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Effect of selenium supplementation on antioxidant markers: a systematic review and meta-analysis of randomized controlled trials.
Hasani M, Djalalinia S, Khazdooz M, Asayesh H, Zarei M, Gorabi AM, Ansari H, Qorbani M, Heshmat R.
Hormones (Athens). 2019 Dec 10. doi: 10.1007/s42000-019-00143-3. [Epub ahead of print]
PMID: 31820398
Abstract
AIM:
The aim of this study is the systematic review and meta-analysis of controlled trial studies to assess the antioxidant effects of selenium (Se) supplementation.
METHODS:
The systematic review and meta-analysis were performed according to the previously published protocol. The PubMed, Web of Sciences, and Scopus databases were meticulously searched for relevant data, without time or language restriction, up to June 1, 2017. All clinical trials which assessed the effect of Se supplementation on antioxidant markers, including oxidative stress index (OSI), antioxidant potency composite (APC) index, plasma malonaldehyde (MDA), total antioxidant capacity (TAC), antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT)), and total antioxidant plasma (TAP), were included. The effect of Se supplementation on antioxidant markers was assessed using standardized mean difference (SMD) and 95% confidence interval (CI). The random-effect meta-analysis method was used to estimate the pooled SMD.
RESULTS:
In total, 13 studies which assessed the effect of Se supplementation on antioxidant markers were included. The random-effect meta-analysis method showed that Se supplementation significantly increased GPX (SMD = 0.54; 95% CI = 0.21-0.87) and TAC (SMD = 0.39, 95% CI = 0.13, 0.66) levels and decreased MDA levels (SMD = - 0.54, 95% CI = - 0.78, - 0.30). The effect of Se supplementation on other antioxidant markers was not statistically significant (P > 0.05).
CONCLUSION:
The findings showed that Se supplementation might reduce oxidative stress by increasing TAC and GPX levels and decreasing serum MDA, both of which are crucial factors for reduction of oxidative stress.
KEYWORDS:
Antioxidant; Selenium; Supplementation

Increased lifespan, decreased mortality, and delayed cognitive decline in osteoarthritis.
Mayburd AL, Baranova A.
Sci Rep. 2019 Dec 9;9(1):18639. doi: 10.1038/s41598-019-54867-8.
PMID: 31819096
Abstract
In absence of therapies targeting symptomatic dementia, better understanding of the biology underlying a cognitive decline is warranted. Here we present the results of a meta-analysis of the impact of osteoarthritis (OA) on cognitive decline and overall mortality. Across 7 independent datasets obtained in studies of populations in the USA, EU and Australia (NBER, NSHAP, TILDA, NACC, Kaiser Permanente, GRIM BOOKS, OAI, with a total of >7 × 107 profiles), OA cohorts demonstrated higher cognitive scores, later dementia onset as well as longer lifespan and lower age-specific all-cause mortality. Moreover, generalized OA with multiple localizations is associated with more significant reduction of mortality and dementia than a singly localized OA or no arthritis. In OA patients with younger ages, all-cause mortality was disproportionally reduced as compared to that in controls, while exponential term of Gompert'z hazard function was increased, accelerating mortality accrual at later ages. Up to 8-10% of poly-osteoarthritic patients are predicted and observed to reach centenarian lifespan, while in matched non-OA population the same benchmark is reached by less than 1% of patients. These results point at a possibility of life-extending and cognition preserving impacts of OA-conditioned immune system.

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Carbohydrate restriction in midlife is associated with higher risk of type 2 diabetes among Australian women: A cohort study.
Rayner J, D'Arcy E, Ross LJ, Hodge A, Schoenaker DAJM.
Nutr Metab Cardiovasc Dis. 2019 Nov 16. pii: S0939-4753(19)30413-2. doi: 10.1016/j.numecd.2019.11.001. [Epub ahead of print]
PMID: 31822429
https://sci-hub.tw/10.1016/j.numecd.2019.11.001
Abstract
BACKGROUND AND AIMS:
Low-carbohydrate diets (LCDs) are increasingly popular but may be nutritionally inadequate. We aimed to examine if carbohydrate restriction in midlife is associated with risk of developing type 2 diabetes (T2DM), and if this association differs by previous gestational diabetes (GDM) diagnosis.
METHODS AND RESULTS:
Dietary intake was assessed for 9689 women from the Australian Longitudinal Study on Women's Health in 2001 (aged 50-55) and 2013 (aged 62-67) via validated food frequency questionnaires. Average long-term carbohydrate restriction was assessed using a low-carbohydrate diet score (highest quartile (Q4) indicating lowest proportion of energy from carbohydrates). Incidence of T2DM between 2001 and 2016 was self-reported at 3-yearly surveys. Log-binomial regression was used to estimate relative risks (RR) and 95% CIs. During 15 years of follow-up, 959 women (9.9%) developed T2DM. Carbohydrate restriction was associated with T2DM after adjustment for sociodemographic factors, history of GDM diagnosis and physical activity (Q4 vs Q1: RR 1.27 [95% CI 1.10, 1.48]), and this was attenuated when additionally adjusted for BMI (1.10 [0.95, 1.27]). Carbohydrate restriction was associated with lower consumption of fruit, cereals and high-fibre bread, and lower intakes of these food groups were associated with higher T2DM risk. Associations did not differ by history of GDM (P for interaction >0.15).
CONCLUSION:
Carbohydrate restriction was associated with higher T2DM incidence in middle-aged women, regardless of GDM history. Health professionals should advise women to avoid LCDs that are low in fruit and grains, and to consume a diet in line with current dietary recommendations.
KEYWORDS:
Carbohydrates; Cohort study; Gestational diabetes; Nutrition; Type 2 diabetes

Associations of low-dose aspirin or other NSAID use with prostate cancer risk in the Danish Diet, Cancer and Health Study.
Skriver C, Dehlendorff C, Borre M, Brasso K, Larsen SB, Tjønneland A, Pottegård A, Hallas J, Sørensen HT, Friis S.
Cancer Causes Control. 2019 Dec 10. doi: 10.1007/s10552-019-01252-5. [Epub ahead of print]
PMID: 31823168
Abstract
PURPOSE:
Epidemiologic studies suggest that use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce prostate cancer risk. We examined these associations overall and according to clinical and lifestyle parameters.
METHODS:
We identified male participants in the Danish Diet, Cancer and Health Study (n = 26,339), holding information on anthropometric measures and lifestyle factors. From Danish nationwide registries and medical records, we retrieved complete prescription histories and prostate cancer occurrence and characteristics. Cox regression was used to estimate hazard ratios (HRs) for prostate cancer associated with low-dose aspirin or nonaspirin NSAID use, overall and by clinical characteristics, anthropometric measures, and lifestyle factors.
RESULTS:
We identified 1,927 prostate cancer cases during a median follow-up of 17.0 years. Low-dose aspirin use was not associated with overall prostate cancer risk, but a reduced HR for nonaggressive prostate cancer (high use [≥ 1,825 tablets]: 0.79; 95% confidence interval (CI) 0.60-1.04) and an increased HR for aggressive disease (high use: 1.27; 95% CI 1.00-1.61) was observed with low-dose aspirin use. Long-term, high-intensity use (≥ 10 years with ≥ 0.25 defined daily doses/day) of nonaspirin NSAIDs was associated with an increased HR for prostate cancer (1.35, 95% CI 0.99-1.84), confined to localized and nonaggressive disease. No consistent variation in HRs was seen in analyses stratified by height, body mass index, smoking, and alcohol use.
CONCLUSION:
Low-dose aspirin or other NSAID use was not associated with reduced prostate cancer risk, neither overall nor according to anthropometric measures, smoking, or alcohol use. The variation according to outcome characteristics warrants further investigation.
KEYWORDS:
Aspirin; Cohort study; Epidemiology; Nonsteroidal anti-inflammatory drugs; Prostate neoplasms; Risk

Risk of type 2 diabetes in metabolically healthy people in different categories of body mass index: an updated network meta-analysis of prospective cohort studies.
Tajik S, Mirzababaei A, Ghaedi E, Kord-Varkaneh H, Mirzaei K.
J Cardiovasc Thorac Res. 2019;11(4):254-263. doi: 10.15171/jcvtr.2019.43. Epub 2019 Oct 24. Review.
PMID: 31824606
Abstract
Introduction: Risk of diabetes mellitus type 2 (T2DM) is variable between individuals due to different metabolic phenotypes. In present network meta-analysis, we aimed to evaluate the risk of T2DM related with current definitions of metabolic health in different body mass index (BMI) categories. Methods: Relevant articles were collected by systematically searching PubMed and Scopus databases up to 20 March 2018 and for analyses we used a random-effects model. Nineteen prospective cohort studies were included in the analyses and metabolically healthy normal weight (MHNW) was considered as the reference group in direct comparison for calculating indirect comparisons in difference type of BMI categories. Results: Total of 199403 participants and 10388 cases from 19 cohort studies, were included in our network meta-analysis. Metabolically unhealthy obesity (MUHO) group poses highest risk for T2DM development with 10 times higher risk when is compared with MHNW (10.46 95% CI; 8.30, 13.18) and after that Metabolically unhealthy overweight (MUOW) individuals were at highest risk of T2DM with 7 times higher risk comparing with MHNW (7.25, 95% CI; 5.49, 9.57). Metabolically healthy overweight and obese (MHOW/MHO) individuals have (1.77, 95% CI; 1.33, 2.35) and (3.00, 95% CI; 2.33, 3.85) risk ratio for T2DM development in comparison with MHNW respectively. Conclusion: In conclusion we found that being classified as overweight and obese increased the risk of T2DM in comparison with normal weight. In addition, metabolically unhealthy (MUH) individuals are at higher risk of T2DM in all categories of BMI compared with metabolically healthy individuals.
KEYWORDS:
BMI; Diabetes Mellitus Type 2; Metabolic Healthy; Metabolic Syndrome; Metabolic Unhealthy; Obesity; T2DM

Natto Intake is Inversely Associated with Osteoporotic Fracture Risk in Postmenopausal Japanese Women.
Kojima A, Ikehara S, Kamiya K, Kajita E, Sato Y, Kouda K, Tamaki J, Kagamimori S, Iki M.
J Nutr. 2019 Dec 11. pii: nxz292. doi: 10.1093/jn/nxz292. [Epub ahead of print]
PMID: 31825069
Abstract
BACKGROUND:
The direct association between intake of Japanese fermented soybeans, namely natto, and bone mineral density (BMD) is known. However, the association with osteoporotic fractures has not been studied.
OBJECTIVE:
This study aimed to investigate whether habitual natto intake is associated with a risk of osteoporotic fractures.
METHODS:
This prospective cohort study included 1417 postmenopausal Japanese women who were enrolled in the Japanese Population-Based Osteoporosis cohort study in 1996, 1999, 2002, and 2006 and were aged ≥45 y at baseline. The intake of natto, tofu, and other soybean products was surveyed with use of a FFQ at baseline. Fractures were ascertained in follow-up surveys conducted in 1999, 2002, 2006, and 2011/2012. Osteoporotic fracture was the primary outcome and was defined as a clinical fracture occurring without strong external force, diagnosed with radiographs by a medical doctor. HRs with 95% CIs were estimated with Cox proportional hazard models.
RESULTS:
During the 17,699 person-years of follow-up (median, 15.2 y), 172 women experienced osteoporotic fractures. After adjustment for age and BMD at the total hip, the HRs compared with those of < 1 pack (approximately 40 g)/wk natto intake were 0.72 (95% CI: 0.52, 0.98) and 0.51 (95% CI: 0.30, 0.87) for 1-6 and ≥7 packs/wk, respectively. After further adjustment for BMI, history of osteoporotic fractures, history of myocardial infarction or stroke, diabetes mellitus, current smoking, alcohol intake, frequency of tofu and other soybean product intakes, and dietary calcium intake, the HRs were 0.79 (95% CI: 0.56, 1.10) and 0.56 (95% CI: 0.32, 0.99) for 1-6 and ≥7 packs/wk, respectively. Frequency of tofu or other soybean product intakes had no association with the risk of osteoporotic fractures.
CONCLUSIONS:
Habitual natto intake may be associated with a reduced risk of osteoporotic fractures independent of confounding factors, including BMD, in Japanese postmenopausal women. This trial was registered at umin.ac.jp as UMIN 000032869.
KEYWORDS:
fermented soybeans; natto; osteoporotic fracture; postmenopausal women; prospective cohort study

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Association of Dietary Magnesium Intake with Fatal Coronary Heart Disease and Sudden Cardiac Death.
Li J, Hovey KM, Andrews CA, Quddus A, Allison MA, Van Horn L, Martin LW, Salmoirago-Blotcher E, Song Y, Manson JE, Albert CM, Lu B, Eaton CB.
J Womens Health (Larchmt). 2019 Dec 12. doi: 10.1089/jwh.2019.7775. [Epub ahead of print]
PMID: 31829773
Abstract
Background: Postmenopausal women represent the highest population-based burden of cardiovascular disease, including sudden cardiac death (SCD). Our understanding of the etiology and risk factors contributing to fatal coronary heart disease (CHD) and SCD, particularly among women, is limited. This study examines the association between dietary magnesium intake and fatal CHD and SCD. Materials and Methods: We examined 153,569 postmenopausal women who participated in the Women's Health Initiative recruited between 1993 and 1998. Magnesium intake at baseline was assessed using a validated food frequency questionnaire, adjusting for energy via the residual method. Fatal CHD and SCD were identified over an average follow-up of 10.5 years. Results: For every standard deviation increase in magnesium intake, there was statistically significant risk reduction, after adjustment for confounders, of 7% for fatal CHD (hazard ratio {HR} 0.93, 95% confidence interval [CI] 0.89-0.97), and 18% risk reduction for SCD (HR 0.82, 95% CI 0.58-1.15) the latter of which did not reach statistical significance. In age-adjusted quartile analysis, women with the lowest magnesium intake (189 mg/day) had the greatest risk for fatal CHD (HR 1.54, 95% CI 1.40-1.69) and SCD (HR 1.70, 95% CI 0.94-3.07). This association was attenuated in the fully adjusted model, with HRs of 1.19 (95% CI 1.06-1.34) for CHD and 1.24 (95% CI 0.58-2.65) for SCD for the lowest quartile of magnesium intake. Conclusions: This study provides evidence of a potential inverse association between dietary magnesium and fatal CHD and a trend of magnesium with SCD in postmenopausal women. Future studies should confirm this association and consider clinical trials to test whether magnesium supplementation could reduce fatal CHD in high-risk individuals.
KEYWORDS:
coronary heart disease; magnesium; sudden cardiac death

High glycemic index and glycemic load diets as risk factors for insomnia: analyses from the Women's Health Initiative.
Gangwisch JE, Hale L, St-Onge MP, Choi L, LeBlanc ES, Malaspina D, Opler MG, Shadyab AH, Shikany JM, Snetselaar L, Zaslavsky O, Lane D.
Am J Clin Nutr. 2019 Dec 11. pii: nqz275. doi: 10.1093/ajcn/nqz275. [Epub ahead of print]
PMID: 31828298
https://sci-hub.tw/10.1093/ajcn/nqz275
Abstract
BACKGROUND:
Previous studies have shown mixed results on the association between carbohydrate intake and insomnia. However, any influence that refined carbohydrates have on risk of insomnia is likely commensurate with their relative contribution to the overall diet, so studies are needed that measure overall dietary glycemic index (GI), glycemic load, and intakes of specific types of carbohydrates.
OBJECTIVE:
We hypothesized that higher GI and glycemic load would be associated with greater odds of insomnia prevalence and incidence.
METHODS:
This was a prospective cohort study with postmenopausal women who participated in the Women's Health Initiative Observational Study, investigating the relations of GI, glycemic load, other carbohydrate measures (added sugars, starch, total carbohydrate), dietary fiber, and specific carbohydrate-containing foods (whole grains, nonwhole/refined grains, nonjuice fruits, vegetables, dairy products) with odds of insomnia at baseline (between 1994 and 1998; n = 77,860) and after 3 y of follow-up (between 1997 and 2001; n = 53,069).
RESULTS:
In cross-sectional and longitudinal analyses, higher dietary GI was associated with increasing odds of prevalent (fifth compared with first quintile OR: 1.11; CI: 1.05, 1.16; P-trend = 0.0014) and incident (fifth compared with first quintile OR: 1.16; CI: 1.08, 1.25; P-trend < 0.0001) insomnia in fully adjusted models. Higher intakes of dietary added sugars, starch, and nonwhole/refined grains were each associated with higher odds of incident insomnia. By contrast, higher nonjuice fruit and vegetable intakes were significantly associated with lower odds of incident insomnia. Also, higher intakes of dietary fiber, whole grains, nonjuice fruit, and vegetables were significantly associated with lower odds of prevalent insomnia.
CONCLUSIONS:
The results suggest that high-GI diets could be a risk factor for insomnia in postmenopausal women. Substitution of high-GI foods with minimally processed, whole, fiber-rich carbohydrates should be evaluated as potential treatments of, and primary preventive measures for, insomnia in postmenopausal women.
KEYWORDS:
epidemiology; glycemic index; glycemic load; insomnia; postmenopausal women

Important Food Sources of Fructose-Containing Sugars and Incident Hypertension: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.
Liu Q, Ayoub-Charette S, Khan TA, Au-Yeung F, Blanco Mejia S, de Souza RJ, Wolever TMS, Leiter LA, Kendall CWC, Sievenpiper JL.
J Am Heart Assoc. 2019 Dec 17;8(24):e010977. doi: 10.1161/JAHA.118.010977. Epub 2019 Dec 12.
PMID: 31826724
https://sci-hub.tw/https://www.ahajournals.org/doi/10.1161/JAHA.118.010977
Abstract
Background Sugar-sweetened beverages are associated with hypertension. We assessed the relation of important food sources of fructose-containing sugars with incident hypertension using a systematic review and meta-analysis of prospective cohort studies. Methods and Results We searched MEDLINE, EMBASE, and Cochrane (through December week 2, 2018) for eligible studies. For each food source, natural log-transformed risk ratios (RRs) for incident hypertension were pooled using pair-wise meta-analysis and linear and nonlinear dose-response meta-analyses. Certainty in our evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. We identified 26 reports, including 15 prospective cohorts (930 677 participants; 363 459 cases). Sugar-sweetened beverages showed harmful (RRper-355-mL, 1.10 [95% CI, 1.08, 1.12]) whereas fruit (RRper-240-g, 0.94 [95% CI, 0.96, 0.99]) and yogurt showed protective associations (RRper-125-g, 0.95 [95% CI, 0.94, 0.97]) with incident hypertension throughout the dose range. One hundred percent fruit juice showed a protective association only at moderate doses (RRat-100-mL, 0.97 [95% CI, 0.94, 0.99]). The pair-wise protective association of dairy desserts was not supported by linear dose-response analysis. Fruit drinks or sweet snacks were not associated with hypertension. Certainty of the evidence was "low" for sugar-sweetened beverages, 100% fruit juice, fruit, and yogurt and "very low" for fruit drinks, sweet snacks, and dairy desserts. Conclusions The harmful association between sugar-sweetened beverages and hypertension does not extend to other important food sources of fructose-containing sugars. Further research is needed to improve our estimates and better understand the dose-response relationship between food sources of fructose-containing sugars and hypertension.
KEYWORDS:
SSBs; dairy; fruit; fruit juice; hypertension; yogurt

Association of hypothyroidism and mortality in the elderly population: A systematic review and meta-analysis.
Tsai TY, Tu YK, Munir KM, Lin SM, Chang RH, Kao SL, Loh CH, Peng CC, Huang HK.
J Clin Endocrinol Metab. 2019 Dec 12. pii: dgz186. doi: 10.1210/clinem/dgz186. [Epub ahead of print]
PMID: 31829418
https://sci-hub.tw/10.1210/clinem/dgz186
Abstract
CONTEXT:
The evidence of whether hypothyroidism increases mortality in the elderly population is currently inconsistent and conflicting.
OBJECTIVE:
To determine the impact of hypothyroidism on mortality in the elderly population.
DATA SOURCES:
PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases from inception until May 10, 2019.
STUDY SELECTION:
Studies evaluating the association between hypothyroidism and all-cause and/or cardiovascular mortality in the elderly population (aged ≥ 60 years) were eligible.
DATA EXTRACTION:
Two reviewers independently extracted data and assessed the quality of studies. The relative risk (RR) was retrieved for synthesis. Random-effects model for meta-analyses was used.
DATA SYNTHESIS:
A total of 27 cohort studies with 1,114,638 participants met the inclusion criteria. Overall, patients with hypothyroidism experienced a higher risk of all-cause mortality than those with euthyroidism (pooled RR=1.26, 95% CI: 1.15-1.37); meanwhile, no significant difference in cardiovascular mortality was found between patients with hypothyroidism and those with euthyroidism (pooled RR=1.10, 95% CI: 0.84-1.43). Subgroup analyses revealed that overt hypothyroidism (pooled RR=1.10, 95% CI: 1.01-1.20) rather than subclinical hypothyroidism (pooled RR=1.14, 95% CI: 0.92-1.41) was associated with increased all-cause mortality. The heterogeneity primarily originated from different study designs (prospective and retrospective) and geographic locations (Europe, North America, Asia, and Oceania).
CONCLUSIONS:
Based on the current evidence, hypothyroidism is significantly associated with increased all-cause mortality instead of cardiovascular mortality among the elderly. We observed considerable heterogeneity, so caution is needed when interpreting the results. Further prospective large-scale high-quality studies are warranted to confirm these findings.
KEYWORDS:
cardiovascular mortality; elderly; hypothyroidism; mortality; overt hypothyroidism; subclinical hypothyroidism

Edited by AlPater

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Association of Adult Weight Gain With Major Health Outcomes Among Middle-aged Chinese Persons With Low Body Weight in Early Adulthood.
Jia G, Shu XO, Liu Y, Li HL, Cai H, Gao J, Gao YT, Wen W, Xiang YB, Zheng W.
JAMA Netw Open. 2019 Dec 2;2(12):e1917371. doi: 10.1001/jamanetworkopen.2019.17371.
PMID: 31834393
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2757482
https://cdn.jamanetwork.com/ama/content_public/journal/jamanetworkopen/938282/zoi190658supp1_prod.pdf?Expires=2147483647&Signature=dxOsBSHWsdXtqipweOwFCBOXRETiWf2TkNwKX37oHf7OMzz2rLyX4LcHht7WduKkaO3Zj~2YgbLjcat--St9Z4jr8MXYLpbQt4mUnOPnAPr1wjp8eYfK1vRtvL5aGePfm4JW9dY6YNd2wutoUja1vGCY3XDjZaboFWiobYFymb2VmvDueZQx8VwZUfoTwMfUlGnEBT7cwNDzUCDnVLNHniq67qnCRTIXqaAGtTPzlyck42-8hDaymw4rAZgOL-ZHk8Xefy1-JlewtHh-rd40o8CBPrqzRkM1cDAEqp8N5kUx1dsBmwAj70VdbNZUhcrZO4Q-Bip~N21I0U-OKRgcAQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA
Abstract
IMPORTANCE:
The association of weight gain from early to middle adulthood with disease risk has not been adequately studied.
OBJECTIVE:
To investigate the association of adult weight gain with major health outcomes in a Chinese population with low body weight in early adulthood.
DESIGN, SETTING, AND PARTICIPANTS:
This population-based cohort study assessed data from 48 377 women and 35 989 men aged 40 to 59 years at recruitment in 2 prospective cohort studies in China. The Shanghai Women's Health Study recruited 74 941 women, aged 40 to 70 years, from January 1, 1996, to December 31, 2000, and the Shanghai Men's Health Study recruited 61 482 men, aged 40 to 74 years, from January 1, 2002, to December 31, 2006. This analysis was conducted from September 1, 2017, to April 30, 2018.
EXPOSURES:
Weight gain from 20 years of age to 40 to 59 years of age.
MAIN OUTCOMES AND MEASURES:
Mortality and incidence of cancers and other chronic diseases.
RESULTS:
This analysis included 48 377 women (mean [SD] age, 47.8 [5.3] years) and 35 989 men (mean [SD] age, 49.6 [5.1] years). Per 5-kg weight gain from early to middle adulthood was associated with an approximately 10% (hazard ratio {HR} 1.09; 95% CI, 1.04-1.14 for men; HR, 1.14; 95% CI, 1.11-1.19 for women) elevated all-cause mortality and a greater than 20% (HR, 1.26; 95% CI, 1.16-1.38 for men; HR, 1.23; 95% CI, 1.14-1.33 for women) cardiovascular disease-related mortality in later life among individuals who reached a body mass index (BMI) of 23 or higher at middle adulthood. Body mass index at middle adulthood also modified the association of weight gain with risk of obesity-related cancers, with weight gain of 20 kg or more associated with increased risks both for men (HR, 1.34; 95% CI, 1.07-1.67) and for women (HR 1.45; 95% CI, 1.24-1.68). No similar associations were found for individuals with a BMI of 18.5 to 22.9. Regardless of BMI, weight gain was associated with elevated risks of type 2 diabetes, hypertension, fatty liver disease, stroke, gout, and gallstones, particularly for type 2 diabetes (HR, 7.87; 95% CI, 6.91-8.97 for women; HR, 4.95; 95% CI, 4.23-5.79 for men) and fatty liver disease (HR, 3.68; 95% CI, 3.42-3.95 for women; HR, 2.83, 95% CI, 2.56-3.13 for men) in individuals with weight gain of 20 kg or more compared with those with a healthy weight.

CONCLUSIONS AND RELEVANCE:
This study found that weight gain from early to middle adulthood was associated with disease incidence and mortality in later life. The BMI at middle adulthood modified the association of weight gain with mortality and cancer incidence but not risk of other major chronic diseases.

Negative emotional states and negative life events: Consequences for cardiovascular health in a general population.
Natt Och Dag Y, Mehlig K, Rosengren A, Lissner L, Rosvall M.
J Psychosom Res. 2019 Nov 29;129:109888. doi: 10.1016/j.jpsychores.2019.109888. [Epub ahead of print]
PMID: 31835155
https://sci-hub.tw/10.1016/j.jpsychores.2019.109888
Abstract
OBJECTIVE:
The contemporary increase in psychological distress observed in many countries is, by itself, a public health issue of great concern. The present study aims to investigate associations between self-reported negative emotional states and negative life events, and cardiovascular disease (CVD).
METHODS:
Prospective cohort study based on the Swedish INTERGENE cohort comprising 3614 men and women, aged 25 to 75. Baseline examinations during 2001-2004 included self-rating depression and anxiety scales, life stress, as well as a wide range of physiological and behavioral parameters, which allowed for relevant adjustments. Cox proportion hazard was used to predict incident CVD, CVD mortality as well as all-cause mortality.
RESULTS:
The results showed a dose-response relationship between depressiveness, anxiety and negative life events on the one hand, and increased risk of CVD. Most of these associations persisted in the fully adjusted models. Furthermore, the youngest age group (25-44 years) generally showed the highest prevalence of psychosocial distress, and also had the highest risks of incident CVD with regard to depression and anxiety.
CONCLUSION:
The associations between psychological distress and later life cardiovascular disease calls for enhanced public health efforts aiming at ameliorating psychological health, not least in younger age groups.

Adherence to the low carbohydrate diet and the risk of breast Cancer in Iran.
Sasanfar B, Toorang F, Esmaillzadeh A, Zendehdel K.
Nutr J. 2019 Dec 12;18(1):86. doi: 10.1186/s12937-019-0511-x.
PMID: 31831005
Abstract
BACKGROUND:
Previous studies on the link between macronutrients and breast cancer have mostly focused on individual macronutrients rather than their combination. This study investigates the association between adherence to a low carbohydrate diet and odds of breast cancer among women.
METHODS:
This hospital-based case-control study was carried out on 412 women with pathologically confirmed breast cancer within the past year and 456 apparently healthy controls that were matched in terms of age and residential place. Dietary data was collected using a 168-item validated FFQ. Participants were classified in terms of quintiles of percentages of energy intake from carbohydrates, proteins, and fats. Then, individuals in the highest quintile of fat and protein intake were given a score of 5 and those in the lowest quintile of these macronutrients were given a score of 1. Participants in the other quintiles of these macronutrients were given the corresponding score. In terms of carbohydrate intake, those in the highest quintile received a score of 1 and those in the lowest quintile received 5. The scores were then summed up to calculate the total low carbohydrate diet (LCD) score, which varied from 3 to 15. A higher score meant greater adherence to a low carbohydrate diet.
RESULTS:
The mean age of study participants was 45.2 y and mean BMI was 28.4 kg/m2. Mean LCD score of participants was 8.9 ± 2.5 (8.9 ± 2.6 in cases and 9.0 ± 2.5 in controls). Although no significant association was observed between adherence to the LCD score and odds of breast cancer in the study population, a trend toward significant positive association was seen between consumption of LCD and odds of breast cancer in postmenopausal women; after controlling for several potential confounders, individuals in the third quartile of LCD score were 1.94 times more likely to have breast cancer than those in the lowest quartile (95% CI: 1.00, 3.76). This association strengthened after controlling for dietary variables (2.50; 1.18-5.32). Even after further adjustment for BMI, this association remained significant (2.64, 1.23-5.67). No significant relationship was observed in premenopausal women, either before or after controlling for confounders.
CONCLUSION:
Adherence to LCD may be associated with increased odds of breast cancer in postmenopausal women. Prospective cohort studies are needed to confirm these findings.
KEYWORDS:
Breast cancer; Carbohydrate; Diet; Fat; Macronutrient; Protein

Edited by AlPater

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Dietary sodium and potassium and risk of diabetes: A prospective study using data from the China Health and Nutrition Survey.
Hao G, Liu K, Halbert JD, Chen H, Wu J, Jing C.
Diabetes Metab. 2019 Dec 12. pii: S1262-3636(19)30188-0. doi: 10.1016/j.diabet.2019.12.002. [Epub ahead of print]
PMID: 31838058
Abstract
AIMS:
- Dietary sodium and potassium intakes are well-known risk factors for cardiovascular outcomes. However, the associations between dietary sodium and potassium and diabetes are still controversial. Our study aimed to examine whether dietary sodium, potassium and the sodium-potassium ratio are associated with the risk of diabetes, based on a large sample of Chinese adults.
METHODS:
- The study data were from the 2004-2009 China Health and Nutrition Survey (CHNS), and 5867 participants were eligible for analysis. Sodium and potassium intakes were estimated based on three consecutive 24-h recalls at an individual level combined with a food inventory at a household level performed over the same 3-day period. Diabetes was defined as fasting glucose ≥ 7.0 mmol/L (≥ 126 mg/dL), HbA1c ≥ 6.5% or use of antidiabetic drugs.
RESULTS:
- Over a mean follow-up of 4.7 years, there were 611 (10.4%) incident cases of diabetes. Participants in the higher quartiles (Q3 and Q4) of sodium intake had significantly higher risks of diabetes than those with the lowest sodium intake [Q3, RR: 1.41, 95% CI: 1.06-1.86 and Q4, RR: 1.35, 95% CI: 1.02-1.80; P < 0.001 for trend). In addition, high sodium intakes were significantly associated with levels of fasting glucose and HbA1c (P < 0.05 for trend), with similar associations also found with sodium-potassium ratios (P < 0.05 for trend), but not for potassium intakes.
CONCLUSION:
- This study found that higher sodium intakes and sodium-potassium ratios were significantly associated with a higher risk of diabetes. Further clinical research is now necessary to confirm these results.
KEYWORDS:
Diabetes; Potassium; Prospective study; Sodium

Social inequalities in multimorbidity, frailty, disability, and transitions to mortality: a 24-year follow-up of the Whitehall II cohort study.
Dugravot A, Fayosse A, Dumurgier J, Bouillon K, Rayana TB, Schnitzler A, Kivimaki M, Sabia S, Singh-Manoux A.
Lancet Public Health. 2019 Dec 11. pii: S2468-2667(19)30226-9. doi: 10.1016/S2468-2667(19)30226-9. [Epub ahead of print]
PMID: 31837974
Abstract
BACKGROUND:
Social inequalities in mortality persist in high-income countries with universal health care, and the mechanisms by which these inequalities are generated remain unclear. We aimed to examine whether social inequalities were present before or after the onset of adverse health conditions (multimorbidity, frailty, and disability).
METHODS:
Our analysis was based on data from the ongoing Whitehall II cohort study, which enrolled British civil servants aged 35-55 years in 1985-88. Participants were assessed for three indicators of socioeconomic status (education, occupational position, and literacy) at age 50 years. Participants underwent clinical examinations (in 2002-04, 2007-09, 2012-13, and 2015-16) for assessment of frailty (two or more of low physical activity, slow walking speed, poor grip strength, weight loss, and exhaustion) and disability (two or more difficulties in bathing, dressing, going to the toilet, transferring, feeding, and walking). In addition, electronic health records were used to assess the incidence of multimorbidity (two or more of diabetes, coronary heart disease, stroke, chronic obstructive pulmonary disease, depression, arthritis, cancer, dementia, and Parkinson's disease) and mortality. In analyses adjusted for sociodemographic factors, we used multistate models to examine social inequalities in transitions from healthy state to adverse health conditions and subsequently to mortality.
FINDINGS:
Of 10 308 individuals in the Whitehall II study cohort, 6425 had relevant data available at 50 years and to the end of follow-up on Aug 31, 2017, and were included in our analysis. Participants were followed up for a median of 23·6 years (IQR 19·6-28·9). 1694 (26·4%) of 6425 participants developed multimorbidity, 1733 (27·0%) became frail, 692 (10·8%) had a disability, and 611 (9·5%) died. Multimorbidity (hazard ratio 4·12 [95% CI 3·41-4·98]), frailty (HR 2·38 [95% CI 1·93-2·93]), and disability (HR 1·73 [95% CI 1·34-2·22]) were associated with increased risk of mortality; these associations were not modified by socioeconomic status. In multistate models, occupation was the socioeconomic status indicator that was most strongly associated with inequalities in the transition from healthy state to multimorbidity (HR 1·54 [95% CI 1·37-1·73]), to frailty (HR 2·08 [95% CI 1·85-2·33]), and to disability (HR 1·44 [95% CI 1·18-1·74]). Socioeconomic status indicators did not affect transitions to mortality in those with multimorbidity, frailty, or disability.

INTERPRETATION:
Socioeconomic status affects the risk of multimorbidity, frailty, and disability, but does not affect the risk of mortality after the onset of these adverse health conditions. Therefore, primary prevention is key to reducing social inequalities in mortality. Of the three adverse health conditions, multimorbidity had the strongest association with mortality, making it a central target for improving population health.

Dietary Calcium Intake and the Risk of Metabolic Syndrome: A Systematic Review and Meta-Analysis.
Han D, Fang X, Su D, Huang L, He M, Zhao D, Zou Y, Zhang R.
Sci Rep. 2019 Dec 13;9(1):19046. doi: 10.1038/s41598-019-55507-x.
PMID: 31836761
https://www.nature.com/articles/s41598-019-55507-x.pdf
Abstract
Growing evidence has suggested a possible relationship between dietary calcium intake and metabolic syndrome (MetS) risk. However, the findings of these observational studies are inconclusive, and the dose-response association between calcium intake and risk of MetS remains to be determined. Here, we identified relevant studies by searching PubMed and Web of Science databases up to December 2018, and selected observational studies reporting relative risk (RR) with 95% confidence interval (CI) for MetS based on calcium intake and estimated the summary RRs using random-effects models. Eight cross-sectional and two prospective cohort studies totaling 63,017 participants with 14,906 MetS cases were identified. A significantly reduced risk of MetS was associated with the highest levels of dietary calcium intake (RR: 0.89; 95% CI: 0.80-0.99; I2 = 75.3%), with stronger association and less heterogeneity among women (RR: 0.74, 95% CI: 0.66-0.83; I2 = 0.0%) than among men (RR: 1.06, 95% CI: 0.82-1.37; I2 = 72.6%). Our dose-response analysis revealed that for each 300 mg/day increase in calcium intake, the risk of MetS decreased by 7% (RR: 0.93; 95% CI: 0.87-0.99; I2 = 77.7%). In conclusion, our findings suggest that dietary calcium intake may be inversely associated with the risk of MetS. These findings may have important public health implications with respect to preventing the disease. Further studies, in particular longitudinal cohort studies and randomized clinical trials, will be necessary to determine whether calcium supplementation is effective to prevent MetS.

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Dietary saturated fat and heart disease: a narrative review.
Heileson JL.
Nutr Rev. 2019 Dec 16. pii: nuz091. doi: 10.1093/nutrit/nuz091. [Epub ahead of print]
PMID: 31841151
https://sci-hub.tw/10.1093/nutrit/nuz091
Abstract
The American Heart Association (AHA) recently published a meta-analysis that confirmed their 60-year-old recommendation to limit saturated fat (SFA, saturated fatty acid) and replace it with polyunsaturated fat to reduce the risk of heart disease based on the strength of 4 Core Trials. To assess the evidence for this recommendation, meta-analyses on the effect of SFA consumption on heart disease outcomes were reviewed. Nineteen meta-analyses addressing this topic were identified: 9 observational studies and 10 randomized controlled trials. Meta-analyses of observational studies found no association between SFA intake and heart disease, while meta-analyses of randomized controlled trials were inconsistent but tended to show a lack of an association. The inconsistency seems to have been mediated by the differing clinical trials included. For example, the AHA meta-analysis only included 4 trials (the Core Trials), and those trials contained design and methodological flaws and did not meet all the predefined inclusion criteria. The AHA stance regarding the strength of the evidence for the recommendation to limit SFAs for heart disease prevention may be overstated and in need of reevaluation.
KEYWORDS:
heart disease; low-density lipoprotein cholesterol; meta-analysis; polyunsaturated fat; saturated fat; trans fat

Intake of vegetables and fruits and the risk of cataract incidence in a Japanese population: the Japan Public Health Center-based Prospective Study.
Adachi S, Sawada N, Yuki K, Uchino M, Iwasaki M, Tsubota K, Tsugane S.
J Epidemiol. 2019 Dec 14. doi: 10.2188/jea.JE20190116. [Epub ahead of print]
PMID: 31839643
Abstract
BACKGROUND:
Although the consumption of vegetables and fruits is reported to influence the risk of cataract, no prospective study of this association from Asia has yet appeared. Here, we investigated the association between vegetable and fruit intake and cataract incidence in a large-scale population-based prospective cohort study in Japan.
METHODS:
This study included 32,387 men and 39,333 women aged 45-74 years who had no past history of cataract and had completed a dietary questionnaire of the Japan Public Health Center-based Prospective Cohort Study. The incidence of cataract was evaluated after five-year follow-up. We used multiple logistic regression analyses to estimate the sex-specific odds ratios (ORs), with adjustment for confounding factors.
RESULTS:
We identified 1,836 incident cataracts in 594 men and 1,242 women. In men, OR for cataract was decreased with higher intake of vegetables (ORQ5 vs Q1=0.77; 95% CI, 0.59-1.01; Ptrend across quartile categories=0.03) and cruciferous vegetables (ORQ5 vs Q1=0.74; 95% CI, 0.57-0.96; Ptrend=0.02). In contrast, OR for cataract was increased with higher intake of vegetables among women (ORQ5 vs Q1=1.28; 95% CI, 1.06-1.53; Ptrend=0.01). Green and yellow vegetable and fruit intake were not associated with cataract in either sex.
CONCLUSIONS:
This study suggests that vegetables may reduce the risk of cataracts in men, but not in women.
KEYWORDS:
cataract risk; food frequency questionnaire; food intake; prospective cohort study

Telomere Length and the Risk of Alzheimer's Disease: The Rotterdam Study.
Fani L, Hilal S, Sedaghat S, Broer L, Licher S, Arp PP, van Meurs JBJ, Ikram MK, Ikram MA.
J Alzheimers Dis. 2019 Dec 9. doi: 10.3233/JAD-190759. [Epub ahead of print]
PMID: 31839608
Abstract
There is a wide interest in biomarkers that capture the burden of detrimental factors as these accumulate with the passage of time, i.e., increasing age. Telomere length has received considerable attention as such a marker, because it is easily quantified and it may aid in disentangling the etiology of dementia or serve as predictive marker. We determined the association of telomere length with risk of Alzheimer's disease and all-cause dementia in a population-based setting. Within the Rotterdam Study, we performed quantitative PCR to measure mean leukocyte telomere length in blood. We determined the association of telomere length with risk of Alzheimer's disease until 2016, using Cox regression models. Of 1,961 participants (mean age 71.4±9.3 years, 57.1% women) with a median follow-up of 8.3 years, 237 individuals were diagnosed with Alzheimer's disease. We found a U-shaped association between telomere length and risk of Alzheimer's disease: compared to the middle tertile the adjusted hazard ratio was 1.59 (95% confidence interval (CI), 1.13-2.23) for the lowest tertile and 1.47 (1.03-2.10) for the highest tertile. Results were similarly U-shaped but slightly attenuated for all-cause dementia. In conclusion, shorter and longer telomere length are both associated with an increased risk of Alzheimer's disease in the general population.
KEYWORDS:
Alzheimer’s disease; dementia; population-based; prospective cohort study; telomere

Assessment of the Metabolic Effects of Isocaloric 2:1 Intermittent Fasting in Mice.
Kim RY, Lee JH, Oh Y, Sung HK, Kim KH.
J Vis Exp. 2019 Nov 27;(153). doi: 10.3791/60174.
PMID: 31840661
https://sci-hub.tw/https://www.jove.com/video/60174/assessment-metabolic-effects-isocaloric-21-intermittent-fasting
Abstract
Intermittent fasting (IF), a dietary intervention involving periodic energy restriction, has been considered to provide numerous benefits and counteract metabolic abnormalities. So far, different types of IF models with varying durations of fasting and feeding periods have been documented. However, interpreting the outcomes is challenging, as many of these models involve multifactorial contributions from both time- and calorie-restriction strategies. For example, the alternate day fasting model, often used as a rodent IF regimen, can result in underfeeding, suggesting that health benefits from this intervention are likely mediated via both caloric restriction and fasting-refeeding cycles. Recently, it has been successfully demonstrated that 2:1 IF, comprising 1 day of fasting followed by 2 days of feeding, can provide protection against diet-induced obesity and metabolic improvements without a reduction in overall caloric intake. Presented here is a protocol of this isocaloric 2:1 IF intervention in mice. Also described is a pair-feeding (PF) protocol required to examine a mouse model with altered eating behaviors, such as hyperphagia. Using the 2:1 IF regimen, it is demonstrated that isocaloric IF leads to reduced body weight gain, improved glucose homeostasis, and elevated energy expenditure. Thus, this regimen may be useful to investigate the health impacts of IF on various disease conditions.

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Discovery of a novel niacin-lipoic acid dimer N2L attenuating atherosclerosis and dyslipidemia with non-flushing effects.
Jiang Y, Jin M, Chen J, Yan J, Liu P, Yao M, Cai W, Pi R.
Eur J Pharmacol. 2019 Dec 14:172871. doi: 10.1016/j.ejphar.2019.172871. [Epub ahead of print]
PMID: 31846627
Abstract
Niacin has been widely used as an antihyperlipidemic drug, but the flushing effect restricted its clinical application. Here, we developed novel niacin-lipoic acid dimers which lead to better lipid modulation, higher synergistic effects and less side effects. We utilized molecular docking simulation to design a novel series of niacin-lipoic acid dimers. The compound N-(2-(5-(1,2-dithiolan-3-yl)pentanamido)ethyl)nicotinamide (N2L) was selected for the in vitro and in vivo evaluation, including the agonist activity in CHO-hGPR109A cells, cell protective effects in HT22 and HUVECs cells, flushing effect in guinea pigs and rats, lipid modulation in C57BL/6 mice and high fat diet-rats and atherosclerotic lesions regulation in apolipoprotein E null mice. N2L worked as potent and selective agonists for the high affinity niacin receptor GPR109A. N2L retained antioxidation and cytoprotection of lipoic acid. In addition, N2L displayed a good therapeutic index regarding lipid modulation and atherosclerotic lesions regulation, and minimized niacin-induced vasodilation (flushing) effect in vivo. N2L showed effective treatment regarding to lipid regulation and atherosclerosis inhibition effects, also with excellent antioxidant effects, safety profiles and non-flushing. All these results suggest N2L promising application prospects in the drug development for the treatment of atherosclerosis.
KEYWORDS:
Agonists; Dimer; GPR109A; Lipoic acid; Niacin

The Effect of Antioxidant Supplementation in Patients with Tinnitus and Normal Hearing or Hearing Loss: A Randomized, Double-Blind, Placebo Controlled Trial.
Petridou AI, Zagora ET, Petridis P, Korres GS, Gazouli M, Xenelis I, Kyrodimos E, Kontothanasi G, Kaliora AC.
Nutrients. 2019 Dec 12;11(12). pii: E3037. doi: 10.3390/nu11123037.
PMID: 31842394
Abstract
Tinnitus is the perception of sound in the absence of any external stimulus. Oxidative stress is possibly involved in its pathogenesis and a variety of antioxidant compounds have been studied as potential treatment approaches. The objective of the present study was to assess the effects of antioxidant supplementation in tinnitus patients. This is a randomized, double-blind, placebo-controlled clinical trial. Patients (N = 70) were randomly allocated to antioxidant supplementation (N = 35) or to placebo (N = 35) for a total of 3 months. Demographic, anthropometric, clinical, and nutritional data were collected. Serum total antioxidant capacity (TAC), oxidized LDL (oxLDL), and superoxide dismutase (SOD), tinnitus loudness, frequency, and minimum masking level (MML), and scores in Tinnitus Handicap Inventory questionnaire (THI), Tinnitus Functional Index (TFI), and Visual Analogue Scale (VAS) were evaluated at baseline and follow-up. Tinnitus loudness and MML significantly decreased from baseline to post measure (p < 0.001) only in the antioxidant group, the overall change being significantly different between the two groups post-intervention (p < 0.001). THI and VAS decreased only in the antioxidant group. Differences in changes in serum TAC, SOD, and oxLDL post-intervention were insignificant. In conclusion, antioxidant therapy seems to reduce the subjective discomfort and tinnitus intensity in tinnitus patients.
KEYWORDS:
a-lipoic acid; antioxidant supplementation; multi-vitamin supplement; oxidative stress; tinnitus

Sustained weight loss and risk of breast cancer in women ≥50 years: a pooled analysis of prospective data.
Teras LR, Patel AV, Wang M, Yaun SS, Anderson K, Brathwaite R, Caan BJ, Chen Y, Connor AE, Eliassen AH, Gapstur SM, Gaudet MM, Genkinger JM, Giles GG, Lee IM, Milne RL, Robien K, Sawada N, Sesso HD, Stampfer MJ, Tamimi RM, Thomson CA, Tsugane S, Visvanathan K, Willett WC, Zeleniuch-Jacquotte A, Smith-Warner SA.
J Natl Cancer Inst. 2019 Dec 13. pii: djz226. doi: 10.1093/jnci/djz226. [Epub ahead of print]
PMID: 31845728
Abstract
BACKGROUND:
Excess body weight is an established cause of postmenopausal breast cancer, but it is unknown if weight loss reduces risk.
METHODS:
Associations between weight change and risk of breast cancer were examined among women aged ≥50 years in the Pooling Project of Prospective Studies of Diet and Cancer. In 10 cohorts, weight assessed on three surveys was used to examine weight change patterns over approximately 10 years (Interval 1 median= 5.2 years; Interval 2 median = 4.0 years). Sustained weight loss was defined as ≥ 2kg lost in Interval 1 that was not regained in Interval 2. Among 180,885 women, 6,930 invasive breast cancers were identified during follow-up.
RESULTS:
Compared with women with stable weight (± 2kg), women with sustained weight loss had a lower risk of breast cancer. This risk reduction was linear and specific to women not using postmenopausal hormones (>2-4.5kg lost: Hazard Ratio (HR)= 0.82, 95% confidence interval (CI): 0.70-0.96; >4.5-<9kg lost: HR = 0.75, 95% CI: 0.63-0.90; ≥9kg lost: HR = 0.68, 95% CI: 0.50-0.93). Women who lost ≥9kg and gained some (but not all) of it back were also at a lower risk of breast cancer. Other patterns of weight loss and gain over the two intervals had a similar risk of breast cancer to women with stable weight.
CONCLUSIONS:
These results suggest that sustained weight loss, even modest amounts, is associated with lower breast cancer risk for women aged ≥50 years. Breast cancer prevention may be a strong weight loss motivator for the two-thirds of American women who are overweight or obese.

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Effects of circadian restricted feeding on parameters of metabolic syndrome among healthy subjects.
Singh RB, Cornelissen G, Mojto V, Fatima G, Wichansawakun S, Singh M, Kartikey K, Sharma JP, Torshin VI, Chibisov S, Kharlitskaya E, Al-Bawareed OA.
Chronobiol Int. 2019 Dec 17:1-8. doi: 10.1080/07420528.2019.1701817. [Epub ahead of print]
PMID: 31847602
https://sci-hub.tw/10.1080/07420528.2019.1701817
Abstract
Experimental studies indicate that energy homeostasis to the circadian clock at the behavioral, physiological, and molecular levels, emphasize that timing of food intake may play a significant role in the development of obesity and central obesity. Therefore, resetting the circadian clock by circadian energy restriction via food intake in the morning or evening, may be used as a new approach for prevention of obesity, metabolic syndrome and related diseases. After ethical clearance and written, informed consent, free living subjects were included if they volunteered to take most of the total daily meals (approximately 2000 Kcal./day) in the evening (4 weeks) or morning (4 weeks). Of 22 adults, half were randomly selected by computer generated numbers to eat in the morning and the other half in the evening, after 8.00 PM. The eating pattern was changed after 4 weeks of intervention and a 4-week washout period, those who ate in the morning were advised to eat in the evening and vice versa. Validated questionnaires were used to assess food intakes, physical activity, and intake of alcohol and tobacco. Physical examination included measurement of body weight, height, and blood pressure (BP) by sphygmomanometer. Data were regularly recorded blindly, in all subjects at start of study and during follow-up. Blood samples were collected after an overnight fast for analysis of blood glucose and Hb1c. Feeding in the evening was associated with significant increase in body weight by 0.80 kg (P < .001), body mass index (BMI) by 0.30 kg/m2 (P < .001) and waist circumference by 1.13 cm (P < .05). Feeding the same amount of energy in the morning was not associated with any significant change in weight, BMI or waist circumference (P > .500). Lesser increases in all three variables were associated with AM versus PM feeding (P < .05). Systolic BP slightly increased on PM and decreased on AM feeding, with a difference between the two responses of 1.55 mmHg (P < .05). Fasting blood glucose was lower on AM than on PM feeding (74.86 vs. 77.95 mg/dl, paired t = 4.220, P < .001). Hb1C increased on PM feeding by 0.28 (from 4.45 to 4.73; t = 9.176, P < .001), but decreased on AM feeding by 0.077 (from 4.53 to 4.45; t = -6.859, P < .001). The difference in Hb1C response between AM and PM feeding is also statistically significant (t = -11.599, P < .001). Eating in the evening can predispose to obesity, central obesity and increases in fasting blood glucose and Hb1c that are indicators of the metabolic syndrome. By contrast, eating in the morning can decrease Hb1c and systolic BP, indicating that it may be protective against the metabolic syndrome.
KEYWORDS:
Food intake; circadian clock; metabolism; morning or evening eating

Association of Strawberries and Anthocyanidin Intake with Alzheimer's Dementia Risk.
Agarwal P, Holland TM, Wang Y, Bennett DA, Morris MC.
Nutrients. 2019 Dec 14;11(12). pii: E3060. doi: 10.3390/nu11123060.
PMID: 31847371
Abstract
BACKGROUND:
Strawberries have been identified to have antioxidant and anti-inflammatory properties that improve neuronal function and cognition, mostly in animal studies. It is unknown if the consumption of strawberries or related bioactives may reduce the risk of Alzheimer's dementia risk.
MATERIAL AND METHODS:
The study was conducted in 925 participants, aged 58-98 years of the Rush Memory and Aging Project. Participants were dementia-free at baseline, completed a food frequency questionnaire, and had at least two annual neurological evaluations. The diagnosis of Alzheimer's dementia was based on structured clinical neurological examination and standardized diagnostic criteria. The association of strawberry intake and incident Alzheimer's dementia was analyzed using proportional hazard models adjusted for age, sex, education, physical activity, participation in cognitive activities, APOE-ɛ4 genotype, dietary intake of other fruits, and total calorie intake.
RESULTS:
A total of 245 participants developed Alzheimer's dementia over the mean follow-up of 6.7 (±3.6) years. Higher strawberry intake was associated with reduced risk of Alzheimer's dementia (HR = 0.76, 95% CI: 0.60-0.96). In separate adjusted models, highest vs. lowest quartile intakes of Vitamin C (HR = 0.64, 95% CI: 0.45, 0.92), Pelargonidin (0.63, 95% CI: 0.43, 0.92), total anthocyanidins (0.69, 95% CI: 0.48, 0.99), and total flavonoids (0.67, 95% CI: 0.46, 0.98) were each associated with lower Alzheimer's dementia risk. These associations remained after further adjustment for cardiovascular conditions.
CONCLUSION:
Consumption of strawberries and foods rich in vitamin C, pelargonidin, anthocyanidins, and total flavonoids may reduce the risk of Alzheimer's dementia.
KEYWORDS:
APOE-ɛ4; cyanidins; diet; flavonoids; pelargonidin; proanthocyanidins

<Editors' Choice> Association between green tea intake and risk of cognitive decline, considering glycated hemoglobin level, in older Japanese adults: the NILS-LSA study.
Shirai Y, Kuriki K, Otsuka R, Kato Y, Nishita Y, Tange C, Tomida M, Imai T, Ando F, Shimokata H.
Nagoya J Med Sci. 2019 Nov;81(4):655-666. doi: 10.18999/nagjms.81.4.655.
PMID: 31849383
Abstract
Positive and negative associations with risk of cognitive decline have been reported for glycated hemoglobin (HbA1c) level and green tea (GT) intake, respectively. This study aimed to assess whether the reduction in the risk of cognitive decline with GT intake depended on HbA1c level. The participants were aged ≥60 years at baseline in the cohort study, wherein examinations were conducted biennially from 2000 to 2012. Subjects (n=1,304) who had no cognitive decline during the first survey and who had participated in the follow-up survey at least once were included. The follow-up end point was the first screening time point for cognitive decline (Mini-Mental State Examination score <27) or the last survey participation. With reference to the Japanese Diabetes Society guideline, the cut-off points for HbA1c level were set at 5.6%, 6.0%, and 6.5%, and lower and higher groups were assigned for each cut-off point. In a multiple Cox proportional hazard model, an interaction between GT intake and HbA1c groups for cognitive decline was observed only at HbA1c 6.0% (P-value for interaction [with Bonferroni's correction] <0.05/3). Lower risks of cognitive decline were found for the HbA1c ≥5.6%, ≥6.0%, and <6.5% groups (hazard ratios: 0.59, 0.34, and 0.77; 95% confidence intervals: 0.41-0.88, 0.19-0.61, and 0.56-1.08 for "≥4 times a day" vs. "<once a day" GT intake, respectively; P-value for trend: 0.06, <0.01, and 0.09, respectively). With respect to blood glucose level, our cohort study showed non-uniformly reduced risk of cognitive decline with GT intake among older Japanese adults.
KEYWORDS:
HbA1c; blood glucose level; cognitive decline; epidemiology; green tea

Association between Plasma N-6 Polyunsaturated Fatty Acids Levels and the Risk of Cardiovascular Disease in a Community-based Cohort Study.
Yang WS, Chen YY, Chen PC, Hsu HC, Su TC, Lin HJ, Chen MF, Lee YT, Chien KL.
Sci Rep. 2019 Dec 17;9(1):19298. doi: 10.1038/s41598-019-55686-7.
PMID: 31848413
Abstract
Most studies support that saturated fatty acid replacement with polyunsaturated fatty acids (PUFAs) may reduce the risk of cardiovascular diseases (CVDs) and put emphasis on the effects of N-3 PUFAs. The reported relationships between N-6 PUFAs and CVD risks vary. We aimed to examine the associations between N-6 PUFA concentrations and CVD risks. In this community-based prospective cohort study on CVD-free patients at baseline (N = 1835, age: 60.6 ± 10.5 years, women: 44.5%), we measured the fatty acid concentrations in the blood using gas chromatography. Four hundred twenty-four participants developed CVDs during follow up. The total N-6 PUFA concentration was inversely associated with the CVD risk, with a 48% lower risk in the highest N-6 PUFA concentration quartile (hazard ratio = 0.52; P for trend <0.001). The estimated population attributable risk of N-6 PUFAs indicated that approximately 20.7% of CVD events would have been prevented if the plasma N-6 PUFA concentration had been higher than the median value. The total N-6 PUFA concentration presented the highest net reclassification improvement (NRI = 7.2%, P = 0.03) for predicting incident CVD. Further studies on N-6 PUFAs, diet habits, and their relationships with healthcare are warranted.

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Chili Pepper Consumption and Mortality in Italian Adults.
Bonaccio M, Di Castelnuovo A, Costanzo S, Ruggiero E, De Curtis A, Persichillo M, Tabolacci C, Facchiano F, Cerletti C, Donati MB, de Gaetano G, Iacoviello L; Moli-sani Study Investigators.
J Am Coll Cardiol. 2019 Dec 24;74(25):3139-3149. doi: 10.1016/j.jacc.2019.09.068.
PMID: 31856971
Abstract
BACKGROUND:
Chili pepper is a usual part of a traditional Mediterranean diet. Yet epidemiological data on the association between chili pepper intake and mortality risk are scarce, with a lack of studies from Mediterranean populations.
OBJECTIVES:
This study sought to examine the association between chili pepper consumption and risk of death in a large sample of the adult Italian general population, and to account for biological mediators of the association.
METHODS:
Longitudinal analysis was performed on 22,811 men and women enrolled in the Moli-sani Study cohort (2005 to 2010). Chili pepper intake was estimated by the EPIC (European Prospective Investigation Into Cancer) Food Frequency Questionnaire and categorized as none/rare consumption, up to 2 times/week, >2 to ≤4 times/week, and >4 times/week.
RESULTS:
Over a median follow-up of 8.2 years, a total of 1,236 deaths were ascertained. Multivariable hazard ratios (HRs) for all-cause and cardiovascular disease (CVD) mortality among participants in the regular (>4 times/week) relative to none/rare intake were 0.77 (95% confidence interval [CI]: 0.66 to 0.90) and 0.66 (95% CI: 0.50 to 0.86), respectively. Regular intake was also inversely associated with ischemic heart disease (HR: 0.56; 95% CI: 0.35 to 0.87) and cerebrovascular (HR: 0.39; 95% CI: 0.20 to 0.75) death risks. The association of chili pepper consumption with total mortality appeared to be stronger in hypertension-free individuals (p for interaction = 0.021). Among known biomarkers of CVD, only serum vitamin D marginally accounted for such associations.
CONCLUSIONS:
In a large adult Mediterranean population, regular consumption of chili pepper is associated with a lower risk of total and CVD death independent of CVD risk factors or adherence to a Mediterranean diet. Known biomarkers of CVD risk only marginally mediate the association of chili pepper intake with mortality.
KEYWORDS:
Mediterranean diet; cardiovascular mortality; cerebrovascular mortality; chili pepper; inflammation; risk factors; total mortality

Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis.
Yao P, Bennett D, Mafham M, Lin X, Chen Z, Armitage J, Clarke R.
JAMA Netw Open. 2019 Dec 2;2(12):e1917789. doi: 10.1001/jamanetworkopen.2019.17789.
PMID: 31860103
Abstract
IMPORTANCE:
Vitamin D and calcium supplements are recommended for the prevention of fracture, but previous randomized clinical trials (RCTs) have reported conflicting results, with uncertainty about optimal doses and regimens for supplementation and their overall effectiveness.
OBJECTIVE:
To assess the risks of fracture associated with differences in concentrations of 25-hydroxyvitamin D (25[OH]D) in observational studies and the risks of fracture associated with supplementation with vitamin D alone or in combination with calcium in RCTs.
DATA SOURCES:
PubMed, EMBASE, Cochrane Library, and other RCT databases were searched from database inception until December 31, 2018. Searches were performed between July 2018 and December 2018.
STUDY SELECTION:
Observational studies involving at least 200 fracture cases and RCTs enrolling at least 500 participants and reporting at least 10 incident fractures were included. Randomized clinical trials compared vitamin D or vitamin D and calcium with control.
DATA EXTRACTION AND SYNTHESIS:
Two researchers independently extracted data according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and assessed possible bias. Rate ratios (RRs) were estimated using fixed-effects meta-analysis. Data extraction and synthesis took place between July 2018 and June 2019.
MAIN OUTCOMES AND MEASURES:
Any fracture and hip fracture.
RESULTS:
In a meta-analysis of 11 observational studies (39 141 participants, 6278 fractures, 2367 hip fractures), each increase of 10.0 ng/mL (ie, 25 nmol/L) in 25 (OH)D concentration was associated with an adjusted RR for any fracture of 0.93 (95% CI, 0.89-0.96) and an adjusted RR for hip fracture of 0.80 (95% CI, 0.75-0.86). A meta-analysis of 11 RCTs (34 243 participants, 2843 fractures, 740 hip fractures) of vitamin D supplementation alone (daily or intermittent dose of 400-30 000 IU, yielding a median difference in 25[OH]D concentration of 8.4 ng/mL) did not find a reduced risk of any fracture (RR, 1.06; 95% CI, 0.98-1.14) or hip fracture (RR, 1.14; 95% CI, 0.98-1.32), but these trials were constrained by infrequent intermittent dosing, low daily doses of vitamin D, or an inadequate number of participants. In contrast, a meta-analysis of 6 RCTs (49 282 participants, 5449 fractures, 730 hip fractures) of combined supplementation with vitamin D (daily doses of 400-800 IU, yielding a median difference in 25[OH]D concentration of 9.2 ng/mL) and calcium (daily doses of 1000-1200 mg) found a 6% reduced risk of any fracture (RR, 0.94; 95% CI, 0.89-0.99) and a 16% reduced risk of hip fracture (RR, 0.84; 95% CI, 0.72-0.97).
CONCLUSIONS AND RELEVANCE:
In this systematic review and meta-analysis, neither intermittent nor daily dosing with standard doses of vitamin D alone was associated with reduced risk of fracture, but daily supplementation with both vitamin D and calcium was a more promising strategy.

The effects of isolated soy protein, isolated soy isoflavones and soy protein containing isoflavones on serum lipids in postmenopausal women: A systematic review and meta-analysis.
Moradi M, Daneshzad E, Azadbakht L.
Crit Rev Food Sci Nutr. 2019 Dec 20:1-15. doi: 10.1080/10408398.2019.1689097. [Epub ahead of print]
PMID: 31858808
Abstract
Background: Many randomized controlled trials (RCTs) have assessed the effects of soy products on serum lipids. However, the responsible soy components and the magnitude of effects in healthy or hypercholesterolemic postmenopausal women are unclear. This review assessed the quality of these RCTs and estimated the effects of isolated soy protein, isolated soy isoflavones and soy protein containing isoflavones on total cholesterol (TC), LDL-C, HDL-C, triglycerides (TG), Apolipoprotein (Apo) A-1 and Apo B among postmenopausal women.Design: Forty-six eligible randomized controlled trials published up to 20 May 2019 were identified from the PubMed, Web of Science and Scopus databases. Weighted mean effect sizes were calculated for net changes in serum lipid concentrations by using random-effect models. Specific subgroup analyses were performed to identify the effect of covariates on serum lipid changes.Results: Soy consumption was associated with significant decrease in TG (mean differences (MD): -5.04 mg/dl; 95% CI: -9.95, -0.13; P = 0.044), TC (MD: -3.02 mg/dl; 95% CI: -5.56, -0.47; P = 0.02), LDL-C (MD: -3.27 mg/dl; 95% CI: -6.01, -0.53; P = 0.019) and HDL-C (MD: -2.28 mg/dl; 95% CI: -4.27, -0.29; P = 0.025). The reduction in LDL-C, TG and HDL were larger in subjects consuming isolated soy protein than isolated soy isoflavones. There was a significant decrease in serum TG and HDL levels with dosages of >25 grams per day soy protein rather than lower dosages of soy protein. The reductions in Apo A-1 were significantly larger in hypercholesterolemic subjects than in healthy subjects.Conclusions: Isolated soy protein significantly reduced serum TG, TC, LDL-C, HDL-C and Apo-B levels in postmenopausal women. Isolated soy isoflavones had a significant lowering effect on serum TC and Apo B levels. Soy protein containing isoflavones significantly reduced TG, TC, LDL-C and Apo B levels. Therefore, hyperlipidemia risk reduction with soy products is not uniform and strongly depends on the protein and isoflavone content of soy products, duration and dosage of consumption.
KEYWORDS:
Apo A-1; Apo B; HDL-C; LDL-C; Soybean proteins; hyperlipidemias; isoflavones; lipids; lipoproteins; meta-analysis; postmenopause; randomized controlled trials; triglycerides

Body mass index, diet, physical inactivity, and the incidence of dementia in 1 million UK women.
Floud S, Simpson RF, Balkwill A, Brown A, Goodill A, Gallacher J, Sudlow C, Harris P, Hofman A, Parish S, Reeves GK, Green J, Peto R, Beral V.
Neurology. 2019 Dec 18. pii: 10.1212/WNL.0000000000008779. doi: 10.1212/WNL.0000000000008779. [Epub ahead of print]
PMID: 31852815
Abstract
OBJECTIVE:
To help determine whether midlife obesity is a cause of dementia and whether low body mass index (BMI), low caloric intake, and physical inactivity are causes or merely consequences of the gradual onset of dementia by recording these factors early in a large 20-year prospective study and relating them to dementia detection rates separately during follow-up periods of <5, 5 to 9, 10 to 14, and 15+ years.
METHODS:
A total of 1,136,846 UK women, mean age 56 (SD 5) years, were recruited in 1996 to 2001 and asked about height, weight, caloric intake, and inactivity. They were followed up until 2017 by electronic linkage to National Health Service records, detecting hospital admissions with mention of dementia. Cox regression yielded adjusted rate ratios (RRs) for first dementia detection during particular follow-up periods.
RESULTS:
Fifteen years after the baseline survey, only 1% were lost to follow-up, and 89% remained alive with no detected dementia, of whom 18,695 had dementia detected later, at a mean age of 77 (SD 4) years. Dementia detection during years 15+ was associated with baseline obesity (BMI 30+ vs 20-24 kg/m2: RR 1.21, 95% confidence interval 1.16-1.26, p < 0.0001) but not clearly with low BMI, low caloric intake, or inactivity at baseline. The latter 3 factors were associated with increased dementia rates during the first decade, but these associations weakened substantially over time, approaching null after 15 years.
CONCLUSIONS:
Midlife obesity may well be a cause of dementia. In contrast, behavioral changes due to preclinical disease could largely or wholly account for associations of low BMI, low caloric intake, and inactivity with dementia detection during the first decade of follow-up.

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Selenium Supplementation and Prostate Health in a New Zealand Cohort.
Karunasinghe N, Ng L, Wang A, Vaidyanathan V, Zhu S, Ferguson LR.
Nutrients. 2019 Dec 18;12(1). pii: E2. doi: 10.3390/nu12010002.
PMID: 31861307
Abstract
BACKGROUND:
There is variable reporting on the benefits of a 200 μg/d selenium supplementation towards reducing prostate cancer impacts. The current analysis is to understand whether stratified groups receive supplementation benefits on prostate health.
METHODS:
572 men were supplemented with 200 µg/d selenium as selinized yeast for six months, and 481 completed the protocol. Selenium and prostate-specific antigen (PSA) levels were measured in serum at pre- and post-supplementation. Changes in selenium and PSA levels subsequent to supplementation were assessed with and without demographic, lifestyle, genetic and dietary stratifications.
RESULTS:
The post-supplementation selenium (p = 0.002) and the gain in selenium (p < 0.0001) by supplementation were significantly dependent on the baseline selenium level. Overall, there was no significant correlation between changes in PSA and changes in selenium levels by supplementation. However, stratified analyses showed a significant inverse correlation between changes in PSA and changes in selenium in men below the median age (p = 0.048), never-smokers (p = 0.031), men carrying the GPX1 rs1050450 T allele (CT, p = 0.022 and TT, p = 0.011), dietary intakes above the recommended daily intake (RDI) for zinc (p < 0.05), and below the RDI for vitamin B12 (p < 0.001).
CONCLUSIONS:
The current analysis shows the influence of life factors on prostate health benefits of supplemental selenium.
KEYWORDS:
dietary nutrients; genotypes; prostate-specific antigen (PSA); selenium supplementation

Association between air pollutants and development of chronic kidney disease: A systematic review and meta-analysis.
Wu MY, Lo WC, Chao CT, Wu MS, Chiang CK.
Sci Total Environ. 2019 Nov 16;706:135522. doi: 10.1016/j.scitotenv.2019.135522. [Epub ahead of print]
PMID: 31864998
Abstract
BACKGROUND:
The association between incident chronic kidney disease (CKD) or end-stage renal disease (ESRD) and exposure to outdoor air pollution is under debate. We aimed to examine this relationship based on a systematic review with random-effects meta-analysis.
METHODS:
We screened the literature on long-term air pollution exposure assessment in the general population using an electronic search of PubMed, Medline, Embase, and Cochrane Library from inception to 20 October 2019. Observational studies investigating the association between long-term exposure to gaseous (CO, SO2, NO2, O3) or particulate (PM2.5 or PM10) outdoor air pollutants and CKD, ESRD, or renal dysfunction were included, and summary risks were estimated.
RESULTS:
Of 4419 identified articles, 23 met our inclusion criteria after screening and 14 were included in the meta-analysis. Pooled effect estimates had the following summary risk ratios (RRs) for CKD: 1.10 (95% confidence intervals [CI] 1.00, 1.21; derived from four studies) per 10 μg/m3 increase in PM2.5 and 1.16 (95% CI 1.05, 1.29; derived from four studies) for PM10; 1.31 (95% CI 0.86, 2.00; derived from two studies) per 10 ppm increase in CO; and 1.11 (95% CI 1.09, 1.14; derived from three studies) per 10 ppb increase in NO2. For the pooled effect on eGFR, increases in PM10 and PM2.5 (of 10 μg/m3) were associated with eGFR decline by -0.83 (95% CI -1.54, -0.12; derived from two studies) and -4.11 (95% CI -12.64, 4.42; derived from two studies) mL/min/1.73 m2, respectively.
CONCLUSIONS:
Air pollution was observed to be associated with CKD and renal function decline. Although more longitudinal studies are required, we argue that air pollution is pernicious to kidney health.
KEYWORDS:
Air pollutants; Albumin creatinine ratio; Chronic kidney disease; Estimated glomerular filtration rate; Meta-analysis; Particulate matter

Influence of regular aspirin intake on PSA values, prostate cancer incidence and overall survival in a prospective screening trial (ERSPC Aarau).
Prause LW, Manka L, Millan C, Lang E, Wyler SF, Grobholz R, Hammerer-Lercher A, Sulser T, Recker F, Kwiatkowski M, Eberli D.
World J Urol. 2019 Dec 21. doi: 10.1007/s00345-019-03054-5. [Epub ahead of print]
PMID: 31865534
Abstract
OBJECTIVES:
To analyze the influence of aspirin (ASA) intake on PSA values and prostate cancer (PCa) development in a prospective screening study cohort.
METHODS:
4314 men from the Swiss section of the European Randomized Study of Screening for Prostate Cancer (ERSPC) were included. A transrectal prostate biopsy was performed in men with a PSA level ≥ 3 ng/ml. Mortality data were obtained through registry linkages. PCa incidence and grade, total PSA, free-to-total PSA and overall survival were compared between ASA users and non-users.
RESULTS:
Median follow-up time was 9.6 years. In 789 men (18.3%) using aspirin [ASA +], the overall PCa incidence was significantly lower (6.8% vs. 9.6%, p = 0.015), but the multivariate Cox regression analysis showed no significant decrease in risk of PCa diagnosis (HR 0.84, p = 0.297). Total PSA values were significantly lower in ASA users for both baseline (1.6 vs. 1.8 ng/ml, p = 0.007) and follow-up visits (1.75 vs. 2.1 ng/ml, p < 0.001). Multivariate Cox regression analysis predicted significantly higher overall mortality risk among ASA users (HR 1.46, p = 0.009).
CONCLUSIONS:
In our study population, PCa incidence was significantly reduced among patients on aspirin. While we did not observe a statistically significant PCa risk reduction during the follow-up period, we found lower PSA values among ASA users compared to non-users, with a more distinct difference after 4 years of ASA intake, suggesting a cumulative effect and a potential protective association between regular ASA intake and PCa development. As for clinical practice, lowering PSA cutoff values by 0.4 ng/ml could be considered in long-term ASA users to avoid a potential bias towards delayed PCa detection.
KEYWORDS:
Acetylsalicylic acid; Aspirin; Chemoprevention; Prostate cancer; Prostate-specific antigen; Screening

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The influence of hormone replacement therapy on lung cancer incidence and mortality.
Titan AL, He H, Lui N, Liou D, Berry M, Shrager JB, Backhus LM.
J Thorac Cardiovasc Surg. 2019 Nov 5. pii: S0022-5223(19)32348-7. doi: 10.1016/j.jtcvs.2019.10.070. [Epub ahead of print]
PMID: 31866083
Abstract
OBJECTIVE:
Data regarding the effects of hormone replacement therapy (HRT) on non-small cell lung cancer (NSCLC) are mixed. We hypothesized HRT would have a protective benefit with reduced NSCLC incidence among women in a large, prospective cohort.
METHODS:
We used data from the multicenter randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (1993-2001). Participants were women aged 50 to 74 years followed prospectively for up to 13 years for cancer screening. The influence of HRT on the primary outcome of NSCLC incidence and secondary outcomes of all-cause and disease-specific mortality were assessed with Kaplan-Meier analysis and Cox proportional hazard models adjusting for covariates.
RESULTS:
In the overall cohort of 75,587 women, 1147 women developed NSCLC after a median follow-up of 11.5 years. HRT use was characterized as 49.4% current users, 17.0% former users, and 33.6% never users. Increased age, smoking, comorbidities, and family history were associated with increased risk of NSCLC. On multivariable analysis, current HRT use was associated with reduced risk of NSCLC compared with never users (hazard ratio, 0.80; 95% confidence interval, 0.70-0.93; P = .009). HRT or oral contraception use was not associated with significant differences in all-cause mortality or disease-specific mortality.
CONCLUSIONS:
These data represent among the largest prospective cohorts suggesting HRT use may have a protective effect on the development of NSCLC among women; the physiological basis of this effect merits further study; however, the results may influence discussion surrounding HRT use in women.
KEYWORDS:
hormone replacement therapy; non–small cell lung cancer; smoking

Midlife Dietary Intakes of Monounsaturated Acids, n-6 Polyunsaturated Acids, and Plant-Based Fat Are Inversely Associated with Risk of Cognitive Impairment in Older Singapore Chinese Adults.
Jiang YW, Sheng LT, Pan XF, Feng L, Yuan JM, Pan A, Koh WP.
J Nutr. 2019 Dec 25. pii: nxz325. doi: 10.1093/jn/nxz325. [Epub ahead of print]
PMID: 31875477
Abstract
BACKGROUND:
Previous studies have shown inconsistent results for the relation between dietary fat intake and cognitive function in the elderly. Furthermore, prospective studies on this topic among the Chinese population are scarce.
OBJECTIVES:
We aimed to examine the association between midlife dietary fat intake and risk of cognitive impairment in the elderly.
METHODS:
Prospective cohort analysis was conducted among 16,736 participants from the Singapore Chinese Health Study. Dietary information was assessed by a validated FFQ at baseline (1993-1998) when participants aged 45-74 y (mean: 53.5; SD: 6.22). Cognitive impairment was identified using the Singapore modified Mini-Mental State Examination at the third follow-up visit (2014-2016) when participants aged 61-96 y (mean: 73.2; SD: 6.41). Multivariable logistic regression models were used to calculate ORs and 95% CIs.
RESULTS:
Cognitive impairment was presented in 2397 participants. When substituted for total carbohydrate, dietary fat intake was inversely related to cognitive impairment (OR comparing extreme quartiles: 0.80; 95% CI: 0.67, 0.94; P-trend = 0.003). The OR (95% CI) comparing extreme quartiles of specific dietary fats was 1.08 (0.89, 1.31; P-trend = 0.51) for SFAs, 0.80 (0.64, 0.99; P-trend = 0.02) for MUFAs, 0.84 (0.72, 0.99; P-trend = 0.02) for PUFAs, 0.92 (0.77, 1.09; P-trend = 0.49) for n-3 PUFAs, and 0.83 (0.70, 0.98; P-trend = 0.01) for n-6 PUFAs. An inverse association was found for plant-based fat (OR: 0.84; 95% CI: 0.72, 0.98; P-trend = 0.02), but not for animal-based fat (OR: 0.96; 95% CI: 0.81, 1.15; P-trend = 0.76). When substituted for SFAs, the OR (95% CI) was 0.77 (0.61, 0.97; P-trend = 0.02) for MUFAs and 0.82 (0.70, 0.95; P-trend = 0.003) for PUFAs.
CONCLUSIONS:
We found that substitution of total carbohydrate or SFAs with MUFAs and PUFAs, particularly n-6 PUFAs, was related to a lower risk of cognitive impairment in elderly Chinese participants. In addition, an inverse association with cognitive impairment was found for plant-based fat.
KEYWORDS:
animal-based fat; cognitive impairment; cohort study; dietary fat; fatty acids; plant-based fat

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Dietary Intakes of Vitamin B-2 (Riboflavin), Vitamin B-6, and Vitamin B-12 and Ovarian Cycle Function among Premenopausal Women.
Kim K, Mills JL, Michels KA, Chaljub EN, Wactawski-Wende J, Plowden TC, Mumford SL.
J Acad Nutr Diet. 2019 Dec 23. pii: S2212-2672(19)31548-5. doi: 10.1016/j.jand.2019.10.013. [Epub ahead of print]
PMID: 31879178
Abstract
BACKGROUND:
Riboflavin, vitamin B-6, and vitamin B-12 are key players in one-carbon metabolism as enzymatic cofactors, and deficiency of these nutrients may influence reproductive outcomes possibly through affecting reproductive hormones.
OBJECTIVE:
The goal was to investigate associations between dietary intakes of riboflavin, vitamin B-6, and vitamin B-12, and menstrual function among premenopausal women.
DESIGN:
This was a secondary analysis of a prospective cohort study conducted at the University at Buffalo during 2005 to 2007.
PARTICIPANTS/SETTING:
Participants were 259 healthy, regularly menstruating women (aged 18 to 44 years) with self-reported menstrual cycles between 21 and 35 days, who were not trying to conceive, and who had not used hormonal contraception during the past 3 months.
MAIN OUTCOME MEASURES:
Intakes of B vitamins were assessed via 24-hour dietary recalls four times per menstrual cycle for two cycles. Serum reproductive hormones and plasma homocysteine were measured eight and three times, respectively, per cycle for two cycles. Anovulatory cycles were determined by progesterone concentrations ≤5 ng/mL (15.9 nmol/L) and no observed serum luteinizing hormone peak during the mid or late luteal phase visit.
STATISTICAL ANALYSIS:
Weighted linear mixed regressions were used to evaluate associations between cycle-averaged B vitamin intakes and hormones and homocysteine, and generalized linear regressions for associations with anovulation. Models were adjusted for age, race, body mass index, physical activity, alternate Mediterranean diet score, intakes of total energy, protein, fiber, and folate, and percentage of energy intake from fat.
RESULTS:
Higher intakes of riboflavin (per 0.1 mg increase in intake) were inversely correlated with estradiol (-0.87%, 95% CI -1.67 to -0.06) and homocysteine levels (-0.61%, 95% CI -1.10 to -0.12). Higher vitamin B-6 intakes were suggestive of higher follicle-stimulating hormone, although the results were not statistically significant (0.63% difference, 95% CI -0.03 to 1.29, per 0.1 mg increase in intake; P=0.06). Small increases in testosterone and decreases in homocysteine were found with vitamin B-12 intake. No associations were observed between intake of B vitamins and a risk of sporadic anovulation.
CONCLUSIONS:
Higher intakes of riboflavin were associated with a small decrease in serum estradiol among healthy, regularly menstruating women. Higher intakes of riboflavin and vitamin B-12 were associated with lower plasma homocysteine concentrations. Overall, riboflavin, vitamin B-6, and vitamin B-12 that are one-carbon nutrients do not appear to influence the ovarian cycle among premenopausal women.
KEYWORDS:
Anovulation; B vitamins; Homocysteine; Reproductive hormones; Riboflavin

Association between Urinary Cadmium to Zinc Intake Ratio with Adult Mortality in a Follow-Up Study of NHANES 1988-1994 and 1999-2004.
Kim K, Melough MM, Sakaki JR, Ha K, Marmash D, Noh H, Chun OK.
Nutrients. 2019 Dec 24;12(1). pii: E56. doi: 10.3390/nu12010056.
PMID: 31878194
Abstract
Cadmium (Cd) is a toxic heavy metal associated with increased mortality, but the effect of zinc (Zn) intake on the association between Cd and mortality is unknown. The objective of this study was to examine the association of urinary Cd to Zn intake ratio (Cd/Zn ratio) and mortality risk. In total, 15642 US adults in NHANES 1988-1994 and 1999-2004 were followed until 2011 (15-year mean follow-up). Of the 5367 total deaths, 1194 were attributed to cancer and 1677 were attributed to CVD. After adjustment for potential confounders, positive associations were observed between urinary Cd and all-cause mortality (HR for highest vs. lowest quartile: 1.38; 95% CI: 1.14-1.68) and cancer mortality (HR: 1.54; CI: 1.05-2.27). Urinary Cd was positively associated with cancer mortality among the lowest Zn consumers, and the association diminished among the highest Zn consumers. Positive relationships were observed between the Cd/Zn ratio and all-cause mortality (HR: 1.54; CI: 1.23-1.93), cancer mortality (HR: 1.65; CI: 1.11-2.47) and CVD mortality (HR: 1.49; CI: 1.18-1.88). In conclusion, these findings indicate that Zn intake may modify the association between Cd and mortality. Furthermore, the Cd/Zn ratio, which was positively associated with mortality from all causes, cancer, and CVD, may be an important predictor of mortality.
KEYWORDS:
NHANES; mortality; urinary Cd/Zn intake ratio; urinary cadmium; zinc intake

Milk Consumption Decreases Risk for Breast Cancer in Korean Women under 50 Years of Age: Results from the Health Examinees Study.
Shin WK, Lee HW, Shin A, Lee JK, Kang D.
Nutrients. 2019 Dec 21;12(1). pii: E32. doi: 10.3390/nu12010032.
PMID: 31877693
Abstract
Epidemiologic studies regarding breast cancer risk related to milk consumption remain controversial. The aim of this study was to evaluate the association between milk consumption and the risk for breast cancer. A total of 93,306 participants, aged 40-69 years, were included in the prospective cohort study in the Health Examinees-Gem (HEXA-G) study between 2004 and 2013. Dietary intake was assessed using a validated food frequency questionnaire. Information on cancer diagnosis in the eligible cohort was retrieved from the Korea Central Cancer Registry through 31 December 2014. The Cox proportional hazards model was used to estimate multivariate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 359 breast cancer cases were observed over a median follow-up period of 6.3 years. Milk consumption was not associated with decreased risk for breast cancer in the total population (p for trend = 0.0687). In women under 50 years of age, however, milk consumption was inversely associated with breast cancer risk. In the comparison between highest (≥1 serving/day) and lowest (<1 serving/week) intake categories of milk, the multivariate HR (95% CI) was 0.58 (0.35-0.97, p for trend = 0.0195)) among women under 50 years of age. In conclusion, our findings show that milk consumption in Korean women aged 50 or younger is associated with a decreased risk for breast cancer, when compared to those who never or rarely consumed milk. Further studies need to be conducted to assess this relationship and confirm these results.
KEYWORDS:
Health Examinees (HEXA) study; Korean women; breast cancer; cohort study; milk consumption

[I believe they used the equivalent of 8 tablespoons of sugar for their scralose doses.]
Effects of Sucralose Ingestion versus Sucralose Taste on Metabolic Responses to an Oral Glucose Tolerance Test in Participants with Normal Weight and Obesity: A Randomized Crossover Trial.
Nichol AD, Salame C, Rother KI, Pepino MY.
Nutrients. 2019 Dec 20;12(1). pii: E29. doi: 10.3390/nu12010029.
PMID: 31877631
Abstract
Here, we tested the hypothesis that sucralose differentially affects metabolic responses to labeled oral glucose tolerance tests (OGTTs) in participants with normal weight and obesity. Participants (10 with normal weight and 11 with obesity) without diabetes underwent three dual-tracer OGTTs preceded, in a randomized order, by consuming sucralose or water, or by tasting and expectorating sucralose (e.g., sham-fed; sweetness control). Indices of β-cell function and insulin sensitivity (SI) were estimated using oral minimal models of glucose, insulin, and C-peptide kinetics. Compared with water, sucralose ingested (but not sham-fed) resulted in a 30 ± 10% increased glucose area under the curve in both weight groups. In contrast, the insulin response to sucralose ingestion differed depending on the presence of obesity: decreased within 20-40 min of the OGTT in normal-weight participants but increased within 90-120 min in participants with obesity. Sham-fed sucralose similarly decreased insulin concentrations within 60 min of the OGTT in both weight groups. Sucralose ingested (but not sham-fed) increased SI in normal-weight participants by 52 ± 20% but did not affect SI in participants with obesity. Sucralose did not affect glucose rates of appearance or β-cell function in either weight group. Our data underscore a physiological role for taste perception in postprandial glucose responses, suggesting sweeteners should be consumed in moderation.
KEYWORDS:
artificial sweeteners; glucose metabolism; insulin; low-calorie sweeteners; non-nutritive sweeteners; oral glucose tolerance test; sucralose

The Lifespan Extension Ability of Nicotinic Acid Depends on Whether the Intracellular NAD+ Level Is Lower than the Sirtuin-Saturating Concentrations.
Yang NC, Cho YH, Lee I.
Int J Mol Sci. 2019 Dec 24;21(1). pii: E142. doi: 10.3390/ijms21010142.
PMID: 31878234
Abstract
Calorie restriction can extend lifespan by increasing intracellular nicotinamide adenine dinucleotide (NAD+), thereby upregulating the activity of sirtuins (Caenorhabditis elegans Sir-2.1; human SIRT1). Nicotinic acid (NA) can be metabolized to NAD+; however, the calorie restriction mimetic (CRM) potential of NA is unclear. This study explored the ability and mechanism of NA to extend the lifespan of human Hs68 cells and C. elegans. We found that NA can efficiently increase the intracellular NAD+ levels in Hs68 cells and C. elegans; however, NA was only able to extend the lifespan of C. elegans. The steady-state NAD+ level in C. elegans was approximately 55 μM. When intracellular NAD+ was increased by a mutation of pme-1 (poly (ADP-ribose) metabolism enzyme 1) or by pretreatment with NAD+ in the medium, the lifespan extension ability of NA disappeared. Additionally, the saturating concentration of NAD+ required by SIRT1 was approximately 200 μM; however, the steady-state concentration of NAD+ in Hs68 cells reached up to 460 μM. These results demonstrate that the lifespan extension ability of NA depends on whether the intracellular level of NAD+ is lower than the sirtuin-saturating concentration in Hs68 cells and in C. elegans. Thus, the CRM potential of NA should be limited to individuals with lower intracellular NAD+.
KEYWORDS:
C. elegans; Hs68 cells; NAD+; calorie restriction mimetic; lifespan; nicotinic acid

NEWS RELEASE 25-DEC-2019
Intermittent fasting: live 'fast,' live longer?
JOHNS HOPKINS MEDICINE
https://www.eurekalert.org/pub_releases/2019-12/jhm-ifl121819.php
>>>>>>>>>>>>>
Why fasting for 16 hours a day may benefit the brain and body
A review of intermittent fasting studies suggests it's a genuinely healthy lifestyle.
intermittent fasting
By Sarah Sloat on December 27, 2019
>>>>>>>>>>>>>>>>>

Effects of Intermittent Fasting on Health, Aging, and Disease.
de Cabo R, Mattson MP.
N Engl J Med. 2019 Dec 26;381(26):2541-2551. doi: 10.1056/NEJMra1905136. Review. No abstract available.
PMID: 31881139

Edited by AlPater

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Effects of lutein supplementation in age-related macular degeneration.
Feng L, Nie K, Jiang H, Fan W.
PLoS One. 2019 Dec 30;14(12):e0227048. doi: 10.1371/journal.pone.0227048. eCollection 2019.
PMID: 31887124
Abstract
The purpose of this meta-analysis was to evaluate the effects of lutein supplementation on macular pigment optical density (MPOD) in randomized controlled trials involving patients with age-related macular degeneration (AMD). A comprehensive search of the literature was performed in PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wan Fang database through December 2018. Nine randomized controlled trials involving 920 eyes (855 with AMD) were included. Meta-analysis suggested that lutein supplementation (10 or 20 mg per day) was associated with an increase in MPOD (mean difference (MD) 0.07; 95% confidence interval (CI) 0.03 to 0.10), visual acuity (MD 0.28; 95%CI 0.06 to 0.50) and contrast sensitivity (MD 0.26; 95%CI 0.22 to 0.30). Stratified analyses showed the increase in MPOD to be faster and greater with higher dose and longer treatment. The available evidence suggests that dietary lutein may be beneficial to AMD patients and the higher dose could make MPOD increase in a shorter time.

Effectiveness of Cherries in Reducing Uric Acid and Gout: A Systematic Review.
Chen PE, Liu CY, Chien WH, Chien CW, Tung TH.
Evid Based Complement Alternat Med. 2019 Dec 4;2019:9896757. doi: 10.1155/2019/9896757. eCollection 2019. Review.
PMID: 31885677
Abstract
BACKGROUND:
Previous studies have reported the use of complementary therapies to reduce the risk of gout attacks. In this study, we assessed the effectiveness of cherries in reducing uric acid levels associated with gout.
METHODS:
We searched for relevant studies on PubMed, Embase, and the Cochrane Library without restrictions on language from inception until August 15, 2019. The risk of bias was evaluated using the PRISMA statement and checklist, and the methodological quality was assessed using the Cochrane Collaboration tool.
RESULTS:
The six studies included in this systematic review reported decreases in the incidence and severity of gout following the ingestion of cherries. Gout patients regularly ingesting cherry extract/juice reported fewer gout flare ups than those patients who did not supplement their diets with cherry products. Overall, we observed a positive correlation between the consumption of tart cherry juice and a decrease in serum uric acid concentration.
CONCLUSIONS:
Current evidence supports an association between cherry intake and a reduced risk of gout attacks. Note however that we were unable to conduct effective meta-analysis due to a lack of relevant studies and a high degree of variation in the methodologies and metrics used in previous studies. Further comprehensive trials or long-term follow-up studies will be required to evaluate the efficacy of cherry intake in treating patients with gout or hyperuricemia.

Lung function as a predictor of incident type 2 diabetes in community-dwelling adults: A longitudinal finding over 12 years from the Korean Genome and Epidemiology Study.
Lee JH, Lee HS, Lee YJ.
Diabetes Metab. 2019 Dec 26. pii: S1262-3636(19)30191-0. doi: 10.1016/j.diabet.2019.12.005. [Epub ahead of print]
PMID: 31884177
Abstract
AIM:
Reduced lung function is associated with type 2 diabetes (T2D), but there are limited data in East Asian populations on the relationship between them. For this reason, this study investigated the longitudinal relationship of lung function with incident T2D in Korean adults.
METHODS:
The study included 7583 non-diabetic adults aged 40-69 years from the Korean Genome and Epidemiology Study. Participants were divided into four groups according to gender-specific quartiles (Q1-Q4) of %PFVC and %PFEV1. Also, HRs with 95% CIs for incident T2D were prospectively analyzed as per American Diabetes Association criteria using multivariate Cox proportional-hazards regression models.
RESULTS:
During a 12-year follow-up, 1403 (18.5%) participants presented with newly developed T2D. HRs (95% CIs) of incident T2D in Q1 vs Q4 (reference) of %PFVC were 1.67 (1.35-2.07) for men and 1.77 (1.39-2.24) for women and, of %PFEV1, 1.58 (1.28-1.95) for men and 1.61 (1.27-2.03) for women, after adjusting for age, waist circumference, smoking status, alcohol intake, regular exercise, education levels, monthly household income, family history of diabetes, fasting plasma glucose, triglycerides, HDL cholesterol and high-sensitivity C-reactive protein levels.
CONCLUSION:
Reduced lung function precedes and significantly predicts the future development of T2D independently of obesity, smoking and inflammation in community-dwelling middle-aged and elderly people.
KEYWORDS:
General population; Incident type 2 diabetes; Lung function; Prospective cohort study

Substitution of sugar-sweetened beverages for other beverages and the risk of developing coronary heart disease: Results from the Harvard Pooling Project of Diet and Coronary Disease.
Keller A, O'Reilly EJ, Malik V, Buring JE, Andersen I, Steffen L, Robien K, Männistö S, Rimm EB, Willett W, Heitmann B.
Prev Med. 2019 Dec 26:105970. doi: 10.1016/j.ypmed.2019.105970. [Epub ahead of print]
PMID: 31883872
Abstract
Sugar-sweetened beverage (SSB) intake is associated with metabolic disorders. The reduction of SSB intake has been promoted to prevent death and disability from chronic diseases. We investigated the association between SSB intake and the risk of coronary events and death, and assessed if substitution of coffee, tea, milk, fruit juice and artificially-sweetened beverages (ASB) for SSBs was associated with a reduced risk of coronary events and death. This was a follow-up study in which data from six studies were pooled and standard observational analyses were performed. Diet intake was assessed at baseline by food-frequency questionnaires. Hazard ratios (HRs) with 95% confidence intervals for the incidence of coronary events and deaths were calculated by Cox proportional hazards regression. The effect of substituting another beverage for SSBs was calculated by taking the difference in the individual effect estimates. During the median 8.2-year follow-up, 4248 coronary events and 1630 coronary deaths were documented among 284,345 individuals. 355 ml daily increase of SSB intake was associated with an increased risk of coronary events (HR: 1.08; 95%CI: 1.02, 1.14) and possibly coronary death (HR: 1.05; 95%CI: 0.96, 1.16). Substitution analyses suggested that replacing SSBs with coffee (HR: 0.93; 95%CI: 0.87, 1.00) or ASB (HR: 0.89; 95%CI: 0.83, 0.97), might be associated with a lower risk of developing coronary events. We found that SSB intake was associated with an increased risk of coronary events and possibly coronary death. Our findings also suggest that replacing SSB's with ASBs or coffee may lower the risk of developing CHD.
KEYWORDS:
Coronary heart diseases; Harvard Pooling Project; Substitution; Sugar-sweetened beverages

The Dose-Response Associations of Sedentary Time with Chronic Diseases and the Risk for All-Cause Mortality Affected by Different Health Status: A Systematic Review and Meta-Analysis.
Zhao R, Bu W, Chen Y, Chen X.
J Nutr Health Aging. 2020;24(1):63-70. doi: 10.1007/s12603-019-1298-3.
PMID: 31886810
Abstract
PURPOSE:
To determine the dose-response associations of sedentary behaviour with cardiovascular diseases (CVD), cancer, and all-cause mortality, and to examine whether the sedentary-associated all-cause mortality risk was affected by appearance of diabetes and hypertension, physical activity, and body mass index (BMI).
DESIGN:
We carried out a systematic review and meta-analysis to search Medline, SportDiscus, and Web of Science for eligible studies.
SETTINGS:
Prospective cohort studies that reported sedentary time and CVD, cancer, and mortality incidents.
MEASUREMENTS:
Two authors independently extracted data based on predefined criteria. The effect estimates were evaluated by hazard ratios (HRs) with 95% confidences (CIs).
RESULTS:
Twenty-four studies met the inclusion criteria. Sitting time showed dose-response associations with CVD, cancer, and all-cause mortality, with each 1-hour increment of sitting time daily accounting for HRs 1.04 (95% CIs 1.02-1.07), 1.01 (1.00-1.02), and 1.03 (1.02-1.03), respectively. The link between sitting time and CVD and all-cause mortality was non-linear (pnon-linear < 0.0001). The relationship between TV viewing and CVD and all-cause mortality was dose-dependent, with HRs 1.07 (1.06-1.09) and 1.04 (1.01-1.06) for per 1-hour increment of TV time every day, respectively. The regression was curved (pnon-linear < 0.0001). When the analysis was stratified by the percentage of diabetes and hypertension, BMI values, and physical activity levels, we found that higher BMI and a greater percentage of diabetes and hypertension further increased all-cause mortality risk in the most sedentary populations, whereas higher physical activity levels decreased it.
CONCLUSION:
Sitting time and TV viewing significantly increased cardiovascular, cancer, and mortality risk; the associations were dose-dependent. More importantly, sedentary behaviour in combination with chronic diseases or high BMI increased all-cause mortality risk whereas physical activity was likely to alleviate the adverse associations.
KEYWORDS:
Sedentary behaviour; cancer; health status; heart diseases; mortality

Sex differences in smoking, alcohol consumption, and risk of Parkinson's disease: A nationwide cohort study.
Kim R, Yoo D, Jung YJ, Han K, Lee JY.
Parkinsonism Relat Disord. 2019 Dec 13. pii: S1353-8020(19)30525-5. doi: 10.1016/j.parkreldis.2019.12.006. [Epub ahead of print]
PMID: 31882374
https://sci-hub.tw/10.1016/j.parkreldis.2019.12.006
Abstract
OBJECTIVE:
We assessed the influence of sex on the effects of smoking and alcohol consumption on the risk of Parkinson's disease (PD).
METHODS:
This population-based cohort study examined data of 6,795,816 Koreans aged ≥40 years from the Korean National Health Insurance Service database who completed a national program for general health check-up at 2009. For a maximum 9 years' observation period, incident PD was tracked, and hazard ratios and 95% confidence intervals (CIs) were computed using the Cox proportional hazard models, adjusted for potential confounding factors for each sex group. We tested interactions on the addictive scale by estimating the relative excess risk due to interaction (RERI).
RESULTS:
3,400,538 men and 3,395,278 women generated 24,365,694 and 24,754,154 person-years, respectively. A total of 13,223 men (0.39%) and 14,818 women (0.44%) developed PD during follow-up. Current smoking and alcohol independently reduced the risk of PD in both sexes. Current male smokers tended to have a lower risk of PD than current female smokers at equal smoking intensity (P < 0.0001 for interaction) and duration (P < 0.0001 for interaction). In contrast, at equal alcohol intakes, PD risk tended to be lower in female drinkers than in male drinkers (P < 0.0001 for interaction). A superadditive interaction between smoking and alcohol was found in current male smokers (RERI, 0.19; 95% CI, 0.04 to 0.34; P = 0.015) and female ex-smokers (RERI, 0.42; 95% CI, 0.09 to 0.76; P = 0.014).
CONCLUSION:
Our data suggest sex-related differences in individual and joint impacts of smoking and alcohol intake on the risk of PD.
KEYWORDS:
Alcohol; Parkinson's disease; Risk factor; Sex; Smoking

[Impact of hypertension, overweight, hypertriglyceridemia and their combination for mortality rate according to the results of a 27-year cohort prospective study].
Dolgalev IV, Brazovskaya NG, Ivanova AY, Shipkhineeva AY, Bogajchuk PM.
Kardiologiia. 2019 Sep 12;59(11S):44-52. doi: 10.18087/cardio.n344. Russian.
PMID: 31884940
Abstract
 To study influence of hypertension, overweight, hypertriglyceridemia and their combinations for all-cause and cardiovascular mortality risk formation. Methods. The prevalence of hypertension, overweight and hypertriglyceridemia was studied (1988-1991) by 27-year prospective cohort study of unorganized population of Tomsk (1546 persons - 916 female and 630 male). The predictive value of these risk factors for all-cause and cardiovascular mortality risk formation were researched in 2015. Hypertension was diagnosed in persons with blood pressure greater or equal to 140/90 mm Hg, overweight was diagnosed in people with body mass index 25 kg/m2, hypertriglyceridemia was diagnosed in individuals having high blood level of triglycerides (greater or equal to 1.7).  Results.  Influence of hypertension for all-cause (relative risk (RR) 2.2) and cardiovascular mortality (RR 3.38) risk formation was detected. A hypertension related elevation of mortality risk was observed both among women and men and in all age groups with the exception of men 40-59 years (the results for cardiovascular mortality in these persons was statistically insignificant). We established that hypertension had the independent significant contribution for mortality risk formation. It is shown that RR of all-cause mortality 1.25 times (cardiovascular mortality 1.8 times) more in overweight persons. Increase of relative mortality risk was detected in overweight women, especially in women 20-39 years old. Hypertriglyceridemia increases relative risk of all-cause mortality 1.46 times, relative risk of cardiovascular mortality 2.15 times, especially in individuals 40-59 years old. It was revealed that hypertriglyceridemia is significant risk factor for all-cause mortality formation only in women. Combination of hypertension and overweight increases the risk of all-cause mortality 2.23 times and the risk of cardiovascular mortality  4.0 times, combination of hypertension and hypertriglyceridemia - 2.83 and 5.06 times,  combination of overweight and hypertriglyceridemia - 1.73 and 2.99 times, respectively. We detected the additional risk of hypertriglyceridemia in individuals with overweight for all-cause (RR 1.53) and cardiovascular (RR 2.18) mortality risk formation compared with overweight persons with normal level of triglycerides and also the additional risk of hypertriglyceridemia (RR 1.51 and 2.04, respectively) in individuals with hypertension compared with normotensive persons (p&lt;0,05). The additional risk of overweight in individuals with hypertension for all-cause mortality was found only in women (RR 3.23). Conclusion. The independent significant impact of hypertension for all-cause and cardiovascular mortality risk formation was revealed by the results of 27-year prospective study. Combination of hypertension and hypertriglyceridemia increases the risk of all-cause mortality 2.8 times and the risk of cardiovascular mortality 5.1 times, combination of hypertension and overweight - 2.2 and 4 times, combination of overweight and hypertriglyceridemia - 1.7 and 3 times, respectively. We detected the additional risk of hypertriglyceridemia for all-cause mortality in overweight people (RR 1.5) and in individuals with hypertension (RR 1.5). Also, the additional risk of hypertriglyceridemia for cardiovascular mortality risk formation in overweight people (RR 2.2) and in persons with hypertension (RR 2.0) was found.

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Longitudinal and nonlinear relations of dietary and Serum cholesterol in midlife with cognitive decline: results from EMCOA study.
An Y, Zhang X, Wang Y, Wang Y, Liu W, Wang T, Qin Z, Xiao R.
Mol Neurodegener. 2019 Dec 30;14(1):51. doi: 10.1186/s13024-019-0353-1.
PMID: 31888696
https://molecularneurodegeneration.biomedcentral.com/track/pdf/10.1186/s13024-019-0353-1
Abstract
BACKGROUND:
Previous studies regarding the cholesterol-cognition relationship in midlife have generated conflicting results. We thus investigated whether dietary and blood cholesterol were associated with cognitive decline.
METHODS:
Participants were drawn from a large cohort study entitled the Effects and Mechanism Investigation of Cholesterol and Oxysterol on Alzheimer's disease (EMCOA) study. We included 2514 participants who completed a selection of comprehensive cognitive tests and were followed for an average of 2.3 years. Blood concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) were assessed and dietary intakes were investigated by food frequency questionnaire (FFQ) at baseline. Apolipoprotein E (APOE) was genotyped by Kompetitive Allele Specific PCR (KASP) sequencing. Non-high-density lipoprotein cholesterol (Non-HDL-C) and LDL-C/HDL-C ratio were calculated. The longitudinal effects of dietary and blood cholesterol on risk of global cognitive decline (decrease in Montreal Cognitive Assessment (MoCA) > 2 points) were examined using Cox proportional hazards models. The nonlinear associations with global and domain-specific cognitive decline was evaluated with mixed effect linear models.
RESULTS:
In Cox proportional hazards models, neither cholesterol nor egg intake was associated with a higher risk of accelerated global cognitive decline. In contrast, the higher serum concentrations of TC, LDL-C, non-HDL-C and LDL-C/HDL-C ratio were positively associated with accelerated global cognitive decline regardless of being evaluated continuously or categorically while higher HDL-C was positively associated with accelerated global cognitive decline only when being evaluated categorically (all P < 0.05). In mixed effect linear models, quadratic and longitudinal relations of dietary cholesterol and egg intakes to global cognition, processing speed and executive function were observed. Moreover, there were inverted U-shaped relations of HDL-C, with processing speed and executive function but U-shaped relations of HDL-C and LDL-C/HDL-C ratio with verbal memory. Adverse linear associations of higher LDL-C and LDL-C/HDL-C ratio with multiple cognitive comes were also revealed. Additionally adjusting for APOE genotype did not modify cholesterol-cognition associations. Dietary and serum cholesterol had variable associations with global and domain-specific cognitive decline across educational groups.
CONCLUSION:
Differential associations between dietary/serum cholesterol and cognitive decline across different domains of function were observed in a particular population of middle-aged and elderly Chinese. Interventions to improve cognitive reserve regarding dietary instruction and lipid management should be tailored according to specific target.
KEYWORDS:
Cholesterol; Cognitive decline; Nonlinear

Impact of calcium, vitamin D, vitamin K, oestrogen, isoflavone and exercise on bone mineral density for osteoporosis prevention in postmenopausal women: a network meta-analysis
Zijun Xu, Huwen Wang, Yue Shi, Qiuming Shen, Lhakpa Tsamlag, Zezhou Wang, Shoukai Yu, Tian Shen, Ying Wang, Yong Cai
British Journal of Nutrition, Volume 123 / Issue 1, 14 January 2020, pp 84 - 103
doi: 10.1017/S0007114519002290 Published Online on 4 September 2019
Abstract
The aim of this network meta-analysis is to compare bone mineral density (BMD) changes among different osteoporosis prevention interventions in postmenopausal women. We searched MEDLINE, Embase and Cochrane Library from inception to 24 February 2019. Included studies were randomised controlled trials (RCT) comparing the effects of different treatments on BMD in postmenopausal women. Studies were independently screened by six authors in three pairs. Data were extracted independently by two authors and synthesised using Bayesian random-effects network meta-analysis. The results were summarised as mean difference in BMD and surface under the cumulative ranking (SUCRA) of different interventions. A total of ninety RCT (10 777 participants) were included. Ca, vitamin D, vitamin K, oestrogen, exercise, Ca + vitamin D, vitamin D + vitamin K and vitamin D + oestrogen were associated with significantly beneficial effects relative to no treatment or placebo for lumbar spine (LS). For femoral neck (FN), Ca, exercise and vitamin D + oestrogen were associated with significantly beneficial intervention effects relative to no treatment. Ranking probabilities indicated that oestrogen + vitamin D is the best strategy in LS, with a SUCRA of 97·29 % (mean difference: +0·072 g/cm2 compared with no treatment, 95 % credible interval (CrI) 0·045, 0·100 g/cm2), and Ca + exercise is the best strategy in FN, with a SUCRA of 79·71 % (mean difference: +0·029 g/cm2 compared with placebo, 95 % CrI –0·00093, 0·060 g/cm2). In conclusion, in postmenopausal women, many interventions are valuable for improving BMD in LS and FN. Different intervention combinations can affect BMD at different sites diversely.

Effect of oral L-citrulline on brachial and aortic blood pressure defined by resting status: evidence from randomized controlled trials.
Yang HH, Li XL, Zhang WG, Figueroa A, Chen LH, Qin LQ.
Nutr Metab (Lond). 2019 Dec 26;16:89. doi: 10.1186/s12986-019-0415-y. eCollection 2019. Review.
PMID: 31889969
Abstract
BACKGROUND:
Experimental evidence indicates that oral L-citrulline (L-Cit) may reduce resting blood pressure (BP) as well as BP responses to exercise and cold exposure (non-resting). However, results from human intervention trials are inconsistent. This study aims to summarize the clinical evidence regarding the effects of L-Cit supplementation on brachial systolic blood pressure (SBP), brachial diastolic blood pressure (DBP), in addition to aortic SBP and aortic DBP at rest and non-resting conditions.
METHODS:
Multiple databases including PubMed, Embase, Cochrane library, Web of Science, and Clinical Trials were searched systematically. Randomized controlled trials of human participants were quantitatively meta-analyzed.
RESULTS:
Fourteen trials contained in eight studies were available for quantitative syntheses for brachial BP. Results showed that L-Cit supplementation significantly reduced both brachial SBP (- 4.490 mmHg, 95% CI: - 7.332 to - 1.648, P = 0.002) and brachial DBP (- 3.629 mmHg, 95% CI: - 5.825 to - 1.434, P = 0.001). Nine of the trials were meta-analyzed for aortic BP which showed that L-Cit intervention significantly reduced aortic SBP (- 6.763 mmHg, 95% CI: - 10.991 to - 2.534, P = 0.002), but not aortic DBP (- 3.396 mmHg, 95% CI: - 7.418 to 0.627, P = 0.098). The observed reducing effects of L-Cit appeared stronger for non-resting than for resting brachial SBP (P for difference = 0.044).
CONCLUSION:
L-Cit supplementation significantly decreased non-resting brachial and aortic SBP. Brachial DBP was significantly lowered by L-Cit regardless of resting status. Given the relatively small number of available trials in the stratified analyses and the potential limitations of these trials, the present findings should be interpreted cautiously and need to be confirmed in future well-designed trials with a larger sample size.
KEYWORDS:
Aortic; Blood pressure; Brachial; L-citrulline; Resting status

Effect of selenium supplementation on glycemic indices: a meta-analysis of randomized controlled trials.
Mahdavi Gorabi A, Hasani M, Djalalinia S, Zarei M, Ejtahed H, Abdar ME, Asayesh H, Azimzadeh M, Qorbani M, Noroozi M.
J Diabetes Metab Disord. 2019 Jul 4;18(2):349-362. doi: 10.1007/s40200-019-00419-w. eCollection 2019 Dec.
PMID: 31890660
Abstract
PURPOSE:
The association between selenium supplementation and glycemic indices seems to be a controversial issue. This systematic review and meta-analysis was conducted to evaluate the effect of selenium supplementation on glycemic indices.
METHODS:
We systematically searched PubMed/MEDLINE, ISI/WOS, and Scopus (from their commencements up to Jan 2016) for relevant studies examining the association between intake of selenium and glycemic indices. The data were extracted from relevant qualified studies and estimated using the random-effect or pooled model and standardized mean difference (SMD) with 95% confidence interval (CI).
RESULTS:
Twelve articles published between 2004 and 2016 were included. In all the studies, the participants were randomly assigned to an intervention group (n = 757) or a control group(n = 684). All the studies were double blind, placebo controlled trials. Selenium supplementation resulted in a significant decrease in homeostasis model of assessment-estimated β-cell function (HOMA-B) (SMD: -0.63; 95%CI: -0.89 to -0.38) and a significant increase in quantitative insulin sensitivity check index (QUICKI) (SMD: by 0.74; 95%CI: 0.49 to 0.1) as compared with the controls. There were no statistically significant improvements in glycemic indices, such as fasting plasma glucose (FPG), insulin, homeostasis model of assessment-estimated insulin resistance (HOMA-IR), Hemoglobin A1c (HbA1c) and adiponectin.
CONCLUSION:
This meta-analysis indicated that selenium supplementation significantly decreased HOMA-B and increased QUICKI score. There was no statistically significant improvement in FPG, insulin, HOMA-IR, HbA1c and adiponectin indices following selenium supplementation.
KEYWORDS:
FPG; Glycemic indices; HbA1c; Insulin; Selenium

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Effect of Flaxseed Supplementation on Lipid Profile: An Updated Systematic Review and Dose-Response Meta-Analysis of Sixty-Two Randomized Controlled Trials.
Hadi A, Askarpour M, Salamat S, Ghaedi E, Symonds ME, Miraghajani M.
Pharmacol Res. 2019 Dec 30:104622. doi: 10.1016/j.phrs.2019.104622. [Epub ahead of print] Review.
PMID: 31899314
Abstract
Raised plasma lipids are one the most important risk factors for cardiovascular disease. Flaxseed contains considerable amounts of α-linolenic acid, phenolic compounds, and lignans, which each have the capacity to reduce circulating lipid concentrations. This study aimed to systematically review current evidence to identify the potential effects of flaxseed supplementation on blood lipid profiles using a meta-analysis of randomized controlled trials (RCTs). PubMed, Scopus, Web of Science, and Google Scholar databases were searched for publications between January 1900 and May 2019. Weighted mean differences (WMDs) were analyzed using a random-effects model. The Cochrane Collaboration tool was also used to assess the risk of bias of the studies included. Sixty-two RCTs with a total of 3772 participants met the eligibility criteria. Our analysis showed that flaxseed supplementation significantly reduced total cholesterol (TC) (WMD = -5.389 mg/dL; 95% CI: -9.483, -1.295, p =  0.010), triglyceride (TG) (WMD = -9.422 mg/dL; 95% CI: -15.514, -3.330, p =  0.002), and low-density lipoprotein cholesterol (LDL-C) (WMD = -4.206 mg/dl; 95% CI: -7.260, -1.151, p =  0.007) concentrations. However, it had no effects on high-density lipoprotein cholesterol (WMD = 0.047 mg/dl; 95% CI: -0.777, 0.872, p = 0.910). This meta-analysis suggested that flaxseed supplementation improves serum TC, TG, and LDL-C, which could delay the progression of heart disease. Further studies with large-scale and better design are now needed to confirm these results.
KEYWORDS:
flaxseed; linseed; lipid profile; meta-analysis; systematic review

Lactalbumin, Not Collagen, Augments Muscle Protein Synthesis with Aerobic Exercise.
Oikawa SY, MacInnis MJ, Tripp TR, McGlory C, Baker SK, Phillips SM.
Med Sci Sports Exerc. 2019 Dec 31. doi: 10.1249/MSS.0000000000002253. [Epub ahead of print]
PMID: 31895298
Abstract
INTRODUCTION:
Protein ingestion and the ensuing hyperaminoacidemia stimulates skeletal muscle protein synthesis (MPS) in the post-exercise period. This response facilitates muscle remodeling, which is important during intensified training. The aim of this study was to determine whether supplementation with α-Lactalbumin (LA), with high leucine and tryptophan contents, would improve responses to short periods of intensified aerobic training compared to supplementation with an isonitrogenous quantity of collagen peptides (CP).
METHODS:
Endurance trained participants (5M, 6F, 24 ± 4 years, V[Combining Dot Above]O2= 53.2 ± 9.1 ml/kg/min, Peak power output (PPO) = 320 ± 48 W; means ± SD) consumed a controlled diet (1.0 g/kg/day protein) and refrained from habitual training for 11 days while taking part in this double-blind randomized, crossover trial. The two intervention phases, which consisted of brief intensified training (4×4-min cycling intervals at 70% of PPO on 3 consecutive days) combined with the ingestion of LA or CP supplements post-exercise (20g) and pre-sleep (40g), were separated by 4d of washout without protein supplementation (i.e., the control phase). In response to each phase, myofibrillar (MyoPS), sarcoplasmic protein synthesis (SarcPS) rates (via H2O ingestion) and parameters of sleep quality were measured.
RESULTS:
LA ingestion increased plasma leucine (p<0.001) and tryptophan concentrations (p<0.001) relative to CP. Intensified training increased MyoPS and SarcPS above the washout phase in LA- and CP- supplemented phases (p<0.01), with increases being 13 ± 5% and 5 ± 7% greater with LA than CP for MyoPS (p<0.01) and SarcPS, respectively (p<0.01).
CONCLUSIONS:
Despite an isonitrogenous diet, MPS was enhanced to a greater extent when trained participants consumed LA compared to CP during intensified aerobic training, suggesting protein quality is an important consideration for endurance-trained athletes aiming to augment adaption to exercise training.

Testosterone administration during energy deficit suppresses hepcidin and increases iron availability for erythropoiesis.
Hennigar SR, Berryman CE, Harris MN, Karl JP, Lieberman HR, McClung JP, Rood JC, Pasiakos SM.
J Clin Endocrinol Metab. 2020 Jan 2. pii: dgz316. doi: 10.1210/clinem/dgz316. [Epub ahead of print]
PMID: 31894236
https://watermark.silverchair.com/dgz316.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAnIwggJuBgkqhkiG9w0BBwagggJfMIICWwIBADCCAlQGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM__UZdlkaN6RzJQSBAgEQgIICJV02DEFTE0tBbnMtAHK8OtuQac6M3H5DmhqFBQcHLlM1Lv3WkcgtQF2Lp36SeGoFr-ml1ahALMDvUwA3HmJQudsBQfdWAivN1fK5kwOpT00pZM-5-4ZaqRRtxVkEzj7OD_TO1O9nhAJItwdPEhyHpcEWCH0lRAywHjgS1jxzoEPigRp0ohNzk0CEpMtnMP0Cr5nKemXHpxfGX3s5XAQgH2zVDhx67hXsEsCqhwJqdRJD-xAO4EXX7VzeKTBXcPE7ADi_9UmSqgKBjAcsY9hsxgR3ws_Kx8FC3y4YHNdlNEZZr0yousPluJn7GXZMzyyeSz6NCk7atYb6psxQL-7OClJPbF411kP0EG0sHYqec0t2PhlJ8OyT63MVw1ZVN5iUxHPWR-Ju8xJrKf8mgeoMWGYvFwZidfDOCgPpm6_elkdELECNlqCPqxOkZyTH-QrqkliwChZ9h1KSQcZ1lpgHkF5wglbly7uTtVJ2vzMSANJr39HXts3Ewugq3HYKYMQBhZMolhTi86z3iuM1RWI4R6Xr0SYOvqT1kVmEur6PofK3lc4lZOUdqOfjTuWfJVvjj6mAhlvhHM21df1SS1c5-TGC3q2gBZMY-HJL8l2oLU4hdvAVDLH5ISca4BXZVhEzc-tXIHUoSnRZaUomBdV3STPJeH6RgBy1ctvq3hQa0kvTMK6coz1dEYC4Z42ZhbuAVjWKtko89Xo-Xho2TwOf6W7StOLaFQ
Abstract
CONTEXT:
Severe energy deprivation markedly inhibits erythropoiesis by restricting iron availability for hemoglobin synthesis.
OBJECTIVE:
The objective of this study was to determine whether testosterone supplementation during energy deficit increased indicators of iron turnover and attenuated the decline in erythropoiesis compared to placebo.
DESIGN:
This was a 3-phase, randomized, double-blind, placebo-controlled trial.
SETTING:
The study was conducted at the Pennington Biomedical Research Center.
PATIENTS OR OTHER PARTICIPANTS:
Fifty healthy young males.
INTERVENTION(S):
Phase 1 was a 14-d free-living, eucaloric controlled-feeding phase; phase 2 was a 28-d inpatient phase were participants were randomized to 200 mg testosterone enanthate/week or an isovolumetric placebo/week during an energy deficit of 55% of total daily energy expenditure; phase 3 was a 14-d free-living, ad libitum recovery period.
MAIN OUTCOME MEASURE(S):
Indices of erythropoiesis, iron status, and hepcidin and erythroferrone were determined.
RESULTS:
Hepcidin declined by 41%, indicators of iron turnover increased, and functional iron stores were reduced with testosterone administration during energy deficit compared to placebo. Testosterone administration during energy deficit increased circulating concentrations of erythropoietin and maintained erythropoiesis, as indicated by an attenuation in the decline in hemoglobin and hematocrit with placebo. Erythroferrone did no differ between groups, suggesting that the reduction in hepcidin with testosterone occurs through an erythroferrone-independent mechanism.
CONCLUSIONS:
These findings indicate that testosterone suppresses hepcidin, through either direct or indirect mechanisms, to increase iron turnover and maintain erythropoiesis during severe energy deficit.
KEYWORDS:
erythropoiesis; hepcidin; iron; testosterone

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Lifestyle Factors and Risk of Myeloproliferative Neoplasms in the NIH-AARP Diet and Health Study.
Podoltsev NA, Wang X, Wang R, Hofmann JN, Liao LM, Zeidan AM, Mesa R, Ma X.
Int J Cancer. 2020 Jan 6. doi: 10.1002/ijc.32853. [Epub ahead of print]
PMID: 31904114
https://sci-hub.tw/10.1002/ijc.32853
Abstract
The etiology of Philadelphia chromosome negative myeloproliferative neoplasms (MPN) is largely unknown. We assessed potential associations between lifestyle factors and MPN risk in the NIH-AARP Diet and Health Study. In this prospective cohort with 463,049 participants aged 50-71 years at baseline (1995-1996) and a median follow-up of 15.5 years, we identified 490 MPN cases, including 190 with polycythemia vera (PV) and 146 with essential thrombocythemia (ET). Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Smoking was not associated with MPN risk in the overall cohort, but analyses stratified by sex suggested that smoking increased the risk of MPN in women (former smoker vs. non-smokers, HR=1.43, 95% CI: 1.03-2.00, p=0.03; current smokers vs. non-smokers, HR=1.71, 95% CI: 1.08-2.71, p=0.02). Coffee consumption was inversely associated with the risk of PV (high vs. low intake, HR=0.53, 95% CI: 0.33-0.84, p-trend<0.01), but not the risk of ET or MPN overall. Further analysis revealed an inverse association between amount of caffeine intake and PV risk (high vs. low intake, HR= 0.55, 95% CI: 0.39-0.79, p-trend<0.01). While the consumption of caffeinated coffee appeared to confer a protective effect against PV, the consumption of decaffeinated coffee did not. This large prospective study identified smoking as a risk factor for MPN in women and suggests that caffeine intake is associated with a lower risk of PV. This article is protected by copyright. All rights reserved.
KEYWORDS:
epidemiology; lifestyle factors; myeloproliferative neoplasms
PMID: 31904114 DOI: 10.1002/ijc.32853

Egg consumption and risk of coronary artery disease in the Million Veteran Program.
Djoussé L, Ho YL, Nguyen XT, Quaden RM, Gagnon DR, Gaziano JM, Cho K.
Clin Nutr. 2019 Dec 24. pii: S0261-5614(19)33203-0. doi: 10.1016/j.clnu.2019.12.017. [Epub ahead of print]
PMID: 31902601
Abstract
BACKGROUND & AIMS:
Limited and inconsistent data are available on the relation between egg consumption and risk of myocardial infarction (MI) and it is unclear if adiposity or type 2 diabetes modifies egg-MI relation. We tested the primary hypothesis that egg consumption is positively associated with incidence of MI among veterans. In secondary analyses, we examined potential effect modification of egg-MI relation by adiposity and type 2 diabetes.
METHODS:
We analyzed data collected on 188,267 US veterans who were enrolled in the Million Veteran Program (MVP) from 2011 to 2018. Information on egg consumption was obtained via self-administered food frequency questionnaire and we used electronic health records to identify incident MI.
RESULTS:
The mean age was 64.4 (SD = 12.0) years and 9.9% of the population were female. We ascertained 10,260 new cases of non-fatal MI during an average follow up of 3.24 years (range: 0.002 to 7.49 y). Hazard ratio (95% CI) for non-fatal MI were 1.00 (ref), 0.93 (0.85-0.1.02), 0.96 (0.87-1.05), 0.98 (0.89-1.07), 1.08 (0.98-1.19), 1.11 (1.00-1.24), and 1.13 (1.00-1.28) for egg consumption of <1/month, 1-3/month, 1/week, 2-4/week, 5-6/week, 1/d, and 2+/d, respectively, controlling for age, sex, race, body mass index, smoking, exercise, alcohol intake, and overall dietary pattern (p non-linear trend 0.019). In secondary analyses, we observed similar results with a composite endpoint including fatal MI, coronary angioplasty and revascularization.
CONCLUSIONS:
Our data showed no association of infrequent consumption of eggs with non-fatal MI but a slightly elevated risk with intake of 1 or more eggs per day among US veterans.
KEYWORDS:
Coronary artery disease; Diet; Epidemiology; Risk factors

Midlife Modifiable Risk Factors for Dementia: A Systematic Review and Meta-analysis of 34 Prospective Cohort Studies.
Li XY, Zhang M, Xu W, Li JQ, Cao XP, Yu JT, Tan L.
Curr Alzheimer Res. 2020 Jan 2. doi: 10.2174/1567205017666200103111253. [Epub ahead of print]
PMID: 31902364
Abstract
OBJECTIVE:
The aim of this study is to assess the association between midlife risk factors and dementia.
METHODS:
PubMed and Cochrane library were systematically searched on May 24, 2018, to retrieve prospective cohort studies. The summary relative risk (RR) and 95% confidence interval (CI) were calculated by the random-effect model to explore the association between midlife risk factors and dementia. Sensitivity analysis and meta-regression were conducted to explore the source of heterogeneity. Publication bias was examined using Begg's and Egger's tests.
RESULTS:
Thirty-four prospective cohort studies were included, among which 24 were eligible for meta-analysis. A total of 159,594 non-demented adults were enrolled at baseline before 65 years and 13,540 people were diagnosed with dementia after follow-up. The pooled results revealed that five factors could significantly increase the dementia risk by 41 to 78%, including obesity (RR, 1.78; 95% CI: 1.31-2.41), diabetes mellitus (RR, 1.69; 95% CI: 1.38-2.07), current smoking (RR, 1.61; 95%, CI: 1.32-1.95), hypercholesterolemia (RR, 1.57; 95% CI: 1.19-2.07), and hypertension (borderline blood pressure RR, 1.41; 95% CI: 1.23-1.62 and high systolic blood pressure (SBP) RR, 1.72; 95% CI: 1.25-2.37). However, the sensitivity analyses found that the results of hypercholesterolemia and high SBP were not reliable, which need to be confirmed by more high-quality studies. No influences due to publication bias were revealed. In the systematic review, another three factors (hyperhomocysteinemia, psychological stress, and heavy drinking) were found to be associated with elevated dementia risk. In addition, physical exercise, a healthy diet, and hormone therapy in middle age were associated with the reduction of dementia risk.
CONCLUSIONS:
Middle-aged people with obesity, diabetes, hypertension, or hypercholesterolemia, and current smokers in midlife are at higher risk of developing dementia later in life.
KEYWORDS:
Dementia; Meta-analysis; Midlife risk factors; Prospective Cohort Studies; Subgroup analyses; Systematic review

Effect of Time Restricted Feeding on Metabolic Risk and Circadian Rhythm Associated with Gut Microbiome in Healthy Males.
Zeb F, Wu X, Chen L, Fatima S, Haq IU, Chen A, Majeed F, Feng Q, Li M.
Br J Nutr. 2020 Jan 6:1-25. doi: 10.1017/S0007114519003428. [Epub ahead of print]
PMID: 31902372
https://www.cambridge.org/core/services/aop-cambridge-core/content/view/A8C3BF83CBE5BF9CAC65ED783FA0FFD2/S0007114519003428a.pdf/div-class-title-effect-of-time-restricted-feeding-on-metabolic-risk-and-circadian-rhythm-associated-with-gut-microbiome-in-healthy-males-div.pdf
Abstract
Time restricted feeding (TRF) confer protection against nutritional challenges that predispose obesity and metabolic risks through involvement of clock genes and gut microbiome, but the underline mechanism is not clearly understood. Therefore, this study examined the effects of TRF on metabolic markers and circadian rhythm associated with gut microbiota in healthy males. Two groups (TRF, n=56; Non-TRF, n=24) of male adults were enrolled. TRF group provided blood at Pre-TRF and Post-TRF, while Non-TRF one time after 25 days of trial. Serum lipid and liver profiles were determined. RT-PCR was applied for circadian and inflammatory genes expression. The 16S rRNA gene were sequenced at Illumina Miseq v3 platform to comprehensively catalogue the composition and abundance of bacteria in stool. We showed that TRF ameliorated the serum lipid and liver profiles of the individuals. In TRF group, gut microbial richness was significantly enhanced, with enrichment of the Prevotellaceae and Bacteroideaceae. TRF enhanced circadian genes expression probably by activation of Sirt1, which is positively associated with gut microbiome richness. TRF could be a safe remedy for the prevention of metabolic diseases related to dyslipidemia, while regulates circadian rhythm associated with gut microbiome modulation.
KEYWORDS:
Circadian rhythm; Gut microbiome; Lipid profile; Metabolic risk; Time restricted feeding

A word of caution against excessive protein intake.
Mittendorfer B, Klein S, Fontana L.
Nat Rev Endocrinol. 2020 Jan;16(1):59-66. doi: 10.1038/s41574-019-0274-7. Epub 2019 Nov 14. Review.
PMID: 31728051
https://sci-hub.tw/10.1038/s41574-019-0274-7
https://sci-hub.tw/10.1038/s41574-019-0274-7
Abstract
Dietary protein is crucial for human health because it provides essential amino acids for protein synthesis. In addition, dietary protein is more satiating than carbohydrate and fat. Accordingly, many people consider the protein content when purchasing food and beverages and report 'trying to eat more protein'. The global market for protein ingredients is projected to reach approximately US$90 billion by 2021, largely driven by the growing demand for protein-fortified food products. This Perspective serves as a caution against the trend of protein-enriched diets and provides an evidence-based counterpoint that underscores the potential adverse public health consequences of high protein intake.

Japanese woman turns 117 years old, extends record as world's oldest person
Kane Tanaka, born in 1903, lives in nursing home in southern Japan
CBC News · Posted: Jan 05, 2020 7:01 AM ET | Last Updated: 5 hours ago
https://www.cbc.ca/news/world/worlds-oldest-person-japan-1.5415517

Diet and Lifestyle in Prostate Cancer.
Wilson KM, Mucci LA.
Adv Exp Med Biol. 2019;1210:1-27. doi: 10.1007/978-3-030-32656-2_1.
Abstract
A variety of diet and lifestyle factors have been studied with respect to prostate cancer risk in large, prospective cohort studies. In spite of this work, and in contrast to other common cancers, few modifiable risk factors have been firmly established as playing a role in prostate cancer. There are several possible explanations for the lack of well-established risk factors. First, prostate cancer has among the highest heritability of all common cancers; second, early life exposures may play an important role in risk, rather than mid- and later-life exposures assessed in most epidemiological studies. Finally, prostate-specific antigen (PSA) screening plays a critical role in prostate cancer detection and incidence rates, which has important implications for epidemiological studies.Among modifiable risk factors, smoking and obesity are consistently associated with higher risk specifically of advanced prostate cancer. There is also considerable evidence for a positive association between dairy intake and overall prostate cancer risk, and an inverse association between cooked tomato/lycopene intake and risk of advanced disease. Several other dietary factors consistently associated with risk in observational studies, including selenium and vitamin E, have been cast into doubt by results from clinical trials. Results for other well-studied dietary factors, including fat intake, red meat, fish, vitamin D, soy and phytoestrogens are mixed.In practical terms, men concerned with prostate cancer risk should be encouraged to stop smoking, be as physically active as possible, and achieve or maintain a healthy weight. These recommendations also have the advantage of having a positive impact on risk of type 2 diabetes, cardiovascular disease, and other chronic diseases. Reducing dairy intake while increasing consumption of fish and tomato products is also reasonable advice.PMID: 31900902
 

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Midlife socioeconomic position and old-age dementia mortality: a large prospective register-based study from Finland.
Korhonen K, Einiö E, Leinonen T, Tarkiainen L, Martikainen P.
BMJ Open. 2020 Jan 6;10(1):e033234. doi: 10.1136/bmjopen-2019-033234.
PMID: 31911519
Abstract
OBJECTIVES:
To assess the association between multiple indicators of socioeconomic position and dementia-related death, and to estimate the contribution of dementia to socioeconomic differences in overall mortality at older ages.
DESIGN:
Prospective population-based register study.
SETTING:
Finland.
PARTICIPANTS:
11% random sample of the population aged 70-87 years resident in Finland at the end of year 2000 (n=54 964).
MAIN OUTCOME MEASURE:
Incidence rates, Kaplan-Meier survival probabilities and Cox regression HRs of dementia mortality in 2001-2016 by midlife education, occupational social class and household income measured at ages 53-57 years.
RESULTS:
During the 528 387 person-years at risk, 11 395 individuals died from dementia (215.7 per 10 000 person-years). Lower midlife education, occupational social class and household income were associated with higher dementia mortality, and the differences persisted to the oldest old ages. Compared with mortality from all other causes, however, the socioeconomic differences emerged later. Dementia accounted for 28% of the difference between low and high education groups in overall mortality at age 70+ years, and for 21% of the difference between lowest and highest household income quintiles. All indicators of socioeconomic position were independently associated with dementia mortality, low household income being the strongest independent predictor (HR=1.24, 95% CI 1.16 to 1.32), followed by basic education (HR=1.14, 1.06 to 1.23). Manual occupational social class was related to a 6% higher hazard (HR=1.06, 1.01 to 1.11) compared with non-manual social class. Adjustment for midlife economic activity, baseline marital status and chronic health conditions attenuated the excess hazard of low midlife household income, although significant effects remained.
CONCLUSION:
Several indicators of socioeconomic position predict dementia mortality independently and socioeconomic inequalities persist into the oldest old ages. The results demonstrate that dementia is among the most important contributors to socioeconomic inequalities in overall mortality at older ages.
KEYWORDS:
Alzheimer's disease; dementia; register study; socioeconomic factors

Measures of body fatness and height in early and mid-to-late adulthood and prostate cancer: risk and mortality in The Pooling Project of Prospective Studies of Diet and Cancer.
Genkinger JM, Wu K, Wang M, Albanes D, Black A, van den Brandt PA, Burke KA, Cook MB, Gapstur SM, Giles GG, Giovannucci E, Goodman GG, Goodman PJ, Håkansson N, Key TJ, Männistö S, Le Marchand L, Liao LM, MacInnis RJ, Neuhouser ML, Platz EA, Sawada N, Schenk JM, Stevens VL, Travis RC, Tsugane S, Visvanathan K, Wilkens LR, Wolk A, Smith-Warner SA.
Ann Oncol. 2020 Jan;31(1):103-114. doi: 10.1016/j.annonc.2019.09.007.
PMID: 31912782
Abstract
BACKGROUND:
Advanced prostate cancer etiology is poorly understood. Few studies have examined associations of anthropometric factors (e.g. early adulthood obesity) with advanced prostate cancer risk.
PATIENTS AND METHODS:
We carried out pooled analyses to examine associations between body fatness, height, and prostate cancer risk. Among 830 772 men, 51 734 incident prostate cancer cases were identified, including 4762 advanced (T4/N1/M1 or prostate cancer deaths) cases, 2915 advanced restricted (same as advanced, but excluding localized cancers that resulted in death) cases, 9489 high-grade cases, and 3027 prostate cancer deaths. Cox proportional hazards models were used to calculate study-specific hazard ratios (HR) and 95% confidence intervals (CI); results were pooled using random effects models.
RESULTS:
No statistically significant associations were observed for body mass index (BMI) in early adulthood for advanced, advanced restricted, and high-grade prostate cancer, and prostate cancer mortality. Positive associations were shown for BMI at baseline with advanced prostate cancer (HR = 1.30, 95% CI = 0.95-1.78) and prostate cancer mortality (HR = 1.52, 95% CI = 1.12-2.07) comparing BMI ≥35.0 kg/m2 with 21-22.9 kg/m2. When considering early adulthood and baseline BMI together, a 27% higher prostate cancer mortality risk (95% CI = 9% to 49%) was observed for men with BMI <25.0 kg/m2 in early adulthood and BMI ≥30.0 kg/m2 at baseline compared with BMI <25.0 kg/m2 in early adulthood and BMI <30.0 kg/m2 at baseline. Baseline waist circumference, comparing ≥110 cm with <90 cm, and waist-to-hip ratio, comparing ≥1.00 with <0.90, were associated with significant 14%-16% increases in high-grade prostate cancer risk and suggestive or significant 20%-39% increases in prostate cancer mortality risk. Height was associated with suggestive or significant 33%-56% risks of advanced or advanced restricted prostate cancer and prostate cancer mortality, comparing ≥1.90 m with <1.65 m.
CONCLUSION:
Our findings suggest that height and total and central adiposity in mid-to-later adulthood, but not early adulthood adiposity, are associated with risk of advanced forms of prostate cancer. Thus, maintenance of healthy weight may help prevent advanced prostate cancer.
KEYWORDS:
BMI; body fatness; height; pooled analysis; prostate cancer; waist

Cancer death rate in U.S. shows large one-year drop
Report 'shows a continued striking decline in overall cancer mortality in the United States'
Thomson Reuters · Posted: Jan 08, 2020
https://www.cbc.ca/news/health/cancer-death-rate-acs-1.5419255
'excess body weight currently accounts for about seven per cent of cancers. "I'm sure that proportion will continue to increase because it takes a decade or two before you see the influence on exposure reflected in cancer rates."'

Risk Factors For Hyperuricemia In Chinese Centenarians And Near-Centenarians.
Han QX, Zhang D, Zhao YL, Liu L, Li J, Zhang F, Luan FX, Liu DW, Liu ZS, Cai GY, Chen XM, Zhu HY.
Clin Interv Aging. 2019 Dec 19;14:2239-2247. doi: 10.2147/CIA.S223048. eCollection 2019.
PMID: 31908434
Abstract
PURPOSE:
Hyperuricemia is an important potential pathogenic factor for hypertension, cardiovascular disease and stroke. The current study aimed to investigate the prevalence of hyperuricemia and its relationship to lifestyle characteristics and dietary habits in centenarians and near-centenarians.
PATIENTS AND METHODS:
In total, 966 centenarians and 788 near-centenarians were included. Community-based surveys were conducted to collect information about lifestyle. Blood examinations were performed using enzymatic assays. T-tests and χ2 tests were used to investigate significant indicators of hyperuricemia, and multivariate logistic regression was used to analyze the related risk factors. A comprehensive analysis of nineteen modifiable factors, including lifestyle characteristics, dietary habits, general characteristics and blood test indexes, was conducted.
RESULTS:
The prevalence of hyperuricemia was 29.02%. The percentage of men, waist circumference (WC), waist-hip ratio, estimated glomerular filtration rate (eGFR), levels of total protein (TP), alanine aminotransferase, aspartate aminotransferase, triglycerides, high-density lipoprotein cholesterol, serum homocysteine, serum uric acid, serum urea and serum creatinine, passive smoking, alcohol consumption, snoring, preference for fried flavors, and meat, seafood and vegetable consumption were significantly different between the hyperuricemia group and the normouricemia group (p<0.05). Multivariate logistic regression analysis showed that WC (OR=1.020), eGFR (OR=0.960), TP level (OR=1.038), serum urea level (OR=1.154), passive smoking (OR=2.589), snoring (OR=2.003), meat consumption (OR=2.506), seafood consumption (OR=1.422) and vegetable consumption (OR=0.521) were significantly associated with the risk of hyperuricemia (p<0.05).
CONCLUSION:
Low eGFR and vegetable consumption, high WC, TP, and serum urea levels, passive smoking, snoring, and high meat and seafood consumption were independent risk factors for hyperuricemia. It is recommended that people at high risk for hyperuricemia should actively limit their intake of fried food, alcohol and purine-rich food, increase their intake of fresh vegetables, actively treat sleep apnea syndrome, avoid passive smoking, maintain a healthy WC and seek to improve their kidney and liver function.
KEYWORDS:
centenarians; dietary; hyperuricemia; lifestyle; risk factors

Physical activity, sedentary leisure-time and risk of incident type 2 diabetes: a prospective study of 512 000 Chinese adults.
Bennett DA, Du H, Bragg F, Guo Y, Wright N, Yang L, Bian Z, Chen Y, Yu C, Wang S, Meng F, Lv J, Chen J, Li L, Clarke R, Chen Z; China Kadoorie Biobank Study Collaborative Group .
BMJ Open Diabetes Res Care. 2019 Dec 18;7(1):e000835. doi: 10.1136/bmjdrc-2019-000835. eCollection 2019.
PMID: 31908799
Abstract
OBJECTIVE:
Aim to examine the independent and joint associations of physical activity (PA) and sedentary leisure-time (SLT) with risk of diabetes and assess the extent to which these associations were mediated by adiposity.
RESEARCH DESIGN AND METHODS:
The prospective China Kadoorie Biobank recruited ~512 000 adults from 10 diverse areas across China. Self-reported PA was estimated based on type, frequency and duration of specific types of PA, covering four domains (occupation, leisure, household and commuting). SLT was defined as hours per day spent watching television, reading or playing card games. Stratified Cox proportional hazards models were used to estimate adjusted HRs (aHRs) for PA and SLT associated with incident diabetes. Analyses were stratified by age-at-risk (5-year intervals), sex and region and adjusted for household income, education, alcohol consumption, smoking, fresh fruit intake, self-reported general health status, family history of diabetes and body mass index (BMI) status. Analyses of total PA, occupational and non-occupational PA and SLT were mutually adjusted for each other, as appropriate.
RESULTS:
After ~9 years of follow-up, there were 14 940 incident diabetes cases among 460 736 participants without prior diabetes or cardiovascular diseases at baseline. The mean (SD) age at baseline was 51 (10.6) years, 59% were women and 43% resided in urban areas. Overall, the mean BMI was 23.5 (3.3) kg/m2, which differed by ~0.5 kg/m2 among individuals in the highest compared with the lowest PA and SLT groups. PA was inversely associated the risk of diabetes 16% (aHR: 0.84, 95% CI 0.81 to 0.88) lower in top than bottom fifth. After further adjustment for BMI this was attenuated to 0.99 (95% CI 0.98 to 1.00). SLT was positively associated with diabetes and each 1 hour per day higher usual level was associated with aHR of 1.13 (95% CI 1.09 to 1.17) for diabetes, attenuated to 1.05 (95% CI 1.01 to 1.09) after further adjustment for BMI.
CONCLUSIONS:
Among Chinese adults, higher levels of PA and lower levels of SLT were associated with lower risks of diabetes with no evidence of effect modification by each other. These associations appeared to arise mainly through adiposity.
KEYWORDS:
adiposity; physical activity; sedentary leisure-time; type 2 diabetes

Replacing Saturated Fats with Unsaturated Fats from Walnuts or Vegetable Oils Lowers Atherogenic Lipoprotein Classes Without Increasing Lipoprotein(a).
Tindall AM, Kris-Etherton PM, Petersen KS.
J Nutr. 2020 Jan 7. pii: nxz313. doi: 10.1093/jn/nxz313. [Epub ahead of print]
PMID: 31909809
Abstract
BACKGROUND:
Walnuts have established lipid-/lipoprotein-lowering properties; however, their effect on lipoprotein subclasses has not been investigated. Furthermore, the mechanisms by which walnuts improve lipid/lipoprotein concentrations are incompletely understood.
OBJECTIVES:
We aimed to examine, as exploratory outcomes of this trial, the effect of replacing SFAs with unsaturated fats from walnuts or vegetable oils on lipoprotein subclasses, cholesterol efflux, and proprotein convertase subtilisin/kexin type 9 (PCSK9).
METHODS:
A randomized, crossover, controlled-feeding study was conducted in individuals at risk of cardiovascular disease (CVD) (n = 34; 62% men; mean ± SD age 44 ± 10 y; BMI: 30.1 ± 4.9 kg/m2). After a 2-wk run-in diet (12% SFAs, 7% PUFAs, 12% MUFAs), subjects consumed the following diets, in randomized order, for 6 wk: 1) walnut diet (WD) [57-99 g/d walnuts, 7% SFAs, 16% PUFAs [2.7% α-linolenic acid (ALA)], 9% MUFAs]; 2) walnut fatty acid-matched diet [7% SFAs, 16% PUFAs (2.6% ALA), 9% MUFAs]; and 3) oleic acid replaces ALA diet (ORAD) [7% SFAs, 14% PUFAs (0.4% ALA); 12% MUFAs] (all percentages listed are of total kilocalories ). Serum collected after the run-in (baseline) and each diet period was analyzed for lipoprotein classes and subclasses (vertical auto profile), cholesterol efflux, and PCSK9. Linear mixed models were used for data analysis.
RESULTS:
Compared with the ORAD, total cholesterol (mean ± SEM -8.9± 2.3 mg/dL; -5.1%; P < 0.001), non-HDL cholesterol (-7.4 ± 2.0 mg/dL; -5.4%; P = 0.001), and LDL cholesterol (-6.9 ± 1.9 mg/dL; -6.5%; P = 0.001) were lower after the WD; no other pairwise differences existed. There were no between-diet differences for HDL-cholesterol or LDL-cholesterol subclasses. Lipoprotein(a) [Lp(a)], cholesterol efflux, and PCSK9 were unchanged after the diets.
CONCLUSIONS:
In individuals at risk of CVD, replacement of SFAs with unsaturated fats from walnuts or vegetable oils improved lipid/lipoprotein classes, including LDL-cholesterol, non-HDL cholesterol, and total cholesterol, without an increase in Lp(a). These improvements were not explained by changes in cholesterol efflux capacity or PCSK9.
KEYWORDS:
PCSK9; cholesterol efflux; lipids; lipoproteins; walnut

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NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis.
Braidy N, Liu Y.
Exp Gerontol. 2020 Jan 6:110831. doi: 10.1016/j.exger.2020.110831. [Epub ahead of print] Review.
PMID: 31917996
Abstract
Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that is present in all living cells. NAD+ acts as an important cofactor and substrate for a multitude of biological processes including energy production, DNA repair, gene expression, calcium-dependent secondary messenger signalling and immunoregulatory roles. The de novo synthesis of NAD+ is primarily dependent on the kynurenine pathway (KP), although NAD+ can also be recycled from nicotinic acid (NA), nicotinamide (NAM) and nicotinamide riboside (NR). NAD+ levels have been reported to decline during ageing and age-related diseases. Recent studies have shown that raising intracellular NAD+ levels represents a promising therapeutic strategy for age-associated degenerative diseases in general and to extend lifespan in small animal models. A systematic review of the literature available on Medline, Embase and Pubmed was undertaken to evaluate the potential health and/or longevity benefits due to increasing NAD+ levels. A total of 1545 articles were identified and 147 articles (113 preclinical and 34 clinical) met criteria for inclusion. Most studies indicated that the NAD+ precursors NAM, NR, nicotinamide mononucleotide (NMN), and to a lesser extent NAD+ and NADH had a favourable outcome on several age-related disorders associated with the accumulation of chronic oxidative stress, inflammation and impaired mitochondrial function. While these compounds presented with a limited acute toxicity profile, evidence is still quite limited and long-term human clinical trials are still nascent in the current literature. Potential risks in raising NAD+ levels in various clinical disorders using NAD+ precursors include the accumulation of putative toxic metabolites, tumorigenesis and promotion of cellular senescence. Therefore, NAD+ metabolism represents a promising target and further studies are needed to recapitulate the preclinical benefits in human clinical trials.
KEYWORDS:
Ageing; Cellular energetics; NAD+; Nicotinamide; Oxidative stress

Tea consumption and the risk of atherosclerotic cardiovascular disease and all-cause mortality: The China-PAR project.
Wang X, Liu F, Li J, Yang X, Chen J, Cao J, Wu X, Lu X, Huang J, Li Y, Zhao L, Shen C, Hu D, Yu L, Liu X, Wu X, Wu S, Gu D.
Eur J Prev Cardiol. 2020 Jan 8:2047487319894685. doi: 10.1177/2047487319894685. [Epub ahead of print]
PMID: 31914807
Abstract
AIMS:
The role of tea consumption in the primary prevention of atherosclerotic cardiovascular disease remains unclear in cohort studies. This prospective cohort study aimed to investigate the associations of tea consumption with the risk of atherosclerotic cardiovascular disease and all-cause mortality.
METHODS:
We included 100,902 general Chinese adults from the project of Prediction for ASCVD Risk in China (China-PAR) in 15 provinces across China since 1998. Information on tea consumption was collected through standardized questionnaires. Outcomes were identified by interviewing study participants or their proxies, and checking hospital records and/or death certificates. Cox proportional hazard regression models were used to calculate hazard ratios and their corresponding 95% confidence intervals related to tea consumption.
RESULTS:
During a median follow-up of 7.3 years, 3683 atherosclerotic cardiovascular disease events, 1477 atherosclerotic cardiovascular disease deaths, and 5479 all-cause deaths were recorded. Compared with never or non-habitual tea drinkers, the hazard ratio and 95% confidence interval among habitual tea drinkers was 0.80 (0.75-0.87), 0.78 (0.69-0.88), and 0.85 (0.79-0.90) for atherosclerotic cardiovascular disease incidence, atherosclerotic cardiovascular disease mortality, and all-cause mortality, respectively. Habitual tea drinkers had 1.41 years longer of atherosclerotic cardiovascular disease-free years and 1.26 years longer of life expectancy at the index age of 50 years. The observed inverse associations were strengthened among participants who kept the habit during the follow-up period.
CONCLUSION:
Tea consumption was associated with reduced risks of atherosclerotic cardiovascular disease and all-cause mortality, especially among those consistent habitual tea drinkers.
KEYWORDS:
Chinese population; Tea consumption; all-cause mortality; atherosclerotic cardiovascular disease; prospective cohort study

Associations of choline-related nutrients with cardiometabolic and all-cause mortality: results from 3 prospective cohort studies of blacks, whites, and Chinese.
Yang JJ, Lipworth LP, Shu XO, Blot WJ, Xiang YB, Steinwandel MD, Li H, Gao YT, Zheng W, Yu D.
Am J Clin Nutr. 2020 Jan 8. pii: nqz318. doi: 10.1093/ajcn/nqz318. [Epub ahead of print]
PMID: 31915809
Abstract
BACKGROUND:
Choline-related nutrients are dietary precursors of a gut microbial metabolite, trimethylamine-N-oxide, which has been linked to cardiometabolic diseases and related death. However, epidemiologic evidence on dietary choline and mortality remains limited, particularly among nonwhite populations.
OBJECTIVES:
This study aimed to investigate the associations of choline-related nutrients with cardiometabolic and all-cause mortality among black and white Americans and Chinese adults.
METHODS:
Included were 49,858 blacks, 23,766 whites, and 134,001 Chinese, aged 40-79 y, who participated in 3 prospective cohorts and lived ≥1 y after enrollment. Cox regression models were used to estimate HRs and 95% CIs for cardiometabolic [e.g., ischemic heart disease (IHD), stroke, and diabetes] and all-cause deaths. To account for multiple testing, P values < 0.003 were considered significant.
RESULTS:
Mean choline intake among blacks, whites, and Chinese was 404.1 mg/d, 362.0 mg/d, and 296.8 mg/d, respectively. During a median follow-up of 11.7 y, 28,673 deaths were identified, including 11,141 cardiometabolic deaths. After comprehensive adjustments, including for overall diet quality and disease history, total choline intake was associated with increased cardiometabolic mortality among blacks and Chinese (HR for highest compared with lowest quintile: 1.26; 95% CI: 1.13, 1.40 and HR: 1.23; 95% CI: 1.11, 1.38, respectively; both P-trend < 0.001); among whites, the association was weaker (HR: 1.12; 95% CI: 0.95, 1.33; P-trend = 0.02). Total choline intake was also associated with diabetes and all-cause mortality in blacks (HR: 1.66; 95% CI: 1.26, 2.19 and HR: 1.20; 95% CI: 1.12, 1.29, respectively), with diabetes mortality in Chinese (HR: 2.24; 95% CI: 1.68, 2.97), and with IHD mortality in whites (HR: 1.31; 95% CI: 1.02, 1.69) (all P-trend < 0.001). The choline-mortality association was modified by alcohol consumption and appeared stronger among individuals with existing cardiometabolic disease. Betaine intake was associated with increased cardiometabolic mortality in Chinese only (HR: 1.16; 95% CI: 1.08, 1.25; P-trend < 0.001).
CONCLUSIONS:
High choline intake was associated with increased cardiometabolic mortality in racially diverse populations.

Legume and soy intake and risk of type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies.
Tang J, Wan Y, Zhao M, Zhong H, Zheng JS, Feng F.
Am J Clin Nutr. 2020 Jan 8. pii: nqz338. doi: 10.1093/ajcn/nqz338. [Epub ahead of print]
PMID: 31915830
Abstract
BACKGROUND:
Previous findings on the associations of legume and soy intake with the risk of type 2 diabetes are conflicting.
OBJECTIVE:
We aimed to summarize the longitudinal associations between legume and soy intake and risk of type 2 diabetes.
METHODS:
We searched for relevant prospective cohort studies in PubMed, EMBASE, and Ovid up to August 2019. Study-specific, multivariable-adjusted RRs and 95% CIs were pooled by random-effects models.
RESULTS:
We identified 15 unique cohorts including 565,810 individuals and 32,093 incident cases. The summary RRs (95% CIs) of incident type 2 diabetes were 0.95 (0.79, 1.14; NS) for total legumes, 0.83 (0.68, 1.01; NS) for total soy, 0.89 (0.71, 1.11; NS) for soy milk, 0.92 (0.84, 0.99) for tofu, 0.84 (0.75, 0.95) for soy protein, and 0.88 (0.81, 0.96) for soy isoflavones, respectively. High heterogeneity was found for total legumes (I2 = 84.8%), total soy (I2 = 90.8%), and soy milk (I2 = 91.7%). Potential sources of heterogeneity were not evident for total legumes or soy milk, whereas for total soy, geographic location (Asia, United States; P = 0.04) and study quality (high, moderate, or low; P = 0.02) significantly predicted heterogeneity. In dose-response analysis, significant linear inverse associations were observed for tofu, soy protein, and soy isoflavones (all P < 0.05). Overall quality of evidence was rated as moderate for total legumes and low for total soy and soy subtypes.
CONCLUSIONS:
Dietary intakes of tofu, soy protein, and soy isoflavones, but not total legumes or total soy, are inversely associated with incident type 2 diabetes. Our findings support recommendations to increase intakes of certain soy products for the prevention of type 2 diabetes. However, the overall quality of evidence was low and more high-quality evidence from prospective studies is needed. This trial was registered as PROSPERO CRD42019126403 (https://www.crd.york.ac.uk/PROSPERO).
KEYWORDS:
cohort; legume; meta-analysis; soy; type 2 diabetes
Food Products That May Cause an Increase in Blood Pressure.
Adamczak M, Wiecek A.
Curr Hypertens Rep. 2020 Jan 8;22(1):2. doi: 10.1007/s11906-019-1007-y. Review.
PMID: 31915940
Abstract
PURPOSE OF REVIEW:
To review latest reports of the food products which might increase blood pressure and therefore might participate in the pathogenesis of hypertension.
RECENT FINDINGS:
Results of clinical study suggest that consumption of high-sodium food leads to transient increase in plasma sodium concentration. This is accompanied by blood pressure increase. Results of both clinical and experimental studies suggest direct vasculotoxic effects of sodium. Increased plasma sodium concentration could mediate its effects on blood pressure by changes in endothelial cell stiffness and glycocalyx integrity. Energy drinks are non-alcoholic beverages with increasing popularity. Clinical, interventional, randomized, placebo controlled, and cross-sectional studies showed that energy drinks may increase arterial blood pressure. Blood pressure increase after exposure for the energy drinks is mainly related to the caffeine content in these drinks. Many case reports were published concerning the clinically significant increase in blood pressure caused by the consumption of liquorice root or food products containing liquorice, such as candies, tea, Pontefract cookies, and chewing gum. Liquorice contains a precursor of glycyrrhetic acid. Glycyrrhetic acid reduces the activity of the 11β-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) isoenzyme, which leads to activation of the mineralocorticoid receptor by cortisol in the distal convoluted tubule resulting in hypertension, hypokalemia, and metabolic alkalosis. The relationship between chronic alcohol intake and blood pressure is well established on the basis of a diverse body of evidence including animal experiments, epidemiological studies, mendelian randomization studies, and interventional studies. Results of recent studies suggested that binge drinking (i.e., episodic consumption of a very high amount of alcohol beverages) has pronounced hypertensinogenic effects. Recently, it was documented that also low doses of alcohol may increase the risk of cardiovascular complications. Therefore, the amount of alcohol consumption that is safe is zero. High-salt food products, energy drinks, food products containing liquorice, and alcoholic beverages have hypertensinogenic properties. Patients with hypertension and other cardiovascular diseases should avoid even accidental consumption of these food products.
KEYWORDS:
Alcohol and hypertension; Blood pressure; Cardiovascular disease; Diet and hypertension; Salt and hypertension; Salt intake

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Tea consumption and risk of stroke in Chinese adults: a prospective cohort study of 0.5 million men and women.
Tian T, Lv J, Jin G, Yu C, Guo Y, Bian Z, Yang L, Chen Y, Shen H, Chen Z, Hu Z, Li L; China Kadoorie Biobank Collaborative Group.
Am J Clin Nutr. 2020 Jan 1;111(1):197-206. doi: 10.1093/ajcn/nqz274.
PMID: 31711152
Abstract
BACKGROUND:
Many cohort studies have explored the relation between tea consumption and stroke risk; however, the conclusions have been inconsistent. In addition, evidence is lacking in China, where the patterns of tea consumption and main types of tea consumed differ substantially from those in high-income countries.
OBJECTIVE:
We aimed to systematically assess the association of tea consumption with the risk of stroke based on a Chinese large-scale cohort study.
METHODS:
A total of 487,377 participants from the China Kadoorie Biobank were included in the present study. Detailed information about tea consumption (including frequency, duration, amount, and tea type) was self-reported at baseline. After ∼4.3 million person-years of follow-up, 38,727 incident cases of stroke were recorded, mainly through linkage with mortality and morbidity registries and based on the national health insurance system.
RESULTS:
Overall, 128,280 adults (26.3%) reported drinking tea almost daily (41.4% men, 15.9% women), predominantly green tea (86.7%). Tea consumption had an inverse and dose-response relation with the risk of stroke (Ptrend < 0.001). Compared with nonconsumers, those who consumed tea occasionally, weekly, and daily had adjusted HRs and 95% CIs of 0.96 (0.94, 0.99), 0.94 (0.90, 0.98), and 0.92 (0.89, 0.95) respectively, with little difference by stroke type. Among those who consumed tea daily, the HRs for stroke decreased with the increasing duration and amount of tea consumed (all P < 0.001). These inverse associations were significant for green tea but not for other types of tea. Among men, but not women, the inverse relations could be detected, and similar inverse associations could be found for male noncurrent alcohol-consumers and noncurrent smokers as well.
CONCLUSIONS:
Among Chinese adults, higher consumption of tea, especially green tea, was associated with a lower risk of ischemic and hemorrhagic stroke.

Serum magnesium and risk of coronary artery disease: are there implications for dietary interventions?
van Dam RM.
Am J Clin Nutr. 2020 Jan 1;111(1):6-7. doi: 10.1093/ajcn/nqz289. No abstract available.
PMID: 31732727
https://sci-hub.tw/10.1093/ajcn/nqz289
>>>>>>>>>>>>>>>>>>>
Serum magnesium and the incidence of coronary artery disease over a median 27 years of follow-up in the Atherosclerosis Risk in Communities (ARIC) Study and a meta-analysis.
Rooney MR, Alonso A, Folsom AR, Michos ED, Rebholz CM, Misialek JR, Chen LY, Dudley S, Lutsey PL.
Am J Clin Nutr. 2020 Jan 1;111(1):52-60. doi: 10.1093/ajcn/nqz256.
PMID: 31622458
Abstract
BACKGROUND:
Low serum magnesium (Mg) concentrations have been associated with higher coronary artery disease (CAD) risk. A previous Atherosclerosis Risk in Communities (ARIC) Study article that evaluated the Mg-CAD association, based on 319 events occurring over 4-7 y, identified a sex-interaction whereby the inverse Mg-CAD association was much stronger among women than men. More than 1700 additional ARIC CAD events have since accrued.
OBJECTIVE:
We aimed to test our hypothesis that serum Mg is inversely and independently associated with long-term CAD risk in ARIC and in a meta-analysis with other prospective studies.
METHODS:
A total of 14,446 ARIC study participants (baseline mean ± SD age: 54 ± 6 y, 57% women, 27% African American) were followed for incident CAD through 2017. CAD events were defined by myocardial infarction or CAD mortality. Serum Mg was modeled as quintiles based on mean visit 1 (1987-1989) and visit 2 (1990-1992) concentrations. Cox regression models were used. We also conducted a random-effects meta-analysis incorporating these contemporary ARIC findings.
RESULTS:
Over a median follow-up of 27 y, 2131 incident CAD cases accrued. Overall, low serum Mg was associated with higher CAD risk after adjustment for demographics, lifestyle factors, and other CAD risk factors than was higher serum Mg (HR Q1 compared with Q5: 1.28; 95% CI: 1.11, 1.47; P-linear trend <0.001). The association was stronger among women (HR Q1 compared with Q5: 1.53; 95% CI: 1.22, 1.92) than men (HR: 1.11; 95% CI: 0.92, 1.34) (P-interaction = 0.05). In the meta-analysis including 5 studies, the pooled RR (95% CI) for CAD in the lowest compared with the highest circulating Mg category was 1.18 (1.06, 1.31) (I2 = 22%, P-heterogeneity = 0.27).
CONCLUSIONS:
In this large community-based cohort and updated meta-analysis, low circulating Mg was associated with higher CAD risk than was higher Mg. Whether increasing Mg concentrations within healthy limits is a useful strategy for CAD prevention remains to be seen.
KEYWORDS:
circulating magnesium; cohort study; coronary artery disease; meta-analysis; observational prospective studies

FGF21, not GCN2, influences bone morphology due to dietary protein restrictions.
McNulty MA, Goupil BA, Albarado DC, Castaño-Martinez T, Ambrosi TH, Puh S, Schulz TJ, Schürmann A, Morrison CD, Laeger T.
Bone Rep. 2019 Dec 31;12:100241. doi: 10.1016/j.bonr.2019.100241. eCollection 2020 Jun.
PMID: 31921941
https://www.sciencedirect.com/science/article/pii/S2352187219300476?via%3Dihub
Abstract
BACKGROUND:
Dietary protein restriction is emerging as an alternative approach to treat obesity and glucose intolerance because it markedly increases plasma fibroblast growth factor 21 (FGF21) concentrations. Similarly, dietary restriction of methionine is known to mimic metabolic effects of energy and protein restriction with FGF21 as a required mechanism. However, dietary protein has been shown to be required for normal bone growth, though there is conflicting evidence as to the influence of dietary protein restriction on bone remodeling. The purpose of the current study was to evaluate the effect of dietary protein and methionine restriction on bone in lean and obese mice, and clarify whether FGF21 and general control nonderepressible 2 (GCN2) kinase, that are part of a novel endocrine pathway implicated in the detection of protein restriction, influence the effect of dietary protein restriction on bone.
METHODS:
Adult wild-type (WT) or Fgf21 KO mice were fed a normal protein (18 kcal%; CON) or low protein (4 kcal%; LP) diet for 2 or 27 weeks. In addition, adult WT or Gcn2 KO mice were fed a CON or LP diet for 27 weeks. Young New Zealand obese (NZO) mice were placed on high-fat diets that provided protein at control (16 kcal%; CON), low levels (4 kcal%) in a high-carbohydrate (LP/HC) or high-fat (LP/HF) regimen, or on high-fat diets (protein, 16 kcal%) that provided methionine at control (0.86%; CON-MR) or low levels (0.17%; MR) for up to 9 weeks. Long bones from the hind limbs of these mice were collected and evaluated with micro-computed tomography (μCT) for changes in trabecular and cortical architecture and mass.
RESULTS:
In WT mice the 27-week LP diet significantly reduced cortical bone, and this effect was enhanced by deletion of Fgf21 but not Gcn2. This decrease in bone did not appear after 2 weeks on the LP diet. In addition, Fgf21 KO mice had significantly less bone than their WT counterparts. In obese NZO mice dietary protein and methionine restriction altered bone architecture. The changes were mediated by FGF21 due to methionine restriction in the presence of cystine, which did not increase plasma FGF21 levels and did not affect bone architecture.
CONCLUSIONS:
This study provides direct evidence of a reduction in bone following long-term dietary protein restriction in a mouse model, effects that appear to be mediated by FGF21.
KEYWORDS:
Dietary restriction; FGF21; GCN2; Microcomputed tomography; Protein restriction

Whey protein but not collagen peptides stimulate acute and longer-term muscle protein synthesis with and without resistance exercise in healthy older women: a randomized controlled trial.
Oikawa SY, Kamal MJ, Webb EK, McGlory C, Baker SK, Phillips SM.
Am J Clin Nutr. 2020 Jan 9. pii: nqz332. doi: 10.1093/ajcn/nqz332. [Epub ahead of print]
PMID: 31919527
Abstract
BACKGROUND:
Aging appears to attenuate the response of skeletal muscle protein synthesis (MPS) to anabolic stimuli such as protein ingestion (and the ensuing hyperaminoacidemia) and resistance exercise (RE).
OBJECTIVES:
The purpose of this study was to determine the effects of protein quality on feeding- and feeding plus RE-induced increases of acute and longer-term MPS after ingestion of whey protein (WP) and collagen protein (CP).
METHODS:
In a double-blind parallel-group design, 22 healthy older women (mean ± SD age: 69 ± 3 y, n = 11/group) were randomly assigned to consume a 30-g supplement of either WP or CP twice daily for 6 d. Participants performed unilateral RE twice during the 6-d period to determine the acute (via [13C6]-phenylalanine infusion) and longer-term (ingestion of deuterated water) MPS responses, the primary outcome measures.
RESULTS:
Acutely, WP increased MPS by a mean ± SD 0.017 ± 0.008%/h in the feeding-only leg (Rest) and 0.032 ± 0.012%/h in the feeding plus exercise leg (Exercise) (both P < 0.01), whereas CP increased MPS only in Exercise (0.012 ± 0.013%/h) (P < 0.01) and MPS was greater in WP than CP in both the Rest and Exercise legs (P = 0.02). Longer-term MPS increased by 0.063 ± 0.059%/d in Rest and 0.173 ± 0.104%/d in Exercise (P < 0.0001) with WP; however, MPS was not significantly elevated above baseline in Rest (0.011 ± 0.042%/d) or Exercise (0.020 ± 0.034%/d) with CP. Longer-term MPS was greater in WP than in CP in both Rest and Exercise (P < 0.001).
CONCLUSIONS:
Supplementation with WP elicited greater increases in both acute and longer-term MPS than CP supplementation, which is suggestive that WP is a more effective supplement to support skeletal muscle retention in older women than CP.
KEYWORDS:
collagen peptides; muscle protein synthesis; older women; protein quality; resistance exercise; whey protein

Modest improvement in CVD risk markers in older adults following quinoa (Chenopodium quinoa Willd.) consumption: a randomized-controlled crossover study with a novel food product.
Pourshahidi LK, Caballero E, Osses A, Hyland BW, Ternan NG, Gill CIR.
Eur J Nutr. 2020 Jan 9. doi: 10.1007/s00394-019-02169-0. [Epub ahead of print]
PMID: 31919583
Abstract
PURPOSE:
To investigate the effect of consuming quinoa biscuits on markers of CVD risk over 4 weeks in free-living older adults.
METHODS:
A randomized-controlled, double-blind crossover trial was conducted in which consenting healthy adults aged 50-75 years (n = 40) consumed 15 g quinoa biscuits (60 g quinoa flour/100 g) or control iso-energetic biscuits (made using wheat flour) daily for 28 consecutive days (4 weeks), in addition to their normal diet. Following a 6-week washout, participants consumed the alternate biscuit for a final 4 weeks. Anthropometry and fasted blood samples were obtained before and after each intervention period.
RESULTS:
At the beginning of the trial, mean ± SD total cholesterol concentrations were 6.02 ± 1.22 mmol/L (3.7-9.2 mmol/L); 33 participants (82.5%) had high cholesterol (> 5 mmol/L). No participants were lost to follow-up and there were no changes in habitual dietary intakes or levels of physical activity between each 4-week intervention period. Significantly greater decreases in total and LDL cholesterol concentrations (- 0.30 ± 0.58 and - 0.25 ± 0.38 mmol/L, respectively), TC: HDL ratio (- 0.11 ± 0.30), weight (- 0.61 ± 0.89 kg) and BMI (- 0.22 ± 0.34 kg/m2) were apparent following consumption of the quinoa versus control biscuits (all P < 0.05). Changes in triglycerides, HDL cholesterol, or PUFA or CRP concentrations were not significant between treatment groups.
CONCLUSION:
Consumption of novel quinoa biscuits produced small, but favorable changes in body weight, BMI, and circulating cholesterol concentrations, all of which may contribute to lowered CVD risk in older adults.
KEYWORDS:
Cardiovascular disease; Cholesterol; Fatty acids; PUFA; Quinoa; Randomized controlled trial

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Bowel movement frequency and risks of major vascular and non-vascular diseases: a population-based cohort study among Chinese adults.
Yang S, Yu C, Guo Y, Bian Z, Fan M, Yang L, Du H, Chen Y, Yan S, Zang Y, Chen J, Chen Z, Lv J, Li L; China Kadoorie Biobank Collaborative Group.
BMJ Open. 2020 Jan 9;10(1):e031028. doi: 10.1136/bmjopen-2019-031028.
PMID: 31924633
https://bmjopen.bmj.com/content/bmjopen/10/1/e031028.full.pdf
Abstract
OBJECTIVE:
The application of bowel movement frequency (BMF) in primary care is limited by the lack of solid evidence about the associations of BMF with health outcomes apart from Parkinson's disease and colorectal cancer. We examined the prospective associations of BMF with major vascular and non-vascular diseases outside the digestive system.
DESIGN:
Population-based prospective cohort study.
SETTING:
The China Kadoorie Biobank in which participants from 10 geographically diverse areas across China were enrolled between 2004 and 2008.
PARTICIPANTS:
487 198 participants aged 30 to 79 years without cancer, heart disease or stroke at baseline were included and followed up for a median of 10 years. The usual BMF was self-reported once at baseline.
PRIMARY AND SECONDARY OUTCOME MEASURES:
Incident events of predefined major vascular and non-vascular diseases.
RESULTS:
In multivariable-adjusted analyses, participants having bowel movements 'more than once a day' had higher risks of ischaemic heart disease (IHD), heart failure, chronic obstructive pulmonary disease, type 2 diabetes mellitus and chronic kidney disease (CKD) when compared with the reference group ('once a day'). The respective HRs (95% CIs) were 1.12 (1.09 to 1.16), 1.33 (1.22 to 1.46), 1.28 (1.22 to 1.36), 1.20 (1.15 to 1.26) and 1.15 (1.07 to 1.24). The lowest BMF ('less than three times a week') was also associated with higher risks of IHD, major coronary events, ischaemic stroke and CKD. The respective HRs were 1.07 (1.02 to 1.12), 1.22 (1.10 to 1.36), 1.11 (1.05 to 1.16) and 1.20 (1.07 to 1.35).
CONCLUSION:
BMF was associated with future risks of multiple vascular and non-vascular diseases. The integration of BMF assessment and health counselling into primary care should be considered.
KEYWORDS:
chronic diseases; cohort study; epidemiology; public health

Severe food restriction activates the central renin angiotensin system.
De Souza AMA, Linares A, Speth RC, Campos GV, Ji H, Chianca D Jr, Sandberg K, De Menezes RCA.
Physiol Rep. 2020 Jan;8(1):e14338. doi: 10.14814/phy2.14338.
PMID: 31925945
https://physoc.onlinelibrary.wiley.com/doi/pdfdirect/10.14814/phy2.14338
Abstract
We previously showed that 2 weeks of a severe food restricted (sFR) diet (40% of the caloric intake of the control (CT) diet) up-regulated the circulating renin angiotensin (Ang) system (RAS) in female Fischer rats, most likely as a result of the fall in plasma volume. In this study, we investigated the role of the central RAS in the mean arterial pressure (MAP) and heart rate (HR) dysregulation associated with sFR. Although sFR reduced basal mean MAP and HR, the magnitude of the pressor response to intracerebroventricular (icv) microinjection of Ang-[1-8] was not affected; however, HR was 57 ± 13 bpm lower 26 min after Ang-[1-8] microinjection in the sFR rats and a similar response was observed after losartan was microinjected. The major catabolic pathway of Ang-[1-8] in the hypothalamus was via Ang-[1-7]; however, no differences were detected in the rate of Ang-[1-8] synthesis or degradation between CT and sFR animals. While sFR had no effect on the AT1 R binding in the subfornical organ (SFO), the organum vasculosum laminae terminalis (OVLT) and median preoptic nucleus (MnPO) of the paraventricular anteroventral third ventricle, ligand binding increased 1.4-fold in the paraventricular nucleus (PVN) of the hypothalamus. These findings suggest that sFR stimulates the central RAS by increasing AT1 R expression in the PVN as a compensatory response to the reduction in basal MAP and HR. These findings have implications for people experiencing a period of sFR since an activated central RAS could increase their risk of disorders involving over activation of the RAS including renal and cardiovascular diseases.
KEYWORDS:
RAS-Fingerprint®; angiotensin converting enzyme (ACE); angiotensin converting enzyme 2 (ACE2); caloric reduction; inadequate food intake

Therapeutic benefit of combining calorie-restricted ketogenic diet and glutamine targeting in late-stage experimental glioblastoma.
Mukherjee P, Augur ZM, Li M, Hill C, Greenwood B, Domin MA, Kondakci G, Narain NR, Kiebish MA, Bronson RT, Arismendi-Morillo G, Chinopoulos C, Seyfried TN.
Commun Biol. 2019 May 29;2(1):200. doi: 10.1038/s42003-019-0455-x.
PMID: 31925059
Abstract
Glioblastoma (GBM) is an aggressive primary human brain tumour that has resisted effective therapy for decades. Although glucose and glutamine are the major fuels that drive GBM growth and invasion, few studies have targeted these fuels for therapeutic management. The glutamine antagonist, 6-diazo-5-oxo-L-norleucine (DON), was administered together with a calorically restricted ketogenic diet (KD-R) to treat late-stage orthotopic growth in two syngeneic GBM mouse models: VM-M3 and CT-2A. DON targets glutaminolysis, while the KD-R reduces glucose and, simultaneously, elevates neuroprotective and non-fermentable ketone bodies. The diet/drug therapeutic strategy killed tumour cells while reversing disease symptoms, and improving overall mouse survival. The therapeutic strategy also reduces edema, hemorrhage, and inflammation. Moreover, the KD-R diet facilitated DON delivery to the brain and allowed a lower dosage to achieve therapeutic effect. The findings support the importance of glucose and glutamine in driving GBM growth and provide a therapeutic strategy for non-toxic metabolic management.

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Every-other-day feeding exacerbates inflammation and neuronal deficits in 5XFAD mouse model of Alzheimer's disease.
Lazic D, Tesic V, Jovanovic M, Brkic M, Milanovic D, Zlokovic BV, Kanazir S, Perovic M.
Neurobiol Dis. 2020 Jan 10:104745. doi: 10.1016/j.nbd.2020.104745. [Epub ahead of print]
PMID: 31931140
https://www.sciencedirect.com/science/article/pii/S0969996120300206?via%3Dihub
Abstract
Food restriction has been widely associated with beneficial effects on brain aging and age-related neurodegenerative diseases such as Alzheimer's disease. However, previous studies on the effects of food restriction on aging- or pathology-related cognitive decline are controversial, emphasizing the importance of the type, onset and duration of food restriction. In the present study, we assessed the effects of preventive every-other-day (EOD) feeding regimen on neurodegenerative phenotype in 5XFAD transgenic mice, a commonly used mouse model of Alzheimer's disease. EOD feeding regimen was introduced to transgenic female mice at the age of 2 months and the effects on amyloid-β (Aβ) accumulation, gliosis, synaptic plasticity, and blood-brain barrier breakdown were analyzed in cortical tissue of 6-month-old animals. Surprisingly, significant increase of inflammation in the cortex of 5XFAD fed EOD mice was observed, reflected by the expression of microglial and astrocytic markers. This increase in reactivity and/or proliferation of glial cells was accompanied by an increase in proinflammatory cytokine TNF-α, p38 MAPK and EAAT2, and a decrease in GAD67. NMDA receptor subunit 2B, related to glutamate excitotoxicity, was increased in the cortex of 5XFAD-EOD mice indicating additional alterations in glutamatergic signaling. Furthermore, 4 months of EOD feeding regimen had led to synaptic plasticity proteins reduction and neuronal injury in 5XFAD mice. However, EOD feeding regimen did not affect Aβ load and blood-brain barrier permeability in the cortex of 5XFAD mice. Our results demonstrate that EOD feeding regimen exacerbates Alzheimer's disease-like neurodegenerative and neuroinflammatory changes irrespective of Aβ pathology in 5XFAD mice, suggesting that caution should be paid when using food restrictions in the prodromal phase of this neurodegenerative disease.
KEYWORDS:
5XFAD; Alzheimer's disease; EOD dietary restriction; Inflammation; Intermittent fasting; Neuritic dystrophy; Synaptic plasticity

A blood test that predicts the risk of dying
Dr. Brian Goldman · CBC News · Posted: Jan 13, 2020
https://www.cbc.ca/radio/whitecoat/a-blood-test-that-predicts-the-risk-of-dying-1.5424633
Incidental lymphopenia and mortality: a prospective cohort study
Marie Warny, Jens Helby, Børge Grønne Nordestgaard, Henrik Birgens and Stig Egil Bojesen
CMAJ January 13, 2020 192 (2) E25-E33; DOI: https://doi.org/10.1503/cmaj.191024
Abstract
BACKGROUND: It is unknown if incidental lymphopenia detected in the general population is associated with higher all-cause and cause-specific mortality. We aimed to identify the associations between lymphopenia and all-cause and cause specific mortality.
METHODS: In a prospective cohort study, we examined and followed participants enrolled in the Copenhagen General Population Study between November 2003 and April 2015. In our analysis, we modelled risks using Cox proportional hazards regression for 3 groups: participants with a lymphocyte count below the 2.5th percentile; those with a lymphocyte count at or between the 2.5th and 97.5th percentiles (reference category); and those with a lymphocyte count above the 97.5th percentile.
RESULTS: The cohort included 108 135 participants with a median age of 68 years. During a median follow-up of 9 (interquartile range [IQR] 0–14) years, 10 372 participants died. We found that participants with lymphopenia (lymphocyte count < 1.1 × 109/L) compared with those with a lymphocyte count in the reference range (1.1–3.7 × 109/L) had higher mortality with multivariable adjusted hazard ratios (HRs) of 1.63 (95% confidence interval [CI] 1.51–1.76) for all causes, 1.67 (95% CI 1.42–1.97) for nonhematologic cancers, 2.79 (95% CI 1.82–4.28) for hematologic cancers, 1.88 (95% CI 1.61–2.20) for cardiovascular diseases, 1.88 (95% CI 1.55–2.29) for respiratory diseases, 1.86 (95% CI 1.53–2.25) for infectious diseases, and 1.50 (95% CI 1.19–1.88) for other causes. For all-cause mortality, the highest absolute 2-year risks of death were observed in women (61%) and men (75%) who smoked and were aged 80 years or older with lymphocyte counts less than 0.5 × 109/L. Participants with a lymphocyte count higher than the reference category had increased mortality (adjusted HR 1.17, 95% CI 1.04–1.31).
INTERPRETATION: We found that lymphopenia was associated with an increased risk of all-cause and cause-specific mortality.

Jeanne Calment's unique 122-year lifespan: facts and factors; longevity history in her genealogical tree.
Robin-Champigneul F.
Rejuvenation Res. 2020 Jan 13. doi: 10.1089/rej.2019.2298. [Epub ahead of print]
PMID: 31928146
https://sci-hub.tw/10.1089/rej.2019.2298
Abstract
Jeanne Calment's (JC) still unmatched validated human lifespan of 122 years and 164 days, over 3 years longer than any other, surprises many. While her case is broadly accepted as a golden standard of validation, her record age still raises skepticism among some. The probability of such a record to be achieved by someone born in the second half of the 19th century, in the world population documentarily eligible to age validation, and also in the G7 countries, can be calculated by applying some logistic and Gompertz mortality models to these populations, taken respectively from the age of 117 and of 100. This probability appears substantial, respectively 7.1% and 4.7%, when using a 4-parameters logistic model which I validated on the observed survivals of centenarians until the age of 118. A 3-year interval with the second oldest is then expected. The known facts and documents constitute consistent evidence that JC died at 122: regular official records during her life, her verified memories from her 19th-century life, her usage of specialized terms and of an abbreviation system specific to this period of time, photos, her signature and handwriting, testimonies from numerous witnesses of her life, plus the expertise of gerontologists. Meanwhile, nothing contradicts her record: the daughter-mother identity swap hypothesis appears unrealistic and not supported by any evidence; especially no plausible motive can be found, on the contrary. The latest paper which defends this hypothesis, "Bayesian assessment of the longevity of JC", contains major errors, making its result subjective and invalid. The study of JC's genealogical tree on 6 generations, using longevity performance and TIAL (Total immediate ancestor longevity) indicators, shows how, in two centuries, her ancestors have been living 10% longer on average at each generation, increasingly overperforming their French 25-year-old contemporaries, from around 7% in the early 18th (...).

Associations between Serum Levels of Cholesterol and Survival to Age 90 in Postmenopausal Women.
Maihofer AX, Shadyab AH, Wild RA, LaCroix AZ.
J Am Geriatr Soc. 2020 Jan 13. doi: 10.1111/jgs.16306. [Epub ahead of print]
PMID: 31930739
Abstract
OBJECTIVES:
Although elevated lipid levels predict increased risk of coronary heart disease and death in middle-aged women and men, evidence is mixed if lipid levels measured in later life predict survival to very old ages. We examined lipid levels and survival to age 90 with or without intact mobility in a large cohort of older women.
DESIGN:
Prospective cohort.
SETTING:
Laboratory collection at a Women's Health Initiative (WHI) center and longitudinal follow-up via mail.
PARTICIPANTS:
Women aged 68 to 81 years at baseline.
MEASUREMENTS:
Serum high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol were collected at baseline. Participant survival status and self-reported mobility was compared across lipid levels.
RESULTS:
HDL and LDL levels were not associated with survival to age 90 after adjustment for cardiovascular risk factors (HDL: quartile (Q) 2: odds ratio [OR] = 1.14 [95% confidence interval [CI] = .94-1.38]; Q3 OR = 1.08 [95% CI = .88-1.33]; Q4 OR = 1.09 [95% CI = .88-1.35]; LDL: Q2 OR = 1.07 [95% CI = .88-1.31]; Q3 OR = 1.27 [95% CI = 1.04-1.55]; Q4 OR = 1.07 [95% CI = .88-1.31]). Similarly, no associations were observed between HDL and LDL levels and survival to age 90 with mobility disability. High HDL was not associated with survival to age 90 with intact mobility after adjustment for other cardiovascular risk factors. Compared with the lowest LDL quartile, the three upper LDL quartiles were associated with greater odds of survival to age 90 with intact mobility (LDL: Q2 OR = 1.31 [95% CI = .99-1.74]; Q3 OR = 1.43 [95% CI = 1.07-1.92]; Q4 OR = 1.35 [95% CI = 1.01-1.80]; P = .05).
CONCLUSION:
Neither higher HDL nor lower LDL levels predicted survival to age 90, but higher LDL predicted healthy survival. These findings suggest the need for reevaluation of healthy LDL levels in older women.
KEYWORDS:
cholesterol; lipid; mobility; postmenopausal; quality of life

High Dietary Intake of Vegetable or Polyunsaturated Fats is Associated With Reduced Risk of Hepatocellular Carcinoma.
Yang W, Sui J, Ma Y, Simon TG, Petrick JL, Lai M, McGlynn KA, Campbell PT, Giovannucci EL, Chan AT, Zhang X.
Clin Gastroenterol Hepatol. 2020 Jan 9. pii: S1542-3565(20)30035-5. doi: 10.1016/j.cgh.2020.01.003. [Epub ahead of print]
PMID: 31927110
Abstract
BACKGROUND & AIMS:
We investigated associations of intake of total fats, specific dietary fats, and fats from different food sources with risk of hepatocellular carcinoma (HCC) using data from the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS).
METHODS:
We analyzed data from a total of 138,483 women and men who participated in the NHS or HPFS. A validated semi-quantitative food frequency questionnaire was sent to NHS participants in 1980, 1984, 1986, and every 4 years thereafter; dietary information was collected from participants in the HPFS in 1986 and every 4 years thereafter. Multivariable hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression.
RESULTS:
After an average follow-up time of 26.6 years, 160 incident HCC cases were documented. Although there was a non-significant association between total fat intake and HCC, intake of vegetable fats reduced risk of HCC (HR for the highest vs lowest quartile, 0.61; 95% CI, 0.39-0.96; Ptrend=.02), but not animal or dairy fats. Replacing animal or dairy fats with an equivalent amount of vegetable fats was associated with a lower risk of HCC (HR per 1 standard deviation, 0.79; 95% CI, 0.65-0.97). Among fat subtypes, monounsaturated and polyunsaturated fatty acids, including n-3 (HR, 0.63; 95% CI, 0.41-0.96; Ptrend=.14) and n-6 polyunsaturated fatty acids (HR, 0.54; 95% CI, 0.34-0.86; Ptrend=.02), were inversely associated with risk of HCC. Higher ratios of monounsaturated or polyunsaturated fat to saturated fat were inversely associated with HCC risk (all Ptrend≤.02). In addition, when replacing saturated fats with monounsaturated or polyunsaturated fats, the HR per 1 standard deviation was 0.77 (95% CI, 0.64-0.92).
CONCLUSIONS:
In an analysis of data from 2 large cohort studies, we found higher intake of vegetable fats and polyunsaturated fats to be associated with lower risk of HCC. Replacing animal or dairy fats with vegetable fats, or replacing saturated fats with monounsaturated or polyunsaturated fats, was associated with reduced risk of HCC.
KEYWORDS:
PUFAs; dairy fat; liver cancer; primary prevention

Effects of high-fiber diets enriched with carbohydrate, protein, or unsaturated fat on circulating short chain fatty acids: results from the OmniHeart randomized trial.
Mueller NT, Zhang M, Juraschek SP, Miller ER, Appel LJ.
Am J Clin Nutr. 2020 Jan 11. pii: nqz322. doi: 10.1093/ajcn/nqz322. [Epub ahead of print]
PMID: 31927581
Abstract
BACKGROUND:
short chain fatty acids (SCFAs; e.g., acetate, propionate, and butyrate) are produced by microbial fermentation of fiber in the colon. Evidence is lacking on how high-fiber diets that differ in macronutrient composition affect circulating SCFAs.
OBJECTIVES:
We aimed to compare the effects of 3 high-fiber isocaloric diets differing in %kcal of carbohydrate, protein, or unsaturated fat on circulating SCFAs. Based on previous literature, we hypothesized that serum acetate, the main SCFA in circulation, increases on all high-fiber diets, but differently by macronutrient composition of the diet.
METHODS:
OmniHeart is a randomized crossover trial of 164 men and women (≥30 y old); 163 participants with SCFA data were included in this analysis. We provided participants 3 isocaloric high-fiber (∼30 g/2100 kcal) diets, each for 6 wk, in random order: a carbohydrate-rich (Carb) diet, a protein-rich (Prot) diet (protein predominantly from plant sources), and an unsaturated fat-rich (Unsat) diet. We used LC-MS to quantify SCFA concentrations in fasting serum, collected at baseline and the end of each diet period. We fitted linear regression models with generalized estimating equations to examine change in ln-transformed SCFAs from baseline to the end of each diet; differences between diets; and associations of changes in SCFAs with cardiometabolic parameters.
RESULTS:
From baseline, serum acetate concentrations were increased by the Prot (β: 0.24; 95% CI: 0.12, 0.35), Unsat (β: 0.21; 95% CI: 0.10, 0.33), and Carb (β: 0.12; 95% CI: 0.01, 0.24) diets; between diets, only Prot compared with Carb was significant (P = 0.02). Propionate was decreased by the Carb (β: -0.10; 95% CI: -0.16, -0.03) and Unsat (β: -0.10; 95% CI: -0.16, -0.04) diets, not the Prot diet; between diet comparisons of Carb vs. Prot (P = 0.006) and Unsat vs. Prot (P = 0.002) were significant. The Prot diet increased butyrate (β: 0.05; 95% CI: 0.00, 0.09) compared with baseline, but not compared with the other diets. Increases in acetate were associated with decreases in insulin and glucose; increases in propionate with increases in leptin, LDL cholesterol, and blood pressure; and increases in butyrate with increases in insulin and glucose, and decreases in HDL cholesterol and ghrelin (Ps < 0.05).
CONCLUSIONS:
Macronutrient composition of high-fiber diets affects circulating SCFAs, which are associated with measures of appetite and cardiometabolic health. 
KEYWORDS:
acetate; butyrate; diet; fiber; macronutrient; microbiome; propionate; protein; short-chain fatty acids; unsaturated fat

Exposure to proton pump inhibitors and risk of pancreatic cancer: a meta-analysis.
Alkhushaym N, Almutairi AR, Althagafi A, Fallatah SB, Oh M, Martin JR, Babiker HM, McBride A, Abraham I.
Expert Opin Drug Saf. 2020 Jan 11. doi: 10.1080/14740338.2020.1715939. [Epub ahead of print]
PMID: 31928106
Abstract
Objectives: To estimate the pooled pancreatic cancer risk among subjects exposed versus not exposed to proton pump inhibitors.Methods: The authors searched PubMed, EMBASE, Scopus, Cochrane Library, and clinicaltrials.gov to identify relevant studies. The authors quantified pancreatic cancer risk among subjects exposed versus not exposed to PPIs, expressed as the pooled (adjusted) odds ratio (OR/aOR) and 95% confidence interval (95%CI) in overall and sensitivity analyses.Results: One randomized trial, two cohort, four case-control, and five nested case-control studies with 700,178 subjects (73,985 cases; 626,193 controls) were retained. An overall association between PPI exposure and pancreatic cancer risk was observed (OR=1.75, 95%CI=1.12-2.72, I2=99%). This was confirmed in sensitivity analyses for high-quality studies, observational studies, case-control studies, studies with pancreatic cancer as the primary outcome, and in sensitivity analyses for diabetes and obesity but not for pancreatitis and smoking. This association was independent of the duration and Defined Daily Dose (DDD) of PPI exposure. In addition to the class effect for PPIs, rabeprazole had a singular significant association with pancreatic cancer (OR=5.40, 95%CI=1.98-14.703, I2=87.9%).Conclusion: The class of PPIs is associated with a 1.75-fold increase in pancreatic cancer risk, confirmed in sensitivity analyses, but was independent of duration, and Defined Daily Dose.
KEYWORDS:
meta-analysis; pancreatic cancer; proton pump inhibitors; risk

The effects and associations of whole-apple intake on diverse cardiovascular risk factors. A narrative review.
Sandoval-Ramírez BA, Catalán Ú, Calderón-Pérez L, Companys J, Pla-Pagà L, Ludwig IA, Romero MP, Solà R.
Crit Rev Food Sci Nutr. 2020 Jan 13:1-14. doi: 10.1080/10408398.2019.1709801. [Epub ahead of print]
PMID: 31928209
Abstract
Apples are among the world's most consumed fruits. However, while the impact of whole-apple intake on cardiovascular disease (CVD) remains unknown. This narrative review summarizes a novel integrated view of whole-apple intake, CVD risk association (through observational studies; OSs), and the effects on CVD risk factors (randomized trials; RTs). In 8 OSs, whole-apple intake was associated with a reduced risk of CVD mortality, ischemic heart disease mortality, stroke mortality, all-cause mortality, and severe abdominal aortic calcification, as well as with lower C-reactive protein (CRP) concentrations. In 8 RTs, whole-apple consumption reduced total cholesterol, low-density lipoprotein cholesterol, systolic blood pressure, pulse pressure, and plasma inflammatory cytokines, and noticeably reduced CRP, whereas it increased high-density lipoprotein cholesterol (HDLc) and improved endothelial function. Thus, consuming between 100 and 150 g/day of whole apples is associated with a lower CVD risk and decreases in blood pressure, pulse pressure, total cholesterol, low-density lipoprotein cholesterol, and inflammation status as well as with increases in HDLc and endothelial function. These results, support the regular consumption of whole apples as an aid in the prevention of CVD.
KEYWORDS:
Apple; blood pressure; cardiovascular; cholesterol; health

Modifiable risk factors for carotid atherosclerosis: a meta-analysis and systematic review.
Ji X, Leng XY, Dong Y, Ma YH, Xu W, Cao XP, Hou XH, Dong Q, Tan L, Yu JT.
Ann Transl Med. 2019 Nov;7(22):632. doi: 10.21037/atm.2019.10.115.
PMID: 31930033
Abstract
BACKGROUND:
Carotid atherosclerosis is a major cause of stroke, but the conclusion about risk factors for carotid atherosclerosis is still controversial. The aim of our present meta-analysis and systematic review was to explore the modifiable risk factors for carotid atherosclerosis.
METHODS:
We searched PubMed from January 1962 to October 2018 to include longitudinal and cross-sectional studies. The results were pooled using random effects model. Heterogeneity was measured by I2 statistic and publication bias was assessed by funnel plots.
RESULTS:
A total of 14,700 articles were screened, of which 76 with 27 factors were eligible. Our meta-analysis of cross-sectional studies indicated nine factors (hyperlipidemia, hyperhomocysteinemia, hypertension, hyperuricemia, smoking, metabolic syndrome, hypertriglyceridemia, diabetes, and higher low density lipoprotein) were significantly associated with the presence of carotid plaque, among which four (hyperlipidemia, hyperhomocysteinemia, hypertension, and hyperuricemia) could elevate the risk of atherosclerosis by at least 50%; and one factor (hypertension) was associated with increased carotid intima-media thickness. In the systematic review, another five factors [negative emotion, socioeconomic strain, alcohol, air pollution, and obstructive sleep apnea syndrome (OSAS)] were also related to the presence of atherosclerosis. The cross-sectional associations with most of the above 14 factors were further confirmed by longitudinal studies. Among them, the managements of 4 factors (hypertension, hyperlipidemia, diabetes and OSAS) were indicated to prevent carotid atherosclerosis by cohort studies.
CONCLUSIONS:
Effective interventions targeting pre-existing disease, negative emotion, lifestyle and diet may reduce the risk of carotid atherosclerosis. Further good-quality prospective studies are needed to confirm these findings.
KEYWORDS:
Carotid atherosclerosis; carotid intima-media thickness; carotid plaque; meta-analysis; risk factors

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The 17β-oestradiol treatment minimizes the adverse effects of protein restriction on bone parameters in ovariectomized Wistar rats: Relevance to osteoporosis and the menopause.
de Quadros VP, Tobar N, Viana LR, Dos Santos RW, Kiyataka PHM, Gomes-Marcondes MCC.
Bone Joint Res. 2020 Jan 8;8(12):573-581. doi: 10.1302/2046-3758.812.BJR-2018-0259.R2. eCollection 2019 Dec.
PMID: 31934328
https://online.boneandjoint.org.uk/doi/epub/10.1302/2046-3758.812.BJR-2018-0259.R2
Abstract
OBJECTIVES:
Insufficient protein ingestion may affect muscle and bone mass, increasing the risk of osteoporotic fractures in the elderly, and especially in postmenopausal women. We evaluated how a low-protein diet affects bone parameters under gonadal hormone deficiency and the improvement led by hormone replacement therapy (HRT) with 17β-oestradiol.
METHODS:
Female Wistar rats were divided into control (C), ovariectomized (OVX), and 17β-oestradiol-treated ovariectomized (OVX-HRT) groups, which were fed a control or an isocaloric low-protein diet (LP; 6.6% protein; seven animals per group). Morphometric, serum, and body composition parameters were assessed, as well as bone parameters, mechanical resistance, and mineralogy.
RESULTS:
The results showed that protein restriction negatively affected body chemical composition and bone metabolism by the sex hormone deficiency condition in the OVX group. The association between undernutrition and hormone deficiency led to bone and muscle mass loss and increased the fragility of the bone (as well as decreasing relative femoral weight, bone mineral density, femoral elasticity, peak stress, and stress at offset yield). Although protein restriction induced more severe adverse effects compared with the controls, the combination with HRT showed an improvement in minimizing these damaging effects, as it was seen that HRT had some efficacy in maintaining muscle and bone mass, preserving the bone resistance and minimizing some deleterious processes during the menopause.
CONCLUSION:
Protein restriction has adverse effects on metabolism, leading to more severe menopausal symptoms, and HRT could minimize these effects. Therefore, special attention should be given to a balanced diet during menopause and HRT.Cite this article: Bone Joint Res 2019;8:573-581.
KEYWORDS:
Hormone replacement therapy; Ovariectomy; Postmenopausal osteoporosis; Protein restriction; Rat

Associations of Perfluoroalkyl substances with blood lipids and Apolipoproteins in lipoprotein subspecies: the POUNDS-lost study.
Liu G, Zhang B, Hu Y, Rood J, Liang L, Qi L, Bray GA, DeJonge L, Coull B, Grandjean P, Furtado JD, Sun Q.
Environ Health. 2020 Jan 13;19(1):5. doi: 10.1186/s12940-020-0561-8.
PMID: 31931806
Abstract
BACKGROUND:
The associations of perfluoroalkyl substance (PFAS) exposure with blood lipids and lipoproteins are inconsistent, and existing studies did not account for metabolic heterogeneity of lipoprotein subspecies. This study aimed to examine the associations between plasma PFAS concentrations and lipoprotein and apolipoprotein subspecies.
METHODS:
The study included 326 men and women from the 2-year Prevention of Obesity Using Novel Dietary Strategies (POUNDS) Lost randomized trial. Five PFASs, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), were measured in plasma at baseline. For lipoprotein and apolipoprotein subspecies, total plasma was fractionated first by apolipoprotein (apo) C-III content and then by density. Each subfraction was then measured for apoB, apoC-III, and apoE concentrations, as well as triglyceride and cholesterol contents, both at baseline and at 2 years.
RESULTS:
For lipids and apolipoproteins in total plasma at baseline, elevated plasma PFAS concentrations were significantly associated with higher apoB and apoC-III concentrations, but not with total cholesterol or triglycerides. After multivariate adjustment of lifestyle factors, lipid-lowering medication use, and dietary intervention groups, PFAS concentrations were primarily associated with lipids or apolipoprotein concentrations in intermediate-to-low density lipoprotein (IDL + LDL) and high-density lipoprotein (HDL) that contain apoC-III. Comparing the highest and lowest tertiles of PFOA, the least-square means (SE) (mg/dl) were 4.16 (0.4) vs 3.47 (0.4) for apoB (P trend = 0.04), 2.03 (0.2) vs 1.66 (0.2) for apoC-III (P trend = 0.04), and 8.4 (0.8) vs 6.8 (0.8) for triglycerides (P trend = 0.03) in IDL + LDL fraction that contains apoC-III. For HDL that contains apoC-III, comparing the highest and lowest tertiles of PFOA, the least-square means (SE) (mg/dl) of apoC-III were 11.9 (0.7) vs 10.4 (0.7) (P trend = 0.01). In addition, elevated PFNA and PFDA concentrations were also significantly associated with higher concentrations of apoE in HDL that contains apoC-III (P trend< 0.01). Similar patterns of associations were demonstrated between baseline PFAS concentrations and lipoprotein subspecies measured at 2 years. Baseline PFAS levels were not associated with changes in lipoprotein subspecies during the intervention.
CONCLUSIONS:
Our results suggest that plasma PFAS concentrations are primarily associated with blood lipids and apolipoproteins in subspecies of IDL, LDL, and HDL that contain apoC-III, which are associated with elevated cardiovascular risk in epidemiological studies. Future studies of PFAS-associated cardiovascular risk should focus on lipid subfractions.
KEYWORDS:
Epidemiology; Lipid subfractions; Perfluoroalkyl substance

Nutrient-wide association study of 92 foods and nutrients and breast cancer risk.
Heath AK, Muller DC, van den Brandt PA, Papadimitriou N, Critselis E, Gunter M, Vineis P, Weiderpass E, Fagherazzi G, Boeing H, Ferrari P, Olsen A, Tjønneland A, Arveux P, Boutron-Ruault MC, Mancini FR, Kühn T, Turzanski-Fortner R, Schulze MB, Karakatsani A, Thriskos P, Trichopoulou A, Masala G, Contiero P, Ricceri F, Panico S, Bueno-de-Mesquita B, Bakker MF, van Gils CH, Olsen KS, Skeie G, Lasheras C, Agudo A, Rodríguez-Barranco M, Sánchez MJ, Amiano P, Chirlaque MD, Barricarte A, Drake I, Ericson U, Johansson I, Winkvist A, Key T, Freisling H, His M, Huybrechts I, Christakoudi S, Ellingjord-Dale M, Riboli E, Tsilidis KK, Tzoulaki I.
Breast Cancer Res. 2020 Jan 13;22(1):5. doi: 10.1186/s13058-019-1244-7.
PMID: 31931881
https://breast-cancer-research.biomedcentral.com/track/pdf/10.1186/s13058-019-1244-7
Abstract
BACKGROUND:
Several dietary factors have been reported to be associated with risk of breast cancer, but to date, unequivocal evidence only exists for alcohol consumption. We sought to systematically assess the association between intake of 92 foods and nutrients and breast cancer risk using a nutrient-wide association study.
METHODS:
Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression was used to quantify the association between each food/nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to be replicated in the independent Netherlands Cohort Study (NLCS).
RESULTS:
Six foods and nutrients were identified as associated with risk of breast cancer in the EPIC study (10,979 cases). Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% CI 1.03-1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03-1.06 and 1.04, 95% CI 1.02-1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94-0.98; 0.96, 95% CI 0.94-0.99; and 0.96, 95% CI 0.95-0.98, respectively). When evaluated in the NLCS (2368 cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk in the NLCS.
CONCLUSIONS:
Our findings confirm a positive association of alcohol consumption and suggest an inverse association of dietary fibre and possibly fruit intake with breast cancer risk.
KEYWORDS:
Alcohol; Breast cancer; Diet; Fibre; Foods; Nutrients

Mitochondrial DNA copy number variation and pancreatic cancer risk in the prospective EPIC cohort.
Gentiluomo M, Katzke VA, Kaaks R, Tjonneland A, Severi G, Perduca V, Boutron-Ruault MC, Weiderpass E, Ferrari P, Johnson T, Schulze MB, Bergmann M, Trichopoulou A, Karakatsani A, La Vecchia C, Palli D, Grioni S, Panico S, Tumino R, Sacerdote C, Bueno-de-Mesquita B, Vermeulen R, Sandanger TM, Quirós JR, Rodríguez-Barranco M, Amiano P, Colorado-Yohar S, Ardanaz E, Sund M, Khaw KT, Wareham NJ, Schmidt JA, Jakszyn P, Morelli L, Canzian F, Campa D.
Cancer Epidemiol Biomarkers Prev. 2020 Jan 13. pii: cebp.0868.2019. doi: 10.1158/1055-9965.EPI-19-0868. [Epub ahead of print]
PMID: 31932413
Abstract
BACKGROUND:
Mitochondrial DNA (mtDNA) copy number in peripheral blood has been found to be associated with risk of developing several cancers. However, data on pancreatic ductal adenocarcinoma (PDAC) are very limited.
METHODS:
To further our knowledge on this topic we measured relative mtDNA copy number by a quantitative real-time PCR assay in peripheral leukocyte samples of 476 PDAC cases and 357 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
RESULTS:
We observed lower mtDNA copy number with advancing age (p=6.54×10-5) and with a high BMI level (p=0.004) and no association with sex, smoking behavior and alcohol consumption. We found an association between increased mtDNA copy number and decreased risk of developing PDAC with an OR=0.35 (95% C.I 0.16-0.79), p=0.01 when comparing the 5th quintile with the 1st using an unconditional logistic regression and OR=0.19 (95% C.I 0.07-0.52), p=0.001 with a conditional analysis. Analyses stratified by BMI showed an association between high mtDNA copy number and decreased risk in the stratum of normal weight, consistent with the main analyses.
CONCLUSIONS:
Our results, suggest a protective effect of a higher number of mitochondria, measured in peripheral blood leukocytes, on PDAC risk.
IMPACT:
Our findings highlight the importance of understanding the mitochondrial biology in pancreatic cancer.

The effects of low-carbohydrate diets on cardiovascular risk factors: A meta-analysis.
Dong T, Guo M, Zhang P, Sun G, Chen B.
PLoS One. 2020 Jan 14;15(1):e0225348. doi: 10.1371/journal.pone.0225348. eCollection 2020.
PMID: 31935216
Abstract
BACKGROUND:
Low-carbohydrate diets are associated with cardiovascular risk factors; however, the results of different studies are inconsistent.
PURPOSE:
The aim of this meta-analysis was to assess the relationship between low-carbohydrate diets and cardiovascular risk factors.
METHOD:
Four electronic databases (PubMed, Embase, Medline, and the Cochrane Library) were searched from their inception to November 2018. We collected data from 12 randomized trials on low-carbohydrate diets including total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, and blood pressure levels, as well as weight as the endpoints. The average difference (MD) was used as the index to measure the effect of a low-carbohydrate diet on cardiovascular risk factors with a fixed-effects model or random-effects model. The analysis was further stratified by factors that might affect the results of the intervention.
RESULTS:
From 1292 studies identified in the initial search results, 12 randomized studies were included in the final analysis, which showed that a low-carbohydrate diet was associated with a decrease in triglyceride levels of -0.15mmol/l (95% confidence interval -0.23 to -0.07). Low-carbohydrate diet interventions lasting less than 6 months were associated with a decrease of -0.23mmol/l (95% confidence interval -0.32 to -0.15), while those lasting 12-23 months were associated with a decrease of -0.17mmol/l (95% confidence interval -0.32 to -0.01). The change in the body weight in the observation groups was -1.58kg (95% confidence interval -1.58 to -0.75); with for less than 6 months of intervention,this change was -1.14 kg (95% confidence interval -1.65 to -0.63),and with for 6-11 months of intervention, this change was -1.73kg (95% confidence interval -2.7 to -0.76). The change in the systolic blood pressure of the observation group was -1.41mmHg (95% confidence interval-2.26 to -0.56); the change in diastolic blood pressure was -1.71mmHg (95% confidence interval-2.36 to -1.06); the change in plasma HDL-C levels was 0.1mmHg (95% confidence interval 0.08 to 0.12); and the change in serum total cholesterol was 0.13mmol/l (95% confidence interval 0.08 to 0.19). The plasma LDL-C level increased by 0.11mmol/l (95% confidence interval 0.02 to 0.19), and the fasting blood glucose level changed 0.03mmol/l (95% confidence interval -0.05 to 0.12),which was not significant.
CONCLUSIONS:
This meta-analysis confirms that low-carbohydrate diets have a beneficial effect on cardiovascular risk factors but that the long-term effects on cardiovascular risk factors require further research.

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Dietary glycemic index and glycemic load during pregnancy and offspring risk of congenital heart defects: a prospective cohort study.
Schmidt AB, Lund M, Corn G, Halldorsson TI, Øyen N, Wohlfahrt J, Olsen SF, Melbye M.
Am J Clin Nutr. 2020 Jan 14. pii: nqz342. doi: 10.1093/ajcn/nqz342. [Epub ahead of print]
PMID: 31942930
Abstract
BACKGROUND:
Prepregnancy diabetes, especially when severely dysregulated, is associated with an increased risk of congenital heart defects in offspring. This suggests that glucose plays a role in embryonic heart development.
OBJECTIVE:
The aim was to investigate the association between midpregnancy dietary glycemic index (GI), glycemic load (GL), and sugar-sweetened beverages and the risk of congenital heart defects in the offspring.
METHODS:
Offspring of mothers from the Danish National Birth Cohort who filled out a food-frequency questionnaire (FFQ) covering midpregnancy dietary intake were included. Individual-level information on GI and GL, offspring congenital heart defects, and health and lifestyle covariates was linked. The association between GI and GL and offspring congenital heart defects was estimated by logistic regression. Further, we evaluated whether maternal intake of sugar-sweetened drinks increased the risk of offspring congenital heart defects.
RESULTS:
In total, 66,387 offspring of women who responded to the FFQ were included; among offspring, 543 had a congenital heart defect. The adjusted OR (aOR) of congenital heart defects among offspring of mothers belonging to the highest versus the lowest GI quintile was 1.02 (95% CI: 0.78, 1.34; P-trend = 0.86). Results were similar for GL (aOR: 0.95; 95% CI: 0.72, 1.24). A high intake of sugar-sweetened carbonated beverages was associated with a statistically significant increased risk of offspring congenital heart defects (highest vs lowest intake-aOR: 2.41; 95% CI: 1.26, 4.64; P-trend = 0.03). No association was found with other types of beverages.
CONCLUSIONS:
The study does not support an association between a high GI and GL in midpregnancy and increased offspring risk of congenital heart defects. Nevertheless, a statistically significant association between sugar-sweetened carbonated beverages and a moderately increased risk of offspring congenital heart defects was observed.
KEYWORDS:
Danish National Birth Cohort; congenital heart defects; food-frequency questionnaire; glycemic index; glycemic load; pregnancy; sugar-sweetened beverages

Dietary Phospholipids: Role in Cognitive Processes Across the Lifespan.
Schverer M, O'Mahony SM, O'Riordan KJ, Donoso F, Roy BL, Stanton C, Dinan TG, Schellekens H, Cryan JF.
Neurosci Biobehav Rev. 2020 Jan 13. pii: S0149-7634(19)31034-6. doi: 10.1016/j.neubiorev.2020.01.012. [Epub ahead of print] Review.
PMID: 31945391
https://sci-hub.tw/10.1016/j.neubiorev.2020.01.012
Abstract
Chronic stress and ageing are two of the most important factors that negatively affect cognitive processes such as learning and memory across the lifespan. To date, pharmacological agents have been insufficient in reducing the impact of both on brain health, and thus, novel therapeutic strategies are required. Recent research has focused on nutritional interventions to modify behaviour and reduce the deleterious consequences of both stress and ageing. In this context, emerging evidence indicate that phospholipids, a specific type of fat, are capable of improving a variety of cognitive processes in both animals and humans. The mechanisms underlying these positive effects are actively being investigated but as of yet are not fully elucidated. In this review, we summarise the preclinical and clinical studies available on phospholipid-based strategies for improved brain health across the lifespan. Moreover, we summarize the hypothesized direct and indirect mechanisms of action of these lipid-based interventions which may be used to promote resilience to stress and improve age-related cognitive decline in vulnerable populations.
KEYWORDS:
ageing; brain health; cognition; dietary phospholipids; gut; microbiota; stress

Low-fat dietary pattern and global cognitive function: Exploratory analyses of the Women's Health Initiative (WHI) randomized Dietary Modification trial.
Chlebowski RT, Rapp S, Aragaki AK, Pan K, Neuhouser ML, Snetselaar LG, Manson JE, Wactawski-Wende J, Johnson KC, Hayden K, Baker LD, Henderson VW, Garcia L, Qi L, Prentice RL.
EClinicalMedicine. 2020 Jan 8;18:100240. doi: 10.1016/j.eclinm.2019.100240. eCollection 2020 Jan.
PMID: 31938786
Abstract
BACKGROUND:
Meta-analyses of observational studies associate adherence to several dietary patterns with cognitive health. However, limited evidence from full scale, randomized controlled trials precludes causal inference regarding dietary effects on cognitive function.
METHODS:
The Women's Health Initiative (WHI) Dietary Modification (DM) randomized trial, in 48,835 postmenopausal women, included a subset of 1,606 WHI Memory Study (WHIMS) participants >= 65 years old, to assess low-fat dietary pattern influence on global cognitive function, evaluated with annual screening (Modified Mini-Mental State Examinations [3MSE]). Participants were randomized by a computerized, permuted block algorithm, stratified by age group and center, to a dietary intervention (40%) to reduce fat intake to 20% of energy and increase fruit, vegetable and grain intake or usual diet comparison groups (60%). The study outcome was possible cognition impairment (failed cognitive function screening) through the 8.5 year (median) dietary intervention. Those failing screening received a comprehensive, multi-phase cognitive function assessment to classify as: no cognitive impairment, mild cognitive impairment, or probable dementia. Exploratory analyses examined the composite endpoint of death after possible cognitive impairment through 18.7 years (median) follow-up. The WHI trials are registered at ClinicalTrials.gov:NCT00000611.
FINDINGS:
Among the 1,606 WHIMS participants, the dietary intervention statistically significantly reduced the incidence of possible cognitive impairment (n = 126; hazard ratio


0.59 95% confidence interval [CI] 0.38-0. 91, P = 0.01) with HR for dietary influence on subsequent mild cognitive impairment of 0.65 (95% CI 0.35-1.19) and HR of 0.63 (95% CI 0.19-2.10) for probable dementia (PD). Through 18.7 years, deaths from all-causes after possible cognitive impairment were non-significantly lower in the dietary intervention group (0.56% vs 0.77%, HR 0.83 95% CI 0.35 to 2.00, P = 0.16).
INTERPRETATION:
Adoption of a low-fat eating pattern, representing dietary moderation, significantly reduced risk of possible cognitive impairment in postmenopausal women.
KEYWORDS:
Cognition; Dietary modification; Low-fat dietary pattern; Randomized clinical trial; Women's Health Initiative

Food consumption and depression among Brazilian adults: results from the Brazilian National Health Survey, 2013.
Sousa KT, Marques ES, Levy RB, Azeredo CM.
Cad Saude Publica. 2019 Dec 20;36(1):e00245818. doi: 10.1590/0102-311X00245818. eCollection 2019.
PMID: 31939555
Abstract
Our study aimed to evaluate the association between food consumption and depression. We used data from the Brazilian National Health Survey; a cross-sectional study carried out in 2013 among 46,785 Brazilian adults. The exposures were regular consumption (≥ 5 times/week) of the markers of healthy (beans, vegetables, fruits, and natural fruit juices) and unhealthy food (sugar sweetened beverages; sweets and the substitution of lunch or dinner for snacks); and a nutritional score elaborated by combining the frequency of consumption of markers of healthy and unhealthy food, the higher the value, the better the diet. The outcome was depression, assessed through the PHQ-9 questionnaire answered by the participants. Those with PHQ-9 scores greater than or equal to 10 were classified as presenting depression. We performed logistic regression models adjusted for potential confounders. Regular consumption of sweets (OR = 1.53; 95%CI: 1.33-1.76) and regular replacement of meals for snacks (OR = 1.52; 95%CI: 1.21-1.90) were positively associated with depression. Regular consumption of sugar sweetened beverages was positively associated with depression among women (OR = 1.27; 95%CI: 1.10-1.48). Regular consumption of beans was negatively associated with depression (OR = 0.74; 95%CI: 0.65-0.84), consistent for both sexes. Comparing the top quintile of the nutritional score (healthier diet) to the bottom quintile (less healthy) we found a negative association with depression (OR = 0.63; 95%CI: 0.52-0.75). Our results add evidence on a possible role of food consumption in depression; future longitudinal studies should explore the mechanisms of these associations.

Impact of intermittent vs. continuous energy restriction on weight and cardiometabolic factors: a 12-month follow-up.
Headland ML, Clifton PM, Keogh JB.
Int J Obes (Lond). 2020 Jan 14. doi: 10.1038/s41366-020-0525-7. [Epub ahead of print]
PMID: 31937907
Abstract
BACKGROUND AND OBJECTIVE:
Intermittent energy restriction continues to gain popularity as a weight loss strategy; however, data assessing it's long-term viability is limited. The objective of this study was to follow up with participants 12 months after they had completed a 12-month dietary intervention trial involving continuous energy restriction and two forms of intermittent energy restriction; a week-on-week-off energy restriction and a 5:2 programme, assessing long-term changes on weight, body composition, blood lipids and glucose.
SUBJECTS AND METHODS:
109 overweight and obese adults, aged 18-72 years, attended a 12-month follow-up after completing a 12-month dietary intervention involving three groups: continuous energy restriction (1000 kcal/day for women and 1200 kcal/day for men), week-on-week-off energy restriction (alternating between the same energy restriction as the continuous group for one week and one week of habitual diet), or 5:2 (500 kcal/day on modified fast days each week for women and 600 kcal/day for men). The primary outcome was weight change at 24 months from baseline, with secondary outcomes of change in body composition, blood lipids and glucose.
RESULTS:
For the 109 individuals who completed the 12-month follow-up (82 female, 15 male, mean BMI 33 kg/m2), weight decreased over time with no differences between week-on and week-off and continuous energy restriction or 5:2 and continuous energy restriction with -4.5 ± 4.9 kg for continuous energy restriction, -2.8 ± 6.5 kg for week-on, week-off and -3.5 ± 5.1 kg for 5:2. Total cholesterol reduced over time and glucose, HDL, LDL and triglycerides were unchanged.
DISCUSSION AND CONCLUSION:
Intermittent energy restriction was as successful in achieving modest weight loss over a 24-month period as continuous energy restriction.

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Association of dietary glycaemic index, glycaemic load, and total carbohydrates with incidence of type-2 diabetes in adults aged ≥40 years: The Multi-Rural Communities Cohort (MRCohort).
Young Kim S, Won Woo H, Lee YH, Hoon Shin D, Shin MH, Youl Choi B, Kyung Kim M.
Diabetes Res Clin Pract. 2020 Jan 14:108007. doi: 10.1016/j.diabres.2020.108007. [Epub ahead of print]
PMID: 31953108
https://sci-hub.tw/https://www.diabetesresearchclinicalpractice.com/article/S0168-8227(19)31185-4/fulltext
Abstract
AIMS:
To examine potential associations between the glycaemic index (GI), glycaemic load (GL), and carbohydrates and the incidence risk of type-2 diabetes (T2D) and the effect modification of obesity among Korean adults aged ≥40 years.
METHOD:
Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for T2D were estimated in 8,310 participants using a modified Poisson regression model. Dietary indices were averaged using repeated dietary assessments during follow-up.
RESULT:
After adjusting for potential confounders, a positive association between GI and T2D was found among women (IRR=1.63, 95% CI=1.06-2.51 in the highest tertile (T3) vs. the lowest tertile (T1) for GI, p trend=0.0310), but not for GL and carbohydrate intake. This positive association with GI was stronger in obese women (IRR=1.91, 95% CI: 1.15-3.19 in T3 vs. T1, p trend=0.0137 for body mass index ≥ 23 kg/m2; IRR=2.35, 95% CI: 1.01-5.48, p trend=0.0350 for waist circumference (WC) ≥ 85 cm). In men, there was no association before stratification by obesity, but IRRs of GI (T3 vs. T1) were significant and stronger with increased WCs (IRR=2.26, 95% CI: 1.02-4.98, p trend=0.0439 for WC ≥90).
CONCLUSION:
GI may be positively associated with the incidence of T2D in women, particularly in obese women. The association of GI with T2D incidence risk may also be positive even in men with high WC.
KEYWORDS:
Carbohydrates; Glycaemic index; Glycaemic load; Prospective cohort study; Type 2 diabetes

Physical Activity Compared to Adiposity and Risk of Liver-Related Mortality: Results from Two Prospective, Nationwide Cohorts.
Simon TG, Kim MN, Luo X, Yang W, Ma Y, Chong DQ, Fuchs CS, Meyerhardt JA, Corey KE, Chung RT, Stampfer M, Zhang X, Giovannucci EL, Chan AT.
J Hepatol. 2020 Jan 15. pii: S0168-8278(20)30013-1. doi: 10.1016/j.jhep.2019.12.022. [Epub ahead of print]
PMID: 31954204
Abstract
BACKGROUND & AIMS:
Obesity in adulthood has been associated with increased risk of liver-related mortality. Whether higher levels of physical activity counteract the excess risk conferred by obesity remains unknown. We simultaneously evaluated the long-term impact of physical activity and adiposity on liver-related mortality, within two nationwide populations.
METHODS:
We conducted a prospective cohort study of 77,238 women and 48,026 men, with detailed, validated assessments of weekly physical activity (metabolic equivalent task [MET]-hours]), adiposity (body mass index [BMI], waist circumference), and diet, alcohol use and clinical comorbidities, biennially from 1986 through 2012. Using Cox proportional hazards regression models, we calculated multivariable adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for liver-related mortality, including death from hepatocellular carcinoma (HCC) and other cirrhosis complications.
RESULTS:
Over 1,856,226 person-years, we recorded 295 liver-related deaths (108 HCC; 187 cirrhosis). Risk of liver-related mortality increased monotonically with higher BMI during adulthood (Ptrend<0.0001) and with weight gain during early-adulthood (Ptrend<0.0001). The risk of liver-related mortality also declined progressively, with increasing physical activity (Ptrend=0.0003); the aHRs across increasing physical activity quintiles were: 1.0, 0.70 (95%CI=0.51-0.96), 0.59 (95%CI=0.42-0.84), 0.52 (95%CI=0.36-0.74) and 0.46 (95%CI=0.31-0.66). Compared to lean-active adults (BMI<25; ≥18 MET-hours/week), the aHRs for obese-active, lean-sedentary, and obese-sedentary adults were: 1.04 (95%CI=0.73-1.37), 2.08 (95%CI=1.21-3.33) and 3.40 (95%CI=2.06-5.56), respectively. Findings were similar for HCC-specific and cirrhosis-specific mortality. Overall, engaging in average-pace walking for >3 hours/week could have prevented 25% of liver-related deaths (95%CI=0.12-0.38).
CONCLUSIONS:
In two prospective, nationwide cohorts, both excess adiposity and reduced PA were significant predictors of liver-related mortality. Achieving higher PA levels counteracted the excess liver-related risks associated with obesity.
KEYWORDS:
cirrhosis; lifestyle; modifiable risk factor; prevention

The relationship between consumption of nitrite or nitrate and risk of non-Hodgkin lymphoma.
Yu M, Li C, Hu C, Jin J, Qian S, Jin J.
Sci Rep. 2020 Jan 17;10(1):551. doi: 10.1038/s41598-020-57453-5.
PMID: 31953513
Abstract
Epidemiologic studies of the relationship between nitrite or nitrate consumption and risk of non-Hodgkin lymphoma (NHL) remain controversial. The current meta-analysis aimed to reexamine the evidence and quantitatively evaluate that relationship. Manuscripts were retrieved from the Web of Science, Chinese National Knowledge Infrastructure and PubMed databases up to May 2019. From the studies included in the review, results were combined and presented as odds ratios (OR). To conduct a dose-response (DR) analysis, studies presenting risk estimates over a series of categories of exposure were selected. Our data indicate that the consumption of nitrite was linked to a significantly increased hazard of NHL (OR: 1.37; 95% CI: 1.14-1.65), rather than nitrate (OR: 1.02; 95% CI: 0.94-1.10). According to Egger's and Begg's tests (P > 0.05), there was no evidence of significant publication bias. Moreover, our DR analysis indicated that the risk of NHL grew by 26% for each additional microgram of nitrite consumed in the diet per day (OR: 1.26; 95% CI: 1.09-1.42). Through subset analysis of the nitrite studies, data from the high-quality studies indicated that consumption was positively associated with carcinogenicity, leading to NHL (OR: 1.44; 95% CI: 1.17-1.77) and positively correlated with the development of diffuse large B-cell lymphoma (OR: 1.55; 95% CI: 1.07-2.26), but not other NHL subtypes. In addition, the data suggested that females (OR: 1.50; 95% CI: 1.15-1.95) and high levels of nitrite intake (OR: 1.64; 95% CI: 1.28-2.09) had a higher risk of NHL. Our meta-analysis supports the hypothesis that nitrite intake, but not that of nitrate, raises the risk of developing NHL. In the future, better designed prospective research studies should be conducted to confirm our findings, clarify potential biological mechanisms and instruct clinicians about NHL prophylaxis.

Red Cell Distribution Width Is Directly Associated with Poor Cognitive Performance among Nonanemic, Middle-Aged, Urban Adults.
Beydoun MA, Hossain S, Beydoun HA, Shaked D, Weiss J, Evans MK, Zonderman AB.
J Nutr. 2020 Jan 1;150(1):128-139. doi: 10.1093/jn/nxz182.
PMID: 31912144
https://watermark.silverchair.com/nxz182.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAlQwggJQBgkqhkiG9w0BBwagggJBMIICPQIBADCCAjYGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM2w8Uzw19FIgDKgLEAgEQgIICB2ulZd0jP61koX9hfWrJhwnEJLHLAsOW9JWnf_sZPQI87JuoRORbgtOK6b8My8ojlRDqsTKa1zhFW2JlZlw6SU5kG_KVPLCRiWJTA1Tw1KkMTK26sqWeA3ruBeDXxTheqDMG1vt7HKTrxvLzmToHAl6hcTn8ym7jcSFypUUbxxN0XttsDYboP3D8_yjAvfxrvJ7g35C4FC5e0rPkglv2Xy0C09AfbG3Ciif1xdA4ZZVstJ2iUDSte9ZzfyOhpuNMjhSXcVUlUlQ6qhFfFFC2-GZ7POU8sXiz_4LbN7Bg0AFiSvPiL7SaKOnv47vafj4vhRD-isHAaiORrEObsD2OUUeOoxG9FEy_bLBOXeaweYAkY1z-fh3Gq5yPUTZxUObkzYEiLNOr7GC1TyV-_0slQc1jhVdQAA9--S1-M-vaM2CzspCNHJkN1mMu_tuEUnYaw_sAu0RDAwBR39b75mpXAqZkYHW_TPhPRIb5AFGGUzwrSKZb7PbXmxYIxmzSl2MD7KE4teulJ68ecZqFnKGy68OJbnB2VCFPQmOydc7_VHmt918a97fSuc-m8KCoNTQ6dmE0CQQjzqsRN4yFJxdbenUec9kVoW39dZDFrn04hG8ENUxRK6VItr1FwzDNr_gfEF3tHbvOqw70JMnm4PWK07qR3gWUwZyku20tVW2EyxwDi4rWQMyfDQ
Abstract
BACKGROUND:
Epidemiological evidence suggests that both anemia and elevated red cell distribution width (RDW) are associated with cognitive impairment. However, the interplay between these 2 predictors has been understudied.
OBJECTIVES:
We examined sex- and anemia-specific associations between RDW and cognitive performance among urban adults in the United States.
METHODS:
Data from the Healthy Aging in Neighborhoods of Diversity Across the Life Span Study (Baltimore, MD; participants aged 30-65 y at baseline, ∼59% African-American, 45% men) were used. Participants were selected based on the completion of 11 cognitive tasks at baseline (2004-2009) and follow-up (2009-2013) visits (mean time between visits: 4.64 ± 0.93 y) and availability of exposure and covariate data, yielding a sample of between 1526 and 1646 adults out of the initial 3720 adults recruited at baseline. Multiple linear mixed-effects regression models were conducted with RDW as the main exposure of interest and anemia/sex as the key effect modifiers.
RESULTS:
Overall, high RDWs were linked to poorer baseline performance on the California Verbal Learning Test (CVLT) List A (per 1 unit increase in RDW %, main effect: γ01 = -0.369 ± 0.114; P = 0.001) and to slower rates of decline on the CVLT Delayed Free Recall (per 1 unit increase in RDW %, RDW × time: γ11 = +0.036 ± 0.013; P = 0.007). Among nonanemic participants, RDWs were consistently associated with poorer baseline performance on the Trailmaking Test, Part A (γ01 = +3.11 ± 0.89; P < 0.001) and on the CVLT List A (γ01 = -0.560 ± 0.158; P < 0.001). Moreover, RDWs were associated with poorer baseline performance on the Brief Test of Attention in the total population (γ01 = -0.123 ± 0.039; P = 0.001) and among men (γ01 = -0.221 ± 0.068; P = 0.001). We did not detect an association between hemoglobin (Hb) and baseline cognitive performance or changes over time.
CONCLUSIONS:
Elevated RDW had a consistent cross-sectional association with poor cognitive performance in the domains of verbal memory and attention among the nonanemic group in a sample of middle-aged, urban adults. Anemia and Hb concentrations were not associated with cognition. More longitudinal studies are needed to replicate our findings.
KEYWORDS:
anemia; cognitive performance; red cell distribution width; urban adults; aging

Carbohydrate-restricted diet alters the gut microbiota, promotes senescence and shortens the life span in senescence-accelerated prone mice.
He C, Wu Q, Hayashi N, Nakano F, Nakatsukasa E, Tsuduki T.
J Nutr Biochem. 2019 Dec 20;78:108326. doi: 10.1016/j.jnutbio.2019.108326. [Epub ahead of print]
PMID: 31952014
Abstract
This study examined the effects of a carbohydrate-restricted diet on aging, brain function, intestinal bacteria and the life span to determine long-term carbohydrate-restriction effects on the aging process in senescence-accelerated prone mice (SAMP8). Three-week-old male SAMP8 were divided into three groups after a week of preliminary feeding. One group was given a controlled diet, while the others fed on high-fat and carbohydrate-restricted diets, respectively. The mice in each group were further divided into two subgroups, of which one was the longevity measurement group. The other groups fed ad libitum until the mice were 50 weeks old. Before the test period termination, passive avoidance test evaluated the learning and memory abilities. Following the test period, serum and various mice organs were obtained and submitted for analysis. The carbohydrate-restricted diet group exhibited significant decrease in the survival rate as compared to the other two diet groups. The passive avoidance test revealed a remarkable decrease in the learning and memory ability of carbohydrate-restricted diet group as compared to the control-diet group. Measurement of lipid peroxide level in tissues displayed a marked increase in the brain and spleen of carbohydrate-restricted diet group than the control-diet and high-fat diet groups. Furthermore, notable serum IL-6 and IL-1β level (inflammation indicators) elevations, decrease in Enterobacteria (with anti-inflammatory action), increase in inflammation-inducing Enterobacteria and lowering of short-chain fatty acids levels in cecum were observed in the carbohydrate-restricted diet group. Hence, carbohydrate-restricted diet was revealed to promote aging and shortening of life in SAMP8.
KEYWORDS:
Aging; Carbohydrate-restricted diet; Gut microbiota; Senescence-accelerated mice; Short-chain fatty acids

Association between breastfeeding and osteoporotic hip fracture in women: a dose-response meta-analysis.
Xiao H, Zhou Q, Niu G, Han G, Zhang Z, Zhang Q, Bai J, Zhu X.
J Orthop Surg Res. 2020 Jan 16;15(1):15. doi: 10.1186/s13018-019-1541-y.
PMID: 31948457
Abstract
OBJECTIVE:
Approximately 300 mg of calcium a day is provided into infants to maintain the physical development of infants, and 5 to 10% bone loss occurs in women during breastfeeding. Hip fractures are considered the most serious type of osteoporotic fracture. We performed this meta-analysis to investigate the association between breastfeeding and osteoporotic hip fractures.
MATERIAL AND METHODS:
PubMed and Embase were searched until May 1, 2019, for studies evaluating the relationship between breastfeeding and osteoporotic hip fracture in women. The quality of the included studies was evaluated by the methodological index for non-randomized studies (MINORS). For the dose-response meta-analysis, we used the "generalized least squares for trend estimation" method proposed by Greenland and Longnecker to take into account the correlation with the log RR estimates across the duration of breastfeeding.
RESULTS:
Seven studies were moderate or high quality, enrolling a total of 103,898 subjects. The pooled outcomes suggested that breastfeeding can decrease the incidence of osteoporotic hip fracture (RR = 0.64 (95% CI 0.43, 0.95), P = 0.027). Dose-response analysis demonstrated that the incidence of osteoporotic hip fracture decreased with the increase of breastfeeding time. The RR and 95% CI for 3 months, 6 months, 12 months, and 24 months were RR = 0.93, 95% CI 0.88, 0.98; RR = 0.87, 95% CI 0.79, 0.96; RR = 0.79, 95% CI 0.67, 0.92; and RR = 0.76, 95% CI 0.59, 0.98, respectively, whereas no significant relationship was found between them when the duration of breastfeeding time was more than 25 months.
CONCLUSIONS:
Our meta-analysis demonstrated that the incidence of osteoporotic hip fracture decreased with the extension of breastfeeding time. However, there is no significant relationship between them when the duration of breastfeeding time was more than 25 months.
KEYWORDS:
Breast feeding; Hip fractures; Meta-analysis

 

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Beta-blocker therapy and risk of vascular dementia: A population-based prospective study.
Holm H, Ricci F, Di Martino G, Bachus E, Nilsson ED, Ballerini P, Melander O, Hansson O, Nägga K, Magnusson M, Fedorowski A.
Vascul Pharmacol. 2020 Jan 17:106649. doi: 10.1016/j.vph.2020.106649. [Epub ahead of print]
PMID: 31958512
Abstract
There are a few studies that report cognitive impairment as a complication of treatment with beta- blockers. We aimed to evaluate the longitudinal association between use of beta-blockers, as a class, and incident risk of all-cause dementia, vascular dementia, Alzheimer's and mixed dementia in the prospective population-based Malmö Preventive Project. We included 18,063 individuals (mean age 68.2, males 63.4%) followed up for 84,506 person-years. Dementia cases were retrieved from the Swedish National Patient Register and validated by review of medical records and neuroimaging data. We performed propensity score matching analysis, resulting in 3720 matched pairs of beta-blocker users and non-users at baseline, and multivariable Cox proportional-hazards regression. Overall, 122 study participants (1.6%) were diagnosed with dementia during the follow-up. Beta-blocker therapy was independently associated with increased risk of developing vascular dementia, regardless of confounding factors (HR: 1.72, 95%CI 1.01-3.78; p = .048). Conversely, treatment with beta-blockers was not associated with increased risk of all-cause, Alzheimer's and mixed dementia (HR:1.15; 95%CI 0.80-1.66; p = .44; HR:0.85; 95%CI 0.48-1.54; P = .59 and HR:1.35; 95%CI 0.56-3.27; p = .50, respectively). We observed that use of beta-blockers, as a class, is associated with increased longitudinal risk of vascular dementia in the general elderly population, regardless of cardiovascular risk factors, prevalent or incident history of atrial fibrillation, stroke, coronary events and heart failure. Further studies are needed to confirm our findings in the general population and to explore the mechanisms underlying the relationship between use of beta- blockers and increased risk of vascular dementia.
KEYWORDS:
Alzheimer; Beta-blocker; Dementia; Mixed dementia; Vascular dementia

The role of the microbiota in sedentary life style disorders and ageing: Lessons from the animal kingdom.
O'Toole PW, Shiels PG.
J Intern Med. 2020 Jan 19. doi: 10.1111/joim.13021. [Epub ahead of print] Review.
PMID: 31957113
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/joim.13021
Abstract
A paradox of so-called developed countries is that, as the major historical causes of human mortality are eliminated or mitigated by medical progress, life-style related diseases have become major killers. Furthermore, as life-span is extended by the combined effects of modern medicine, health-span is struggling to keep apace because of the burden of non-communicable diseases linked to diet and sedentary life-style. The gut microbiome is now recognized as a plastic environmental risk factor for many of these diseases, the microbiome being defined as the complex community of co-evolved commensal microbes that breaks down components of a complex diet, modulates innate immunity, and produces signalling molecules and metabolites that can impact on diverse regulatory systems in mammals. Aspects of the so-called "Western" life-style linked to disease risk such as energy dense diet and antibiotic treatment are known to affect the composition and function of the microbiome. Here we review the detailed mechanisms whereby the gut microbiome may modulate risk of diseases linked to sedentary life-style, and ageing related health loss. We focus on the comparative value of natural animal models such as hibernation for studying metabolic regulation, and the challenge of extrapolating from animal models to processes that occur in human ageing.

Time-restricted feeding improves markers of cardiometabolic health in physically active college-age men: a 4-week randomized pre-post pilot study.
McAllister MJ, Pigg BL, Renteria LI, Waldman HS.
Nutr Res. 2019 Dec 4;75:32-43. doi: 10.1016/j.nutres.2019.12.001. [Epub ahead of print]
PMID: 31955013
Abstract
Time-restricted feeding (TRF) has been shown to improve body composition, blood lipids, and reduce markers of inflammation and oxidative stress. However, most of these studies come from rodent models and small human samples, and it is not clear if the benefits are dependent upon a caloric deficit, or the time restriction nature of TRF. Based off of previous research, we hypothesized that humans following an ad libitum TRF protocol would reduce caloric intake and this caloric deficit would be associated with greater improvements in cardiometabolic health including blood pressure, body composition, blood lipids, and markers of inflammation and antioxidant status compared to an isocaloric TRF protocol. The purpose of this study was to: (1) examine the impact of TRF on markers of cardio-metabolic health and antioxidant status and (2) determine if the adaptations from TRF would differ under ad libitum compared to isocaloric conditions. Twenty-three healthy men were randomized to either an ad libitum or isocaloric 16:8 (fasting: feeding) TRF protocol. A total of 22 men completed the 28-day TRF protocol (mean ± SD; age: 22 ± 2.5 yrs.; height: 178.4 ± 6.9 cm; weight: 90.3 ± 24 kg; BMI: 28.5 ± 8.3 kg/m2). Fasting blood samples were analyzed for glucose, lipids, as well as adiponectin, human growth hormone, insulin, cortisol, C-reactive protein, superoxide dismutase, total nitrate/nitrite, and glutathione. Time-restricted feeding in both groups was associated with significant (P < .05) reductions in body fat, blood pressure, and significant increases in adiponectin and HDL-c. No changes in caloric intake were detected. In summary, the results from this pilot study in metabolically healthy, active young men, suggest that TRF can improve markers of cardiometabolic health.
KEYWORDS:
Antioxidants; Diet; Inflammation; Intermittent fasting; Oxidative stress; Weight loss

Coffee consumption and breast cancer risk in the SUN project.
Sánchez-Quesada C, Romanos-Nanclares A, Navarro AM, Gea A, Cervantes S, Martínez-González MÁ, Toledo E.
Eur J Nutr. 2020 Jan 18. doi: 10.1007/s00394-020-02180-w. [Epub ahead of print]
PMID: 31955220
Abstract
INTRODUCTION:
Breast cancer prevalence is growing worldwide. Many factors, such as diet and lifestyle could be determinants of the incidence of breast cancer. Coffee has been extensively studied in relation to several chronic diseases because of its multiple effects in health maintenance and its elevated consumption. We studied the relationship between coffee intake and breast cancer risk in the SUN (Seguimiento Universidad de Navarra) prospective cohort.
MATERIALS AND METHODS:
We evaluated 10,812 middle-aged, Spanish female university graduates from the SUN Project, initially free of breast cancer. Coffee consumption was assessed with a 136-item validated food-frequency questionnaire (FFQ). Incident breast cancer cases were confirmed by a trained oncologist using medical records and by consultation of the National Death Index. We fitted Cox regression models to assess the relationship between baseline categories of coffee consumption and the incidence of breast cancer during follow-up. We stratified the analysis by menopausal status.
RESULTS:
During 115,802 person-years of follow-up, 101 new cases of breast cancer were confirmed. Among postmenopausal women, more than 1 cup of coffee per day was associated with a lower incidence of breast cancer (HR 0.44; 95% confidence interval: 0.21, 0.92) in the fully adjusted model, compared to women who consumed one cup of coffee or less per day. We observed no significant differences in regard to premenopausal women.
CONCLUSION:
Even though the number of cases was low, slight indications of an inverse association between coffee consumption and breast cancer risk among postmenopausal women were observed. Further longitudinal studies are warranted to confirm this finding.
KEYWORDS:
Breast cancer; Coffee; Postmenopausal breast cancer; SUN cohort

Becoming a parent: A systematic review and meta-analysis of changes in BMI, diet, and physical activity.
Corder K, Winpenny EM, Foubister C, Guagliano JM, Hartwig XM, Love R, Clifford Astbury C, van Sluijs EMF.
Obes Rev. 2020 Jan 19. doi: 10.1111/obr.12959. [Epub ahead of print] Review.
PMID: 31955517
Abstract
Obesity prevalence rises fastest during young adulthood when weight, diet, and physical activity may be influenced by life events, including becoming a parent, but the impact is uncertain. We searched six electronic databases to July 2019 for longitudinal studies (both sexes) aged 15 to 35 years with a prospective pre-pregnancy/parenthood and post-delivery outcome. Of 11 studies (across 15 papers), six studies (women only) were eligible for meta-analysis of the difference in change in body mass index (BMI; kg/m2 ) between remaining without children and becoming a parent. Mean (±SD) BMI gain for non-mothers was 2.8 ± 1.3 kg/m2 (~7.5 kg for 164-cm woman) over 5.6 ± 3.1 years; 12.3% of baseline BMI (22.8 ± 2.5 kg/m2 ). Becoming a mother was associated with an additional BMI increase of 0.47 ± 0.26 kg/m2 (~1.3 kg), 4.3% of baseline BMI (22.8 ± 5.6 kg/m2 ); the one study including men reported no difference in change. Physical activity results were equivocal; 2/4 studies (women) and 2/2 (men) showed a greater decline in parents versus non-parents; diet (three studies) varied by dietary measure, mostly indicating no difference. Becoming a mother is associated with 17% greater absolute BMI gain than remaining childless. Motherhood BMI gain is additional to an alarming BMI increase among young women, highlighting the need for obesity prevention among all young women, including mothers.
KEYWORDS:
emerging adulthood; mother; overweight; weight gain

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