistribution in later stages of life, how the associations between abdominal obesity and the risk of morbidity and mortality have changed with age have not been elucidated, especially for waist to height ratio (WHtR).
To compare the strength of association between obesity indices and chronic diseases at baseline, and the subsequent mortality risk among US adults.
We included 21 109 participants from National Health and Nutrition Examination Survey 1999-2014. We performed logistic regression and receiver operating curve analysis to examine the discriminatory power of obesity indicators on cardiometabolic diseases and cancer at baseline. Sex-stratified and age-stratified Cox models were constructed to explore the prospective association between obesity indices and all-cause, cardiovascular and cancer mortality.
Elevated WHtR, elevated waist circumference (WC) and body mass index (BMI)-classified obesity are associated with higher odds of hypertension (OR: 1.37-2.13), dyslipidemia (OR: 1.06 to 1.75, all p<0.05) and diabetes (OR: 1.40-3.16, all p<0.05). WHtR had significantly better discriminatory power to predict cardiometabolic health than BMI, especially for diabetes (area under the curve: 0.709 vs 0.654). After multivariable adjustment, all obesity indicators are associated with lower risk of all-cause mortality among females aged ≥65 years (HR: 0.64 to 0.85), but the association was only significant for BMI when obesity indicators were mutually adjusted (HR: 0.79).
CWHtR and WC appeared to be the better indicators for cardiometabolic health than BMI. However, BMI had a stronger and inverse association with a greater risk of all-cause mortality among older females.

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Lipoprotein Particle Predictors of Arterial Stiffness after 17 Years of Follow Up: The Malmö Diet and Cancer Study.
Hartz J, Krauss RM, Göttsater M, Melander O, Nilsson P, Mietus-Snyder M.
Int J Vasc Med. 2020 Apr 28;2020:4219180. doi: 10.1155/2020/4219180. eCollection 2020.
PMID: 32411471
Central arterial stiffness is a surrogate of cardiovascular risk and predicts cardiovascular mortality. Apolipoprotein B lipoproteins are also established cardiovascular risk factors. It is not known whether specific lipoprotein subclasses measured in the Malmö Diet and Cancer Study and previously shown to be associated with coronary heart disease also predict arterial stiffening after a mean period of 17 years.
Lipoprotein particle analysis was performed on 2,505 men and women from Malmö, Sweden, from 1991 to 1994, and arterial stiffness was assessed by carotid-femoral pulse wave velocity (c-fPWV) on this same cohort from 2007 to 2012. Associations between c-fPWV and lipoprotein particles were determined with multiple linear regression, controlling for sex, presence of diabetes, waist-to-hip circumference, and smoking status at baseline, as well as heart rate (measured at the carotid artery), mean arterial pressure, antihypertensive and lipid-lowering medications, C-reactive protein (CRP), and age at the time of c-fPWV measurement.
The results confirm that triglycerides (TG) and high-density lipoprotein cholesterol (HDL-c) but not low-density lipoprotein cholesterol (LDL-c) predict c-fPWV. We identify a positive predictive association for very small, small, and medium (high risk), but not large LDL particles. There was a negative association for large HDL particles. The relationships between c-fPWV and high-risk LDL particles were unaffected by adjusting for LDL-c or CRP and were only mildly attenuated by adjusting for the homeostatic model for insulin resistance (HOMA-IR). Due to the collinearity of very small, small, and medium LDL particles and dyslipidemia (elevated TG and decreased HDL-c), the observed relationship between c-fPWV and high-risk LDL particles became insignificant after controlling for the concentration of HDL-c, large cholesterol-rich HDL particles, and TG.
The development of central arterial stiffness previously associated with combined dyslipidemia may be mediated in part by LDL particles, particularly the very small-, small-, and medium-sized LDL particles.

Do We Need to Be Concerned about Bone Mineral Density in Vegetarians and Vegans?
Shapses SA.
J Nutr. 2020 May 1;150(5):983-984. doi: 10.1093/jn/nxaa095. No abstract available.
PMID: 32271915
Differences in Bone Mineral Density between Adult Vegetarians and Nonvegetarians Become Marginal when Accounting for Differences in Anthropometric Factors.
Karavasiloglou N, Selinger E, Gojda J, Rohrmann S, Kühn T.
J Nutr. 2020 May 1;150(5):1266-1271. doi: 10.1093/jn/nxaa018.
PMID: 32055831
Persons following plant-based diets have lower bone mineral density (BMD) and higher fracture risk, possibly due to suboptimal nutrient supply. However, anthropometric measures were not considered as potential confounders in many previous studies, and body mass index (BMI) is positively associated with BMD but also generally lower among vegans and vegetarians.
Our objective was to investigate if BMD measurements differ between vegetarians and nonvegetarians from the adult general population when accounting for important determinants of BMD, especially BMI and waist circumference.
Using data from the NHANES (cycles 2007-2008 and 2009-2010), we evaluated the differences in BMD (femoral neck, total femoral, and total lumbar spine) between adult vegetarians and nonvegetarians. Linear regression models were used to determine the associations between BMD and diet. Statistical models were adjusted for important factors, i.e., age, sex, race/ethnicity, smoking status, alcohol consumption, serum vitamin D and calcium concentrations, waist circumference, and BMI.
In statistical models adjusted for age, sex, race/ethnicity, menopausal status, and education level, BMD values were significantly lower among vegetarians than among nonvegetarians (P < 0.001). These differences were attenuated upon adjustment for lifestyle factors, and became statistically nonsignificant upon adjustment for anthropometric variables (BMI and waist circumference) for femoral neck (0.77 compared with 0.79 g/cm2 among vegetarians versus nonvegetarians, P = 0.10) and total femoral BMD (0.88 compared with 0.90 g/cm2, P = 0.12). A small but statistically significant difference remained for total lumbar spine BMD (1.01 compared with 1.04 g/cm2, P = 0.005).
These findings suggest that lower BMD among adult vegetarians is in larger parts explained by lower BMI and waist circumference.
adults; anthropometry; body mass index; bone mineral density; diet; plant-based diets; vegetarians

Snacking on whole almonds for 6 weeks improves endothelial function and lowers LDL cholesterol but does not affect liver fat and other cardiometabolic risk factors in healthy adults: the ATTIS study, a randomized controlled trial.
Dikariyanto V, Smith L, Francis L, Robertson M, Kusaslan E, O'Callaghan-Latham M, Palanche C, D'Annibale M, Christodoulou D, Basty N, Whitcher B, Shuaib H, Charles-Edwards G, Chowienczyk PJ, Ellis PR, Berry SEE, Hall WL.
Am J Clin Nutr. 2020 May 15. pii: nqaa100. doi: 10.1093/ajcn/nqaa100. [Epub ahead of print]
PMID: 32412597
There is convincing evidence that daily whole almond consumption lowers blood LDL cholesterol concentrations, but effects on other cardiometabolic risk factors such as endothelial function and liver fat are still to be determined.
We aimed to investigate whether isoenergetic substitution of whole almonds for control snacks with the macronutrient profile of average snack intakes, had any impact on markers of cardiometabolic health in adults aged 30-70 y at above-average risk of cardiovascular disease (CVD).
The study was a 6-wk randomized controlled, parallel-arm trial. Following a 2-wk run-in period consuming control snacks (mini-muffins), participants consumed either whole roasted almonds (n = 51) or control snacks (n = 56), providing 20% of daily estimated energy requirements. Endothelial function (flow-mediated dilation), liver fat (MRI/magnetic resonance spectroscopy), and secondary outcomes as markers of cardiometabolic disease risk were assessed at baseline and end point.
Almonds, compared with control, increased endothelium-dependent vasodilation (mean difference 4.1%-units of measurement; 95% CI: 2.2, 5.9), but there were no differences in liver fat between groups. Plasma LDL cholesterol concentrations decreased in the almond group relative to control (mean difference -0.25 mmol/L; 95% CI: -0.45, -0.04), but there were no group differences in triglycerides, HDL cholesterol, glucose, insulin, insulin resistance, leptin, adiponectin, resistin, liver function enzymes, fetuin-A, body composition, pancreatic fat, intramyocellular lipids, fecal SCFAs, blood pressure, or 24-h heart rate variability. However, the long-phase heart rate variability parameter, very-low-frequency power, was increased during nighttime following the almond treatment compared with control (mean difference 337 ms2; 95% CI: 12, 661), indicating greater parasympathetic regulation.
Whole almonds consumed as snacks markedly improve endothelial function, in addition to lowering LDL cholesterol, in adults with above-average risk of CVD.This trial was registered at clinicaltrials.gov as NCT02907684.
almonds; cardiometabolic disease; cardiovascular disease; dietary intervention; endothelial function; liver fat

Female reproductive factors and the risk of dementia: A nationwide cohort study.
Yoo JE, Shin DW, Han K, Kim D, Won HS, Lee J, Kim S, Nam GE, Park HS.
Eur J Neurol. 2020 May 12. doi: 10.1111/ene.14315. Online ahead of print.
PMID: 32396982
Background: To investigate whether female reproductive factors are associated with dementia.
Methods: We identified 4,696,633 postmenopausal women without dementia using the Korean National Health Insurance System database. Data on reproductive factors were collected using self-administered questionnaire. Dementia was determined using dementia diagnosis codes and anti-dementia drugs prescription. Cox proportional hazards regression was conducted to assess hazard ratio (HR) for dementia according to reproductive factors.
Results: During the median follow-up of 5.74 years, there were 212,227 new cases of all-cause dementia (4.5%), 162,901 cases of Alzheimer's disease (3.5%), and 24,029 cases of vascular dementia (0.5%). The HR of dementia was 1.15 (95% confidence intervals [CI] 1.03-1.16) for menarcheal age ≥ 17 years compared with menarcheal age 13-14 years, 0.79 (0.77-0.81) for menopausal age ≥ 55 years compared with menopausal age < 40 years, and 0.81 (0.79-0.82) for fertility duration ≥ 40 years compared with fertility duration < 30 years. While having 1 parity (HR 0.89, 95% CI 0.85-0.94) and breast feeding < 6 months (HR 0.92, 95% CI 0.88-0.95) was associated with lower risk of dementia, having ≥ 2 parity (HR 1.04, 95% CI 0.99-1.05) and breast feeding ≥ 12 months (HR 1.14, 95% CI 1.01-1.07) were associated with higher risk of dementia than women without parity or breast feeding history. Use of hormone replacement therapy and oral contraceptives independently reduced the dementia risk by 15% and 10%, respectively.
Conclusions: Female reproductive factors are independent risk factors for dementia incidence, with higher risk associated with shorter lifetime endogenous estrogen exposure.
Keywords: Dementia; Duration of fertility; Hormone replacement therapy; Menarche; Menopause.

Sugar-Sweetened Beverage Intake and Cardiovascular Disease Risk in the California Teachers Study.
Pacheco LS, Lacey JV Jr, Martinez ME, Lemus H, Araneta MRG, Sears DD, Talavera GA, Anderson CAM.
J Am Heart Assoc. 2020 May 13:e014883. doi: 10.1161/JAHA.119.014883. Online ahead of print.
PMID: 32397792
Background Sugar-sweetened beverage (SSB) consumption has been associated with cardiometabolic risk. However, the association between total and type of SSB intake and incident cardiovascular disease (CVD) end points such as myocardial infarction, stroke, and revascularization is limited. Methods and Results We examined the prospective association of baseline SSB consumption with incident CVD in 106 178 women free from CVD and diabetes mellitus in the CTS (California Teachers Study), a cohort of female teachers and administrators, followed since 1995. SSBs were defined as caloric soft drinks, sweetened bottled waters or teas, and fruit drinks, and derived from a self-administered food frequency questionnaire. CVD end points were based on annual linkage with statewide inpatient hospitalization records. Cox proportional hazards models were used to assess the association between SSB consumption and incident CVD. A total of 8848 CVD incident cases were documented over 20 years of follow-up. After adjusting for potential confounders, we observed higher hazard ratios (HRs) for CVD (HR, 1.19; 95% CI, 1.06-1.34), revascularization (HR, 1.26; 95% CI, 1.04-1.54]), and stroke (HR, 1.21; 95% CI, 1.04-1.41) in women who consumed ≥1 serving per day of SSBs compared with rare/never consumers. We also observed a higher risk of CVD in women who consumed ≥1 serving per day of fruit drinks (HR, 1.42; 95% CI, 1.00-2.01 [P trend=0.021]) and caloric soft drinks (HR, 1.23; 95% CI, 1.05-1.44 [P trend=0.0002]), compared with rare/never consumers. Conclusions Consuming ≥1 serving per day of SSB was associated with CVD, revascularization, and stroke. SSB intake might be a modifiable dietary target to reduce risk of CVD among women.
Keywords: cardiovascular disease; nutritional epidemiology; observational study; sugar‐sweetened beverages.

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Step by Step: Association of Device-Measured Daily Steps With All Cause-Mortality - a Prospective Cohort Study.
Hansen BH, Dalene KE, Ekelund U, Fagerland MW, Kolle E, Steene-Johannessen J, Tarp J, Anderssen SA.
Scand J Med Sci Sports. 2020 May 19. doi: 10.1111/sms.13726. Online ahead of print.
PMID: 32427398
Introduction: Walking is free, does not require special training, and can be done almost everywhere. Therefore, walking is a feasible behavior on which to tailor public health messages. This study assess the prospective association and dose-response relationship between daily steps and all-cause mortality.
Materials and methods: Daily steps were measured by waist-mounted accelerometers in 2,183 individuals (53% women) for seven consecutive days at baseline (2008-09). Participants were followed for a median period of 9.1 years and associations between steps and all-cause mortality determined by registry linkage were assessed using Cox proportional hazard regression with adjustment for relevant covariates.
Results: Mean age was 57.0 (SD 10.9) years at baseline. Median (IQR) daily steps across ascending quartiles were 4651 (3495-5325), 6862 (6388-7350), 8670 (8215-9186), and 11467 (10556-13110), respectively. During follow-up, 119 individuals died (68% men). Higher number of daily steps was associated with a lower risk of all-cause mortality with hazard ratios of 1.00 (referent), 0.52 (0.29-0.93), 0.50 (0.27-0.94), and 0.43 (0.21-0.88) across ascending quartiles of daily steps in the multivariable-adjusted model with follow-up commencing two years after baseline. Risk differences per 1000 individuals for ascending quartiles were 6.8 (2.9-9.3), 7.1 (0.8-11.1), and 8.0 (1.7-12.1), respectively.
Conclusions: Daily steps were associated with lower mortality risk in a non-linear dose-response pattern. The risk is almost halved when comparing the least active referent against the second quartile equivalent to a difference of about 2200 daily steps. Encouraging those least active to increase their daily steps may have substantial public health implications.
Keywords: Steps; all-cause mortality; device-measured; prospective cohort; walking.

Association of dairy consumption with metabolic syndrome, hypertension and diabetes in 147 812 individuals from 21 countries.
Bhavadharini B, Dehghan M, Mente A, Rangarajan S, Sheridan P, Mohan V, Iqbal R, Gupta R, Lear S, Wentzel-Viljoen E, Avezum A, Lopez-Jaramillo P, Mony P, Varma RP, Kumar R, Chifamba J, Alhabib KF, Mohammadifard N, Oguz A, Lanas F, Rozanska D, Bengtsson Bostrom K, Yusoff K, Tsolkile LP, Dans A, Yusufali A, Orlandini A, Poirier P, Khatib R, Hu B, Wei L, Yin L, Deeraili A, Yeates K, Yusuf R, Ismail N, Mozaffarian D, Teo K, Anand SS, Yusuf S.
BMJ Open Diabe
PMID: 32423962
Objective: Our aims were to assess the association of dairy intake with prevalence of metabolic syndrome (MetS) (cross-sectionally) and with incident hypertension and incident diabetes (prospectively) in a large multinational cohort study.
Methods: The Prospective Urban Rural Epidemiology (PURE) study is a prospective epidemiological study of individuals aged 35 and 70 years from 21 countries on five continents, with a median follow-up of 9.1 years. In the cross-sectional analyses, we assessed the association of dairy intake with prevalent MetS and its components among individuals with information on the five MetS components (n=112 922). For the prospective analyses, we examined the association of dairy with incident hypertension (in 57 547 individuals free of hypertension) and diabetes (in 131 481 individuals free of diabetes).
Results: In cross-sectional analysis, higher intake of total dairy (at least two servings/day compared with zero intake; OR 0.76, 95% CI 0.71 to 0.80, p-trend<0.0001) was associated with a lower prevalence of MetS after multivariable adjustment. Higher intakes of whole fat dairy consumed alone (OR 0.72, 95% CI 0.66 to 0.78, p-trend<0.0001), or consumed jointly with low fat dairy (OR 0.89, 95% CI 0.80 to 0.98, p-trend=0.0005), were associated with a lower MetS prevalence. Low fat dairy consumed alone was not associated with MetS (OR 1.03, 95% CI 0.77 to 1.38, p-trend=0.13). In prospective analysis, 13 640 people with incident hypertension and 5351 people with incident diabetes were recorded. Higher intake of total dairy (at least two servings/day vs zero serving/day) was associated with a lower incidence of hypertension (HR 0.89, 95% CI 0.82 to 0.97, p-trend=0.02) and diabetes (HR 0.88, 95% CI 0.76 to 1.02, p-trend=0.01). Directionally similar associations were found for whole fat dairy versus each outcome.
Conclusions: Higher intake of whole fat (but not low fat) dairy was associated with a lower prevalence of MetS and most of its component factors, and with a lower incidence of hypertension and diabetes. Our findings should be evaluated in large randomized trials of the effects of whole fat dairy on the risks of MetS, hypertension, and diabetes.
Keywords: adult diabetes; endocrinology; hypertension; nutrition.

Sex-specific associations of habitual intake of soy protein and isoflavones with risk of type 2 diabetes.
Woo HW, Kim MK, Lee YH, Shin DH, Shin MH, Choi BY.
Clin Nutr. 2020 May 4:S0261-5614(20)30209-0. doi: 10.1016/j.clnu.2020.04.035. Online ahead of print.
PMID: 32418714
Background & aims: A possible mechanism by which intake of soy isoflavones leads to an improvement in glucose metabolism has been suggested. However, epidemiological evidence of a link between dietary soy isoflavone and type 2 diabetes is not convincing. This study aimed to evaluate the prospective associations between intake of dietary soy protein and isoflavones (total isoflavones, daidzein and genistein) and risk of type 2 diabetes in a community-based cohort of Korean adults aged ≥ 40 years, the Korean Multi-Rural Communities Cohort (MRCohort).
Methods: A total of 8269 participants who did not have type 2 diabetes were enrolled. Dietary intake was calculated using a food frequency questionnaire.
Results: Over 50,063 person-years of follow-up, 531 participants developed type 2 diabetes. Significant dose-response inverse associations were observed between dietary soy protein and isoflavones (quartiles) and type 2 diabetes in women (incidence rate ratio, IRR = 0.63, 95% CI = 0.45-0.87, P for trend = 0.0078 for soy protein; IRR = 0.62, 95% CI = 0.45-0.86, P for trend = 0.0031 for total isoflavones for the highest quartile compared with the lowest quartile). Similar significant linear trends were found for both daidzein and genistein. However, there were no significant associations with soy protein and isoflavones in men. The sex-specific differences in associations between soy protein and isoflavones intakes and type 2 diabetes risk were statistically significant (all P for interaction < 0.05).
Conclusions: Habitual intake of soy protein and isoflavones may be inversely associated with type 2 diabetes in women, but not in men. Dietary soy components may play different roles in the development of type 2 diabetes in men and women.
Keywords: Isoflavones; Korea; Prospective; Soy protein; Type 2 diabetes.

Mixing of Apples and Oranges in Milk Research: A Cohort Analysis of Non-Fermented Milk Intake and All-Cause Mortality.
Michaëlsson K, Byberg L.
Nutrients. 2020 May 13;12(5). pii: E1393. doi: 10.3390/nu12051393.
PMID: 32413977
Mortality in relation to type of milk intake is unclear. We present mortality rates by intake of non-fermented milk fat content type and examine the degree of bias when other fat content types of non-fermented milk are kept in the reference category. For this purpose, we used a longitudinal cohort consisting of 61,433 women who had been administered food frequency questionnaires in 1987-1990 and in 1997, and analyzed time to death. Non-fermented milk consumption was divided into low ≤0.5%, medium 1.5%, or high fat 3%. For each specific type of milk, the first analysis (A) is restricted to those who consumed less than one serving per day of the other milk subtypes. In the second analysis (B), everyone is retained, i.e., leading to a reference category "contaminated" with other milk consumers. During follow-up, 22,391 women died. Highest (≥3 glasses/day) vs. lowest consumption category of milk (<1 glass/day) with 0.5% fat content was associated with a multivariable hazard ratio (HR) of 1.71 (95%CI 1.57-1.86) in analysis A, whereas the same comparison with a "contaminated" reference category in analysis B provided a HR of 1.34 (95%CI 1.24-1.45), p-value for homogeneity <0.0001. The corresponding HRs for 1.5% fat milk were: 1.82 (95%CI 1.63-2.04) and 1.38 (95%CI 1.25-1.51), and for 3% fat milk 1.95 (95%CI 1.77-2.15) and 1.40 (95%CI 1.29-1.52). HR for ≥3 glasses/day of total milk was 1.95 (95%CI 1.84-2.06). We observe a higher mortality in women with high milk consumption, irrespective of milk fat content. A "contaminated" reference group substantially attenuates the actual estimates.
cohort; dairy; fat; milk; mortality; non-fermented

Distribution of daily protein intake across meals and lower extremity functioning in community-dwelling Spanish older adults: a prospective cohort study.
Estrada-DeLeón DB, Struijk EA, Caballero F, Rodríguez-Artalejo F, Lopez-Garcia E.
Eur J Nutr. 2020 May 16. doi: 10.1007/s00394-020-02273-6. [Epub ahead of print]
PMID: 32417947
Total dietary protein intake has been associated with better physical function in older adults. However, it is unclear whether an even mealtime distribution of protein intake also has an impact on physical functioning. The aim of this study was to examine the prospective association between distribution of daily protein intake across meals and the risk of impaired lower extremity function (ILEF).
We used information of 2975 individuals ≥ 60 years from the Seniors-ENRICA cohort. Habitual dietary protein intake was assessed in 2008-2010 with a validated diet history. For each participant, dietary protein intake across meals was determined using the coefficient of variation (CV) of the distribution. Study participants were followed up until 2017 to identify incident ILEF, assessed with the short physical performance battery (SPPB).
Over a median follow-up of 6.3 years, we identified 521 participants with ILEF (SPPB ≤ 6). After adjusting for potential confounders including total protein intake/kg/day, a higher CV (less even distribution) of protein intake did not show an association with the risk of ILEF [hazard ratios (HR) and 95% confidence intervals (CI) for second and third vs. the first tertile: 1.08 (0.87-1.34), and 1.06 (0.85-1.32), respectively; p trend = 0.60]. When assessing each component of the SPPB, a higher CV of protein intake was associated with higher risk of impaired standing balance (HR for tertile 3 vs. tertile 1: 1.26 (1.03-1.54); p trend = 0.02).
The mealtime distribution of protein intake was not associated with ILEF. The possibility of a detrimental effect of uneven distribution of protein on standing balance needs to be further investigated.
Cohort study; Older people; Physical function; Protein intake; Protein intake distribution

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Impact of Combined Hormonal Contraceptive Use on Weight Loss: A Secondary Analysis of a Behavioral Weight-Loss Trial.
Caldwell AE, Zaman A, Ostendorf DM, Pan Z, Swanson BB, Phelan S, Wyatt HR, Bessesen DH, Melanson EL, Catenacci VA.
Obesity (Silver Spring). 2020 Jun;28(6):1040-1049. doi: 10.1002/oby.22787.
PMID: 3244147
Objective: This study aimed to perform a preliminary investigation of the impact of combined hormonal contraceptive (CHC) use on weight loss during an 18-month behavioral weight-loss trial.
Methods: Adults (n = 170; 18-55 years; BMI 27-42 kg/m2 ) received a weight-loss intervention that included a reduced-calorie diet, a progressive exercise prescription, and group-based behavioral support. Premenopausal women (n = 110) were classified as CHC users (CHC, n = 17) or non-CHC users (non-CHC, n = 93). Changes in weight were examined within groups using a linear mixed model, adjusted for age and randomized group assignment.
Results: At 6 M, weight was reduced from baseline in both CHC (mean, -6.7 kg; 95% CI: -9.8 to -3.7 kg) and non-CHC (-9.1 kg; -9.1 to -6.4 kg). Between 6 and 18 M, CHC regained weight (4.9 kg; 0.9 to 8.9 kg), while weight remained relatively unchanged in non-CHC (-0.1 kg; -1.8 to 1.6 kg). At 18 M, weight was relatively unchanged from baseline in CHC (-1.8 kg; -7.3 to 3.6 kg) and was reduced from baseline in non-CHC (-7.9 kg; -10.2 to -5.5 kg).
Conclusions: In this secondary data analysis, CHC use was associated with weight regain after initial weight loss. Prospective studies are needed to further understand the extent to which CHC use influences weight loss and maintenance.
Abdominal Obesity and Its Attribution to All-cause Mortality in the General Population with 14 Years Follow-up: Findings from Shanxi Cohort in China.
Zhai Y, Ren ZP, Zhang M, Zhang J, Jiang Y, Mi SQ, Wang ZQ, Zhao YF, Song PK, Yin ZX, Zhao WH.
Biomed Environ Sci. 2020 Apr 20;33(4):227-237. doi: 10.3967/bes2020.032.
PMID: 32438960
Objective: This study aimed to assess the association of waist circumference (WC) with all-cause mortality among Chinese adults.
Methods: The baseline data were from Shanxi Province of 2002 China Nutrition and Health Survey. The death investigation and follow-up visit were conducted from December 2015 to March 2016. The visits covered up to 5,360 of 7,007 participants, representing a response rate of 76.5%. The Cox regression model and floating absolute risk were used to estimate hazard ratio and 95% floating CI of death by gender and age groups (≥ 60 and < 60 years old). Sensitivity analysis was performed by excluding current smokers; participants with stroke, hypertension, and diabetes; participants who accidentally died; and participants who died during the first 2 years of follow-up.
Results: This study followed 67,129 person-years for 12.5 years on average, including 615 deaths. The mortality density was 916 per 100,000 person-years. Low WC was associated with all-cause mortality among men. Multifactor-adjusted hazard ratios ( HR) were 1.60 (1.35-1.90) for WC < 75.0 cm and 1.40 (1.11-1.76) for WC ranging from 75.0 cm to 79.9 cm. Low WC (< 70.0 cm and 70.0-74.9 cm) and high WC (≥ 95.0 cm) groups had a high risk of mortality among women. The adjusted HRs of death were 1.43 (1.11-1.83), 1.39 (1.05-1.84), and 1.91 (1.13-3.22).
Conclusion: WC was an important predictor of death independent of body mass index (BMI). WC should be used as a simple rapid screening and predictive indicator of the risk of death.
Keywords: All-cause mortality; Cohort study; Waist circumference.

Road Traffic Noise Exposure and Filled Prescriptions for Antihypertensive Medication: A Danish Cohort Study.
Thacher JD, Poulsen AH, Roswall N, Hvidtfeldt U, Raaschou-Nielsen O, Jensen SS, Ketzel M, Brandt J, Overvad K, Tjønneland A, Münzel T, Sørensen M.
Environ Health Perspect. 2020 May;128(5):57004. doi: 10.1289/EHP6273. Epub 2020 May 14.
PMID: 32438890
Background: Epidemiological research on effects of transportation noise on incident hypertension is inconsistent.
Objectives: We aimed to investigate whether residential road traffic noise increases the risk for hypertension.
Methods: In a population-based cohort of 57,053 individuals 50-64 years of age at enrollment, we identified 21,241 individuals who fulfilled our case definition of filling ≥2 prescriptions and ≥180 defined daily doses of antihypertensive drugs (AHTs) within a year, during a mean follow-up time of 14.0 y. Residential addresses from 1987 to 2016 were obtained from national registers, and road traffic noise at the most exposed façade as well as the least exposed façade was modeled for all addresses. Analyses were conducted using Cox proportional hazards models.
Results: We found no associations between the 10-y mean exposure to road traffic noise and filled prescriptions for AHTs, with incidence rate ratios (IRRs) of 0.999 [95% confidence intervals (CI): 0.980, 1.019)] per 10-dB increase in road traffic noise at the most exposed façade and of 1.001 (95% CI: 0.977, 1.026) at the least exposed façade. Interaction analyses suggested an association with road traffic noise at the least exposed façade among subpopulations of current smokers and obese individuals.
Conclusion: The present study does not support an association between road traffic noise and filled prescriptions for AHTs.

Assessment of Deaths From COVID-19 and From Seasonal Influenza.
Faust JS, Del Rio C.
JAMA Intern Med. 2020 May 14. doi: 10.1001/jamainternmed.2020.2306. Online ahead of print.
PMID: 32407441 No abstract available.
"Between 2013-2014 and 2018-2019, the reported yearly estimated influenza deaths ranged from 23 000 to 61 000.3 Over that same time period, however, the number of counted influenza deaths was between 3448 and 15 620 yearly.4 On average, the CDC estimates of deaths attributed to influenza were nearly 6 times greater than its reported counted numbers. Conversely, COVID-19 fatalities are at present being counted and reported directly, not estimated. As a result, the more valid comparison would be to compare weekly counts of COVID-19 deaths to weekly counts of seasonal influenza deaths."

Association of nut intake with risk factors, cardiovascular disease, and mortality in 16 countries from 5 continents: analysis from the Prospective Urban and Rural Epidemiology (PURE) study.
de Souza RJ, Dehghan M, Mente A, Bangdiwala SI, Ahmed SH, Alhabib KF, Altuntas Y, Basiak-Rasała A, Dagenais GR, Diaz R, Amma LI, Kelishadi R, Khatib R, Lear SA, Lopez-Jaramillo P, Mohan V, Poirier P, Rangarajan S, Rosengren A, Ismail R, Swaminathan S, Wentzel-Viljoen E, Yeates K, Yusuf R, Teo KK, Anand SS, Yusuf S; PURE study investigators.
Am J Clin Nutr. 2020 May 20:nqaa108. doi: 10.1093/ajcn/nqaa108. Online ahead of print.
PMID: 32433740
Background: The association of nuts with cardiovascular disease and deaths has been investigated mostly in Europe, the USA, and East Asia, with few data available from other regions of the world or from low- and middle-income countries.
Objective: To assess the association of nuts with mortality and cardiovascular disease (CVD).
Methods: The Prospective Urban Rural Epidemiology study is a large multinational prospective cohort study of adults aged 35-70 y from 16 low-, middle-, and high-income countries on 5 continents. Nut intake (tree nuts and ground nuts) was measured at the baseline visit, using country-specific validated FFQs. The primary outcome was a composite of mortality or major cardiovascular event [nonfatal myocardial infarction (MI), stroke, or heart failure].
Results: We followed 124,329 participants (age = 50.7 y, SD = 10.2; 41.5% male) for a median of 9.5 y. We recorded 10,928 composite events [deaths (n = 8,662) or major cardiovascular events (n = 5,979)]. Higher nut intake (>120 g per wk compared with <30 g per mo) was associated with a lower risk of the primary composite outcome of mortality or major cardiovascular event [multivariate HR (mvHR): 0.88; 95% CI: 0.80, 0.96; P-trend = 0.0048]. Significant reductions in total (mvHR: 0.77; 95% CI: 0.69, 0.87; P-trend <0.0001), cardiovascular (mvHR: 0.72; 95% CI: 0.56, 0.92; P-trend = 0.048), and noncardiovascular mortality (mvHR: 0.82; 95% CI: 0.70, 0.96; P-trend = 0.0046) with a trend to reduced cancer mortality (mvHR: 0.81; 95% CI: 0.65, 1.00; P-trend = 0.081) were observed. No significant associations of nuts were seen with major CVD (mvHR: 0.91; 95% CI: 0.81, 1.02; P-trend = 0.14), stroke (mvHR: 0.98; 95% CI: 0.84, 1.14; P-trend = 0.76), or MI (mvHR: 0.86; 95% CI: 0.72, 1.04; P-trend = 0.29).
Conclusions: Higher nut intake was associated with lower mortality risk from both cardiovascular and noncardiovascular causes in low-, middle-, and high-income countries.
Keywords: cardiovascular disease; global health; mortality; nuts; prospective cohort.

Effect of green tea consumption on blood lipids: a systematic review and meta-analysis of randomized controlled trials.
Xu R, Yang K, Li S, Dai M, Chen G.
Nutr J. 2020 May 20;19(1):48. doi: 10.1186/s12937-020-00557-5.
PMID: 32434539 Review.
Background: Strong epidemiologic evidence indicates that green tea intake is protective against hyperlipidemia; however, randomized controlled studies have presented varying results. In the present study, we aimed to conduct a literature review and meta-analysis to assess the effect of green tea on blood lipids.
Methods: PubMed, Embase, and the Cochrane Library were electronically explored from inception to September 2019 for all relevant studies. Random effect models were used to estimate blood lipid changes between green tea supplementation and control groups by evaluating the weighted mean differences (WMD) with 95% confidence intervals (CIs). The risk of bias for study was assessed using the Cochrane tool. Publication bias was evaluated using funnel plots and Egger's tests.
Results: Thirty-one trials with a total of 3321 subjects were included in the meta-analysis. In general, green tea intake significantly lowered the total cholesterol (TC); WMD: - 4.66 mg/dL; 95% CI: - 6.36, - 2.96 mg/dL; P < 0.0001) and low-density lipoprotein (LDL) cholesterol (WMD:- 4.55 mg/dL; 95% CI: - 6.31, - 2.80 mg/dL; P < 0.0001) levels compared with those in the control. Green tea consumption did not affect high-density lipoprotein (HDL) cholesterol; however, it reduced the triglycerides compared with that in the control (WMD: - 3.77 mg/dL; 95% CI: - 8.90, 1.37 mg/dL; P = 0.15). In addition, significant publication bias from funnel plots or Egger's tests was not evident.
Conclusions: Collectively, consumption of green tea lowers LDL cholesterol and TC, but not HDL cholesterol or triglycerides in both normal weight subjects and those who were overweight/obese; however, additional well-designed studies that include more diverse populations and longer duration are warranted.
Keywords: Catechin; Cholesterol; Green tea; Meta-analysis; Triglycerides.

Monounsaturated fat rapidly induces hepatic gluconeogenesis and whole-body insulin resistance.
Sarabhai T, Kahl S, Szendroedi J, Markgraf DF, Zaharia OP, Barosa C, Herder C, Wickrath F, Bobrov P, Hwang JH, Jones JG, Roden M.
JCI Insight. 2020 May 21;5(10):134520. doi: 10.1172/jci.insight.134520.
PMID: 32434996
BACKGROUNDWhile saturated fat intake leads to insulin resistance and nonalcoholic fatty liver, Mediterranean-like diets enriched in monounsaturated fatty acids (MUFA) may have beneficial effects. This study examined effects of MUFA on tissue-specific insulin sensitivity and energy metabolism.METHODSA randomized placebo-controlled cross-over study enrolled 16 glucose-tolerant volunteers to receive either oil (OIL, ~1.18 g/kg), rich in MUFA, or vehicle (VCL, water) on 2 occasions. Insulin sensitivity was assessed during preclamp and hyperinsulinemic-euglycemic clamp conditions. Ingestion of 2H2O/acetaminophen was combined with [6,6-2H2]glucose infusion and in vivo 13C/31P/1H/ex vivo 2H-magnet resonance spectroscopy to quantify hepatic glucose and energy fluxes.RESULTSOIL increased plasma triglycerides and oleic acid concentrations by 44% and 66% compared with VCL. Upon OIL intervention, preclamp hepatic and whole-body insulin sensitivity markedly decreased by 28% and 27%, respectively, along with 61% higher rates of hepatic gluconeogenesis and 32% lower rates of net glycogenolysis, while hepatic triglyceride and ATP concentrations did not differ from VCL. During insulin stimulation hepatic and whole-body insulin sensitivity were reduced by 21% and 25%, respectively, after OIL ingestion compared with that in controls.CONCLUSIONA single MUFA-load suffices to induce insulin resistance but affects neither hepatic triglycerides nor energy-rich phosphates. These data indicate that amount of ingested fat, rather than its composition, primarily determines the development of acute insulin resistance.
Keywords: Diabetes; Endocrinology; Glucose metabolism; Insulin signaling; Metabolism.

Association of cardiovascular diseases with milk intake among general Chinese adults.
Wang XY, Liu FC, Yang XL, Li JX, Cao J, Lu XF, Huang JF, Li Y, Chen JC, Zhao LC, Shen C, Hu DS, Zhao YX, Yu L, Liu XQ, Wu XP, Gu DF.
Chin Med J (Engl). 2020 May 20;133(10):1144-1154. doi: 10.1097/CM9.0000000000000786.
PMID: 32433046
Background: The association of milk intake with cardiovascular disease (CVD) and cause-specific mortality remained controversial and evidence among the Chinese population was limited. We aimed to study the relationship between milk intake and CVDs among general Chinese adults.
Methods: A total of 104,957 participants received questionnaire survey. Results of physical examination such as anthropometric measurements and biochemical tests during 2007 to 2008, demographic data and their information on milk intake were collected through standardized questionnaires. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) of CVD incidence, cause-specific mortality and all-cause mortality related to milk intake. Restricted cubic splines (RCSs) were applied to examine dose-response associations.
Results: Among the 91,757 participants with a median follow-up period of 5.8 years, we documented 3877 CVD cases and 4091 all-cause deaths. Compared with participants who never consumed milk, the multivariate-adjusted HRs (95% CIs) of CVD incidence for 1 to 150 g/day, 151 to 299 g/day, and ≥300 g/day were 0.94 (0.86-1.03) (P > 0.05), 0.77 (0.66-0.89) (P < 0.05), and 0.59 (0.40-0.89) (P < 0.05), respectively; each 100 g increase of daily milk intake was associated with 11% lower risk of CVD incidence (HR, 0.89; 95% CI: 0.85-0.94; P < 0.001), and 11% lower risk of CVD mortality (HR, 0.89; 95% CI: 0.82-0.97; P = 0.008) after adjustment for age, sex, residential area, geographic region, education level, family history of CVD, smoking, alcohol drinking, physical activity level, body mass index, and healthy diet status (ideal or not). RCS analyses also showed a linear dose-response relationship with CVD (P for overall significance of the curve <0.001; P for non-linearity = 0.979; P for linearity <0.001) and stroke (P for overall significance of the curve = 0.010; P for non-linearity = 0.998; P for linearity = 0.002) incidence, and CVD mortality (P for overall significance of the curve = 0.045; P for non-linearity = 0.768; P for linearity = 0.014) within the current range of daily milk intake.
Conclusions: Daily milk intake was associated with lower risk of CVD incidence and mortality in a linear inverse relationship. The findings provide new evidence for dietary recommendations in CVD prevention among Chinese adults and people with similar dietary pattern in other countries.

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The effects of vitamin K-rich green leafy vegetables on bone metabolism: A 4-week randomised controlled trial in middle-aged and older individuals.
Sim M, Lewis JR, Prince RL, Levinger I, Brennan-Speranza TC, Palmer C, Bondonno CP, Bondonno NP, Devine A, Ward NC, Byrnes E, Schultz CJ, Woodman R, Croft K, Hodgson JM, Blekkenhorst LC.
Bone Rep. 2020 Apr 26;12:100274. doi: 10.1016/j.bonr.2020.100274. eCollection 2020 Jun.
PMID: 32455149 Free PMC article.
Background: High vegetable intake is associated with beneficial effects on bone. However, the mechanisms remain uncertain. Green leafy vegetables are a rich source of vitamin K1, which is known to have large effects on osteoblasts and osteocalcin (OC) metabolism.

Objective: To examine the effects of consumption of two to three extra serves of green leafy vegetables daily on bone metabolism.

Methods: Thirty individuals (mean age 61.8 ± 9.9 years, 67% male) completed three experimental phases in a randomised controlled crossover design, each lasting four weeks, with a washout period of four weeks between phases (clinical trial registration: ACTRN12615000194561). The three experimental phases were: (i) increased dietary vitamin K1 by consuming green leafy vegetables (H-K; ~200 g/d containing 164.3 [99.5-384.7] μg/d of vitamin K1); (ii) low vitamin K1 by consuming vitamin K1-poor vegetables (L-K; ~200 g/d containing 9.4 [7.7-11.6] μg/d of vitamin K1); and (iii) control (CON) where participants consumed an energy-matched non-vegetable control. OC forms, total OC (tOC), carboxylated OC (cOC) and undercarboxylated OC (ucOC), were measured in serum pre- and post-intervention for each experimental phase using a sandwich-electrochemiluminescence immunoassay.

Results: Pre-intervention tOC, ucOC and ucOC:tOC levels were similar between phases (P > .05). Following H-K, but not L-K, tOC, ucOC and ucOC:tOC levels were significantly lower compared to pre-intervention levels (P ≤ .001) and compared to CON (~14%, 31% and 19%, respectively, all P < .05), while cOC remained unchanged.

Conclusions: In middle-aged healthy men and women, an easily achieved increase in dietary intake of vitamin K1-rich green leafy vegetables substantially reduces serum tOC and ucOC suggesting increased entry of OC into bone matrix, where it may improve the material property of bone. In conjunction with previous epidemiological and randomised controlled trial data, these findings suggest that interventions to increase vegetable intake over extended periods should include bone end points including fracture risk.

Keywords: Ageing; BMD, bone mineral density; Bone; CON, control; CTX, collagen type I C-terminal cross-linked telopeptide; FFQ, food frequency questionnaire; GCMS, gas-chromatography mass spectrometry; H-K, experimental phase with high vitamin K1 intake; L-K, experimental phase with low vitamin K1 intake; METs, metabolic equivalents; MK, menaquinones; Nutrition; OC, osteocalcin; Osteocalcin; P1NP, N-terminal propeptide of type I collagen; PK, phylloquinone; RCT, randomised controlled trial; USDA, United States Department of Agriculture; VIABP, Vegetable intake and blood pressure study; VKDP, vitamin K dependant proteins; Vitamin K; cOC, carboxylated osteocalcin; tOC, total osteocalcin; ucOC, undercarboxylated osteocalcin; ucOC:tOC, fraction of undercarboxylated osteocalcin.

Relationship between body mass index, risk of venous thromboembolism and pulmonary embolism: A systematic review and dose-response meta-analysis of cohort studies among four million participants.
Rahmani J, Haghighian Roudsari A, Bawadi H, Thompson J, Khalooei Fard R, Clark C, Ryan PM, Ajami M, Rahimi Sakak F, Salehisahlabadi A, Abdulazeem HM, Jamali MR, Mirzay Razaz J.
Thromb Res. 2020 May 15;192:64-72. doi: 10.1016/j.thromres.2020.05.014. Online ahead of print.
PMID: 32454303 Review.
Background: The relationship between body mass index (BMI) and risk of venous thromboembolism (VTE) and pulmonary embolism (PE) is a controversial issue. This dose-response meta-analysis was performed to investigate the association between BMI and risk of VTE and PE incidence based on cohort studies.
Method: A comprehensive systematic search was conducted up to August 2019 in MEDLINE/PubMed, SCOPUS, and Cochrane. DerSimonian and Laird random-effects models were run to estimate combined hazard ratios (HRs) with 95% confidence intervals (CIs). Dose-response analysis was also carried out based on BMI values.
Results: Eleven articles with 16 arms and 3,910,747 participants were eligible for inclusion in this systematic review and meta-analysis. Pooled results showed a positive association between BMI and risk of VTE in the obese participants compared to participants classified in the normal BMI category (HR: 1.62, 95% CI: 1.29-2.04, I2 = 95%). Furthermore, results showed a significant association between lower BMI (underweight versus normal BMI category) and reduced risk of PE (HR: 0.80, 95% CI: 0.70-0.92, I2 = 9%) and higher risk of PE in obese versus normal BMI participants (HR: 2.24, 95% CI: 1.93-2.60, I2 = 0%). There was a significant linear relationship between BMI and risk of VTE (p < 0.001) and PE (p < 0.001).
Conclusions: This systematic review and dose-response meta-analysis with 3,910,747 participants highlights obesity as a significant risk factor related to the incidence of VTE and PE.
Keywords: Body mass index; Pulmonary embolism; Venous thromboembolism.

Relationship between body mass index, risk of venous thromboembolism and pulmonary embolism: A systematic review and dose-response meta-analysis of cohort studies among four million participants.
Rahmani J, Haghighian Roudsari A, Bawadi H, Thompson J, Khalooei Fard R, Clark C, Ryan PM, Ajami M, Rahimi Sakak F, Salehisahlabadi A, Abdulazeem HM, Jamali MR, Mirzay Razaz J.
Thromb Res. 2020 May 15;192:64-72. doi: 10.1016/j.thromres.2020.05.014. Online ahead of print.
PMID: 32454303 Review.
We conducted the first large-scale general population study on lifestyle risk factors (smoking, physical inactivity, obesity, and excessive alcohol intake) for COVID-19 using prospective cohort data with national registry linkage to hospitalisation. Participants were 387,109 men and women (56.4 ±8.8 yr; 55.1% women) residing in England from UK Biobank study. Physical activity, smoking, and alcohol intake, were assessed by questionnaire at baseline (2006-2010). Body mass index, from measured height and weight, was used as an indicator of overall obesity. Outcome was cases of COVID-19 serious enough to warrant a hospital admission from 16-March-2020 to 26-April-2020. There were 760 COVID-19 cases. After adjustment for age, sex and mutually for each lifestyle factor, physical inactivity (Relative risk, 1.32, 95% confidence interval, 1.10, 1.58), smoking (1.42;1.12, 1.79) and obesity (2.05 ;1.68, 2.49) but not heavy alcohol consumption (1.12; 0.93, 1.35) were all related to COVID-19. We also found a dose-dependent increase in risk of COVID-19 with less favourable lifestyle scores, such that participants in the most adverse category had 4-fold higher risk (4.41; 2.52 -7.71) compared to people with the most optimal lifestyle. C-reactive protein levels were associated with elevated risk of COVID-19 in a dose-dependent manner, and partly (10 - 16%) explained associations between adverse lifestyle and COVID-19. Based on UK risk factor prevalence estimates, unhealthy behaviours in combination accounted for up to 51% of the population attributable fraction of severe COVID-19. Our findings suggest that an unhealthy lifestyle synonymous with an elevated risk of non-communicable disease is also a risk factor for COVID-19 hospital admission, which might be partly explained by low grade inflammation. Adopting simple lifestyle changes could lower the risk of severe infection.
Keywords: C-reactive protein; Physical activity; coronavirus; infection; obesity; population cohort; smoking.

Trajectories of Handgrip Strength and Their Associations with Mortality among Older Adults in Korea: Analysis of the Korean Longitudinal Study of Aging.
Bae KH, Jo YH, Lee DR, Lee J.
Korean J Fam Med. 2020 May 27. doi: 10.4082/kjfm.19.0140. Online ahead of print.
PMID: 32456407
Background: Handgrip strength (HGS) is a good predictor of adverse health outcomes in later life. This prospective study aimed to investigate whether HGS trajectory patterns were associated with all-cause mortality among older adults in Korea.
Methods: This study used the database of the 2006-2016 Korean Longitudinal Study of Aging. Study participants included 3,069 adults aged ≥65 years without a previous history of cancer. The trajectory model was developed to identify different homogeneous trajectory patterns of HGS according to study period. Cox proportional hazards models were then applied to investigate the association between HGS and all-cause mortality.
Results: The survival probability according to HGS during the follow-up period decreased as base HGS weakened. We identified four distinct trajectory groups of HGS among men and three among women. The risk of mortality increased as the HGS of both males and females decreased. Compared with the highest HGS group, the adjusted hazard ratios for all-cause mortality of the lowest, lower-mid, and upper-mid HGS groups among males were 3.46 (95% confidence interval [CI], 2.17-6.69), 2.26 (95% CI, 1.47-3.48), and 1.58 (95% CI, 1.07-2.32). Those of the low and mid HGS groups among females were 2.69 (95% CI, 1.39-5.21) and 1.97 (95% CI, 1.05-3.69).
Conclusion: The faster HGS declined over time, the greater the all-cause mortality risk increased compared with the slowly decreasing or maintained HGS groups among men and women. HGS measurement among older adults will be helpful in assessing their health statuses and pre-assessing disease-associated morbidity.
Keywords: Aged; Hand Strength; Korea; Mortality.

Do Centenarians Die Healthier than Younger Elders? A Comparative Epidemiological Study in Spain.
Clerencia-Sierra M, Ioakeim-Skoufa I, Poblador-Plou B, González-Rubio F, Aza-Pascual-Salcedo M, Gimeno-Miguel MMA, Prados-Torres A.
J Clin Med. 2020 May 21;9(5):E1563. doi: 10.3390/jcm9051563.
PMID: 32455809
This study aims to describe the clinical course, drug use, and health services use characteristics during the last year of life of elders who die being centenarians and to identify key aspects differentiating them from elders who die at an earlier age, with a particular focus on sex differences. We conducted an observational, population-based study in the EpiChron Cohort (Aragón, Spain). The population was stratified by sex and into three age sub-populations (80-89, 90-99, and ≥100 years), and their characteristics were described and compared. Multimorbidity was the rule in our elders, affecting up to 3 in 4 centenarians and 9 in 10 octogenarians and nonagenarians. Polypharmacy was also observed in half of the centenarian population and in most of the younger elders. Risk factors for cardiovascular disease (i.e., hypertension, dyslipidaemia, diabetes), cerebrovascular disease and dementia were amongst the most common chronic conditions in all age groups, whereas the gastroprotective drugs and antithrombotic agents were the most dispensed drugs. Centenarians presented in general lower morbidity and treatment burden and lower use of both primary and hospital healthcare services than octogenarians and nonagenarians, suggesting a better health status. Sex-differences in their clinical characteristics were more striking in octogenarians and tended to decrease with age.
Keywords: aged 80 and over; delivery of healthcare; electronic health records; multimorbidity; multiple chronic conditions; polypharmacy; real-world data.

Dietary plant and animal protein intake and decline in estimated glomerular filtration rate among elderly women: a 10-year longitudinal cohort study.
Bernier-Jean A, Prince RL, Lewis JR, Craig JC, Hodgson JM, Lim WH, Teixeira-Pinto A, Wong G.
Nephrol Dial Transplant. 2020 May 26:gfaa081. doi: 10.1093/ndt/gfaa081. Online ahead of print.
PMID: 32457981
Background: Many older women demonstrate an age-related accelerating rate of renal decline that is associated with increased rates of bone disease, cardiovascular disease and mortality. Population-based protein restriction has been studied principally in patients with reduced renal function. In this investigation, we examined the hypothesis of a differential effect of plant-derived protein compared with animal-derived protein on renal function in older women.
Methods: We assessed dietary intake from a validated food frequency questionnaire and the estimated glomerular filtration rate (eGFR) (using the Chronic Kidney Disease Epidemiology Collaboration creatinine and cystatin C equation) at baseline, 5 and 10 years in the Longitudinal Study of Aging Women cohort. We tested the association between plant- and animal-sourced protein intake and kidney function using linear mixed modeling.
Results: A total of 1374 Caucasian women [mean (standard deviation, SD) age = 75 years (2.7) and mean (SD) baseline eGFR = 65.6 mL/min/1.73 m2 (13.1)] contributed to the analysis. The average decline in eGFR was 0.64 mL/min/1.73 m2/year [95% confidence interval (CI) 0.56-0.72]. Higher intakes of plant-sourced protein were associated with slower declines in eGFR after adjusting for covariates including animal protein and energy intake (P = 0.03). For each 10 g of plant protein, the yearly decline in eGFR was reduced by 0.12 mL/min/1.73 m2 (95% CI 0.01-0.23), principally associated with fruit-, vegetable- and nut-derived protein. The intake of animal protein was not associated with eGFR decline (P = 0.84).
Conclusions: Older women consuming a diet that is richer in plant-sourced protein have a slower decline in kidney function. These data extend support for the health benefits of plant-rich diets in the general population to maintain kidney health.
Keywords: animal protein; chronic renal insufficiency; cohort study; glomerular filtration rate; nutrition; plant protein; protein intake.

Fears of coronavirus second wave prompt flu push at U.S. pharmacies, drugmakers
Caroline Humer, Julie Steenhuysen
May 26, 2020
NEW YORK (Reuters) - U.S. pharmacy chains are preparing a big push for flu vaccinations when the season kicks off in October, hoping to curb tens of thousands of serious cases that could coincide with a second wave of coronavirus infections.

Associations of dietary protein intake with all-cause, cardiovascular disease, and cancer mortality: A systematic review and meta-analysis of cohort studies.
Qi XX, Shen P.
Nutr Metab Cardiovasc Dis. 2020 Mar 17:S0939-4753(20)30090-9. doi: 10.1016/j.numecd.2020.03.008. Online ahead of print.
PMID: 32451273
Background and aims: The relationships between dietary protein intake and risk of all-cause, cardiovascular disease (CVD), and cancer mortality are still unclear. We conducted a systematic review with meta-analysis of cohort studies to summarize the evidence.
Methods and results: We searched PubMed and Web of Science for relevant studies through February 2020. The associations of total, animal, and plant proteins with all-cause, CVD, and cancer mortality were evaluated. Study-specific relative risks (RR) were pooled using the fixed effect model when no significant heterogeneity was detected; otherwise the random effect model was employed. Twelve cohort studies were eligible for the study. Increased total protein showed no clear association with risk of all-cause, CVD, and cancer mortality. In the stratified analysis by protein sources, higher plant protein intake was associated with a reduced risk of all-cause mortality (highest vs lowest intake: RR = 0.92; 95% CI: 0.88, 0.96; each 3% increment of intake: RR = 0.97; 95% CI: 0.94, 0.99), and may be associated with a reduced risk of CVD mortality (highest vs lowest intake: RR = 0.90; 95% CI: 0.80, 1.01; each 3% increment of intake: RR = 0.95; 95% CI: 0.91, 0.99). Moreover, higher intake of animal protein may be associated with an increased risk of CVD mortality (highest vs lowest intake: RR = 1.11; 95% CI: 1.01, 1.22; each 3% increment of intake: RR = 1.02; 95% CI: 0.98, 1.06).
Conclusion: This study demonstrates that higher plant protein intake is associated with a reduced risk of all-cause and CVD-related mortality. Persons should be encouraged to increase their plant protein intake to potentially decrease their risk of death.
Keywords: Cancer; Cardiovascular disease; Dietary protein; Meta-analysis; Mortality.

Coffee and tea consumption in the early adult lifespan and left ventricular function in middle age: the CARDIA study.
Nwabuo CC, Betoko AS, Reis JP, Moreira HT, Vasconcellos HD, Guallar E, Cox C, Sidney S, Ambale-Venkatesh B, Lewis CE, Schreiner PJ, Lloyd-Jones D, Kiefe CI, Gidding SS, Lima JAC.
ESC Heart Fail. 2020 May 25. doi: 10.1002/ehf2.12684. Online ahead of print.
PMID: 32449612
Aims: The long-term impact of coffee or tea consumption on subclinical left ventricular (LV) systolic or diastolic function has not been previously studied. We examined the association between coffee or tea consumption beginning in early adulthood and cardiac function in midlife.
Methods and results: We investigated 2735 Coronary Artery Risk Development in Young Adults (CARDIA) study participants with long-term total caffeine intake, coffee, and tea consumption data from three visits over a 20 year interval and available echocardiography indices at the CARDIA Year-25 exam (2010-2011). Linear regression models were used to assess the association between caffeine intake, tea, and coffee consumption (independent variables) and echocardiography outcomes [LV mass, left atrial volume, and global longitudinal strain (GLS), LV ejection fraction (LVEF), and transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity (E/e´)]. Models were adjusted for standard cardiovascular risk factors, socioeconomic status, physical activity, alcohol use, and dietary factors (calorie intake, whole and refined grain intake, and fruit and vegetable consumption). Mean (standard deviation) age was 25.2 (3.5) years at the CARDIA Year-0 exam (1985-1986), 57.4% were women, and 41.9% were African-American. In adjusted multivariable linear regression models assessing the relationship between coffee consumption and GLS, beta coefficients when comparing coffee drinkers of <1, 1-2, 3-4, and >4 cups/day with non-coffee drinkers were β = -0.30%, P < 0.05; β = -0.35%, P < 0.05; β = -0.32%, P < 0.05; β = -0.40%, P > 0.05; respectively (more negative values implies better systolic function). In adjusted multivariable linear regression models assessing the relationship between coffee consumption and E/e´, beta coefficients when comparing coffee drinkers of <1, 1-2, 3-4, and >4 cups/day with non-coffee drinkers were β = -0.29, P < 0.05; β = -0.38, P < 0.01; β = -0.20, P > .05; and β = -0.37, P > 0.05, respectively (more negative values implies better diastolic function). High daily coffee consumption (>4 cups/day) was associated with worse LVEF (β = -1.69, P < 0.05). There were no associations between either tea drinking or total caffeine intake and cardiac function (P > 0.05 for all).
Conclusions: Low-to-moderate daily coffee consumption from early adulthood to middle age was associated with better LV systolic and diastolic function in midlife. High daily coffee consumption (>4cups/day) was associated with worse LV function. There was no association between caffeine or tea intake and cardiac function.
Keywords: Coffee; Left ventricle; Left ventricular function; Tea; caffeine.

Analysis of the dose-response relationship of leisure-time physical activity to cardiovascular disease and all-cause mortality: the REGICOR study.
Clará A, Berenguer G, Pérez-Fernández S, Schröder H, Ramos R, Grau M, Dégano IR, Fernández-Sanlés A, Marrugat J, Elosua R.
Rev Esp Cardiol (Engl Ed). 2020 May 20:S1885-5857(20)30110-9. doi: 10.1016/j.rec.2020.02.011. Online ahead of print.
PMID: 32446794 English, Spanish.
Introduction and objectives: Regular leisure-time physical activity (LTPA) has been consistently recognized as a protective factor for cardiovascular diseases (CVD) and all-cause mortality. However, the pattern of this relationship is still not clear. The aim of this study was to assess the relationship of LTPA with incident CVD and mortality in a Spanish population.
Methods: A prospective population-based cohort of 11 158 randomly selected inhabitants from the general population. LTPA was assessed by a validated questionnaire. Mortality and CVD outcomes were registered during the follow-up (median: 7.24 years). The association between LTPA and outcomes of interest (all-cause mortality and cardiovascular disease) was explored using a generalized additive model with penalized smoothing splines and multivariate Cox proportional hazard models.
Results: We observed a significant nonlinear association between LTPA and all-cause and CVD mortality, and fatal and nonfatal CVD. Moderate-vigorous intensity LTPA, but not light-intensity LTPA, were associated with beneficial effects. The smoothing splines identified a cutoff at 400 MET-min/d. Below this threshold, each increase of 100 MET-min/d in moderate-vigorous LTPA contributed with a 16% risk reduction in all-cause mortality (HR, 0.84; 95%CI, 0.77-0.91), a 27% risk reduction in CVD mortality (HR, 0.73; 95%CI, 0.61-0.87), and a 12% risk reduction in incident CVD (HR, 0.88; 95%CI, 0.79-0.99). No further benefits were observed beyond 400 MET-min/d.
Conclusions: Our results support a nonlinear inverse relationship between moderate-vigorous LTPA and CVD and mortality. Benefits of PA are already observed with low levels of activity, with a maximum benefit around 3 to 5 times the current recommendations.
Keywords: Actividad física; Cardiovascular disease; Dose-response relationship; Enfermedad cardiovascular; Mortalidad; Mortality; Physical activity; Relación dosis-respuesta.


Association of Longitudinal Patterns of Habitual Sleep Duration With Risk of Cardiovascular Events and All-Cause Mortality.
Wang YH, Wang J, Chen SH, Li JQ, Lu QD, Vitiello MV, Wang F, Tang XD, Shi J, Lu L, Wu SL, Bao YP.
JAMA Netw Open. 2020 May 1;3(5):e205246. doi: 10.1001/jamanetworkopen.2020.5246.
PMID: 32442289
Importance: Single self-reported measures of sleep duration are associated with adverse health outcomes; however, long-term patterns of self-reported sleep duration and their association with cardiovascular events (CVEs) and all-cause mortality remain unknown.
Objective: To determine whether trajectories of long-term vs single-measure sleep duration are associated with subsequent risk of CVEs and all-cause mortality.
Design, setting, and participants: The Kailuan study is a prospective, population-based cohort study that began in 2006. The present cohort included 52 599 Chinese adults without atrial fibrillation, myocardial infarction, stroke, or cancer to 2010. Trajectories in sleep duration from January 1, 2006, to December 31, 2010, were identified to investigate the association with risk of CVEs and all-cause mortality from January 1, 2010, to December 31, 2017. Data analysis was conducted from July 1 to October 31, 2019.
Exposures: Habitual self-reported nocturnal sleep durations were collected in 2006, 2008, and 2010. Trajectories in sleep duration for 4 years were identified by latent mixture modeling.
Main outcomes and measures: All-cause mortality and first incident CVEs (atrial fibrillation, myocardial infarction, and stroke) from 2010 to 2017 were confirmed by medical records. Based on the baseline sleep duration and patterns over time, 4 trajectories were categorized (normal stable, normal decreasing, low increasing, and low stable).
Results: Of the 52 599 adults included in the study (mean [SD] age at baseline, 52.5 [11.8] years), 40 087 (76.2%) were male and 12 512 (23.8%) were female. Four distinct 4-year sleep duration trajectory patterns were identified: normal stable (range, 7.4 to 7.5 hours [n = 40 262]), normal decreasing (mean decrease from 7.0 to 5.5 hours [n = 8074]), low increasing (mean increase from 4.9 to 6.9 hours [n = 3384]), and low stable (range, 4.2 to 4.9 hours [n = 879]). During a mean (SD) follow-up of 6.7 (1.1) years, 2361 individuals died and 2406 had a CVE. Compared with the normal-stable pattern and adjusting for potential confounders, a low-increasing pattern was associated with increased risk of first CVEs (hazard ratio, 1.22; 95% CI, 1.04-1.43), a normal-decreasing pattern was associated with increased risk of all-cause mortality (HR, 1.34; 95% CI, 1.15-1.57), and the low-stable pattern was associated with the highest risk of CVEs (HR, 1.47; 95% CI, 1.05-2.05) and death (HR, 1.50; 95% CI, 1.07-2.10).
Conclusions and relevance: In this study, sleep duration trajectories with lower or unstable patterns were significantly associated with increased risk of subsequent first CVEs and all-cause mortality. Longitudinal sleep duration patterns may assist in more precise identification of different at-risk groups for possible intervention. People reporting consistently sleeping less than 5 hours per night should be regarded as a population at higher risk for CVE and mortality.

Edited by AlPater

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Effects of total fat intake on body fatness in adults.
Hooper L, Abdelhamid AS, Jimoh OF, Bunn D, Skeaff CM.
Cochrane Database Syst Rev. 2020 Jun 1;6:CD013636. doi: 10.1002/14651858.CD013636.
PMID: 32476140 Review.
Background: The ideal proportion of energy from fat in our food and its relation to body weight is not clear. In order to prevent overweight and obesity in the general population, we need to understand the relationship between the proportion of energy from fat and resulting weight and body fatness in the general population.
Objectives: To assess the effects of proportion of energy intake from fat on measures of body fatness (including body weight, waist circumference, percentage body fat and body mass index) in people not aiming to lose weight, using all appropriate randomised controlled trials (RCTs) of at least six months duration.
Search methods: We searched CENTRAL, MEDLINE, Embase, Clinicaltrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) to October 2019. We did not limit the search by language.
Selection criteria: Trials fulfilled the following criteria: 1) randomised intervention trial, 2) included adults aged at least 18 years, 3) randomised to a lower fat versus higher fat diet, without the intention to reduce weight in any participants, 4) not multifactorial and 5) assessed a measure of weight or body fatness after at least six months. We duplicated inclusion decisions and resolved disagreement by discussion or referral to a third party.
ata collection and analysis: We extracted data on the population, intervention, control and outcome measures in duplicate. We extracted measures of body fatness (body weight, BMI, percentage body fat and waist circumference) independently in duplicate at all available time points. We performed random-effects meta-analyses, meta-regression, subgrouping, sensitivity, funnel plot analyses and GRADE assessment.
Main results: We included 37 RCTs (57,079 participants). There is consistent high-quality evidence from RCTs that reducing total fat intake results in small reductions in body fatness; this was seen in almost all included studies and was highly resistant to sensitivity analyses (GRADE high-consistency evidence, not downgraded). The effect of eating less fat (compared with higher fat intake) is a mean body weight reduction of 1.4 kg (95% confidence interval (CI) -1.7 to -1.1 kg, in 53,875 participants from 26 RCTs, I2 = 75%). The heterogeneity was explained in subgrouping and meta-regression. These suggested that greater weight loss results from greater fat reductions in people with lower fat intake at baseline, and people with higher body mass index (BMI) at baseline. The size of the effect on weight does not alter over time and is mirrored by reductions in BMI (MD -0.5 kg/m2, 95% CI -0.6 to -0.3, 46,539 participants in 14 trials, I2 = 21%), waist circumference (MD -0.5 cm, 95% CI -0.7 to -0.2, 16,620 participants in 3 trials; I2 = 21%), and percentage body fat (MD -0.3% body fat, 95% CI -0.6 to 0.00, P = 0.05, in 2350 participants in 2 trials; I2 = 0%). There was no suggestion of harms associated with low fat diets that might mitigate any benefits on body fatness. The reduction in body weight was reflected in small reductions in LDL (-0.13 mmol/L, 95% CI -0.21 to -0.05), and total cholesterol (-0.23 mmol/L, 95% CI -0.32 to -0.14), with little or no effect on HDL cholesterol (-0.02 mmol/L, 95% CI -0.03 to 0.00), triglycerides (0.01 mmol/L, 95% CI -0.05 to 0.07), systolic (-0.75 mmHg, 95% CI -1.42 to -0.07) or diastolic blood pressure(-0.52 mmHg, 95% CI -0.95 to -0.09), all GRADE high-consistency evidence or quality of life (0.04, 95% CI 0.01 to 0.07, on a scale of 0 to 10, GRADE low-consistency evidence).
Authors' conclusions: Trials where participants were randomised to a lower fat intake versus a higher fat intake, but with no intention to reduce weight, showed a consistent, stable but small effect of low fat intake on body fatness: slightly lower weight, BMI, waist circumference and percentage body fat compared with higher fat arms. Greater fat reduction, lower baseline fat intake and higher baseline BMI were all associated with greater reductions in weight. There was no evidence of harm to serum lipids, blood pressure or quality of life, but rather of small benefits or no effect.

Physical capability markers used to define sarcopenia and their association with cardiovascular and respiratory outcomes and all-cause mortality: A prospective study from UK Biobank.
Petermann-Rocha F, Frederick KH, Welsh P, Mackay D, Brown R, Gill JMR, Sattar N, Gray SR, Pell JP, Celis-Morales CA.
Maturitas. 2020 May 5:S0378-5122(20)30247-4. doi: 10.1016/j.maturitas.2020.04.017. Online ahead of print.
PMID: 32471663
Introduction: It is unclear what combinations of physical capability markers used to define sarcopenia have the strongest associations with health outcomes.
Aim: To compare the associations between different combinations of physical capability markers of sarcopenia with cardiovascular and respiratory outcomes and all-cause mortality.
Study design: 469,830 UK Biobank participants were included in this prospective study. Four groups were derived based on combinations of three physical capability markers used to define sarcopenia or severe sarcopenia: gait speed, grip strength and muscle mass. Outcomes studied were all-cause mortality, as well as incidence and mortality from cardiovascular disease (CVD), respiratory disease and chronic obstructive pulmonary disease (COPD).
Results: All combinations of physical capability markers used to define sarcopenia or severe sarcopenia identified individuals at increased risk of respiratory disease and all-cause mortality. However, the definition most strongly associated with a wide range of adverse health outcomes was the combination of slow gait speed plus low muscle mass, followed by severe sarcopenia, and the combination of slow gait speed plus low grip strength. The current definition of sarcopenia (low grip strength plus low muscle mass) had the weakest associations with all-cause (HR: 1.35 [95% CI: 1.07 to 1.71]) and respiratory mortality (HR: 1.88 [95% CI: 1.15 to 3.10]), as well as respiratory disease (HR: 1.38 [95% CI: 1.11 to 1.73]) and COPD incidence (HR: 2.08 [95% CI: 1.14 to 3.79]).
Conclusions: Associations of sarcopenia with adverse outcomes were strongest when sarcopenia was defined as slow gait speed plus low muscle mass, followed by severe sarcopenia, suggesting that this combination of physical capability markers should be still considered in the diagnosis of sarcopenia.
Keywords: EWGSOP2; Incidence; Mortality; Muscle strength.

Healthy lifestyle and risk of incident heart failure with preserved and reduced ejection fraction among post-menopausal women: The women's health initiative study.
Noel CA, LaMonte MJ, Roberts MB, Pearlman DH, Banack H, Allison M, Shadyab AH, Haring B, Laddu D, Martin LW, Nguyen PK, Manson JE, Eaton CB.
Prev Med. 2020 May 27:106155. doi: 10.1016/j.ypmed.2020.106155. Online ahead of print.
PMID: 32473271
We examined associations of diet, physical activity, cigarette smoking, and body mass index (BMI), separately and as a cumulative lifestyle score, with incident hospitalized HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). This analysis included 40,095 postmenopausal women in the Women's Health Initiative clinical trial and observational studies, aged 50-79 years and without self-reported HF at baseline. A healthy lifestyle score (HLS) was developed, in which women received 1 point for each healthy lifestyle. A weighted HLS was also created to examine the independent magnitude of each of the lifestyle factors in HF subtypes. Trained adjudicators determined cases of incident hospitalized HF, HFpEF, HFrEF through March 2018. Multiple variable Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). During a mean follow-up period of 14.5 years, 659 incident HFrEF and 1276 HFpEF cases were documented. Across unweighted HLS of 0 (referent), 1, 2, 3, and 4, multivariable adjusted HRs (95% CI) for HFrEF were 1.00, 0.52 (0.38, 0.71), 0.40 (0.29, 0.56), 0.33 (0.23, 0.48), and 0.33 (0.19, 0.56) (P-trend = 0.03) and for HFpEF were 1.00, 0.47 (0.37, 0.59), 0.39 (0.30, 0.49), 0.26 (0.20, 0.34), and 0.23 (0.15, 0.35) (P-trend < 0.001). Results were similar for the weighted HLS. Our findings suggest that following a healthy lifestyle pattern is associated with lower risks of HFpEF and HFrEF among postmenopausal women.
Keywords: Body mass index; Diet quality; Heart failure; Lifestyle score; Physical activity; Smoking.

Age, sex and disease-specific associations between resting heart rate and cardiovascular mortality in the UK BIOBANK.
Raisi-Estabragh Z, Cooper J, Judge R, Khanji MY, Munroe PB, Cooper C, Harvey NC, Petersen SE.
PLoS One. 2020 May 29;15(5):e0233898. doi: 10.1371/journal.pone.0233898. eCollection 2020.
PMID: 32470091
Objective: To define the sex, age, and disease-specific associations of resting heart rate (RHR) with cardiovascular and mortality outcomes in 502,534 individuals from the UK Biobank over 7-12 years of prospective follow-up.
Methods: The main outcomes were all-cause, cardiovascular, and ischaemic heart disease mortality. Additional outcomes included incident acute myocardial infarction (AMI), fatal AMI, and cancer mortality. We considered a wide range of confounders and the effects of competing hazards. Results are reported as hazard ratios (HR) for all-cause mortality and sub-distribution hazard ratios (SHR) for other outcomes with corresponding 95% confidence intervals (CI) per 10bpm increment of RHR.
Results: In men, for every 10bpm increase of RHR there was 22% (HR 1.22, CI 1.20 to 1.24, p = 3×10-123) greater hazard of all-cause and 17% (SHR 1.17, CI 1.13 to 1.21, p = 5.6×10-18) greater hazard of cardiovascular mortality; for women, corresponding figures were 19% (HR 1.19, CI 1.16 to 1.22, p = 8.9×10-45) and 14% (SHR 1.14, CI 1.07 to 1.22, p = 0.00008). Associations between RHR and ischaemic outcomes were of greater magnitude amongst men than women, but with similar magnitude of association for non-cardiovascular cancer mortality [men (SHR 1.18, CI 1.15-1.21, p = 5.2×10-46); women 15% (SHR 1.15, CI 1.11-1.18, p = 3.1×10-18)]. Associations with all-cause, incident AMI, and cancer mortality were of greater magnitude at younger than older ages.
Conclusions: RHR is an independent predictor of mortality, with variation by sex, age, and disease. Ischaemic disease appeared a more important driver of this relationship in men, and associations were more pronounced at younger ages.

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Association between alcohol intake, mild cognitive impairment and progression to dementia: a dose-response meta-analysis.
Lao Y, Hou L, Li J, Hui X, Yan P, Yang K.
Aging Clin Exp Res. 2020 Jun 1. doi: 10.1007/s40520-020-01605-0. Online ahead of print.
PMID: 32488474 Review.
Background: Mild cognitive impairment (MCI) is a cognitive state falling between normal aging and dementia. The relation between alcohol intake and risk of MCI as well as progression to dementia in people with MCI (PDM) remained unclear.
Objective: To synthesize available evidence and clarify the relation between alcohol intake and risk of MCI as well as PDM.
Method: We searched electronic databases consisting of PubMed, EMBASE, Cochrane Library, and China Biology Medicine disc (CBM) from inception to October 1, 2019. Prospective studies reporting at least three levels of alcohol exposure were included. Categorical meta-analysis was used for quantitative synthesis of the relation between light, moderate and heavy alcohol intake with risk of MCI and PDM. Restricted cubic spline and fixed-effects dose-response models were used for dose-response analysis.
Result: Six cohort studies including 4244 individuals were finally included. We observed an unstable linear relation between alcohol intake (drinks/week) and risk of MCI (P linear = 0.0396). It suggested that a one-drink increment per week of alcohol intake was associated with an increased risk of 3.8% for MCI (RR, 1.038; 95% CI 1.002-1.075). Heavy alcohol intake (> 14 drinks/week) was associated with higher risk of PDM (RR = 1.76; 95% CI 1.10-2.82). And we found a nonlinear relation between alcohol intake and risk of PDM. Drinking more than 16 drinks/week (P nonlinear = 0.0038, HR = 1.42; 95% CI 1.00-2.02), or 27.5 g/day (P nonlinear = 0.0047, HR = 1.46; 95% CI 1.00-2.11) would elevate the risk of PDM.
Conclusion: There was a nonlinear dose-response relation between alcohol intake and risk of PDM. Excessive alcohol intake would elevate the risk of PDM.

Meta-analysis of the association between nut consumption and the risks of cancer incidence and cancer-specific mortality.
Zhang D, Dai C, Zhou L, Li Y, Liu K, Deng YJ, Li N, Zheng Y, Hao Q, Yang S, Song D, Wu Y, Zhai Z, Cao S, Dai Z.
Aging (Albany NY). 2020 Jun 2;12. doi: 10.18632/aging.103292. Online ahead of print.
PMID: 32487780
Previous studies have indicated a correlation between nut intake and cancer risk in humans. This meta-analysis aimed to determine the relationship between nut consumption and the risks of cancer incidence and mortality. The PubMed, Embase, and Web of Science databases were searched up to August 2019. Relative risks and 95% confidence intervals were calculated using random-effects and fixed-effects models. We included 38 studies on nut consumption and cancer risk and 9 studies on cancer-specific mortality. Compared with no nut intake, nut intake was associated with a lower cancer risk (Relative Risk=0.90; 95% confidence interval, 0.86-0.94). Inverse associations were observed with colorectal cancer, gastric cancer, pancreatic cancer, and lung cancer in subgroup analyses. Tree nut consumption was found to reduce cancer risk (Relative Risk=0.88; 95% confidence interval, 0.79-0.99). Dose-response curves suggested that protective benefits against cancer increased with increased nut intake (P=0.005, P-nonlinearity=0.0414). An inverse correlation with cancer-specific mortality (Odd Ratio=0.90; 95% confidence interval, 0.88-0.92) was observed. In conclusion, nut consumption is inversely associated with the risks of cancer incidence and mortality; a higher intake is significantly associated with a lower cancer risk.
Keywords: cancer; meta-analysis; mortality; nuts; risk.

Effects of Vegetarian Diets on Blood Pressure Lowering: A Systematic Review with Meta-Analysis and Trial Sequential Analysis.
Lee KW, Loh HC, Ching SM, Devaraj NK, Hoo FK.
Nutrients. 2020 May 29;12(6):E1604. doi: 10.3390/nu12061604.
PMID: 32486102
The beneficial effects of a vegetarian diet on blood pressure (BP) control have been reported in previous systematic reviews; however, so far, their relative effectiveness is not well established. Here, we performed a systematic review together with trial sequential analysis to determine the effect of a vegetarian diet on the reduction of blood pressure. We searched the randomized controlled trial (RCT) through Medline, PubMed and Cochrane Central Register. Fifteen eligible RCTs with 856 subjects were entered into the analysis. The pooled results demonstrated that vegetarian diet consumption significantly lowered the systolic blood pressure (weighted mean difference (WMD), -2.66 mmHg (95% confidence interval (CI) = -3.76, -1.55, p < 0.001) and diastolic BP was WMD, -1.69 95% CI = -2.97, -0.41, p < 0.001) as compared to an omnivorous diet. In subgroup analysis, a vegan diet demonstrated a greater reduction in systolic BP (WMD, -3.12 mm Hg; 95% CI = -4.54, -1.70, p < 0.001) as compared with a lacto-ovo-vegetarian diet (WMD, -1.75 mm Hg, 95% CI -5.38, 1.88, p = 0.05). The vegan diet has showed a similar trend in terms of diastolic blood pressure reduction (WMD, -1.92 mm Hg (95% CI = -3.18, -0.66, p < 0.001) but those with a lacto-ovo-vegetarian diet showed no changes in diastolic BP reduction (WMD, 0.00, 95% CI = 0.00, 0.00), p =0.432). In conclusion, vegetarian diets are associated with significant reductions in BP compared with omnivorous diets, suggesting that they may play a key role in the primary prevention and overall management of hypertension.
Keywords: diet; hypertension; plant-based diets; vegan; vegetarian.

Differential Effects of Testosterone on Peripheral Neutrophils, Monocytes and Platelets in Men: Findings from Two Trials.
Gagliano-Jucá T, Pencina KM, Guo W, Li Z, Huang G, Basaria S, Bhasin S.
Andrology. 2020 Jun 2. doi: 10.1111/andr.12834. Online ahead of print.
PMID: 32485095
Background: Testosterone treatment increases erythrocytes in men, but its effects on leukocyte and platelet counts are unknown and could affect its safety.
Objective: To determine if testosterone affects circulating leukocytes and platelets in men.
Methods: Secondary analyses of two randomized testosterone trials were performed: the 5α-Reductase (5aR) and OPTIMEN Trials. In 5aR trial, 102 healthy men, 21-50 years (mean age 38), received a long-acting GnRH-agonist, and 50, 125, 300, or 600 mg* week-1 testosterone enanthate (TE) plus placebo or 2.5 mg* day-1 dutasteride for 20-weeks. In OPTIMEN, 78 functionally-limited men, ≥65 years (mean age 72) with protein intake ≤0.83 g* kg-1 * day-1 were randomized to controlled diets with 0.8 g* kg-1 * day-1 protein or 1.3 g* kg-1 * day-1 protein plus placebo or TE (100 mg* week-1 ) for 6 months. Changes from baseline in total and differential leukocyte count, and platelet count were evaluated.
Results: In 5aR, testosterone administration was associated with increases in total leukocyte (estimated change from baseline 40, 490, 1230, and 1280 cells/µL, p<0.001), neutrophil (65.1, 436.1, 1177.2, and 1192.2 cells/µL, p<0.001), monocyte (-20.2, 24.5, 90.6, and 143.9 cells/µL, p<0.001), platelet (-7.3, 8.4, 8.7 and 8.9 * 103 cells/µL, p=0.033), and erythrocyte counts. Testosterone did not affect absolute lymphocyte count. Similar increase in total leukocyte count was observed with testosterone treatment in OPTIMEN (change 0.77* 103 cells/µL, P vs placebo=0.004).
Conclusions: Testosterone administration in men differentially increases neutrophil and monocyte counts. These findings, together with its erythropoietic effects, suggest that testosterone promotes the differentiation of hematopoietic progenitors into the myeloid lineage. These findings have potential mechanistic, therapeutic and safety implications.

Vegans, Vegetarians, and Omnivores: How Does Dietary Choice Influence Iodine Intake? A Systematic Review.
Eveleigh ER, Coneyworth LJ, Avery A, Welham SJM.
Nutrients. 2020 May 29;12(6):E1606. doi: 10.3390/nu12061606.
PMID: 32486114
Vegan and vegetarian diets are becoming increasingly popular. Dietary restrictions may increase the risk of iodine deficiency. This systematic review aims to assess iodine intake and status in adults following a vegan or vegetarian diet in industrialised countries. A systematic review and quality assessment were conducted in the period May 2019-April 2020 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were identified in Ovid MEDLINE, Embase, Web of Science, PubMed, Scopus, and secondary sources. Fifteen articles met inclusion criteria. Participants included 127,094 adults (aged ≥ 18 years). Vegan groups presented the lowest median urinary iodine concentrations, followed by vegetarians, and did not achieve optimal status. The highest iodine intakes were recorded in female vegans (1448.0 ± 3879.0 µg day-1) and the lowest in vegetarians (15.6 ± 21.0 µg day-1). Omnivores recorded the greatest intake in 83% of studies. Seaweed contributed largely to diets of vegans with excessive iodine intake. Vegans appear to have increased risk of low iodine status, deficiency and inadequate intake compared with adults following less restrictive diets. Adults following vegan and vegetarian diets living in countries with a high prevalence of deficiency may be more vulnerable. Therefore, further monitoring of iodine status in industrialised countries and research into improving the iodine intake and status of adults following vegan and vegetarian diets is required.
Keywords: iodine deficiency; iodine intake; iodine status; vegan; vegetarian.

Magnesium levels in relation to rates of preterm birth: a systematic review and meta-analysis of ecological, observational, and interventional studies.
Zhang Y, Xun P, Chen C, Lu L, Shechter M, Rosanoff A, He K.
Nutr Rev. 2020 Jun 1:nuaa028. doi: 10.1093/nutrit/nuaa028. Online ahead of print.
PMID: 32483597
Context: Experimental studies suggest that magnesium levels in pregnant women may affect the length of gestation, as magnesium affects the activity of smooth muscle in the uterus. Little is known about the association between magnesium levels or supplementation and the rate of preterm birth.
Objective: The aim of this systematic review was to summarize the data on magnesium soil levels and preterm birth rates from ecological, observational, and interventional studies.
Data sources: Soil magnesium levels were obtained from US Geological Survey data, and preterm birth rates were acquired from the March of Dimes Foundation. Relevant epidemiological and clinical studies published until April 2019 in peer-reviewed journals were retrieved from PubMed, Google Scholar, and related reference lists.
Study selection: Original studies published in English, conducted in humans, and in which magnesium (dietary/supplemental intake or biomarkers) was an exposure and preterm birth was an outcome were included.
Data extraction: Eleven studies were included in the systematic review. Meta-analysis was performed on 6 studies. Overall relative risk (RR) and corresponding 95%CIs for risk of preterm birth in relation to magnesium supplementation were estimated by a random-effects model.
Results: The ecological study revealed an inverse correlation between magnesium content in soil and rates of preterm birth across the United States (r = -0.68; P < 0.001). Findings from 11 observational studies generally support an inverse association between serum magnesium levels and rates of preterm birth. Of the 6 eligible randomized controlled trials, which included 3068 pregnant women aged 20 to 35 years and 352 preterm infants, the pooled RR was 0.58 (95%CI, 0.35-0.96) for women in the magnesium supplementation group compared with women in the control group.
Conclusions: Accumulated evidence from ecological, observational, and interventional studies consistently indicates that adequate magnesium intake during pregnancy may help reduce the incidence of preterm birth.
Keywords: magnesium supplementation; preterm birth; serum magnesium; soil magnesium.

The effects of garlic (Allium sativum) supplementation on inflammatory biomarkers, fatigue, and clinical symptoms in patients with active rheumatoid arthritis: A randomized, double-blind, placebo-controlled trial.
Moosavian SP, Paknahad Z, Habibagahi Z, Maracy M.
Phytother Res. 2020 Jun 1. doi: 10.1002/ptr.6723. Online ahead of print.
PMID: 32478922
Based on the antiinflammatory properties of garlic, current study was conducted to evaluate the garlic supplement effects on serum levels of some inflammatory biomarkers, clinical symptoms, and fatigue in women with active rheumatoid arthritis. In this randomized, double-blind, placebo-controlled trial study, 70 women with RA were randomly divided into two groups: The intervention group was supplemented with 1,000 mg of garlic, and the control group received placebo for 8 weeks. At baseline and at the end of the study, clinical symptoms, fatigue, serum level of C-reactive protein (CRP), tumor necrosis factor-a (TNF-a), and erythrocyte sedimentation rate (ESR) were determined. After intervention, serum levels of CRP (p = .018) and TNF-a (p < .001) decreased significantly in the garlic group as compared with the placebo group. Also, pain intensity, tender joint count, disease activity score (DAS-28), and fatigue were significantly decreased in the intervention group compared with the control group (p < .001; for all). Swollen joint count was significantly decreased in the garlic group (p < .001), but not in the placebo group (p = .123). No significant changes were observed for ESR. Garlic supplementation by improving inflammatory mediators and clinical symptoms can be considered as a potential adjunct treatment in patients with RA. However, further studies with larger duration are needed.
Keywords: clinical symptoms; fatigue; garlic; inflammatory biomarkers; rheumatoid arthritis.

Lysosome activity is modulated by multiple longevity pathways and is important for lifespan extension in C. elegans.
Sun Y, Li M, Zhao D, Li X, Yang C, Wang X.
Elife. 2020 Jun 2;9:e55745. doi: 10.7554/eLife.55745. Online ahead of print.
PMID: 32482227
Lysosomes play important roles in cellular degradation to maintain cell homeostasis. In order to understand whether and how lysosomes alter with age and contribute to lifespan regulation, we characterized multiple properties of lysosomes during the aging process in C. elegans. We uncovered age-dependent alterations in lysosomal morphology, motility, acidity and degradation activity, all of which indicate a decline in lysosome function with age. The age-associated lysosomal changes are suppressed in the long-lived mutants daf-2, eat-2 and isp-1, which extend lifespan by inhibiting insulin/IGF-1 signaling, reducing food intake and impairing mitochondrial function, respectively. We found that 43 lysosome genes exhibit reduced expression with age, including genes encoding subunits of the proton pump V-ATPase and cathepsin proteases. The expression of lysosome genes is upregulated in the long-lived mutants, and this upregulation requires the functions of DAF-16/FOXO and SKN-1/NRF2 transcription factors. Impairing lysosome function affects clearance of aggregate-prone proteins and disrupts lifespan extension in daf-2, eat-2 and isp-1 worms. Our data indicate that lysosome function is modulated by multiple longevity pathways and is important for lifespan extension.
Keywords: C. elegans; cell biology.

Association of body mass index with risk of cognitive impairment and dementia: A systematic review and meta-analysis of prospective studies.
Qu Y, Hu HY, Ou YN, Shen XN, Xu W, Wang ZT, Dong Q, Tan L, Yu JT.
Neurosci Biobehav Rev. 2020 May 29:S0149-7634(20)30415-2. doi: 10.1016/j.neubiorev.2020.05.012. Online ahead of print.
PMID: 32479774 Review.
Controversies persist about the associations of body mass index (BMI) with risk of cognitive impairment and dementia. This study aimed to evaluate these association from various aspects, in which Embase, PubMed and Cochrane databases were searched to identify prospective studies up to May 2019. Random-effects meta-analyses and dose-response meta-analysis were conducted, involving twenty-nine of 20,083 identified literatures. Meta-analysis showed that midlife underweight, obesity and late-life underweight conferred 1.39-, 1.31- and 1.64-fold excess risk for cognitive impairment and dementia, while late-life overweight and obesity conferred 21% and 25% reduced risk. In dose-response meta-analysis, all cause dementia (ACD), Alzheimer's disease (AD) and vascular dementia (VaD) risk in midlife was significantly elevated when BMI surpassed 29, 30 and 32 kg/m2. AD risk in late-life was decreased when BMI was under 27 kg/m2, while this protection for VaD was absent when BMI surpassed 39 kg/m2. Higher BMI produced opposite exerted opposite effects on dementia in mid- and late-age population. Firstly reported, a dose-response relationship further supports the guideline from the standpoint of dementia prevention.
Keywords: Alzheimer’s disease; body mass index; cognitive impairment; dementia; dose-response; meta-analysis; vascular dementia.

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Serum 25-Hydroxyvitamin D, Albumin, and Mortality among Chinese Older Adults: A Population-based Longitudinal Study.
Jin X, Xiong S, Ju SY, Zeng Y, Yan LL, Yao Y.
J Clin Endocrinol Metab. 2020 Jun 5:dgaa349. doi: 10.1210/clinem/dgaa349. Online ahead of print.
PMID: 32502237
Context: The associations between serum 25-hydroxyvitamin D concentrations [25(OH)D] and all-cause mortality have been inconsistent in existing literatures. One plausible reason is the interaction of intrinsic vitamin D with other biological conditions such as malnutrition and chronic inflammation.
Objective: To explore the associations between serum levels of 25(OH)D, albumin, and all-cause mortality and further evaluate their interactions in elderly people.
Design: Population-based longitudinal study.
Setting and participants: Data were obtained from 1,834 people aged from 65 to 112 who had their serum 25(OH)D and albumin assayed at baseline in 2011. Participants' survival status was ascertained at the 2014 and 2018 follow-up survey waves.
Main outcome measures: All-cause mortality.
Results: Among the 1,834 participants, both serum 25(OH)D and albumin concentrations were inversely associated with all-cause mortality (Ps<0.001). In addition, the interaction effect of 25(OH)D and albumin on all-cause mortality was observed among the participants (P=0.001). In the group with a higher albumin level (≥40 g/L), participants with a lower level of 25(OH)D (<50 nmol/L) had higher risk of mortality than their counterparts (Hazard ratio: 1.92, 95% Confidence Interval =1.45-2.56), and the association was more pronounced in women. In the group with a lower albumin level (<40 g/L), the associations failed to reach statistical significance in all participants as well as in women and in men.
Conclusions: Serum 25(OH)D and albumin levels were inversely associated with all-cause mortality in Chinese older adults. The association between 25(OH)D and mortality was more pronounced in participants with higher albumin levels.
Keywords: 25-hydroxyvitamin D; Albumin; Longevity.

Dietary Intake of Homocysteine Metabolism-Related B-Vitamins and the Risk of Stroke: A Dose-Response Meta-Analysis of Prospective Studies.
Chen L, Li Q, Fang X, Wang X, Min J, Wang F.
Adv Nutr. 2020 Jun 5:nmaa061. doi: 10.1093/advances/nmaa061. Online ahead of print.
PMID: 32503038
Observational studies regarding the putative associations between dietary intake of homocysteine metabolism-related B-vitamins (vitamin B-6, folate, and vitamin B-12) and stroke risk have yielded inconsistent results. Thus, we conducted a systematic meta-analysis of prospective studies in order to examine the relation between the dietary (from diet and supplements) intake of these B-vitamins and the risk of stroke. PubMed and Web of Science were searched for relevant articles published through to 25 February, 2020, and RR of stroke in relation to dietary intake of vitamin B-6, folate, and vitamin B-12 were pooled using a random-effects model. Eleven publications of 12 prospective studies comprising 389,938 participants and 10,749 cases were included in the final analysis. We found that dietary intake of vitamin B-6 and folate were associated with a reduced risk of stroke, and this inverse association remained significant in studies with >10 y of follow-up periods and among participants without a pre-existing stroke event. A dose-response analysis revealed a linear inverse association between folate and vitamin B-6 intake and the risk of stroke, with a pooled RR of 0.94 (95% CI: 0.90-0.98) and 0.94 (95% CI: 0.89-0.99) for each 100 μg/d increment in folate intake and 0.5 mg/d increment in vitamin B-6 intake, respectively. In contrast, we found no significant association between dietary vitamin B-12 intake and the risk of stroke, with an RR of 1.01 (95% CI: 0.97-1.06) per 3 μg/d increase. In conclusion, our findings suggest that increased intake of vitamin B-6 and folate is associated with a reduced risk of stroke, supporting the notion that increasing habitual folate and vitamin B-6 intake may provide a small but beneficial effect with respect to stroke.
Keywords: B-vitamins; dietary intake; dose-response; meta-analysis; stroke.

Potassium Intake and Blood Pressure: A Dose-Response Meta-Analysis of Randomized Controlled Trials.
Filippini T, Naska A, Kasdagli MI, Torres D, Lopes C, Carvalho C, Moreira P, Malavolti M, Orsini N, Whelton PK, Vinceti M.
J Am Heart Assoc. 2020 Jun 5:e015719. doi: 10.1161/JAHA.119.015719. Online ahead of print.
PMID: 32500831
Background Epidemiologic studies, including trials, suggest an association between potassium intake and blood pressure (BP). However, the strength and shape of this relationship is uncertain. Methods and Results We performed a meta-analysis to explore the dose-response relationship between potassium supplementation and BP in randomized-controlled trials with a duration ≥4 weeks using the recently developed 1-stage cubic spline regression model. This model allows use of trials with at least 2 exposure categories. We identified 32 eligible trials. Most were conducted in adults with hypertension using a crossover design and potassium supplementation doses that ranged from 30 to 140 mmol/d. We observed a U-shaped relationship between 24-hour active and control arm differences in potassium excretion and BP levels, with weakening of the BP reduction effect above differences of 30 mmol/d and a BP increase above differences ≈80 mmol/d. Achieved potassium excretion analysis also identified a U-shaped relationship. The BP-lowering effects of potassium supplementation were stronger in participants with hypertension and at higher levels of sodium intake. The BP increase with high potassium excretion was noted in participants with antihypertensive drug-treated hypertension but not in their untreated counterparts. Conclusions We identified a nonlinear relationship between potassium intake and both systolic and diastolic BP, although estimates for BP effects of high potassium intakes should be interpreted with caution because of limited availability of trials. Our findings indicate an adequate intake of potassium is desirable to achieve a lower BP level but suggest excessive potassium supplementation should be avoided, particularly in specific subgroups.
Keywords: blood pressure; dietary supplement; dose‐response meta‐analysis; potassium.

SIRT1 accelerates the progression of activity-based anorexia.
Robinette TM, Nicholatos JW, Francisco AB, Brooks KE, Diao RY, Sorbi S, Ricca V, Nacmias B, Brieño-Enríquez MA, Libert S.
Nat Commun. 2020 Jun 4;11(1):2814. doi: 10.1038/s41467-020-16348-9.
PMID: 32499508
Food consumption is fundamental for life, and eating disorders often result in devastating or life-threatening conditions. Anorexia nervosa (AN) is characterized by a persistent restriction of energy intake, leading to lowered body weight, constant fear of gaining weight, and psychological disturbances of body perception. Herein, we demonstrate that SIRT1 inhibition, both genetically and pharmacologically, delays the onset and progression of AN behaviors in activity-based anorexia (ABA) models, while SIRT1 activation accelerates ABA phenotypes. Mechanistically, we suggest that SIRT1 promotes progression of ABA, in part through its interaction with NRF1, leading to suppression of a NMDA receptor subunit Grin2A. Our results suggest that AN may arise from pathological positive feedback loops: voluntary food restriction activates SIRT1, promoting anxiety, hyperactivity, and addiction to starvation, exacerbating the dieting and exercising, thus further activating SIRT1. We propose SIRT1 inhibition can break this cycle and provide a potential therapy for individuals suffering from AN.

Association of whole grains intake and the risk of digestive tract cancer: a systematic review and meta-analysis.
Zhang XF, Wang XK, Tang YJ, Guan XX, Guo Y, Fan JM, Cui LL.
Nutr J. 2020 Jun 3;19(1):52. doi: 10.1186/s12937-020-00556-6.
PMID: 32493399 Review.
Background: Several epidemiological studies have investigated the association between whole grains intake and digestive tract cancer risk; however, the results are still controversial. The purpose of this meta-analysis was to assess the association.
Methods: Studies published before March 2020 were searched in database and other sources. The risk ratio (RR) with the 95% confidence interval (CI) were pooled using fix or random-effects models.
Results: This meta-analysis included 34 articles reporting 35 studies, 18 studies of colorectal cancer, 11 studies of gastric cancer and 6 studies of esophagus cancer, involving 2,663,278 participants and 28,921 cases. Comparing the highest-intake participants with the lowest-intake participants for whole grains, we found that the intake of whole grains were inversely related to colorectal cancer (RR = 0.89, 95% CI: 0.84-0.93, P < 0.001), gastric cancer (RR = 0.64, 95% CI: 0.53-0.79, P < 0.001), esophagus cancer (RR = 0.54, 95% CI: 0.44-0.67, P < 0.001), respectively. However, subgroup analysis of colorectal cancer found no significant association in the case-control studies and studies of sample size < 500, and subgroup analysis of gastric cancer found no significant association in the cohort studies and studies of American population. No study significantly affected the findings in the sensitivity analysis. No publication bias was found in the studies for colorectal cancer and esophagus cancer except in the studies for gastric cancer.
Conclusion: This meta-analysis provides further evidence that whole grains intake was associated with a reduced risk of digestive tract cancer. Our result supports the dietary guidelines that increase whole grains intake to reduce the risk of digestive tract cancer.
Keywords: Colorectal cancer; Digestive tract cancer; Esophagus cancer; Gastric cancer; Meta-analysis; Whole grains.

Resistance training and total and site-specific cancer risk: a prospective cohort study of 33,787 US men.
Rezende LFM, Lee DH, Keum N, Wu K, Eluf-Neto J, Tabung FK, Giovannucci EL.
Br J Cancer. 2020 Jun 4. doi: 10.1038/s41416-020-0921-8. Online ahead of print.
PMID: 32493991
Background: Muscle-strengthening activities have been recommended for health benefits. However, it is unclear whether resistance training is associated with cancer risk, independent of total physical activity.
Methods: A prospective cohort study followed 33,787 men from the Health Professionals Follow-up Study (1992-2014). Cumulative average of resistance training (hours/week) was assessed through biennial questionnaires up to 2 years before cancer diagnosis. Cox regression model was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI).
Results: During 521,221 person-years of follow-up, we documented 5,158 cancer cases. Resistance training was not associated with total cancer risk (HR per 1-h/week increase: 1.01; 95% CI 0.97, 1.05). We found an inverse association between resistance training and bladder cancer (HR per 1-h/week increase: 0.80; 95% CI 0.66, 0.96) and kidney cancer (HR per 1-h/week increase 0.77; 95% CI 0.58, 1.03; Ptrend = 0.06), but the association was marginal for the latter after adjustment for confounders and total physical activity. Compared to participants engaging in aerobic activities only, combined resistance training and aerobic activities showed stronger inverse associations with kidney cancer risk.
Conclusions: Resistance training was associated with lower risk of bladder and kidney cancers. Future studies are warranted to confirm our findings.

Insulin-like Growth Factor-1 and IGF Binding Proteins Predict All-Cause Mortality and Morbidity in Older Adults.
Zhang WB, Aleksic S, Gao T, Weiss EF, Demetriou E, Verghese J, Holtzer R, Barzilai N, Milman S.
Cells. 2020 Jun 1;9(6):E1368. doi: 10.3390/cells9061368.
PMID: 32492897
While the growth hormone/insulin-like growth factor-1 (GH/IGF-1) pathway plays essential roles in growth and development, diminished signaling via this pathway in model organisms extends lifespan and health-span. In humans, circulating IGF-1 and IGF-binding proteins 3 and 1 (IGFBP-3 and 1), surrogate measures of GH/IGF-1 system activity, have not been consistently associated with morbidity and mortality. In a prospective cohort of independently-living older adults (n = 840, mean age 76.1 ± 6.8 years, 54.5% female, median follow-up 6.9 years), we evaluated the age- and sex-adjusted hazards for all-cause mortality and incident age-related diseases, including cardiovascular disease, diabetes, cancer, and multiple-domain cognitive impairment (MDCI), as predicted by baseline total serum IGF-1, IGF-1/IGFBP-3 molar ratio, IGFBP-3, and IGFBP-1 levels. All-cause mortality was positively associated with IGF-1/IGFBP-3 molar ratio (HR 1.28, 95% CI 1.05-1.57) and negatively with IGFBP-3 (HR 0.82, 95% CI 0.680-0.998). High serum IGF-1 predicted greater risk for MDCI (HR 1.56, 95% CI 1.08-2.26) and composite incident morbidity (HR 1.242, 95% CI 1.004-1.538), whereas high IGFBP-1 predicted lower risk for diabetes (HR 0.50, 95% CI 0.29-0.88). In conclusion, higher IGF-1 levels and bioavailability predicted mortality and morbidity risk, supporting the hypothesis that diminished GH/IGF-1 signaling may contribute to human longevity and health-span.
Keywords: IGF-1; IGFBP-1; IGFBP-3; age-related disease; cognitive impairment; diabetes; health-span; longevity; older adults.

Edited by AlPater

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Influence of Long-Term Fasting on Blood Redox Status in Humans.
Wilhelmi de Toledo F, Grundler F, Goutzourelas N, Tekos F, Vassi E, Mesnage R, Kouretas D.
Antioxidants (Basel). 2020 Jun 6;9(6):E496. doi: 10.3390/antiox9060496.
PMID: 32517172
Fasting is increasingly practiced to improve health and general well-being, as well as for its cytoprotective effects. Changes in blood redox status, linked to the development of a variety of metabolic diseases, have been recently documented during calorie restriction and intermittent fasting, but not with long-term fasting (LF). We investigated some parameters of the blood redox profile in 109 subjects before and after a 10-day fasting period. Fasting resulted in a significant reduction in body weight, improved well-being and had a beneficial modulating effect on blood lipids and glucose regulation. We observed that fasting decreased lipid peroxidation (TBARS) and increased total antioxidant capacity (TAC) in plasma, concomitant with a uric acid elevation, known to be associated with fasting and did not cause gout attacks. Reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx) and catalase in erythrocytes did not show significant changes. In addition, reduction in body weight, waist circumference, and glucose levels were associated to a reduced lipid peroxidation. Similar results were obtained by grouping subjects on the basis of the changes in their GSH levels, showing that a period of 10 days fasting improves blood redox status regardless of GSH status in the blood.
Keywords: GSH; antioxidants; oxidative stress; prolonged fasting; redox biomarkers.

Food restriction induces functional resilience to sleep restriction in rats.
Loomis S, McCarthy A, Dijk DJ, Gilmour G, Winsky-Sommerer R.
Sleep. 2020 Apr 13:zsaa079. doi: 10.1093/sleep/zsaa079. Online ahead of print.
PMID: 32518958
Study objectives: Sleep restriction (SR) leads to performance decrements across cognitive domains but underlying mechanisms remain largely unknown. The impact of SR on performance in rodents is often assessed using tasks in which food is the reward. Investigating how the drives of hunger and sleep interact to modulate performance may provide insights into mechanisms underlying sleep loss-related performance decrements.
Methods: Three experiments were conducted in male adult Wistar rats to assess: (1) effects of food restriction on performance in the simple response latency task (SRLT) across the diurnal cycle (n = 30); (2) interaction of food restriction and SR (11 h) on SRLT performance, sleep electroencephalogram, and event-related potentials (ERP) (n = 10-13); and (3) effects of food restriction and SR on progressive ratio (PR) task performance to probe the reward value of food reinforcement (n = 19).
Results: Food restriction increased premature responding on the SRLT at the end of the light period of the diurnal cycle. SR led to marked impairments in SRLT performance in the ad libitum-fed group, which were absent in the food-restricted group. After SR, food-restricted rats displayed a higher amplitude of cue-evoked ERP components during the SRLT compared with the ad libitum group. SR did not affect PR performance, while food restriction improved performance.
Conclusions: Hunger may induce a functional resilience to negative effects of sleep loss during subsequent task performance, possibly by maintaining attention to food-related cues.
Keywords: attention; circadian rhythm; cognition; effort; event-related potentials; hunger; motivation; sleep deprivation; vigilance.

Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution.
Yap YW, Rusu PM, Chan AY, Fam BC, Jungmann A, Solon-Biet SM, Barlow CK, Creek DJ, Huang C, Schittenhelm RB, Morgan B, Schmoll D, Kiens B, Piper MDW, Heikenwälder M, Simpson SJ, Bröer S, Andrikopoulos S, Müller OJ, Rose AJ.
Nat Commun. 2020 Jun 9;11(1):2894. doi: 10.1038/s41467-020-16568-z.
PMID: 32518324
Dietary protein dilution (DPD) promotes metabolic-remodelling and -health but the precise nutritional components driving this response remain elusive. Here, by mimicking amino acid (AA) supply from a casein-based diet, we demonstrate that restriction of dietary essential AA (EAA), but not non-EAA, drives the systemic metabolic response to total AA deprivation; independent from dietary carbohydrate supply. Furthermore, systemic deprivation of threonine and tryptophan, independent of total AA supply, are both adequate and necessary to confer the systemic metabolic response to both diet, and genetic AA-transport loss, driven AA restriction. Dietary threonine restriction (DTR) retards the development of obesity-associated metabolic dysfunction. Liver-derived fibroblast growth factor 21 is required for the metabolic remodelling with DTR. Strikingly, hepatocyte-selective establishment of threonine biosynthetic capacity reverses the systemic metabolic response to DTR. Taken together, our studies of mice demonstrate that the restriction of EAA are sufficient and necessary to confer the systemic metabolic effects of DPD.

Levels and changes in body mass index decomposed into fat and fat-free mass index: relation to long-term all-cause mortality in the general population.
Sørensen TIA, Frederiksen P, Heitmann BL.
Int J Obes (Lond). 2020 Jun 9. doi: 10.1038/s41366-020-0613-8. Online ahead of print.
PMID: 32518354
Background: In the general population, body mass index (BMI = weight (kg)/(height (m))2) shows a U-shaped relation to mortality, which is attributable to a combination of an inverse association with fat-free mass index (FFMI) and a direct association with fat mass index (FMI). However, preceding changes in body composition related to diseases, health behaviors, or social conditions that are also influencing later mortality may confound these associations.
Objective: To examine associations of FFMI and FMI, adjusted for preceding changes in FFMI and FMI over a 6 years period, with all-cause mortality in a healthy general population.
Methods: The study population was a random subset of adult Danes, participating in the Danish MONICA project; 989 men and 962 women, born 1922, 1932, 1942, and 1952, and examined in 1987-88 and 1993-94. They had no known major co-morbidities until start of follow-up in 1993-94, and were followed up for 18 years. Measures included height, weight, and bio-impedance, from which BMI, FFMI, and FMI were calculated, and information on educational level, smoking, alcohol drinking, leisure-time physical activity, which were obtained by questionnaires. We analyzed the relation between body composition and all-cause mortality by Cox proportional hazards model with splines, stratified by birth cohorts, and with adjustment for preceding changes in body composition and for the covariates including gender. We estimated hazard ratios (HR) with 95% confidence intervals (CI) relative to HR = 1.00 at the median values of BMI, FMI, and FFMI.
Results: During 18 years of follow-up, 286 men and 200 women died. BMI showed the well-known U-shaped association with mortality, and FMI was directly and FFMI inversely associated with mortality. Associations were not significantly modified by gender. Preceding changes in BMI, FMI, and FFMI were only weakly and not significantly associated with mortality. Associations for FMI and FFMI were monotonic, but curve-linear with a higher mortality above and below the respective median values of FMI and FFMI: at the 5th percentiles of FMI and FFMI, HRs were 0.80 (CI 0.57-1.13) and 2.01 (1.24-3.27), and at the 95th percentiles, HRs were 2.16 (1.38-3.38) and 0.81 (0.52-1.27), respectively.
Conclusions: In an apparently healthy general population, a large fat mass and a small fat-free mass are associated with greater risk of early mortality, also after adjusting for preceding changes in body composition, health behaviors, and educational level.

Effect of the Fat Eaten at Breakfast on Lipid Metabolism: A Crossover Trial in Women with Cardiovascular Risk.
Delgado-Alarcón JM, Hernández Morante JJ, Aviles FV, Albaladejo-Otón MD, Morillas-Ruíz JM.
Nutrients. 2020 Jun 6;12(6):E1695. doi: 10.3390/nu12061695.
PMID: 32517188
Recent studies point out that not only the daily intake of energy and nutrients but the time of day when they are ingested notably regulates lipid metabolism and cardiovascular risk (CVR). Therefore, the aim of the study was to assess if the type of fat ingested at breakfast can modify lipid metabolism in women with CVR. A randomized, crossover clinical trial was performed. Sixty volunteers were randomly assigned to a (A) polyunsaturated fatty acid (PUFA)-rich breakfast, (B) saturated fatty acid (SFA)-rich breakfast, or (C) monounsaturated fatty acid (MUFA)-rich breakfast. Plasma lipoprotein and apolipoprotein subfractions were determined. Our data showed that the PUFA-rich breakfast decreased lipoprotein (a) (Lp(a)), very low-density lipoproteins (VLDL), and intermediate-density lipoproteins (IDL), and increased high-density lipoproteins (HDL). A similar trend was observed for the MUFA-rich breakfast, whereas the SFA-rich breakfast, although it decreased VLDL, also increased IDL and reduced HDL. The PUFA-rich breakfast also decreased β-lipoproteins and apolipoprotein-B. In summary, varying the type of fat eaten at breakfast is enough to significantly modify the lipid metabolism of women with CVR, which can be of great relevance to establish new therapeutic strategies for the treatment of these subjects.
Keywords: apolipoprotein; breakfast; cardiovascular risk; fatty acid; lipoprotein.

The Association Between Maternal Prenatal Fish Intake and Child Autism-Related Traits in the EARLI and HOME Studies.
Vecchione R, Vigna C, Whitman C, Kauffman EM, Braun JM, Chen A, Xu Y, Hamra GB, Lanphear BP, Yolton K, Croen LA, Fallin MD, Irva Hertz-Picciotto, Newschaffer CJ, Lyall K.
J Autism Dev Disord. 2020 Jun 9. doi: 10.1007/s10803-020-04546-9. Online ahead of print.
PMID: 32519188
We examined the association between prenatal fish intake and child autism-related traits according to Social Responsiveness Scale (SRS) and cognitive development scores in two US prospective pregnancy cohorts. In adjusted linear regression analyses, higher maternal fish intake in the second half of pregnancy was associated with increased child autism traits (higher raw SRS scores; ß = 5.60, 95%CI 1.76, 12.97). Differences by fish type were suggested; shellfish and large fish species were associated with increases, and salmon with decreases, in child SRS scores. Clear patterns with cognitive scores in the two cohorts were not observed. Future work should further evaluate potential critical windows of prenatal fish intake, and the role of different fish types in association with child autism-related outcomes.
Keywords: Autism; Maternal fish intake; Prenatal diet; Quantitative traits; Social responsiveness scale.

Association of maternal caffeine intake during pregnancy with low birth weight, childhood overweight, and obesity: a meta-analysis of cohort studies.
Jin F, Qiao C.
Int J Obes (Lond). 2020 Jun 9. doi: 10.1038/s41366-020-0617-4. Online ahead of print.
PMID: 32518355 Review.
Background: Epidemiological studies reported inconsistent results on the associations between maternal caffeine intake during pregnancy and risk of low birth weight (LBW) and childhood overweight and obesity in their offspring.
Methods: We conducted a meta-analysis of cohort studies to quantitatively assess these associations. Pertinent studies were identified by searching PubMed and Embase through June 2019. Study-specifics risk estimates were combined using fixed effects models, or random-effects models when significant heterogeneity was detected. Dose-response analysis was modeled by using restricted cubic splines.
Results: A total of 15 cohort studies, with 102,347 pregnancy women, was included in the meta-analysis. The pooled relative risk (RR) for LBW was 1.33 (95% CI: 1.12, 1.57) for mothers with the highest compared with the lowest level of caffeine intake during pregnancy, with significant heterogeneity across studies (I2 = 49.3%, P = 0.032). The pooled RR was 1.07 (95% CI: 1.02, 1.11) for each 100 mg/day increase of caffeine intake. The pooled RR for childhood overweight and obesity was 1.39 (95% CI: 1.15, 1.69) for mothers with the highest compared with the lowest level of caffeine intake during pregnancy. No significant heterogeneity across studies was detected (I2 = 38.9%, P = 0.179). The pooled RR was 1.31 (95% CI: 1.11, 1.55) for each 100 mg/day increase of caffeine intake. No evidence of publication bias was indicated.
Conclusions: Maternal caffeine intake during pregnancy is associated with higher risk of LBW and childhood overweight and obesity. Further studies may focus on investigating the potential mechanisms before the recommendation of complete avoidance of caffeine intake during pregnancy.

Consumption of flavonoid-rich fruits and risk of coronary heart disease: a prospective cohort study.
Yang Y, Dong JY, Cui R, Muraki I, Yamagishi K, Sawada N, Iso H, Tsugane S; Japan Public Health Center-based Prospective Study Group.
Br J Nutr. 2020 Jun 9:1-26. doi: 10.1017/S0007114520001993. Online ahead of print.
PMID: 32513342
Although the association between fruit consumption and coronary heart disease (CHD) risk was well studied, few studies have focused on flavonoid-rich fruits (FRFs), in particular strawberries and grapes. We aimed to verify the association of total and specific FRF consumption with risk of CHD by a large prospective cohort study. A total of 87,177 men and women aged 44-75 who were free of cardiovascular disease and cancer at study baseline were eligible for the present analysis. FRF consumption was assessed using a food frequency questionnaire. Cox proportional hazards regression models were used to estimate the hazard ratios of CHD in relation to FRF consumption with adjustment for potential risk factors and confounders. During a mean follow-up of 13.2 years, we identified 1156 incident CHD cases. After fully adjustment for covariates including demographics, lifestyles, and dietary factors, the HRs were 0.93 (95% CI: 0.77, 1.11), 0.91 (95% CI: 0.75, 1.11), 0.84 (95% CI: 0.67, 1.04), and 0.78 (95% CI: 0.62, 0.99) for the second, third, fourth, and fifth quintiles compared with lowest quintile of FRF consumption. Regarding specific fruits, we observed a significant inverse association for citrus fruit consumption and a borderline inverse association for strawberry consumption, while no association was observed for apple/pear, or grape consumption. Although the associations appeared to be stronger in women, they were not significantly modified by sex. Higher consumption of FRFs, in particular, citrus fruits, may be associated with a lower risk of developing CHD.
Keywords: coronary heart disease; flavonoids; fruits; incidence; prospective cohort study.

Effects of Potassium or Sodium Supplementation on Mineral Homeostasis: a Controlled Dietary Intervention Study.
Humalda JK, Yeung SMH, Geleijnse JM, Gijsbers L, Riphagen IJ, Hoorn EJ, Rotmans JI, Vogt L, Navis G, Bakker SJL, De Borst MH.
J Clin Endocrinol Metab. 2020 Jun 7:dgaa359. doi: 10.1210/clinem/dgaa359. Online ahead of print.
PMID: 32506135
Context: Although dietary potassium and sodium intake may influence calcium-phosphate metabolism, and bone health, the effects on bone mineral parameters, including fibroblast growth factor 23 (FGF23) are unclear.
Objective: Here, we investigated the effects of potassium or sodium supplementation on bone mineral parameters.
Design: setting, participants: We performed a post-hoc analysis of a dietary controlled randomized, blinded, placebo-controlled crossover trial. Pre-hypertensive individuals not using antihypertensive medication (n=36) received capsules containing potassium chloride (3 grams/day), sodium chloride (3 grams/day) or placebo. Linear mixed-effect models were used to estimate treatment effects.
Results: Potassium supplementation increased plasma phosphate (from 1.10±0.19 to 1.15±0.19 mmol/L, P=0.004), in line with increase in tubular maximum of phosphate reabsorption (TmP/GFR; from 0.93±0.21 to 1.01±0.20 mmol/L, P<0.001). FGF23 decreased (114.3 [96.8-135.0] to 108.5 [93.5-125.9] RU/mL, [P=0.01]), without change in parathyroid hormone and 25(OH)-vitamin D3. Fractional calcium excretion decreased (from 1.25±0.50 to 1.11±0.46 %, P=0.03) without change in plasma calcium. Sodium supplementation decreased both plasma phosphate (from 1.10±0.19 to 1.06±0.21 mmol/L, P=0.03) and FGF23 (from 114.3 [96.8-135.0] to 108.7 [92.3-128.1] RU/mL, P=0.02). Urinary and fractional calcium excretion increased (from 4.28±1.91 to 5.45±2.51 mmol/24 hrs, P<0.001, and from 1.25±0.50 to 1.44±0.54 %, P=0.004, respectively).
Conclusions: Potassium supplementation led to a decrease in FGF23, which was accompanied by increase in plasma phosphate and decreased calcium excretion. Sodium supplementation reduced FGF23, but this was accompanied by decrease in phosphate and increase in fractional calcium excretion. Our results indicate distinct effects of potassium and sodium intake on bone mineral parameters, including FGF23.
Keywords: Diet controlled clinical trial; calcium-phosphate metabolism; fibroblast growth factor 23; nutrition; potassium; sodium.

Soy consumption and incidence of gestational diabetes mellitus: the Japan Environment and Children's Study.
Dong JY, Kimura T, Ikehara S, Cui M, Kawanishi Y, Kimura T, Ueda K, Iso H; Japan Environment and Children’s Study Group.
Eur J Nutr. 2020 Jun 6. doi: 10.1007/s00394-020-02294-1. Online ahead of print.
PMID: 32506178
Background: Intervention studies have shown that isoflavone treatment improved glucose metabolism, indicating that soy intake may have a potential role in diabetes prevention.
Objectives: We aimed to investigate the prospective association of soy isoflavone and soy food intakes with incidence of gestational diabetes mellitus (GDM) in a birth cohort study.
Methods: We recruited 97,454 pregnant women (median gestational age 12 weeks) between January 2011 and March 2014. Dietary intakes during the 12 months preceding study enrollment were assessed by a semi-quantitative food frequency questionnaire. The relative risks of GDM associated with soy isoflavone and soy food intakes were obtained by Poisson regression. Demographic information, histories of diseases, socioeconomic status, lifestyles, and dietary habits, obtained by a self-administrated questionnaire, were used for covariate adjustments.
Results: We identified 1904 cases of GDM (2.2%) among 84,948 women. Compared with those in the lowest quintile of soy isoflavone intake, women in the highest quintile were found to have experienced a significantly lower risk of GDM (multivariate relative risk = 0.82; 95% confidence interval: 0.70, 0.95; P for trend = 0.05). Similar results were observed for genistein and daidzein. Regarding soy foods, intakes of miso soup and natto were inversely associated with GDM incidence (both P for trend ≤ 0.01), whereas the association for tofu intake appeared to be nonlinear (P for trend = 0.74).
Conclusions: Higher intakes of miso soup and natto before and during early pregnancy, compared with lower intakes, may be associated with a lower incidence of GDM.
Keywords: Cohort study; Gestational diabetes mellitus; Isoflavone; Prevention; Soy.

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Effects of low-dose milk protein supplementation following low-to-moderate intensity exercise training on muscle mass in healthy older adults: a randomized placebo-controlled trial.
Nakayama K, Saito Y, Sanbongi C, Murata K, Urashima T.
Eur J Nutr. 2020 Jun 10. doi: 10.1007/s00394-020-02302-4. Online ahead of print.
PMID: 32524231
Purpose: The purpose of this study was to examine whether long-term ingestion of low-dose milk protein supplementation causes a greater increase in muscle mass and strength of older adults during low-to-moderate intensity exercise training intervention than isocaloric carbohydrate.

Methods: In a randomized, double-blind, and placebo-controlled design, 122 healthy older adults (60-84 year) received either an acidified milk protein drink containing 10 g of milk protein (MILK; n = 61) or an isocaloric placebo drink (PLA; n = 61) daily throughout 6 months of body weight and medicine ball exercise training. Measurements before and after the intervention included body composition, physical performance and blood biochemistry.
Results: Lean body mass significantly increased in the MILK group (+ 0.54 kg, p < 0.001), but did not change in the PLA group (- 0.10 kg, p = 0.534). The increases in the MILK group were significantly greater than in the PLA group (p = 0.004). Fat mass (- 0.77 kg) and plasma uric acid levels (- 0.3 mg/dL) significantly decreased only in the MILK group (p < 0.001), with a significant group difference (p = 0.002 and p < 0.001, respectively). Most of the physical performance tests significantly improved in both groups, but no group differences were found.
Conclusion: We conclude that low-dose milk protein supplementation (10 g of protein/day) combined with low-to-moderate intensity exercise training is associated with increased muscle mass, but not improved physical performance compared to carbohydrate combined with exercise in healthy older adults.
Keywords: Aging; Elderly; Hypertrophy; Lean body mass; Physical performance; Sarcopenia.

l-Serine and EPA Relieve Chronic Low-Back and Knee Pain in Adults: A Randomized, Double-Blind, Placebo-Controlled Trial.
Sasahara I, Yamamoto A, Takeshita M, Suga Y, Suzuki K, Nishikata N, Takada M, Hashimoto M, Mine T, Kobuna Y, Nagao K.
J Nutr. 2020 Jun 10:nxaa156. doi: 10.1093/jn/nxaa156. Online ahead of print.
PMID: 32520991
Background: Multisite pain, including low-back and knee pain, is a major health issue that greatly decreases quality of life.
Objectives: This study analyzed the effects of l-serine, which provides necessary components for nerve function, and EPA, which exerts anti-inflammatory properties, on pain scores of adults with pain in at least the low back and knee for ≥3 mo.
Methods: This was a randomized, double-blind, placebo-controlled, parallel-group study. The Japan Low Back Pain Evaluation Questionnaire (JLEQ) and Japanese Knee Osteoarthritis Measure (JKOM) were applied as primary outcomes. The Brief Pain Inventory (BPI) and safety evaluation were secondary outcomes. We enrolled 120 participants aged ≥20 y (36 men and 84 women: mean ± SD age = 40.8 ± 10.9 y). The participants were randomly allocated to either the active group (daily ingestion of 594 mg l-serine and 149 mg EPA) or placebo group. The study period consisted of 8-wk dosing and 4-wk posttreatment observation. ANCOVA between groups for each time point was conducted using the baseline scores as covariates.
Results: The JLEQ scores (active compared with placebo: 14.2 ± 11.2 compared with 19.0 ± 10.2) at week 8 were lower in the active group (P < 0.001). The JKOM scores at week 4 (11.7 ± 9.0 compared with 13.9 ± 7.9), week 8 (10.4 ± 7.9 compared with 13.1 ± 7.1), and week 12 (10.3 ± 7.4 compared with 13.8 ± 7.5) were lower in the active group (P ≤ 0.04). Additionally, the active group had 11-27% better scores compared with the placebo group for BPI1 (worst pain), BPI3 (average pain), and BPI5D (pain during moving) at week 4 (P ≤ 0.028) and week 8 (P ≤ 0.019), respectively, and BPI5D was 23% better in the active group at week 12 (P = 0.007). No adverse events were observed.
Conclusions: l-Serine and EPA were effective for pain relief in adults with low-back and knee pain after multiplicity adjustment.This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry as UMIN000035056.
Keywords: Brief Pain Inventory (BPI); Japan Low Back Pain Evaluation Questionnaire (JLEQ); Japanese Knee Osteoarthritis Measure (JKOM); clinical; low-back and knee pain; multiple site pain; neuropathic pain.

Exercise and Protein Effects on Strength and Function with Weight Loss in Older Women.
Evans EM, Straight CR, Reed RA, Berg AC, Rowe DA, Johnson MA.
Med Sci Sports Exerc. 2020 Jun 8. doi: 10.1249/MSS.0000000000002429. Online ahead of print.
PMID: 32520876
Obesity negatively impacts lower extremity physical function (LEPF) in older adults. Exercise and a higher protein diet are both known to positively and independently impact body composition, muscle strength and LEPF during weight loss; however, their potential interactive effects have not been well characterized in older women.
Purpose: The aim of this study was to determine the relative efficacy of a higher protein diet with or without exercise to improve body composition, muscle strength, and LEPF in older inactive overweight/obese women after weight loss.
Methods: Postmenopausal women (BMI=31.1±5.1 kg/m, 69.2±3.6 y) completed a 6-month weight loss program after randomization to three groups (n=72 randomized; 15% drop-out): 1) higher protein diet (PRO, ~30% energy from protein; n=20), 2) PRO plus exercise (PRO+EX; n=19), or 3) a conventional protein control diet plus EX (CON+EX, ~18% energy from protein; n=22). EX was supervised, multicomponent (aerobic, muscle strengthening, balance, flexibility) and 3 sessions/week. Body composition was measured via dual-energy X-ray absorptiometry; leg strength by isokinetic dynamometry; and LEPF via 6-minute walk, 8-foot up and go, and 30-second chair stand tests.
Results: Changes in weight (-7.5±4.1 kg; -9.2±4.8%), fat mass, and leg lean mass did not differ among groups (all P>0.50). Despite weight loss, muscle strength improved in the exercise groups (PRO+EX and CON+EX) whereas it declined in the PRO group (P=0.008). For all LEPF measures, the PRO group had attenuated improvements compared to both PRO+EX and CON+EX (all P<0.01).
Conclusion: Exercise during weight loss is critical to preserve strength and enhance LEPF; however, a higher protein diet does not appear to influence body composition, muscle strength or LEPF changes when combined with multicomponent exercise.

Grapefruit juice enhances the systolic blood pressure-lowering effects of dietary nitrate-containing beetroot juice.
O'Gallagher K, Borg Cardona S, Hill C, Al-Saedi A, Shahed F, Floyd CN, McNeill K, Mills CE, Webb AJ.
Br J Clin Pharmacol. 2020 Jun 10. doi: 10.1111/bcp.14420. Online ahead of print.
PMID: 32520418
Introduction: Dietary nitrate from sources such as beetroot juice lowers blood pressure (BP) via the nitrate-nitrite-nitric oxide (NO) pathway. However, NO and nitrite are inactivated via re-oxidation to nitrate, potentially limiting their activity. Cytochrome P450-3A4 inhibition with troleandomycin prevents nitrite re-oxidation to nitrate in rodent liver. Grapefruit juice contains the CYP3A4 inhibitor furanocoumarin. We therefore hypothesized that grapefruit juice would enhance BP-lowering with beetroot juice by maintaining circulating [nitrite].
Methods: We performed a randomized, placebo-controlled, 7-hour crossover study in 11 healthy volunteers, attending on 3 occasions, receiving: a 70ml-shot of active beetroot juice (Beet-It®) and either (i) 250 ml grapefruit juice ("Active Beet+GFJ"), or (ii) 250 ml water (Buxton®, "Active Beet+H2 O"); or (iii) Placebo Beet+GFJ.
Results: The addition of grapefruit juice to active beetroot juice lowered systolic BP (SBP): Active Beet+GFJ versus Active Beet+H2 O (P=0.02), and pulse pressure, PP (P=0.0003). Peak mean differences in SBP and PP were seen at T=5 hours: -3.3mmHg (95% CI -6.43 to -0.15) and at T=2.5 hours: -4.2 mmHg (95% CI -0.3 to -8.2), respectively. Contrary to the hypothesis, plasma [nitrite] was lower with Active Beet+GFJ versus Active Beet+H2 O (P=0.006), as was salivary nitrite production (P=0.002) and saliva volume (-0.34 ml/min (95% CI -0.05 to -0.68)). The taste score of Beet+GFJ was 1.4/10 points higher than Beet+H2 O (P=0.03).
Conclusions: Grapefruit juice enhanced beetroot juice's effect on lowering SBP and PP despite decreasing plasma [nitrite]. Besides suggesting more complex mechanisms, there is potential for maximising the clinical benefit of dietary nitrate and targeting isolated systolic hypertension.
Keywords: blood pressure; cytochrome p450; nitric oxide.

Sex-and race-specific associations of protein intake with change in muscle mass and physical function in older adults: the Health, Aging, and Body Composition (Health ABC) Study.
Elstgeest LE, Schaap LA, Heymans MW, Hengeveld LM, Naumann E, Houston DK, Kritchevsky SB, Simonsick EM, Newman AB, Farsijani S, Visser M, Wijnhoven HA; Health ABC Study.
Am J Clin Nutr. 2020 Jun 10:nqaa099. doi: 10.1093/ajcn/nqaa099. Online ahead of print.
PMID: 32520344
Background: Protein intake recommendations advise ≥0.8 g/kg body weight (BW)/d, whereas experts propose a higher intake for older adults (1.0-1.2 g/kg BW/d). It is unknown whether optimal protein intake differs by sex or race.
Objectives: We examined the shape of sex- and race-specific associations of dietary protein intake with 3- and 6-y changes in appendicular lean mass (aLM) and gait speed and also 6-y incidence of mobility limitation in community-dwelling older men and women.
Methods: We used data on men (n = 1163) and women (n = 1237) aged 70-81 y of the Health, Aging, and Body Composition Study. Protein intake was assessed using an FFQ (1998-1999). aLM and gait speed were measured at baseline and at 3 and 6 y. Difficulty walking one-quarter mile or climbing stairs was measured every 6 mo over 6 y. Prospective associations were evaluated with linear and Cox regression models, comparing fit of models with and without spline functions. All analyses were stratified by sex and additionally by race.
Results: Mean ± SD protein intake was 0.94 ± 0.36 g/kg adjusted body weight (aBW)/d in men and 0.95 ± 0.36 g/kg aBW/d in women. There were no strong indications of nonlinear associations. In women, higher protein intake was associated with less aLM loss over 3 y (adjusted B per 0.1 g/kg aBW/d: 39.4; 95% CI: 11.6, 67.2), specifically in black women, but not over 6 y or with gait speed decline. In men, protein intake was not associated with changes in aLM and gait speed. Higher protein intake was associated with a lower risk of mobility limitation in men (adjusted HR per 1.0 g/kg aBW/d: 0.55; 95% CI: 0.34, 0.91) and women (adjusted HR: 0.56; 95% CI: 0.33, 0.94), specifically white women.
Conclusions: Associations between protein intake and physical outcomes may vary by sex and race. Therefore, it is important to consider sex and race in future studies regarding protein needs in older adults.
Keywords: appendicular lean body mass; community-dwelling; gait speed; mobility limitation; old age; optimal intake; physical performance; spline functions.

Alcohol Consumption and Risk of Hospitalizations and Mortality in the Atherosclerosis Risk in Communities (ARIC) Study.
Daya NR, Rebholz CM, Appel LJ, Selvin E, Lazo M.
Alcohol Clin Exp Res. 2020 Jun 11. doi: 10.1111/acer.14393. Online ahead of print.
PMID: 32524620
Background: Public health recommendations on the benefits and harms of moderate alcohol intake require a thorough and unbiased understanding of all potential effects of various levels and patterns of alcohol consumption. We seek to evaluate the associations between patterns of current and past alcohol consumption with hospitalizations and mortality.
Methods: Data came from a prospective cohort of 12,327 adults (56% women, 78% white, mean age 60 years) participating in the Atherosclerosis Risk in Communities (ARIC) study visit 3 (1993-1995). Current and past alcohol consumption was based on self-report. Hospitalizations and mortality were ascertained through December 31, 2017. Negative binomial and cox proportional hazards regressions were used.
Results: 24.8% of the study population reported never drinking, 48.3% reported currently drinking without a history of heavy drinking, 4.2% reported currently drinking with a history of heavy drinking, 19.2% reported being former drinkers without a history of heavy drinking and 3.4% reported being former drinkers with a history of heavy drinking. Compared to those who reported drinking ≤1-7 drinks/week, never drinkers [incident rate ratio (IRR): 1.21 (95% confidence interval 1.13, 1.29] and former drinkers with [IRR: 1.43 (1.26, 1.63)] or without [IRR: 1.21 (1.13, 1.30)] a history of heavy drinking had a positive association with all-cause hospitalization (P<0.001). Those who reported drinking ≤1-7 drinks/week had the lowest all-cause mortality rate [19.2 per 1,000 person years (18.4, 20.1)] and former drinkers with a history of heavy drinking had the highest [43.7 per 1,000 person years (39.0, 49.1)].
Conclusions: The positive associations with hospitalization and mortality were stronger among never and former drinkers compared to those who consume ≤1-7 drinks/week. Former drinkers with a history of heavy drinking had a stronger positive association with adverse health outcomes than former drinkers without a history of heavy drinking, highlighting the impact of this pattern of alcohol consumption.
Keywords: Alcohol; hospitalizations; mortality.

Associations of Exercise Types with All-Cause Mortality among U.S. Adults.
Sheehan CM, Li L.
Med Sci Sports Exerc. 2020 Jun 8. doi: 10.1249/MSS.0000000000002406. Online ahead of print.
PMID: 32520868
Purpose: Exercising benefits physical and mental health as well as longevity. However, the extent to which different types of exercise are differentially associated with the risk of mortality is less clear. This study examined whether 15 different types of exercise were uniquely associated with all-cause mortality in a nationally representative sample of noninstitutionalized American adults aged between 18 and 84 years.
Methods: A total of 26,727 American adults in the National Health Interview Survey (NHIS) who reported their exercise type(s) in 1998 were prospectively followed for all-cause mortality through the end of 2015. We applied a series of discrete time logistic models to estimate odds ratios (OR) and 95% confidence intervals (CI) for all-cause mortality.
Results: During 17 years of follow-up, 4,955 deaths occurred. After adjusting for total volume of other exercises and confounders (demographic factors, socioeconomic status, and health behaviors and status), walking, aerobics, stretching, weight lifting, cycling, and stair climbing were related to lower risks of mortality (ORs ranged from 0.78 to 0.93). When adjusting for engagement in all exercise types and confounders, stretching (OR = 0.90, 95%CI = 0.83-0.97) and playing volleyball (OR = 0.53, 95%CI = 0.31-0.93) were uniquely associated with lower risks of mortality.
Conclusion: These findings suggest that some types of exercise have unique benefits for longevity, but most are indistinguishable in relation to longevity. Future studies should further investigate the unique contribution of specific exercises and the joint contribution of multiple exercises and how to promote greater exercise participation.

Whole-genome sequencing of Chinese centenarians reveals important genetic variants in aging WGS of centenarian for genetic analysis of aging.
Shen S, Li C, Xiao L, Wang X, Lv H, Shi Y, Li Y, Huang Q.
Hum Genomics. 2020 Jun 10;14(1):23. doi: 10.1186/s40246-020-00271-7.
PMID: 32522283
Background: Genetic research on longevity has provided important insights into the mechanism of aging and aging-related diseases. Pinpointing import genetic variants associated with aging could provide insights for aging research.
Methods: We performed a whole-genome sequencing in 19 centenarians to establish the genetic basis of human longevity.
Results: Using SKAT analysis, we found 41 significantly correlated genes in centenarians as compared to control genomes. Pathway enrichment analysis of these genes showed that immune-related pathways were enriched, suggesting that immune pathways might be critically involved in aging. HLA typing was next performed based on the whole-genome sequencing data obtained. We discovered that several HLA subtypes were significantly overrepresented.
Conclusions: Our study indicated a new mechanism of longevity, suggesting potential genetic variants for further study.
Keywords: Centenarian; Longevity; WGS.

Autologous fecal transplantation from a lean state potentiates caloric restriction effects on body weight and adiposity in obese mice.
Pérez-Matute P, Íñiguez M, de Toro M, Recio-Fernández E, Oteo JA.
Sci Rep. 2020 Jun 10;10(1):9388. doi: 10.1038/s41598-020-64961-x.
PMID: 32523094
Autologous fecal transplantation (FT-A) emerges as a promising strategy to modulate gut microbiota with minimal side effects since individual´s own feces are transplanted. With the premise of improving obesity and its associated disorders, we investigated if fecal microbiota transplantation (FMT), heterologous and autologous, potentiates the effects of a moderate caloric restriction (CR) in high-fat diet (HFD)-induced obese mice. Mice were randomized into control, HFD, CR (12 weeks on HFD and 6 weeks under CR), FT-H (similar to CR and FMT carried out with feces from controls, weeks 17 & 18), and FT-A (administration of their own feces before developing obesity at weeks 17 & 18). Our study demonstrated that FMT, and, especially, FT-A potentiates the effects of a moderate CR on weight loss and adiposity in the short term, by decreasing feed efficiency and increasing adipose tissue lipolysis. Although FT-A produced a significant increase in bacterial richness/diversity, FMT did not significantly modify gut microbiota composition compared to the CR at phyla and bacteria genera levels, and only significant increases in Bifidobacterium and Blautia genera were observed. These results could suggest that other mechanisms different from bacterial microbiota engraftment participates in these beneficial effects. Thus, FT-A represents a very positive synergetic approach for obese patients that do not respond well to moderate restrictive diets.

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Pro-Senescence and Anti-Senescence Mechanisms of Cardiovascular Aging: Cardiac MicroRNA Regulation of Longevity Drug-Induced Autophagy.
Pulakat L, Chen HH.
Front Pharmacol. 2020 May 26;11:774. doi: 10.3389/fphar.2020.00774. eCollection 2020.
PMID: 32528294 Free PMC article. Review.
Pro-Senescence and Anti-Senescence Mechanisms of Cardiovascular Aging: Cardiac MicroRNA Regulation of Longevity Drug-Induced Autophagy.
Pulakat L, Chen HH.
Front Pharmacol. 2020 May 26;11:774. doi: 10.3389/fphar.2020.00774. eCollection 2020.
PMID: 32528294 Free PMC article. Review.

Thyroid hormones and frailty in persons experiencing extreme longevity.
Arosio B, Monti D, Mari D, Passarino G, Ostan R, Ferri E, De Rango F, Franceschi C, Cesari M, Vitale G.
Exp Gerontol. 2020 Jun 7:111000. doi: 10.1016/j.exger.2020.111000. Online ahead of print.
PMID: 32525032
Context: The aging phenotype is quite heterogeneous, being the result of the capability of each individual to successfully or unsuccessfully response to stressors. The reduction of homeostatic reserve characterizing aging is accompanied by a remodeling of the endocrine system. Frailty has been indicated as a promising way for capturing the physiological decline as well as the biological aging of the individuals. In particular, the Frailty Index (FI), based on the assumption that health deficits tend to accumulate with aging, represents a quantitative measure of extreme interest.
Objective: The study aims to correlate the thyroid hormone levels with FI in a population of centenarians and their offspring to capture the effects of thyroid remodeling in extreme longevity.
Study design: The study described 593 well-characterized Italian subjects, including 180 centenarians, as well as 276 centenarian's offspring and 137 age-matched controls.
Results: FT3 levels and FT3/FT4 ratio were significantly lower (p < 0.001) and TSH levels higher (p < 0.001) in centenarians compared to the other groups, analysing both overall subjects and excluding subjects with hormone levels out of the normal ranges. In overall centenarians, we observed a negative correlation between FI and FT3 (ρ: -0.281, p < 0.001), FT3/FT4 (ρ: -0.344, p < 0.001) and TSH (ρ: -0.223, p 0.003) and a positive association between FI and FT4 (ρ: 0.189, p = 0.001). In centenarians with hormone levels within the normal ranges, similar negative correlations were observed between FI and FT3 (ρ: -0.201, p = 0.02) and FT3/FT4 (ρ: -0.264, p = 0.002). In this sub-analysis, FI positively correlated with FT4 and age (ρ: 0.167, p = 0.05; ρ: 0.219, p = 0.005, respectively). Conversely, no significant correlations were observed between hormone levels and FI in offspring and controls.
Conclusions: We found an association between thyroid hormone levels and frailty in centenarians, underlying the significant role of thyroid in the aging process and longevity.
Keywords: Centenarians; Frailty; Frailty index; Longevity; Thyroid hormones.

Metabolic Effects of Late Dinner in Healthy Volunteers - A Randomized Crossover Clinical Trial.
Gu C, Brereton N, Schweitzer A, Cotter M, Duan D, Børsheim E, Wolfe RR, Pham LV, Polotsky VY, Jun JC.
J Clin Endocrinol Metab. 2020 Jun 11:dgaa354. doi: 10.1210/clinem/dgaa354. Online ahead of print.
PMID: 32525525
Context: Consuming calories later in the day is associated with obesity and metabolic syndrome. We hypothesized that eating a late dinner alters substrate metabolism during sleep in a manner that promotes obesity.
Objective: To examine the impact of late dinner on nocturnal metabolism in healthy volunteers.
Design and setting: This is a randomized crossover trial of late dinner (LD, 22:00) versus routine dinner (RD, 18:00), with a fixed sleep period (23:00-07:00) in a laboratory setting.
Participants: 20 healthy volunteers (10 males, 10 females), aged 26.0 ± 0.6 years, BMI 23.2 ± 0.7 kg/m2, accustomed to a bedtime between 22:00-01:00.
Interventions: An isocaloric macronutrient diet was administered on both visits. Dinner (35% daily kcal, 50% carbohydrate, 35% fat) with an oral lipid tracer ([2H31] palmitate, 15 mg/kg) was given at 18:00 on RD and 22:00 on LD.
Main outcome measures: Nocturnal and next-morning hourly plasma glucose, insulin, triglycerides, free fatty acids (FFAs), cortisol, dietary fatty acid oxidation, and overnight polysomnography.
Results: LD caused a 4-hour shift in the postprandial period, overlapping with the sleep phase. Independent of this shift, the postprandial period following LD was characterized by higher glucose, a triglyceride peak delay, and lower FFA and dietary fatty acid oxidation. LD did not affect sleep architecture, but increased plasma cortisol. These metabolic changes were most pronounced in habitual earlier sleepers determined by actigraphy monitoring.
Conclusion: LD induces nocturnal glucose intolerance, and reduces fatty acid oxidation and mobilization, particularly in earlier sleepers. These effects might promote obesity if they recur chronically.
Keywords: Late eating; cortisol; fatty acid oxidation; glucose; lipids; sleep.

Association of Age of Onset of Hypertension With Cardiovascular Diseases and Mortality.
Wang C, Yuan Y, Zheng M, Pan A, Wang M, Zhao M, Li Y, Yao S, Chen S, Wu S, Xue H.
J Am Coll Cardiol. 2020 Jun 16;75(23):2921-2930. doi: 10.1016/j.jacc.2020.04.038.
PMID: 32527401
Background: The relations of hypertension onset age with cardiovascular diseases (CVD) and all-cause mortality remain inconclusive.
Objectives: This study sought to examine the associations of hypertension onset age with CVD and all-cause mortality.
Methods: This prospective study included 71,245 participants free of hypertension and CVD in the first survey (July 2006 to October 2007) of the Kailuan study, a prospective cohort study in Tangshan, China. All participants were followed biennially until December 31, 2017. A total of 20,221 new-onset hypertension cases were identified during follow-up. We randomly selected 1 control participant for each new-onset hypertensive participant, matching for age (±1 year) and sex, and included 19,887 case-control pairs. We used weighted Cox regression models to calculate the average hazard ratios of incident CVD and all-cause mortality across the age groups.
Results: During an average follow-up of 6.5 years, we identified 1,672 incident CVD cases and 2,008 deaths. After multivariate adjustment, with the increase in hypertension onset age, the hazards of outcomes were gradually attenuated. The average hazard ratio (95% confidence interval) of CVD and all-cause mortality were 2.26 (1.19 to 4.30) and 2.59 (1.32 to 5.07) for the hypertension onset age <45 years old group, 1.62 (1.24 to 2.12) and 2.12 (1.55 to 2.90) for the 45- to 54-year age group, 1.42 (1.12 to 1.79) and 1.30 (1.03 to 1.62) for the 55- to 64-year age group, and 1.33 (1.04 to 1.69) and 1.29 (1.11 to 1.51) for the ≥65-year age group, respectively (p for interaction = 0.38 for CVD and <0.01 for death).
Conclusions: Hypertension was associated with a higher risk for CVD and all-cause mortality, and the associations were stronger with a younger age of onset.
Keywords: cardiovascular disease risk; early-onset hypertension; mortality risk.

The effect of soy isoflavones on arterial stiffness: a systematic review and meta-analysis of randomized controlled trials.
Man B, Cui C, Zhang X, Sugiyama D, Barinas-Mitchell E, Sekikawa A.
Eur J Nutr. 2020 Jun 11. doi: 10.1007/s00394-020-02300-6. Online ahead of print.
PMID: 32529287 Review.
Purpose: Some but not all randomized controlled trials (RCTs) of soy isoflavones showed their beneficial effect on arterial stiffness, a predictor of cardiovascular events, dementia, and all-cause mortality, independent of traditional risk factors. To test the hypothesis that supplementation of soy isoflavones reduces arterial stiffness, we performed a systematic review and meta-analysis of RCTs of soy isoflavones on arterial stiffness.
Methods: The protocol of this systematic review was registered with PROSPERO (CRD42019126128) and written in accordance with PRISMA. The PubMed, Embase, and clinicaltrials.gov databases were searched using the following criteria: human subjects, soy isoflavones as intervention, and arterial stiffness as primary outcome. A random-effects meta-analysis was used to pool estimates across studies. Standardized mean difference (SMD) was used to synthesize quantitative results.
Results: Among 998 articles retrieved, 8 articles met our criteria. Duration of intervention was relatively short (maximum of 12 weeks). Outcome measurements extracted were pulse wave velocity (PWV), systemic arterial compliance (SAC), augmentation index (AI), and cardio-ankle vascular index (CAVI). Soy isoflavones reduced arterial stiffness compared to placebo (standardized mean difference - 0.33, 95% confidence interval - 0.47, - 0.19). Subgroup analyses showed no difference between treatment effects for intervention duration (< 6 weeks vs. ≥ 6 weeks) or gender (women only vs. men only vs. combined). Sensitivity analysis showed no difference in the effect of soy isoflavones between PWV, CAVI, SAC, and AI.
Conclusion: Supplementation of soy isoflavones reduced arterial stiffness. Longer duration trials with larger number of participants are warranted.
Keywords: Arterial stiffness; Meta-analysis; Randomized controlled trials; Soy isoflavones.

Sugar and artificially sweetened beverages and risk of obesity, type 2 diabetes mellitus, hypertension, and all-cause mortality: a dose-response meta-analysis of prospective cohort studies.
Qin P, Li Q, Zhao Y, Chen Q, Sun X, Liu Y, Li H, Wang T, Chen X, Zhou Q, Guo C, Zhang D, Tian G, Liu D, Qie R, Han M, Huang S, Wu X, Li Y, Feng Y, Yang X, Hu F, Hu D, Zhang M.
Eur J Epidemiol. 2020 Jun 11. doi: 10.1007/s10654-020-00655-y. Online ahead of print.
PMID: 32529512 Review.
Although consumption of sugar-sweetened beverages (SSBs) and artificially sweetened beverages (ASBs) has increasingly been linked with obesity, type 2 diabetes mellitus, hypertension, and all-cause mortality, evidence remains conflicted and dose-response meta-analyses of the associations are lacking. We conducted an updated meta-analysis to synthesize the knowledge about their associations and to explore their dose-response relations. We comprehensively searched PubMed, EMBASE, Web of Science, and Open Grey up to September 2019 for prospective cohort studies investigating the associations in adults. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated for the dose-response association. Restricted cubic splines were used to evaluate linear/non-linear relations. We included 39 articles in the meta-analysis. For each 250-mL/d increase in SSB and ASB intake, the risk increased by 12% (RR = 1.12, 95% CI 1.05-1.19, I2 = 67.7%) and 21% (RR = 1.21, 95% CI 1.09-1.35, I2 = 47.2%) for obesity, 19% (RR = 1.19, 95% CI 1.13-1.25, I2 = 82.4%) and 15% (RR = 1.15, 95% CI 1.05-1.26, I2 = 92.6%) for T2DM, 10% (RR = 1.10, 95% CI 1.06-1.14, I2 = 58.4%) and 8% (RR = 1.08, 95% CI 1.06-1.10, I2 = 24.3%) for hypertension, and 4% (RR = 1.04, 95% CI 1.01-1.07, I2 = 58.0%) and 6% (RR = 1.06, 95% CI 1.02-1.10, I2 = 80.8%) for all-cause mortality. For SSBs, restricted cubic splines showed linear associations with risk of obesity (Pnon-linearity = 0.359), T2DM (Pnon-linearity = 0.706), hypertension (Pnon-linearity = 0.510) and all-cause mortality (Pnon-linearity = 0.259). For ASBs, we found linear associations with risk of obesity (Pnon-linearity = 0.299) and T2DM (Pnon-linearity = 0.847) and non-linear associations with hypertension (Pnon-linearity = 0.019) and all-cause mortality (Pnon-linearity = 0.048). Increased consumption of SSBs and ASBs is associated with risk of obesity, T2DM, hypertension, and all-cause mortality. However, the results should be interpreted cautiously because the present analyses were based on only cohort but not intervention studies.
Keywords: All-cause mortality; Hypertension; Meta-analysis; Obesity; Prospective cohort studies; Sweetened beverages; Type 2 diabetes mellitus.

Fruits and vegetables intake and gastric cancer risk: a pooled analysis within the Stomach cancer Pooling (StoP) Project.
Ferro A, Costa AR, Morais S, Bertuccio P, Rota M, Pelucchi C, Hu J, Johnson KC, Zhang ZF, Palli D, Ferraroni M, Yu GP, Bonzi R, Peleteiro B, López-Carrillo L, Tsugane S, Hamada GS, Hidaka A, Malekzadeh R, Zaridze D, Maximovitch D, Vioque J, Navarrete-Munoz EM, Alguacil J, Castaño-Vinyals G, Wolk A, Håkansson N, Hernández-Ramírez RU, Pakseresht M, Ward MH, Pourfarzi F, Mu L, López-Cervantes M, Persiani R, Kurtz RC, Lagiou A, Lagiou P, Boffetta P, Boccia S, Negri E, Camargo MC, Curado MP, La Vecchia C, Lunet N.
Int J Cancer. 2020 Jun 11. doi: 10.1002/ijc.33134. Online ahead of print.
PMID: 32525569
A low intake of fruits and vegetables is a risk factor for gastric cancer, though there is uncertainty regarding the magnitude of the associations. In this study, the relation between fruits and vegetables intake and gastric cancer was assessed, complementing a previous work on the association between consumption of citrus fruits and gastric cancer. Data from 25 studies (8456 cases and 21 133 controls) with information on fruits and/or vegetables intake were used. A two-stage approach based on random effects models was used to pool study-specific adjusted (sex, age, and the main known risk factors for gastric cancer) odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Exposure-response relations, including linear and non-linear associations, were modelled using one and two-order fractional polynomials. Gastric cancer risk was lower for a higher intake of fruits (OR: 0.76, 95%CI: 0.64-0.90), non-citrus fruits (OR: 0.86, 95%CI: 0.73-1.02), vegetables (OR: 0.68, 95%CI: 0.56-0.84), and fruits and vegetables (OR: 0.61, 95%CI: 0.49-0.75); results were consistent across sociodemographic and lifestyles categories, as well as study characteristics. Exposure-response analyses showed an increasingly protective effect of portions/day of fruits (OR: 0.64, 95%CI: 0.57-0.73 for six portions), non-citrus fruits (OR: 0.71, 95%CI: 0.61-0.83 for six portions), vegetables (OR: 0.51, 95%CI: 0.43-0.60 for ten portions). A protective effect of all fruits, non-citrus fruits and vegetables was confirmed, supporting further dietary recommendations to decrease the burden of gastric cancer. This article is protected by copyright. All rights reserved.
Keywords: fruits; gastric cancer; nutrition; pooled analyses; vegetables.

Coffee consumption and risk of colorectal cancer in the Cancer Prevention Study-II Nutrition Cohort.
Um CY, McCullough ML, Guinter MA, Campbell PT, Jacobs EJ, Gapstur SM.
Cancer Epidemiol. 2020 Jun 8;67:101730. doi: 10.1016/j.canep.2020.101730. Online ahead of print.
PMID: 32526644
Background: The association between coffee consumption and colorectal cancer risk generally appears null, but recent evidence suggests that risk may vary by coffee type. We examined associations of caffeinated and decaffeinated coffee intake with colorectal cancer risk overall and with colon and rectum separately, among older U.S. men and women.
Methods: In 1999, 47,010 men and 60,051 women with no previous diagnosis of cancer, aged 47-96 years, in the Cancer Prevention Study-II Nutrition Cohort completed a food frequency questionnaire that assessed caffeinated and decaffeinated coffee intake; consumption was updated in 2003. A total of 1829 colorectal cancer cases were verified through June 2015. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard rate ratios (HRs) and 95% confidence intervals (CIs), adjusting for smoking history, alcohol, caffeinated/decaffeinated coffee intake (depending on the model), and other colorectal cancer risk factors.
Results: Consumption of ≥2 cups/day of decaffeinated coffee, compared to no decaffeinated coffee, was associated with lower risk of overall colorectal cancer (HR = 0.82, 95% CI: 0.69-0.96, P-trend = 0.04), colon cancer (HR = 0.82, 95% CI: 0.69-0.99, P-trend = 0.05) and rectal cancer (HR = 0.63, 95% CI: 0.40-0.99, P-trend = 0.17). Consumption of ≥2 cups/day of caffeinated coffee was associated with higher risk of rectal cancer (HR = 1.37, 95% CI: 0.99-1.89, P-trend = 0.04), but not with colorectal or colon cancer.
Conclusion: In this prospective study, higher intake of decaffeinated coffee was associated with lower risk of colorectal, colon, and rectal cancers. Further study on associations of caffeinated and decaffeinated coffee with colorectal cancer risk by subsite is needed.
Keywords: Caffeine; Coffee; Cohort study; Colorectal cancer; Colorectal subsite.

Effects of oily fish intake on cognitive and socioemotional function in healthy 8-9-year-old children: the FiSK Junior randomized trial.
Teisen MN, Vuholm S, Niclasen J, Aristizabal-Henao JJ, Stark KD, Geertsen SS, Damsgaard CT, Lauritzen L.
Am J Clin Nutr. 2020 Jun 12:nqaa050. doi: 10.1093/ajcn/nqaa050. Online ahead of print.
PMID: 32529206
Background: Long-chain n-3 PUFAs (n-3 LCPUFAs) accrete in the brain during childhood and affect brain development. Randomized trials in children show inconsistent effects of n-3 LCPUFAs on cognitive and socioemotional function, and few have investigated effects of fish per se.
Objectives: We aimed to investigate the effects of oily fish consumption on overall and domain-specific cognitive and socioemotional scores and explore sex differences.
Methods: Healthy 8-9-y-old children (n = 199) were randomly allocated to receive ∼300 g/wk oily fish or poultry (control) for 12 ± 2 wk. At baseline and endpoint, we assessed attention, processing speed, executive functions, memory, emotions, and behavior with a large battery of tests and questionnaires and analyzed erythrocyte fatty acid composition.
Results: One hundred and ninety-seven (99%) children completed the trial. Children in the fish group consumed 375 (25th-75th percentile: 325-426) g/wk oily fish resulting in 2.3 (95% CI: 1.9, 2.6) fatty acid percentage points higher erythrocyte n-3 LCPUFA than in the poultry group. The overall cognitive performance score tended to improve by 0.17 (95% CI: -0.01, 0.35) points in children who received fish compared with poultry, supported by n-3 LCPUFA dose dependency. This was driven mainly by fewer errors [-1.9 (95% CI: -3.4, -0.3)] in an attention task and improved cognitive flexibility measured as faster reaction time [-51 ms (95% CI: -94, -7 ms)] in a complex relative to a simple task ("mixing cost"). The fish intervention furthermore reduced parent-rated Strength and Difficulties Questionnaire total difficulties by -0.89 (95% CI: -1.60, -0.18) points mainly due to a -0.63 (95% CI: -1.11, -0.16) points reduction in internalizing problems that was reflected in tendency to a decrease in the overall socioemotional problems score of -0.13 (95% CI: -0.26, 0.01) points. The overall effects were similar in boys and girls.
Conclusions: Oily fish dose-dependently improved cognitive function, especially attention and cognitive flexibility, and reduced socioemotional problems. The results support the importance of n-3 LCPUFAs for optimal brain function and fish intake recommendations in children.
Keywords: boys; cognitive performance; docosahexaenoic acid (22:6n–3, DHA); eicosapentaenoic acid (20:5n–3, EPA); externalizing problems; girls; internalizing problems; omega-3; prosocial behavior.

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Association of FTO and ADRB2 gene variation with energy restriction induced adaptations in resting energy expenditure and physical activity.
Camps SGJA, Verhoef SPM, Bouwman FG, Mariman ECM, Westerterp KR.
Gene X. 2019 May 18;3:100019. doi: 10.1016/j.gene.2019.100019. eCollection 2019 Sep.
PMID: 32550549 Free PMC article.
Background: Energy restriction induces adaptations in resting energy expenditure (REE) and physical activity; inter-individual variability could be ascribed to genetic predisposition.The aim was to examine if changes in REE and physical activity as a result of weight loss were affected by candidate single nucleotide polymorphisms (SNPs).
Methods: 148 subjects (39 men, 109 women), mean ± SD age: 41 ± 9 year; body mass index (BMI): 31.9 ± 3.0 kg/m2, followed a very low energy diet for 8 weeks. SNPs were selected from six candidate genes: ADRB2, FTO, MC4R, PPARG2, PPARD and PPARGC1A. REE (ventilated hood) and physical activity (tri-axial accelerometer) were assessed before and after the diet. General linear modelling included gender, age and additional relevant covariates for all parameters.
Results: The heterozygotic genotype of FTO was associated with a higher amount of physical activity (1.71 Mcounts/d; CI 1.62-1.81) compared to the homozygotic major genotype (1.50 Mcounts/d; CI 1.40-1.59) (P < 0.001) while the homozygotic risk allele genotype was not different (1.56 Mcounts/d; CI 1.39-1.74) at baseline; moreover, a similar pattern was observed after energy restriction. Carrying the homozygotic minor genotype of ADRB2 was associated with a larger decrease in REE (P < 0.05) and greater adaptive thermogenesis (P < 0.05) after weight loss.
Conclusion: Carrying the minor ADRB2 allele homozygous was associated with a larger diet induced metabolic adaptation in energy expenditure and suggest a central role for reduced lipid mobilization. Carrying the risk allele of FTO homozygous was not associated with lower physical activity at baseline or after weight loss. Heterozygous carriers of one FTO risk allele showed greater physical activity before and after weight loss which might protect them in part from the higher obesity risk associated with FTO.
Keywords: ADRB2, β2-adrenergic receptor; Adaptive thermogenesis; BMI, body mass index; Energy balance; FFM, fat-free mass; FM, fat mass; FTO, fat mass and obesity associated; GLM, general linear modelling; Genetic predisposition; MC4R, melanocortin 4 receptor; Metabolic adaptation; PPARD, peroxisome proliferator-activated receptorδ; PPARGC1A, peroxisome proliferator-activated receptorγ coactivator-1α; REE, resting energy expenditure; REEm, resting energy expenditure, measured; REEp, resting energy expenditure, predicted; SNPs, single nucleotide polymorphisms; VLED, very low energy diet; Weight loss.

Homocysteine and the Risk of Cardiovascular Events and All-Cause Death in Elderly Population: A Community-Based Prospective Cohort Study.
Zhang Z, Gu X, Fang X, Tang Z, Guan S, Liu H, Wu X, Wang C, Zhao Y.
Ther Clin Risk Manag. 2020 May 22;16:471-481. doi: 10.2147/TCRM.S239496. eCollection 2020.
PMID: 32547044 Free PMC article.
Background: The association between homocysteine and cardiovascular diseases (CVD) and all-cause death was inconclusive. A community-based prospective cohort study was carried out in Beijing to evaluate this association in elderly population for more effective clinical prediction and primary prevention of CVD.
Patients and methods: Participants were randomly selected from Beijing, China. Questionnaire survey, physical examinations, and laboratory tests were carried out to collect baseline information and investigate clinical characteristics. Each participant was predetermined to be followed by 5 years. CVD events and death were collected as primary variables. A Cox regression analysis was performed to assess the risk of CVD events, CVD death, and all-cause death contributed by homocysteine as well as some other risk factors.
Results: A total of 1257 participants with an average age of 69.16 years were enrolled in this study. After adjusting for confounders, the hazard ratios (HRs) and 95% confidence intervals of CVD event, CVD death, and all-cause death caused by intermediate-to-severe hyperhomocysteinemia as compared with normal homocysteine levels were 1.68 (95% CI 1.06-2.67), 1.97 (95% CI 0.95-4.29) and 2.02 (95% CI 1.26-3.24), respectively. Intermediate-to-severe hyperhomocysteinemia increased the risks of CVD event (HR 2.07, 95% CI 1.01-4.26) and all-cause death (HR 3.08, 95% CI 1.56-6.07) among male participants. However, the positive association was not statistically significant among female participants (HR 1.59, 95% CI 0.83-3.04 for CVD event and HR 0.90, 95% CI 0.52-6.07 for all-cause death). Every 5μmol/L increment in homocysteine concentration was shown to be associated with a 4% (HR 1.04, 95% CI 1.01-1.07) and 5% (HR 1.05, 95% CI 1.01-1.07) higher risk of CVD events and all-cause death in all participants. There was no significant association between moderate hyperhomocysteinemia and the risk of the CVD events and all-cause death.
Conclusion: Intermediate-to-severe hyperhomocysteinemia was significantly associated with CVD events and all-cause death in elderly population without a history of ischemia or congestive heart failure (CHF). The positive association was pronounced among males.
Keywords: all-cause death; cardiovascular disease; homocysteine; prospective cohort study.

Alcohol Drinking and Health in Ageing: A Global Scale Analysis of Older Individual Data through the Harmonised Dataset of ATHLOS.
Tyrovolas S, Panaretos D, Daskalopoulou C, Gine-Vazquez I, Niubo AS, Olaya B, Bobak M, Prince M, Prina M, Ayuso-Mateos JL, Caballero FF, Garcia-Esquinas E, Holger A, Scherbov S, Sanderson W, Gheno I, Koupil I, Bickenbach J, Chatterji S, Koskinen S, Raggi A, Pajak A, Tobiasz-Adamczyk B, Haro JM, Panagiotakos D.
Nutrients. 2020 Jun 11;12(6):E1746. doi: 10.3390/nu12061746.
PMID: 32545243
We investigated the relation between alcohol drinking and healthy ageing by means of a validated health status metric, using individual data from the Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) project. For the purposes of this study, the ATHLOS harmonised dataset, which includes information from individuals aged 65+ in 38 countries, was analysed (n = 135,440). Alcohol drinking was reflected by means of three harmonised variables: alcohol drinking frequency, current and past alcohol drinker. A set of 41 self-reported health items and measured tests were used to generate a specific health metric. In the harmonised dataset, the prevalence of current drinking was 47.5% while of past drinking was 26.5%. In the pooled sample, current alcohol drinking was positively associated with better health status among older adults ((b-coef (95% CI): 1.32(0.45 to 2.19)) and past alcohol drinking was inversely related (b-coef (95% CI): -0.83 (-1.51 to -0.16)) with health status. Often alcohol consumption appeared to be beneficial only for females in all super-regions except Africa, both age group categories (65-80 years old and 80+), both age group categories, as well as among all the financial status categories (all p < 0.05). Regional analysis pictured diverse patterns in the association for current and past alcohol drinkers. Our results report the need for specific alcohol intake recommendations among older adults that will help them maintain a better health status throughout the ageing process.
Keywords: ATHLOS; ageing; alcohol drinking; health status; older adults.

Individual and Combined Associations of Modifiable Lifestyle and Metabolic Health Status With New-Onset Diabetes and Major Cardiovascular Events: The China Cardiometabolic Disease and Cancer Cohort (4C) Study.
Li M, Xu Y, Wan Q, Shen F, Xu M, Zhao Z, Lu J, Gao Z, Chen G, Wang T, Xu Y, Zhao J, Chen L, Shi L, Hu R, Ye Z, Tang X, Su Q, Qin G, Wang G, Luo Z, Qin Y, Huo Y, Li Q, Zhang Y, Chen Y, Liu C, Mu Y, Wang Y, Wu S, Yang T, Chen L, Yu X, Yan L, Deng H, Ning G, Bi Y, Wang W.
Diabetes Care. 2020 Jun 15:dc200256. doi: 10.2337/dc20-0256. Online ahead of print.
PMID: 32540923
Objective: We aimed to determine the individual and combined associations of lifestyle and metabolic factors with new-onset diabetes and major cardiovascular events among a Chinese population aged ≥40 years.
Research design and methods: Baseline lifestyle information, waist circumference, blood pressure, lipid profiles, and glycemic status were obtained in a nationwide, multicenter, prospective study of 170,240 participants. During the up to 5 years of follow-up, we detected 7,847 individuals with new-onset diabetes according to the American Diabetes Association 2010 criteria and 3,520 cardiovascular events, including cardiovascular death, myocardial infarction, stroke, and hospitalized or treated heart failure.
Results: On the basis of 36.13% (population-attributable fraction [PAF]) risk attributed to metabolic risk components collectively, physical inactivity (8.59%), sedentary behavior (6.35%), and unhealthy diet (4.47%) moderately contributed to incident diabetes. Physical inactivity (13.34%), unhealthy diet (8.70%), and current smoking (3.38%) significantly contributed to the risk of major cardiovascular events, on the basis of 37.42% PAF attributed to a cluster of metabolic risk factors. Significant associations of lifestyle health status with diabetes and cardiovascular events were found across all metabolic health categories. Risks of new-onset diabetes and major cardiovascular events increased simultaneously according to the worsening of lifestyle and metabolic health status.
Conclusions: We showed robust effects of lifestyle status on new-onset diabetes and major cardiovascular events regardless of metabolic status and a graded increment of risk according to the combination of lifestyle and metabolic health, highlighting the importance of lifestyle modification regardless of the present metabolic status.

Α higher ratio of serum uric acid to serum creatinine could predict the risk of total and cause specific mortality- insight from a US national survey.
Mazidi M, Katsiki N, Banach M.
Int J Cardiol. 2020 Jun 11:S0167-5273(20)33291-5. doi: 10.1016/j.ijcard.2020.05.098. Online ahead of print.
PMID: 32535029

Impact of Serum Calcium Levels on Alzheimer's Disease: A Mendelian Randomization Study.
He Y, Zhang H, Wang T, Han Z, Ni QB, Wang K, Wang L, Zhang Y, Hu Y, Jin S, Sun BL, Liu G.
J Alzheimers Dis. 2020 Jun 8. doi: 10.3233/JAD-191249. Online ahead of print.
PMID: 32538835
Background: Altered calcium homeostasis is hypothesized to underlie Alzheimer's disease (AD). However, it remains unclear whether serum calcium levels are genetically associated with AD risk.
Objective: To develop effective therapies, we should establish the causal link between serum calcium levels and AD.
Methods: Here, we performed a Mendelian randomization study to investigate the causal association of increased serum calcium levels with AD risk using the genetic variants from a large-scale serum calcium genome-wide association study (GWAS) dataset (61,079 individuals of European descent) and a large-scale AD GWAS dataset (54,162 individuals including 17,008 AD cases and 37,154 controls of European descent). Here, we selected the inverse-variance weighted (IVW) as the main analysis method. Meanwhile, we selected other three sensitivity analysis methods to examine the robustness of the IVW estimate.
Results: IVW analysis showed that the increased serum calcium level (per 1 standard deviation (SD) increase 0.5 mg/dL) was significantly associated with a reduced AD risk (OR = 0.57, 95% CI 0.35-0.95, p = 0.031). Meanwhile, all the estimates from other sensitivity analysis methods were consistent with the IVW estimate in terms of direction and magnitude.
Conclusion: In summary, we provided evidence that increased serum calcium levels could reduce the risk of AD. Meanwhile, randomized controlled study should be conducted to clarify whether diet calcium intake or calcium supplement, or both could reduce the risk of AD.
Keywords: Alzheimer’s disease; Mendelian randomization; genome-wide association study; inverse-variance weighted; serum calcium.

The association between consumption of monounsaturated fats from animal- v. plant-based foods and the risk of type 2 diabetes: a prospective nationwide cohort study.
Zhuang P, Zhang Y, Mao L, Wang L, Wu F, Cheng L, Jiao J.
Br J Nutr. 2020 Feb 27:1-10. doi: 10.1017/S0007114520000677. Online ahead of print.
PMID: 32102700
Although higher dietary intake of MUFA has been shown to improve glycaemic control and lipid profiles, whether MUFA consumption from different sources is linked to the development of type 2 diabetes (T2D) remains unclear. We aimed to prospectively assess the associations of plant-derived MUFA (P-MUFA) and animal-derived MUFA (A-MUFA) intakes with T2D risk in a nationwide oriental cohort. Overall, 15 022 Chinese adults, aged ≥20 years, from the China Health and Nutrition Survey (CHNS 1997-2011) were prospectively followed up for a median of 14 years. Consumption of MUFA from plant and animal sources was assessed using 3-d 24-h recalls in each survey, and the cumulative average of intake was calculated. Multivariable-adjusted Cox models were constructed to estimate the hazard ratios (HR) of T2D according to quartiles of MUFA intake. P-MUFA were mainly consumed from cooked vegetable oils, fried bread sticks and rice, while A-MUFA were mainly consumed from pork, lard and eggs. Intake of P-MUFA was associated with a higher risk of T2D (HRQ4 v. Q1 1·50 (95 % CI 1·18, 1·90); Ptrend = 0·0013), whereas A-MUFA showed no significant association (HRQ4 v. Q1 0·84 (95 % CI 0·59, 1·20); Ptrend = 0·30). When further considering the cooking method of food sources, consumption of P-MUFA from fried foods was positively associated with T2D risk (HRQ4 v. Q1 1·60 (95 % CI 1·26, 2·02); Ptrend = 0·0006), whereas non-fried P-MUFA were not associated. Intake of MUFA from fried plant-based foods may elevate T2D risk among the Chinese population.
Keywords: Animal sources of fat; China Health and Nutrition Survey; MUFA; Nationwide cohorts; Plant sources of fat; Type 2 diabetes.

Body mass index, waist circumference, and mortality risks over 27 years of follow-up in old age.
O'Súilleabháin PS, Sutin AR, Gerstorf D.
Ann Epidemiol. 2020 Jun;46:20-23. doi: 10.1016/j.annepidem.2020.04.008. Epub 2020 May 11.
PMID: 32532369
Purpose: This study investigates the predictive effects of body mass index (BMI) and waist circumference (WC) for all-cause mortality in old age over 27 years of follow-up.
Methods: Participants were from the Berlin Aging Study (n = 444, M ± SD = 84.55 ± 8.38 years). Reported significance values for hazard ratios were adjusted for age, sex, socioeconomic status, smokers, depressive illness, functional status, cholesterol, and objectively assessed physical diseases.
Results: BMI emerged as a significant predictor of all-cause mortality after adjustment. WC was not a significant predictor of mortality either within the unadjusted model or when fully adjusted, including BMI. After the introduction of WC alongside all covariates, the effect for BMI remained significant. A significant quadratic effect for BMI and mortality within the fully adjusted model also emerged.
Conclusions: Our results suggest that lower BMI in the oldest old is associated with increased mortality hazards, and risks were particularly elevated for people who are underweight. This study found no evidence that higher BMI in old age is associated with increased mortality hazards relative to normal weight ranges.
Keywords: Aging; Body mass index; Health; Mortality; Waist circumference.

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Prevalence, correlates and outcomes of multimorbidity among the middle-aged and elderly: Findings from the China Health and Retirement Longitudinal Study.
Zhang Y, Zhou L, Liu S, Qiao Y, Wu Y, Ke C, Shen Y.
Arch Gerontol Geriatr. 2020 Jun 4;90:104135. doi: 10.1016/j.archger.2020.104135. Online ahead of print.
PMID: 32554217
Background: The multimorbidity associated with ageing has been prevalent worldwide and poses major challenges to the health care system. However, the research about multimorbidity in China is far from sufficient. Additionally, international studies on the influencing factors of multimorbidity and the impact on disability/mortality are still inconsistent. The aim of this study was to examine the prevalence, correlates and outcomes of multimorbidity among the middle-aged and elderly Chinese population.
Methods: We used data from the China Health and Retirement Longitudinal Study (CHARLS). Logistic regression was performed to analyze the influencing factors of multimorbidity. The Cox proportional hazard model was used to evaluate the impact of multimorbidity on functional disability and all-cause mortality.
Results: The prevalence of multimorbidity was 55.12 % in the whole study population and 65.60 % among people aged ≥ 65 years. Multimorbidity was significantly associated with old age (OR: 2.76, 95 % CI: 2.31-3.30), females (OR: 1.21, 95 % CI: 1.01-1.44), ex-smoker (OR: 2.07, 95 % CI: 1.58-2.72), ex-drinker (OR: 2.18, 95 % CI: 1.66-2.87), obesity (OR: 2.87, 95 % CI: 2.30-3.57), lower education (OR:1.32, 95 % CI: 1.08-1.61), living alone (OR: 1.26, 95 % CI: 1.02-1.55) and unemployment (OR: 1.66, 95 % CI: 1.11-2.48). Moreover, multimorbidity was correlated with disability (HR: 2.27, 95 % CI: 1.93-2.66) and all-cause mortality (HR: 1.95, 95 % CI: 1.36-2.80) after multivariable adjustment.
Conclusions: Multimorbidity is highly prevalent in China and possesses significantly negative effects on health outcomes. Identification of the key population and tailored interventions on their modifiable risk factors should be paid much importance.
Keywords: All-cause mortality; CHARLS; Multimorbidity; Risk factor.

Exploring the effect of loneliness on all-cause mortality: Are there differences between older adults and younger and middle-aged adults?
Lara E, Moreno-Agostino D, Martín-María N, Miret M, Rico-Uribe LA, Olaya B, Cabello M, Haro JM, Ayuso-Mateos JL.
Soc Sci Med. 2020 May 30;258:113087. doi: 10.1016/j.socscimed.2020.113087. Online ahead of print.
PMID: 32554229
Objective: This study aims to investigate the association between loneliness and all-cause mortality over a six-year follow-up period using the overall sample and by age groups (18-59 years and 60+ years).
Method: Data from a longitudinal, prospective study of a nationally-representative sample of the Spanish non-institutionalized adult population were analysed (n = 4467). Mortality was ascertained via linkage to the National Death Index or obtained during the household visits. The UCLA Loneliness Scale was used to measure loneliness. Sex, age, education, physical activity, tobacco consumption, body mass index, disability, depression, living situation, and social participation were also considered as covariates. Multivariable Cox proportional hazard models were carried out.
Results: A higher level of loneliness was not associated with mortality risk in fully covariate-adjusted models over the entire population (HR = 1.02; 95% CI = 0.94, 1.12). The interaction term between loneliness and age groups was significant, indicating that the rate for survival of loneliness varied by age (HR = 1.29; 95% CI = 1.02, 1.63 for young- and middle-aged individuals; HR = 0.96; 95% CI = 0.89, 1.04 for older adults).
Conclusions: The development of interventions aimed at tackling loneliness among young- and middle-aged adults might contribute to a mortality risk reduction. Future research is warranted to test whether our results can be replicated.
Keywords: Age differences; All-cause mortality; Loneliness; Population-based study; Spain.

Association of Sedentary Behavior With Cancer Mortality in Middle-aged and Older US Adults.
Gilchrist SC, Howard VJ, Akinyemiju T, Judd SE, Cushman M, Hooker SP, Diaz KM.
JAMA Oncol. 2020 Jun 18. doi: 10.1001/jamaoncol.2020.2045. Online ahead of print.
PMID: 32556069
Importance: Sedentary behavior is associated with several health outcomes, including diabetes, cardiovascular disease, and all-cause mortality. Less is known about the association between objectively measured sedentary behavior and cancer mortality, as well as the association with physical activity.
Objective: To examine the association between accelerometer-measured sedentary behavior (total volume and accrual in prolonged, uninterrupted bouts) and cancer mortality.
Design, setting, and participants: A prospective cohort study conducted in the contiguous US included 8002 black and white adults aged 45 years or older enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. The present analysis was performed from April 18, 2019, to April 21, 2020.
Exposures: Sedentary time, light-intensity physical activity (LIPA), and moderate- to vigorous-intensity physical activity (MVPA) were measured using a hip-mounted accelerometer worn for 7 consecutive days.
Main outcomes and measures: Cancer mortality.
Results: Of the 8002 study participants, 3668 were men (45.8%); mean (SD) age was 69.8 (8.5) years. Over a mean (SD) follow-up of 5.3 (1.5) years, 268 participants (3.3%) died of cancer. In multivariable-adjusted models, including MVPA, greater total sedentary time was associated with a greater risk of cancer mortality (tertile 2 vs tertile 1: hazard ratio

, 1.45; 95% CI, 1.00-2.11; tertile 3 vs tertile 1: HR, 1.52; 95% CI, 1.01-2.27). Longer sedentary bout duration was not significantly associated with greater cancer mortality risk: after adjustment for MVPA (tertile 2 vs tertile 1: HR, 1.26; 95% CI, 0.90-1.78; tertile 3 vs tertile 1: HR, 1.36; 95% CI, 0.96-1.93). Replacing 30 minutes of sedentary time with LIPA was significantly associated with an 8% (per 30 minutes: HR, 0.92; 95% CI, 0.86-0.97) lower risk of cancer mortality; MVPA was significantly associated with a 31% (per 30 minutes: HR, 0.69; 95% CI, 0.48-0.97) lower risk of cancer mortality.
Conclusions and relevance: In this cohort study, greater sedentary time, as measured with accelerometry, appeared to be independently associated with cancer mortality risk. Replacing sedentary time with either LIPA or MVPA may be associated with a lower risk of cancer mortality. These findings suggest that the total volume of sedentary behavior is a potential cancer mortality risk factor and support the public health message that adults should sit less and move more to promote longevity.

Preliminary evidence of effects of potassium chloride on a metabolomic path to diabetes and cardiovascular disease.
Chatterjee R, Davenport CA, Kwee L, D'Alessio D, Svetkey LP, Lin PH, Slentz CA, Ilkayeva O, Johnson J, Edelman D, Shah SH.
Metabolomics. 2020 Jun 18;16(7):75. doi: 10.1007/s11306-020-01696-w.
PMID: 32556595
Introduction: Low potassium intake can affect cardiovascular disease (CVD) risk and cardiometabolic risk factors.
Objective: We hypothesize that potassium chloride (KCl) supplementation can improve cardiovascular risk metabolomic profile.
Methods: In this secondary analysis of a pilot randomized clinical trial (RCT) of 26 participants with prediabetes randomized to KCl or placebo, we performed targeted mass-spectrometry-based metabolomic profiling on baseline and 12-week (end-of-study) plasma samples. Principal component analysis (PCA) was used to reduce the many correlated metabolites into fewer, independent factors that retain most of the information in the original data.
Results: Those taking KCl had significant reductions (corresponding to lower cardiovascular risk) in the branched-chain amino acids (BCAA) factor (P = 0.004) and in valine levels (P = 0.02); and non-significant reductions in short-chain acylcarnitines (SCA) factor (P = 0.11).
Conclusions: KCl supplementation may improve circulating BCAA levels, which may reflect improvements in overall cardiometabolic risk profile.
Clinical trials registry: Clinicaltrials.gov identifier: NCT02236598; https://clinicaltrials.gov/ct2/show/NCT02236598.
Keywords: Branched-chain amino acids; Cardiovascular disease risk; Metabolites; Potassium chloride; Potassium supplements; Prediabetes.

Combining a high dose of metformin with the SIRT1 activator, SRT1720, reduces lifespan in aged mice fed a high-fat diet.
Palliyaguru DL, Minor RK, Mitchell SJ, Palacio HH, Licata JJ, Ward TM, Abulwerdi G, Elliott P, Westphal C, Ellis JL, Sinclair DA, Price NL, Bernier M, de Cabo R.
J Gerontol A Biol Sci Med Sci. 2020 Jun 18:glaa148. doi: 10.1093/gerona/glaa148. Online ahead of print.
PMID: 32556267
SRT1720, a sirtuin1-activator, and metformin (MET), an antidiabetic drug, confer health and lifespan benefits when administered individually. It is unclear whether combination of the two compounds could lead to additional benefits. Groups of 56-week-old C57BL/6J male mice were fed a high-fat diet (HFD) alone or supplemented with either SRT1720 (2 g/kg food), a high dose of MET (1% w/w food), or a combination of both. Animals were monitored for survival, body weight, food consumption, body composition and rotarod performance. Mice treated with MET alone did not have improved longevity, and lifespan was dramatically reduced by combination of MET with SRT1720. Although all groups of animals were consuming similar amounts of food, mice on MET or MET+SRT1720 showed a sharp reduction in body weight. SRT1720+MET mice also had lower percent body fat combined with better performance on the rotarod compared to controls. These data suggest that co-treatment of SRT1720 with MET is detrimental to survival at the doses used and, therefore, risk-benefits of combining lifespan-extending drugs especially in older populations needs to be systematically evaluated.
Keywords: Metformin; SRT1720; Sirtuin; combination; lifespan.

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Handgrip strength and health outcomes: Umbrella review of systematic reviews with meta-analyses of observational studies.
Soysal P, Hurst C, Demurtas J, Firth J, Howden R, Yang L, Tully MA, Koyanagi A, Ilie PC, López-Sánchez GF, Schwingshackl L, Veronese N, Smith L.
J Sport Health Sci. 2020 Jun 18:S2095-2546(20)30075-2. doi: 10.1016/j.jshs.2020.06.009. Online ahead of print.
PMID: 32565244
Purpose: The aim of the present study was to assess both the credibility and strength of evidence arising from systematic reviews with meta-analyses of observational studies on handgrip strength and health outcomes.
Methods: An umbrella review of systematic reviews with meta-analyses of observational studies was conducted. We assessed meta-analyses of observational studies based on random-effect summary effect sizes and their p values, 95% prediction intervals, heterogeneity, small-study effects, and excess significance. We graded the evidence from convincing (Class I) to weak (Class IV).
Results: From 504 articles returned in a search of the literature, 8 systematic reviews were included in our review, with a total of 11 outcomes. Overall, 9 of the 11 of the outcomes reported nominally significant summary results (p < 0.05), with 4 associations surviving the application of the more stringent p value (p < 10-6). No outcome presented convincing evidence. Three associations showed Class II evidence (i.e., highly suggestive): (1) higher handgrip values at baseline were associated with a minor reduction in mortality risk in the general population (n = 34 studies; sample size = 1,855,817; relative risk (RR) = 0.72; 95% confidence interval (CI): 0.67-0.78), (2) cardiovascular death risk in mixed populations (n = 15 studies; RR = 0.84; 95%CI: 0.78-0.91), and (3) incidence of disability (n = 7 studies; RR = 0.76; 95%CI: 0.66-0.87).
Conclusion: The present results show that handgrip strength is a useful indicator for general health status and specifically for early all-cause and cardiovascular mortality, as well as disability. To further inform intervention strategies, future research is now required to fully understand mechanisms linking handgrip strength scores to these health outcomes.
Keywords: Handgrip strength; Health outcomes; Meta-analysis; Umbrella review.

Systematic review of the prospective association of daily step counts with risk of mortality, cardiovascular disease, and dysglycemia.
Hall KS, Hyde ET, Bassett DR, Carlson SA, Carnethon MR, Ekelund U, Evenson KR, Galuska DA, Kraus WE, Lee IM, Matthews CE, Omura JD, Paluch AE, Thomas WI, Fulton JE.
Int J Behav Nutr Phys Act. 2020 Jun 20;17(1):78. doi: 10.1186/s12966-020-00978-9.
PMID: 32563261
Background: Daily step counts is an intuitive metric that has demonstrated success in motivating physical activity in adults and may hold potential for future public health physical activity recommendations. This review seeks to clarify the pattern of the associations between daily steps and subsequent all-cause mortality, cardiovascular disease (CVD) morbidity and mortality, and dysglycemia, as well as the number of daily steps needed for health outcomes.
Methods: A systematic review was conducted to identify prospective studies assessing daily step count measured by pedometer or accelerometer and their associations with all-cause mortality, CVD morbidity or mortality, and dysglycemia (dysglycemia or diabetes incidence, insulin sensitivity, fasting glucose, HbA1c). The search was performed across the Medline, Embase, CINAHL, and the Cochrane Library databases from inception to August 1, 2019. Eligibility criteria included longitudinal design with health outcomes assessed at baseline and subsequent timepoints; defining steps per day as the exposure; reporting all-cause mortality, CVD morbidity or mortality, and/or dysglycemia outcomes; adults ≥18 years old; and non-patient populations.
Results: Seventeen prospective studies involving over 30,000 adults were identified. Five studies reported on all-cause mortality (follow-up time 4-10 years), four on cardiovascular risk or events (6 months to 6 years), and eight on dysglycemia outcomes (3 months to 5 years). For each 1000 daily step count increase at baseline, risk reductions in all-cause mortality (6-36%) and CVD (5-21%) at follow-up were estimated across a subsample of included studies. There was no evidence of significant interaction by age, sex, health conditions or behaviors (e.g., alcohol use, smoking status, diet) among studies that tested for interactions. Studies examining dysglycemia outcomes report inconsistent findings, partially due to heterogeneity across studies of glycemia-related biomarker outcomes, analytic approaches, and sample characteristics.
Conclusions: Evidence from longitudinal data consistently demonstrated that walking an additional 1000 steps per day can help lower the risk of all-cause mortality, and CVD morbidity and mortality in adults, and that health benefits are present below 10,000 steps per day. However, the shape of the dose-response relation is not yet clear. Data are currently lacking to identify a specific minimum threshold of daily step counts needed to obtain overall health benefit.
Keywords: Accelerometer; Diabetes; Physical activity; Physical activity guidelines; Prevention; Public health; Walking.

Contributions of Modifiable Risk Factors to Dementia Incidence: A Bayesian Network Analysis.
Liang JH, Lu L, Li JY, Qu XY, Li J, Qian S, Wang YQ, Jia RX, Wang CS, Xu Y.
J Am Med Dir Assoc. 2020 Jun 17:S1525-8610(20)30325-X. doi: 10.1016/j.jamda.2020.04.006. Online ahead of print.
PMID: 32563753 Review.
Objective: To determine and compare the contributions of modifiable risk factors (RFs) with the prevention of dementia in older adults.
Design: A systematic review and Bayesian network meta-analysis (NMA). The observational group was set as a reference to collect all existing RFs and compare them with each other.
Setting and participants: An exhaustive and comprehensive literature search strategy was used to identify relevant prospective cohort studies from several online databases from their inception to May 1, 2019. Participants without dementia were adults aged greater than 50 years.
Measures: The required data were extracted from the eligible studies to facilitate the Bayesian NMA.
Results: Forty-three cohort studies with 277,294 participants were included in this NMA. Using the observation group as the reference, all defined RFs, except for antioxidants, were associated with lower risks of all-cause dementia [no sleep disturbances (odds ratio, OR 0.43, 95% credible interval, CrI 0.24-0.62), a high level of education (OR 0.50, 95% CrI 0.34-0.66), no history of diabetes (OR 0.57, 95% CrI 0.36-0.78), nonobese patients (OR 0.61, 95% CrI 0.39-0.83), no smoking history (OR 0.62, 95% CrI 0.45-0.79), living with family members (OR 0.67, 95% CrI 0.45-0.89), participation in physical exercise (OR 0.73, 95% CrI 0.46-0.94), abstinence from drinking (OR 0.78, 95% CrI 0.56-0.99), and no history of hypertension (OR 0.80, 95% CrI 0.65-0.96)].
Conclusions/relevance: The findings provide reliable support for the hypothesis that modifiable somatic and lifestyle factors are strong predictors of all-cause dementia.

Saturated Fats and Health: A Reassessment and Proposal for Food-based Recommendations: JACC State-of -the-Art Review.
Astrup A, Magkos F, Bier DM, Brenna JT, de Oliveira Otto MC, Hill JO, King JC, Mente A, Ordovas JM, Volek JS, Yusuf S, Krauss RM.
J Am Coll Cardiol. 2020 Jun 16:S0735-1097(20)35687-4. doi: 10.1016/j.jacc.2020.05.077. Online ahead of print.
PMID: 32562735 Review.
The recommendation to limit dietary saturated fatty acid (SFA) intake has persisted despite mounting evidence to the contrary. Most recent meta-analyses of randomized trials and observational studies found no beneficial effects of reducing SFA intake on cardiovascular disease (CVD) and total mortality, and instead found protective effects against stroke. Although SFAs increase low-density lipoprotein (LDL)-cholesterol, in most individuals, this is not due to increasing levels of small, dense LDL particles, but rather larger LDL which are much less strongly related to CVD risk. It is also apparent that the health effects of foods cannot be predicted by their content in any nutrient group, without considering the overall macronutrient distribution. Whole-fat dairy, unprocessed meat, eggs and dark chocolate are SFA-rich foods with a complex matrix that are not associated with increased risk of CVD. The totality of available evidence does not support further limiting the intake of such foods.
Keywords: cardiovascular disease; diet; food matrix; saturated fat.

Personal activity intelligence and mortality - Data from the Aerobics Center Longitudinal Study.
Nauman J, Sui X, Lavie CJ, Wen CP, Laukkanen JA, Blair SN, Dunn P, Arena R, Wisløff U.
Prog Cardiovasc Dis. 2020 Jun 16:S0033-0620(20)30113-4. doi: 10.1016/j.pcad.2020.05.005. Online ahead of print.
PMID: 32560967
Importance: Personal activity intelligence (PAI) is a novel activity metric that can be integrated into self-assessment heart rate devices, and translates heart rate variations during exercise into a weekly score. Previous studies relating to PAI have been conducted in the same populations from Norway where the PAI metric has been derived, limiting generalizability of the results.
Objective: To test whether PAI is associated with total and cause-specific mortality in a large cohort from the United States.
Design: Aerobics Center Longitudinal Study (ACLS) - a prospective cohort between January 1974 and December 2002 with a mean follow-up of 14.5 years.
Setting: Population-based.
Participants: 56,175 relatively healthy participants (26.5% women) who underwent extensive preventive medical examinations at Cooper Clinic (Dallas, TX).
Exposure: Personal activity intelligence (PAI) score per week was estimated and divided into 4 groups (PAI scores of 0, ≤50, 51-99, and ≥100).
Main outcomes and measures: Total and cause-specific mortality.
Results: During a median follow-up time of 14.9 (interquartile range, 6.7-21.4) years, there were 3434 total deaths including 1258 cardiovascular (CVD) deaths. Compared with the inactive (0 PAI) group, participants with a baseline weekly ≥100 PAI had lower risk of mortality: adjusted hazard ratio (AHR), 0.79: 95% CI, 0.71-0.87 for all-cause mortality, and AHR, 0.72: 95% CI, 0.60-0.87 for CVD mortality among men; AHR, 0.85: 95% CI, 0.64-1.12 for all-cause mortality, and AHR, 0.48: 95% CI, 0.26-0.91 for CVD mortality among women. For deaths from ischemic heart disease (IHD), PAI score ≥100 was associated with lower risk in both men and women (AHR, 0.70: 95% CI, 0.55-0.88). Obtaining ≥100 weekly PAI was also associated with significantly lower risk of CVD mortality in pre-specified age groups, and in participants with known CVD risk factors. Participants with ≥100 weekly PAI gained 4.2 (95% CI, 3.5-4.6) years of life when compared with those who were inactive at baseline.
Conclusions and relevance: PAI is associated with long-term all-cause, CVD, and IHD, mortality. Clinicians and the general population can incorporate PAI recommendations and thresholds in their physical activity prescriptions and weekly physical activity assessments, respectively, to maximize health outcomes.
Key points: Question: What is the association between personal activity intelligence (PAI), a novel activity metric, and mortality in a large cohort from the United States?
Findings: In this prospective study of 56,175 healthy participants at baseline, followed-up for a mean of 14.5 years, ≥100 PAI score/week was associated with significant 21% lower risk of all-cause and 30% lower risk of CVD mortality in comparison with inactive people. Participants with ≥100 PAI/week lived on average 4.2 years longer compared with inactive. Meaning: PAI is associated with long-term all-cause and CVD mortality. Clinicians and general population may incorporate PAI recommendations into weekly physical activity assessments to maximize CVD prevention.
Keywords: Activity metric; Cardiovascular disease; Exercise; Mortality; Physical activity.

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A mushroom diet reduced the risk of pregnancy-induced hypertension and macrosomia: a randomized clinical trial.
Sun L, Niu Z.
Food Nutr Res. 2020 Jun 8;64. doi: 10.29219/fnr.v64.4451. eCollection 2020.
PMID: 32577117 Free PMC article.
Background: Pregnancy-induced hypertension (PIH) is a disease characterized by high blood pressure detected after 20 weeks of pregnancy, affecting approximately 10% of pregnant women worldwide. Effective strategies are imperatively needed to prevent and treat PIH.
Methods: Subjects were required to consume 100 g mushroom daily from pre-pregnancy to the 20th week of gestation. The gestational hypertension and related primary and secondary outcomes of the mushroom diet (MD) group and placebo group were investigated to compare the intervention of a MD on the PIH and preeclampsia-associated maternal and child health conditions.
Results: A total of 582 and 580 subjects belonging to the MD group and placebo group were included for the analysis, respectively. Compared to the placebo, the MD significantly reduced the incidence of gestational hypertension (P = 0.023), preeclampsia (P = 0.014), gestational weight gain (P = 0.017), excessive gestational weight gain (P = 0.032) and gestational diabetes (P = 0.047). Stratified analysis showed that the MD lowered the risk of PIH for overweighed women (P = 0.036), along with the percentage of macrosomia (P = 0.007).
Conclusion: An MD could serve as a preventative strategy for lowering the risk of PIH and could control newborn birthweight while reducing comorbidities including gestational weight gain, diabetes etc.
Keywords: clinical trial; mushroom; non-pharmacological intervention; preeclampsia; pregnancy-induced hypertension.

Coffee consumption and risk of hypertension: A prospective analysis in the cohort study.
Miranda AM, Goulart AC, Benseñor IM, Lotufo PA, Marchioni DM.
Clin Nutr. 2020 Jun 7:S0261-5614(20)30289-2. doi: 10.1016/j.clnu.2020.05.052. Online ahead of print.
PMID: 32576389
Background: Coffee is one of the most widely consumed beverages around the world. Dietary habits, specifically, coffee consumption has long been a suspected cause of hypertension. However, previous findings on coffee consumption and its association with the incidence of hypertension are not homogeneous and still inconsistent.
Purpose: To examine the association of habitual coffee consumption with the risk of developing hypertension in a middle-aged Brazilian cohort.
Methods: Data were from the multicenter prospective cohort "Brazilian Longitudinal Study for Adult Health - ELSA-Brasil". The cohort comprises 15,105 civil servants, aged 35-74 years at baseline, who were sampled from universities located in six Brazilian cities. For the present study, we analyzed data from 8780 participants initially free of hypertension during a mean follow-up of 3.9 years. The consumption of coffee was obtained at baseline using a previously validated semi-quantitative food frequency questionnaire (FFQ). Subsequently coffee intake was categorized into four categories (cups/day): never/almost never, ≤1, 1-3, and >3. Hypertension status was defined as a systolic blood pressure ≥140 mmHg or a diastolic blood pressure ≥90 mmHg, use of antihypertensive drug treatment, or both. Poisson regression model with a robust variance was performed to estimate relative risk (RR) and confidence interval (95% CI) for hypertension according to baseline coffee consumption. The effect of interaction between coffee consumption and smoking status was assessed.
Results: Most participants (90%) drank coffee, and the median total coffee intake was 150 mL/day. A total of 1285 participants developed hypertension. Compared to participants who never or almost never drink coffee, the risk of hypertension was lower for individuals consuming 1-3 cups/day (RR 0.82, 95% CI: 0.68-0.97) (P for interaction=0.018). After stratification by smoking status the analysis revealed a decreased risk of hypertension in never smokers drinking 1-3 cups of coffee per day (RR 0.79, 95% CI: 0.64-0.98), whereas the hypertension risk among former and current smokers was not associated with coffee consumption significantly. Moreover, upper category of coffee drinking (>3 cups/day) the association was not significant for risk of hypertension.
Conclusion: The association between coffee consumption and incidence of hypertension was related to smoking status. The beneficial effect of moderate coffee intake (1-3 cups/day) on risk of hypertension was observed only in never smokers.
Keywords: Coffee; ELSA-Brasil; Hypertension; Prospective cohort; Smoking.

Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial.
de Groot S, Lugtenberg RT, Cohen D, Welters MJP, Ehsan I, Vreeswijk MPG, Smit VTHBM, de Graaf H, Heijns JB, Portielje JEA, van de Wouw AJ, Imholz ALT, Kessels LW, Vrijaldenhoven S, Baars A, Kranenbarg EM, Carpentier MD, Putter H, van der Hoeven JJM, Nortier JWR, Longo VD, Pijl H, Kroep JR; Dutch Breast Cancer Research Group (BOOG).
Nat Commun. 2020 Jun 23;11(1):3083. doi: 10.1038/s41467-020-16138-3.
PMID: 32576828
Short-term fasting protects tumor-bearing mice against the toxic effects of chemotherapy while enhancing therapeutic efficacy. We randomized 131 patients with HER2-negative stage II/III breast cancer, without diabetes and a BMI over 18 kg m-2, to receive either a fasting mimicking diet (FMD) or their regular diet for 3 days prior to and during neoadjuvant chemotherapy. Here we show that there was no difference in toxicity between both groups, despite the fact that dexamethasone was omitted in the FMD group. A radiologically complete or partial response occurs more often in patients using the FMD (OR 3.168, P = 0.039). Moreover, per-protocol analysis reveals that the Miller&Payne 4/5 pathological response, indicating 90-100% tumor-cell loss, is more likely to occur in patients using the FMD (OR 4.109, P = 0.016). Also, the FMD significantly curtails chemotherapy-induced DNA damage in T-lymphocytes. These positive findings encourage further exploration of the benefits of fasting/FMD in cancer therapy. 

The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan.
Yen K, Mehta HH, Kim SJ, Lue Y, Hoang J, Guerrero N, Port J, Bi Q, Navarrete G, Brandhorst S, Lewis KN, Wan J, Swerdloff R, Mattison JA, Buffenstein R, Breton CV, Wang C, Longo V, Atzmon G, Wallace D, Barzilai N, Cohen P.
Aging (Albany NY). 2020 Jun 23;12. doi: 10.18632/aging.103534. Online ahead of print.
PMID: 32575074
Humanin is a member of a new family of peptides that are encoded by short open reading frames within the mitochondrial genome. It is conserved in animals and is both neuroprotective and cytoprotective. Here we report that in C. elegans the overexpression of humanin is sufficient to increase lifespan, dependent on daf-16/Foxo. Humanin transgenic mice have many phenotypes that overlap with the worm phenotypes and, similar to exogenous humanin treatment, have increased protection against toxic insults. Treating middle-aged mice twice weekly with the potent humanin analogue HNG, humanin improves metabolic healthspan parameters and reduces inflammatory markers. In multiple species, humanin levels generally decline with age, but here we show that levels are surprisingly stable in the naked mole-rat, a model of negligible senescence. Furthermore, in children of centenarians, who are more likely to become centenarians themselves, circulating humanin levels are much greater than age-matched control subjects. Further linking humanin to healthspan, we observe that humanin levels are decreased in human diseases such as Alzheimer's disease and MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes). Together, these studies are the first to demonstrate that humanin is linked to improved healthspan and increased lifespan.
Keywords: aging; humanin; mitochondria; peptides.

Synchronization of the circadian clock by time-restricted feeding with progressive increasing calorie intake. Resemblances and differences regarding a sustained hypocaloric restriction.
García-Gaytán AC, Miranda-Anaya M, Turrubiate I, López-De Portugal L, Bocanegra-Botello GN, López-Islas A, Díaz-Muñoz M, Méndez I.
Sci Rep. 2020 Jun 22;10(1):10036. doi: 10.1038/s41598-020-66538-0.
PMID: 32572063
Circadian rhythms are the product of the interaction of molecular clocks and environmental signals, such as light-dark cycles and eating-fasting cycles. Several studies have demonstrated that the circadian rhythm of peripheral clocks, and behavioural and metabolic mediators are re-synchronized in rodents fed under metabolic challenges, such as hyper- or hypocaloric diets and subjected to time-restricted feeding protocols. Despite the metabolic challenge, these approaches improve the metabolic status, raising the enquiry whether removing progressively the hypocaloric challenge in a time-restricted feeding protocol leads to metabolic benefits by the synchronizing effect. To address this issue, we compared the effects of two time-restricted feeding protocols, one involved hypocaloric intake during the entire protocol (HCT) and the other implied a progressive intake accomplishing a normocaloric intake at the end of the protocol (NCT) on several behavioural, metabolic, and molecular rhythmic parameters. We observed that the food anticipatory activity (FAA) was driven and maintained in both HCT and NCT. Resynchronization of hepatic molecular clock, free fatty acids (FFAs), and FGF21 was elicited closely by HCT and NCT. We further observed that the fasting cycles involved in both protocols promoted ketone body production, preferentially beta-hydroxybutyrate in HCT, whereas acetoacetate was favoured in NCT before access to food. These findings demonstrate that time-restricted feeding does not require a sustained calorie restriction for promoting and maintaining the synchronization of the metabolic and behavioural circadian clock, and suggest that metabolic modulators, such as FFAs and FGF21, could contribute to FAA expression.

Leucine-Enriched Protein Supplementation Increases Lean Body Mass in Healthy Korean Adults Aged 50 Years and Older: A Randomized, Double-Blind, Placebo-Controlled Trial.
Kang Y, Kim N, Choi YJ, Lee Y, Yun J, Park SJ, Park HS, Chung YS, Park YK.
Nutrients. 2020 Jun 18;12(6):E1816. doi: 10.3390/nu12061816.
PMID: 32570811
Early prevention of sarcopenia could be an important strategy for muscle retention, but most studies have focused on subjects aged 65 or older. Therefore, in this study we investigated the effects of leucine-enriched protein supplementation on muscle condition in a sample including late middle-aged adults. A 12-week intervention was performed for 120 healthy community-dwelling adults by providing either leucine-enriched protein supplement [leucine 3 g, protein mixture (casein 50% + whey 40% + soy 10%) 17 g, vitamin D 800IU (20 µg), calcium 300 mg, fat 1.1 g, carbohydrate 2.5 g] or isocaloric carbohydrate supplement twice per day. Appendicular skeletal muscle mass index (ASMI) and lean body mass (LBM) were measured by dual-energy X-ray absorptiometry. A total of 111 participants completed the study, with a dropout rate of 9.2%. LBM normalized by height and body weight (LBM/Wt) was significantly increased (p < 0.001) in the intervention group (0 wk: 633.9 ± 8.5 vs. 12 wk 636.9 ± 8.4 in the intervention group; 0 wk: 638.6 ± 8.3 vs. 12 wk: 632.9 ± 8.1 in the control group). In subgroup analyses, significant differences remained only in subjects between 50 and 64 years of age. We concluded that leucine-enriched protein supplementation can have beneficial effects by preventing muscle loss, mainly for late middle-aged adults.
Keywords: lean body mass; leucine; protein; sarcopenia.

Age-at-onset-dependent effects of sulfur amino acid restriction on markers of growth and stress in male F344 rats.
Nichenametla SN, Mattocks DAL, Malloy VL.
Aging Cell. 2020 Jun 22. doi: 10.1111/acel.13177. Online ahead of print.
PMID: 32573078
Trade-offs in life-history traits are clinically and mechanistically important. Sulfur amino acid restriction (SAAR) extends lifespan. But whether this benefit comes at the cost of other traits including stress resistance and growth is unclear. We investigated the effects of SAAR on growth markers (body weight, IGF1, and IGFBP3) and physiological stresses. Male-F344 rats were fed control (0.86% Met) and SAAR (0.17% Met) diets starting at 2, 10, and 20 months. Rats were injected with keyhole-limpet-hemocyanin (KLH) to measure immune responses (anti-KLH-IgM, anti-KLH-IgG, and delayed-type-hypersensitivity [DTH]). Markers of ER stress (FGF21 and adiponectin), detoxification capacity (glutathione [GSH] concentrations, GSH-S-transferase [GST], and cytochrome-P450 -reductase [CPR] activities), and low-grade inflammation (C-reactive protein [CRP]) were also determined. SAAR decreased body weight, liver weight, food intake, plasma IGF1, and IGFBP3; the effect size diminished with increasing age-at-onset. SAAR increased FGF21 and adiponectin, but stress damage markers GRP78 and Xbp1s/us were unchanged, suggesting that ER stress is hormetic. SAAR increased hepatic GST activity despite lower GSH, but CPR activity was unchanged, indicative of enhanced detoxification capacity. Other stress markers were either uncompromised (CRP, anti-KLH-IgM, and DTH) or slightly lower (anti-KLH-IgG). Increases in stress markers were similar across all ages-at-onset, except for adiponectin, which peaked at 2 months. Overall, SAAR did not compromise stress responses and resulted in maximal benefits with young-onset. In survival studies, median lifespan extension with initiation at 52 weeks was 7 weeks (p = .05); less than the 33.5-week extension observed in our previous study with 7-week initiation. Findings support SAAR translational studies and the need to optimize Met dose based on age-at-onset.
Keywords: ER stress; cysteine; glutathione; hormesis; lifespan; methionine; trade-offs; translational.

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