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  1. 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
  2. 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
  3. 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
  4. 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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    Dietary Interventions for Gout and Effect on Cardiovascular Risk Factors: A Systematic Review. Vedder D, Walrabenstein W, Heslinga M, de Vries R, Nurmohamed M, van Schaardenburg D, Gerritsen M. Nutrients. 2019 Dec 4;11(12). pii: E2955. doi: 10.3390/nu11122955. Review. PMID: 31817107 [pdf availed free from Medline abstract.] Abstract Gout is one of the most prevalent inflammatory rheumatic disease. It is preceded by hyperuricemia and associated with an increased risk for cardiovascular disease, both related to unhealthy diets. The objective of this systematic review is to better define the most appropriate diet addressing both disease activity and traditional cardiovascular risk factors in hyperuricemic patients. We included clinical trials with patients diagnosed with hyperuricemia or gout, investigating the effect of dietary interventions on serum uric acid (SUA) levels, gout flares and-if available-cardiovascular risk factors. Eighteen articles were included, which were too heterogeneous to perform a meta-analysis. Overall, the risk of bias of the studies was moderate to high. We distinguished four groups of dietary interventions: Calorie restriction and fasting, purine-low diets, Mediterranean-style diets, and supplements. Overall, fasting resulted in an increase of SUA, whilst small (SUA change +0.3 to -2.9 mg/dL) but significant effects were found after low-calorie, purine-low, and Mediterranean-style diets. Studies investigating the effect on cardiovascular risk factors were limited and inconclusive. Since Mediterranean-style diets/DASH (Dietary Approach to Stop Hypertension) have shown to be effective for the reduction of cardiovascular risk factors in other at-risk populations, we recommend further investigation of such diets for the treatment of gout. KEYWORDS: DASH; Mediterranean diet; blood pressure; cardiovascular disease; cholesterol; diet; gout; hyperuricemia; metabolic syndrome x; purine low die
  6. Association of Aspirin Therapy with Risk of Hepatocellular Carcinoma: a systematic review and dose-response analysis of cohort studies with 2.5 million participants. Wang S, Yu Y, Ryan PM, Dang M, Clark C, Kontogiannis V, Rahmani J, Varkaneh HK, Salehisahlabadi A, Day AS, Zhang Y. Pharmacol Res. 2019 Dec 6:104585. doi: 10.1016/j.phrs.2019.104585. [Epub ahead of print] Review. PMID: 31816436 https://sci-hub.tw/10.1016/j.phrs.2019.104585 Abstract Although aspirin is commonly used for the prevention of cardiovascular disease, evidence from research has shown that these beneficial effects might extend to hepatocellular carcinoma (HCC). This dose-response analysis was performed to investigate the association between aspirin use and risk of HCC. A systematic search was conducted in MEDLINE/PubMed, SCOPUS, Cochrane, and Web of Science databases from inception up to 29th October 2019. DerSimonian and Laird Random-effects model was used to estimate pooled hazard ratios (HRs) from included studies. Overall, eight studies containing 2,604,319 participants evaluating the association between aspirin use and risk of HCC were uncovered and included in the present meta-analysis. Pooled results of included studies showed a significant reduction in risk of HCC in participants who used aspirin (HR 0.59, 95% CI 0.47-0.75, Pheterogeneity = 0.001, I2 = 90%). In total, 13636 cases of HCC detected during the follow-up period of these studies. Furthermore, linear dose-response model showed an significant inverse association between aspirin dose and risk of HCC (exp (b) = 0.994, p < 0.001), while non-linear dose-response analysis revealed an even more robust association (Coef1=-0.008, p1 = 0.04, Coef2 = 0.033, p2 = 0.13). This systematic review and dose-response analysis identified significant inverse relation between aspirin and risk of HCC using both linear and non-linear models. KEYWORDS: Aspirin; Hepatocellular Carcinoma; Liver Cancer Quantitative Association Between Serum/Dietary Magnesium and Cardiovascular Disease/Coronary Heart Disease Risk: A Dose-Response Meta-analysis of Prospective Cohort Studies. Zhao L, Hu M, Yang L, Xu H, Song W, Qian Y, Zhao M. J Cardiovasc Pharmacol. 2019 Dec;74(6):516-527. doi: 10.1097/FJC.0000000000000739. PMID: 31815866 Abstract BACKGROUND: The quantitative association between serum/dietary magnesium and cardiovascular disease (CVD) remains unclear. We conducted a dose-response meta-analysis to evaluate the quantitative association between serum/dietary magnesium and CVD, including coronary heart disease (CHD). METHODS: PubMed, China National Knowledge Infrastructure, and Web of Science were searched for publications. STATA 12.0 was used to analyze data. We used the random-effects model to reduce heterogeneity. RESULTS: Eighteen prospective cohort studies with 544,581 participants and 22,658 CVD cases were included. The follow-up duration was 1-28 years. The pooled relative risk (RR) of CVD for the relatively normal versus lowest serum and dietary magnesium level was 0.64 {[95% confidence interval (CI): 0.51-0.80] and 0.90 [95% CI: 0.84-0.96]}. The pooled RR of CHD for the relatively normal versus lowest serum and dietary magnesium level was 0.70 (95% CI: 0.57-0.85) and 0.86 (95% CI: 0.77-0.94). We noted a significant association between increasing serum magnesium levels (per 0.1-mg/dL increase) and risk of CVD (RR: 0.93, 95% CI: 0.88-0.97) and CHD (RR: 0.90, 95% CI: 0.84-0.96) and between dietary magnesium levels (per 100-mg/d increase) and risk of CVD (RR: 0.90, 95% CI: 0.83-0.96) and CHD (RR: 0.92, 95% CI: 0.82-0.98). Serum/dietary Mg level comparisons presented a 7%-10% decrease in CVD/CHD risk. The dose-response meta-analyses showed linear relationships between serum magnesium and CVD (Pnonlinearity = 0.833) or CHD (Pnonlinearity = 0.193) and dietary magnesium and CVD (Pnonlinearity = 0.463) or CHD (Pnonlinearity = 0.440). CONCLUSIONS: Increasing dietary magnesium or serum magnesium level is linearly and inversely associated with the risk of total CVD and CHD events. Hearing Impairment, Household Composition, Marital Status, and Mortality among U.S. Adults. Denney JT, Boardman JD. J Gerontol B Psychol Sci Soc Sci. 2019 Dec 9. pii: gbz157. doi: 10.1093/geronb/gbz157. [Epub ahead of print] PMID: 31814013 https://watermark.silverchair.com/gbz157.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAApEwggKNBgkqhkiG9w0BBwagggJ-MIICegIBADCCAnMGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMRZWOp0XGk7aiwYB1AgEQgIICRFO5MTZXsGqWZ1v4MCZo2nYtNgcQZFFD5u1TINKmHeXiTVAd0iM19uMLd7V8S1F-BEly0thuLOCLZdhqxbcrrocqdZC5N3Heq4pCWb0WVTwrtP0umiljrCVhZYzqHoc5fAywE510bqNl5P3KUyw8T3PHag0CVHuYEyMuxAIK5jFI0Oz_yXmdjzfHcCkzX4EfY37pWql0qA0TZzrHwn09fMKyRhtI2Op7BygIZKxbFndAzK_kP2HaJaVyvRL5lMz1HqxBNme-bUyqOL52m-a9EK6OVLMD5gqlPne7eguXKjsyT8fQfzngsLXi0YrOefW2AixI5HEWKJJaDlgxUzQldoO2foo8rfD9PuUJ0hI4t4qgEMFrYUaxuAs119WiI5pU6BBq8LKPduAmGXpn4VHduMDdO7X4mlFtFeHTJhXWNZ-RAqJ8HrJ--aKCFA7MkRrBDpTAzbhBqBkmavHBHFq6loDG1L5Qr7KP6wV5P8thZT_deSUtDMtFZTrTXZLXjOan3aRTFA0n4B0gemi1CZcLFQfRyM3UJe91Zv_Cvb-HWKZbuoHPUbR1iferjzn8vQqAQG4pfaLRcgadHnaai-2UiJr9jF51_ZTrhWgMG9pNn7hjsBHophDUy-OLT3YAqCL1wEsGNFZk9bpIzT0B0rCtltqNg2bXkKCSDUCrD9clxm7pVPCeHn9VmBGCJ85Z8afd0XsmcYP0pTwxJjJPj2hp3n9tfp_J6oOVje0PL2rDH_ASD3BapxZ8aD24xR4iZ83vQCcOxaM Abstract OBJECTIVE: This study investigates associations between hearing impairment, household composition, marital status, and all-cause mortality for a representative sample of United States adults aged 40 and older (N = 198,902). METHOD: We use data from 11 waves of the National Health Interview Survey (2004-2014) linked to prospective mortality status through 2015. The risk of mortality over the follow-up period is estimated using Cox proportional hazard models. RESULTS: Compared to those with good to excellent hearing, adults with moderate to severe hearing impairments and deaf adults had 11% and 21% higher risk of death from any cause over the follow-up period, respectively. Household composition and marital status, as indicators of household social support systems, associated independently with the risk of mortality but did not substantively change the association between hearing impairment and mortality. DISCUSSION: Hearing impairment represents an important contributor to the length of life for adults age 40 and older, independent of other important and established determinants of mortality. KEYWORDS: Hearing Impairment; Household Composition; Marital Status; Mortality Premature mortality attributable to socioeconomic inequality in England between 2003 and 2018: an observational study. Lewer D, Jayatunga W, Aldridge RW, Edge C, Marmot M, Story A, Hayward A. Lancet Public Health. 2019 Dec 5. pii: S2468-2667(19)30219-1. doi: 10.1016/S2468-2667(19)30219-1. [Epub ahead of print] PMID: 31813773 Abstract BACKGROUND: Low socioeconomic position is consistently associated with increased risk of premature death. The aim of this study is to measure the aggregate scale of inequality in premature mortality for the whole population of England. METHODS: We used mortality records from the UK Office for National Statistics to study all 2 465 285 premature deaths (defined as those before age 75 years) in England between Jan 1, 2003, and Dec 31, 2018. Socioeconomic position was defined using deciles of the Index of Multiple Deprivation: a measure of neighbourhood income, employment, education levels, crime, health, availability of services, and local environment. We calculated the number of expected deaths by applying mortality rates in the least deprived decile to other deciles, within the strata of age, sex, and time. The mortality rates attributable to socioeconomic inequality was defined as the difference between the observed and expected deaths. We also used life table modelling to estimate years-of-life lost attributable to socioeconomic inequality. FINDINGS: 35·6% (95% CI 35·3-35·9) of premature deaths were attributable to socioeconomic inequality, equating to 877 082 deaths, or one every 10 min. The biggest contributors were ischaemic heart disease (152 171 excess deaths), respiratory cancers (111 083) and chronic obstructive pulmonary disease (83 593). The most unequal causes of death were deaths due to tuberculosis, opioid use, HIV, psychoactive drugs use, viral hepatitis, and obesity, each with more than two-thirds attributable to inequality. Inequality was greater among men and peaked in early childhood and at age 40-49 years. The proportion of deaths attributable to inequality increased during the study period, particularly for women, because mortality rates among the most deprived women (excluding cardiovascular diseases) plateaued, and for some diseases increased. A mean of 14·4 months of life before age 75 years are lost due to socioeconomic inequality. INTERPRETATION: One in three premature deaths are attributable to socioeconomic inequality, making this our most important public health challenge. Interventions that address upstream determinants of health should be prioritised. A little stress in the first years of life extends the lifespan, as shown in research on intestinal worms BY ISAAC NOVAK DECEMBER 5, 2019 https://upnewsinfo.com/2019/12/05/a-little-stress-in-the-first-years-of-life-extends-the-lifespan-as-shown-in-research-on-intestinal-worms/ >>>>>>>>>>>>>>>>> Developmental ROS individualizes organismal stress resistance and lifespan. Bazopoulou D, Knoefler D, Zheng Y, Ulrich K, Oleson BJ, Xie L, Kim M, Kaufmann A, Lee YT, Dou Y, Chen Y, Quan S, Jakob U. Nature. 2019 Dec 4. doi: 10.1038/s41586-019-1814-y. [Epub ahead of print] PMID: 31801997 Abstract A central aspect of aging research concerns the question of when individuality in lifespan arises1. Here we show that a transient increase in reactive oxygen species (ROS), which occurs naturally during early development in a subpopulation of synchronized Caenorhabditis elegans, sets processes in motion that increase stress resistance, improve redox homeostasis and ultimately prolong lifespan in those animals. We find that these effects are linked to the global ROS-mediated decrease in developmental histone H3K4me3 levels. Studies in HeLa cells confirmed that global H3K4me3 levels are ROS-sensitive and that depletion of H3K4me3 levels increases stress resistance in mammalian cell cultures. In vitro studies identified SET1/MLL histone methyltransferases as redox sensitive units of the H3K4-trimethylating complex of proteins (COMPASS). Our findings implicate a link between early-life events, ROS-sensitive epigenetic marks, stress resistance and lifespan.
  7. Relation of Total Sugars, Sucrose, Fructose, and Added Sugars With the Risk of Cardiovascular Disease: A Systematic Review and Dose-Response Meta-analysis of Prospective Cohort Studies. Khan TA, Tayyiba M, Agarwal A, Mejia SB, de Souza RJ, Wolever TMS, Leiter LA, Kendall CWC, Jenkins DJA, Sievenpiper JL. Mayo Clin Proc. 2019 Dec;94(12):2399-2414. doi: 10.1016/j.mayocp.2019.05.034. PMID: 31806098 https://www.mayoclinicproceedings.org/article/S0025-6196(19)30614-7/pdf Abstract OBJECTIVE: To determine the association of total and added fructose-containing sugars on cardiovascular (CVD) incidence and mortality. METHODS: MEDLINE, EMBASE and Cochrane Library were searched from January 1, 1980, to July 31, 2018. Prospective cohort studies assessing the association of reported intakes of total, sucrose, fructose and added sugars with CVD incidence and mortality in individuals free from disease at baseline were included. Risk estimates were pooled using the inverse variance method, and dose-response analysis was modeled. RESULTS: Eligibility criteria were met by 24 prospective cohort comparisons (624,128 unique individuals; 11,856 CVD incidence cases and 12,224 CVD mortality cases). Total sugars, sucrose, and fructose were not associated with CVD incidence. Total sugars (risk ratio, 1.09 [95% confidence interval, 1.02 to 1.17]) and fructose (1.08 [1.01 to 1.15]) showed a harmful association for CVD mortality, there was no association for added sugars and a beneficial association for sucrose (0.94 [0.89 to 0.99]). Dose-response analyses showed a beneficial linear dose-response gradient for sucrose and nonlinear dose-response thresholds for harm for total sugars (133 grams, 26% energy), fructose (58 grams, 11% energy) and added sugars (65 grams, 13% energy) in relation to CVD mortality (P<.05). The certainty of the evidence using GRADE was very low for CVD incidence and low for CVD mortality for all sugar types. CONCLUSION: Current evidence supports a threshold of harm for intakes of total sugars, added sugars, and fructose at higher exposures and lack of harm for sucrose independent of food form for CVD mortality. Further research of different food sources of sugars is needed to define better the relationship between sugars and CVD. Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium. Brunner FJ, Waldeyer C, Ojeda F, Salomaa V, Kee F, Sans S, Thorand B, Giampaoli S, Brambilla P, Tunstall-Pedoe H, Moitry M, Iacoviello L, Veronesi G, Grassi G, Mathiesen EB, Söderberg S, Linneberg A, Brenner H, Amouyel P, Ferrières J, Tamosiunas A, Nikitin YP, Drygas W, Melander O, Jöckel KH, Leistner DM, Shaw JE, Panagiotakos DB, Simons LA, Kavousi M, Vasan RS, Dullaart RPF, Wannamethee SG, Risérus U, Shea S, de Lemos JA, Omland T, Kuulasmaa K, Landmesser U, Blankenberg S; Multinational Cardiovascular Risk Consortium. Lancet. 2019 Dec 3. pii: S0140-6736(19)32519-X. doi: 10.1016/S0140-6736(19)32519-X. [Epub ahead of print] PMID: 31810609 Abstract BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. Effects of cinnamon supplementation on body weight and composition in adults: A systematic review and meta-analysis of controlled clinical trials. Yazdanpanah Z, Azadi-Yazdi M, Hooshmandi H, Ramezani-Jolfaie N, Salehi-Abargouei A. Phytother Res. 2019 Dec 4. doi: 10.1002/ptr.6539. [Epub ahead of print] Review. PMID: 31800140 Abstract BACKGROUND: This systematic review and meta-analysis aimed to investigate the effect of cinnamon on body weight, body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), and body fat mass including the maximum number of studies. METHODS: Medline, ISI Web of Science, Scopus, Google Scholar, and Cochrane library were searched with no limitation from inception up to August 2019 for relevant randomized controlled clinical trials (RCTs). The RCTs' risk of bias was assessed using the Cochrane collaboration's tool. Random-effects model was used for meta-analysis. RESULTS: Twenty-one RCTs with 1,480 participants were included. The meta-analysis showed that cinnamon supplementation significantly reduces BMI [weighted mean difference (WMD) = -0.40 kg/m2 , 95% confidence interval (CI): -0.57, -0.22 kg/m2 , p < .001, I2 = 78.9%], body weight (WMD = -0.92 kg; 95% CI: -1.51, -0.33 kg; p = .002; I2 = 84.2%), and WHR (WMD = -0.02, 95% CI: -0.038, -0.018; p < 0.001; I2 = 0%). Cinnamon supplementation did not significantly affect the WC (WMD = -1.76 cm, 95% CI: -3.57, -0.045 cm; p = .056; I2 = 90.8%) and body fat mass (WMD = -0.87%, 95% CI: -1.87, 0.025%; p = .057; I2 = 78.6%). CONCLUSION: Cinnamon supplementation significantly reduces body weight, BMI, and WHR. Future high-quality long-term RCTs are recommended to confirm these results. KEYWORDS: anthropometric indices; body composition; body weight; cinnamon; meta-analysis; systematic review Effect of n-3 long-chain polyunsaturated fatty acids on mild cognitive impairment: a meta-analysis of randomized clinical trials. Zhang X, Han H, Ge X, Liu L, Wang T, Yu H. Eur J Clin Nutr. 2019 Dec 5. doi: 10.1038/s41430-019-0544-4. [Epub ahead of print] Review. PMID: 31804628 Abstract N-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) have positive effect on cognitive function with mild cognitive impairment (MCI) is still controversial. The aim for this meta-analysis was to assess the scientific evidence published in the last 10 years on the effects of n-3 LC-PUFAs intake on MCI patients to explore whether n-3 LC-PUFAs have positive effective. A comprehensive literature search was developed using the Google Scholar, EMBASE, and PubMed database. The pooled effect for all studies was calculated using random-effects model. And the terms of weighted mean difference (WMD) with 95% confidence interval (CI) was pooled and indicated the effects. Heterogeneity was assessed by I2 statistics. A total of seven randomized clinical trials involving 213 cases of intervention and 221 cases of placebo were included in this analysis. Compared with placebo, n-3 LC-PUFAs supplements effectively improved cognition in elders with MCI (WMD = 0.85, 95% CI: 0.04-1.67, Z = 2.05, P = 0.04). Slight heterogeneity was detected across studies. Our results provided further evidence that n-3 LC-PUFAs may have beneficial effect in elderly with MCI. The association of dietary macronutrients with anthropometric changes, using iso-energetic substitution models: Tehran lipid and glucose study. Hosseini-Esfahani F, Koochakpoor G, Mirmiran P, Ebrahimof S, Azizi F. Nutr Metab (Lond). 2019 Nov 27;16:83. doi: 10.1186/s12986-019-0411-2. eCollection 2019. PMID: 31798665 Free Article Abstract BACKGROUND: The consequences of optimal dietary macronutrient compositions especially quality of proteins on weight gain still remain controversial. The aim of the current study was to evaluate the iso-energetic substitution of dietary macronutrients in relation to anthropometric changes. METHODS: This prospective study was conducted on 2999 men and 4001 women aged 20-70 years who were followed for 3.6 years. A valid and reliable 168-item semi-quantitative food frequency questionnaire was used to assess usual dietary intakes. Weight (kg) and waist circumference (WC) (cm) changes were calculated by subtracting the weight and WC at baseline from their measurements at follow up. Participants were divided into two groups; those with no change or decrease in weight or WC and those with increase in weight or WC. Dietary macronutrients (percentage of energy) divided by 5 to calculate one unit. RESULTS: A one unit higher proportion of carbohydrates at the expense of all types of fatty acids was associated with weight loss in men (P < 0.05). A one unit higher proportion of plant proteins at the expense of animal protein (β = - 0.84), non-starch carbohydrates (β = - 0.86), saturated fat (β = - 0.76), mono-unsaturated fat (β = - 0.76) and poly-unsaturated fat (β = - 0.86) was associated with weight loss (P < 0.05). A one unit higher proportion of plant proteins at the expense of animal proteins (OR: 0.49), non-starch carbohydrates (OR: 0.49), saturated fat (OR: 0.49), mono-unsaturated fat (OR: 0.49), and poly-unsaturated fat (OR: 0.48) was associated with a lower risk of increase in WC (P < 0.05). CONCLUSIONS: A higher proportion of dietary plant protein in replacement of simple carbohydrates, fats and animal proteins was associated with a lower increase in weight or WC. KEYWORDS: Macronutrients composition; Obesity; Plant proteins; Replacement Chronic inflammation in the etiology of disease across the life span. Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C, Ferrucci L, Gilroy DW, Fasano A, Miller GW, Miller AH, Mantovani A, Weyand CM, Barzilai N, Goronzy JJ, Rando TA, Effros RB, Lucia A, Kleinstreuer N, Slavich GM. Nat Med. 2019 Dec;25(12):1822-1832. doi: 10.1038/s41591-019-0675-0. Epub 2019 Dec 5. Review. PMID: 31806905 https://sci-hub.tw/10.1038/s41591-019-0675-0 Abstract Although intermittent increases in inflammation are critical for survival during physical injury and infection, recent research has revealed that certain social, environmental and lifestyle factors can promote systemic chronic inflammation (SCI) that can, in turn, lead to several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease and autoimmune and neurodegenerative disorders. In the present Perspective we describe the multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants and psychological stress. Furthermore, we suggest potential strategies for advancing the early diagnosis, prevention and treatment of SCI. The smell of longevity: a combination of Volatile Organic Compounds (VOCs) can discriminate centenarians and their offspring from age-matched subjects and young controls. Conte M, Conte G, Martucci M, Monti D, Casarosa L, Serra A, Mele M, Franceschi C, Salvioli S. Geroscience. 2019 Dec 5. doi: 10.1007/s11357-019-00143-6. [Epub ahead of print] PMID: 31808027 Abstract Aging is characterized by dynamic changes at metabolic level that lead to modifications in the composition of the metabolome. Since the identification of biomarkers that can discriminate people of different age and health status has recently attracted a great interest, we wondered whether age-specific changes in the metabolome could be identified and serve as new and informative biomarkers of aging and longevity. In the last few years, a specific branch of metabonomics devoted to the study of volatile organic compounds (VOCs) has been developed. To date, little is known about the profile of specific VOCs in healthy aging and longevity in humans; therefore, we investigated the profile of VOCs in both urine and feces samples from 73 volunteers of different age including centenarians that represent useful "super-controls" to identify potential biomarkers of successful aging and footprints of longevity. To this purpose, we performed a discriminant analysis by which we were able to identify specific profiles of urinary and fecal VOCs. Such profiles can discriminate different age groups, from young to centenarians, and, even more interesting, centenarians' offspring from age-matched controls. Moreover, we were able to identify VOCs that are specific for the couples "centenarians - offspring" or the trios "centenarians - offspring - spouse," suggesting the possible existence of a familiar component also for VOCs profile. KEYWORDS: Biomarkers; Centenarians; Human longevity; Volatile organic compounds Intermittent fasting increases adult hippocampal neurogenesis. Baik SH, Rajeev V, Fann DY, Jo DG, Arumugam TV. Brain Behav. 2019 Dec 5:e01444. doi: 10.1002/brb3.1444. [Epub ahead of print] PMID: 31804775 https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/brb3.1444 Abstract INTRODUCTION: Intermittent fasting (IF) has been suggested to have neuroprotective effects through the activation of multiple signaling pathways. Rodents fasted intermittently exhibit enhanced hippocampal neurogenesis and long-term potentiation (LTP) at hippocampal synapses compared with sedentary animals fed an ad libitum (AL) diet. However, the underlying mechanisms have not been studied. In this study, we evaluated the mechanistic gap in understanding IF-induced neurogenesis. METHODS: We evaluated the impact of 3 months of IF (12, 16, and 24 hr of food deprivation on a daily basis) on hippocampal neurogenesis in C57BL/6NTac mice using immunoblot analysis. RESULTS: Three-month IF significantly increased activation of the Notch signaling pathway (Notch 1, NICD1, and HES5), neurotrophic factor BDNF, and downstream cellular transcription factor, cAMP response element-binding protein (p-CREB). The expression of postsynaptic marker, PSD95, and neuronal stem cell marker, Nestin, was also increased in the hippocampus in response to 3-month IF. CONCLUSIONS: These findings suggest that IF may increase hippocampal neurogenesis involving the Notch 1 pathway. KEYWORDS: Notch; brain-derived neurotrophic factor; hippocampus; intermittent fasting; neurogenesis Carotenoid Intake and Circulating Carotenoids Are Inversely Associated with the Risk of Bladder Cancer: A Dose-Response Meta-analysis. Wu S, Liu Y, Michalek JE, Mesa RA, Parma DL, Rodriguez R, Mansour AM, Svatek R, Tucker TC, Ramirez AG. Adv Nutr. 2019 Dec 4. pii: nmz120. doi: 10.1093/advances/nmz120. [Epub ahead of print] PMID: 31800007 Abstract Some evidence indicates that carotenoids may reduce the risk of bladder cancer (BC), but the association is unclear. We conducted a systematic review and meta-analysis of case-control and cohort studies investigating the relation between carotenoid intake or circulating carotenoid concentrations and BC risk in men and women. All relevant epidemiologic studies were identified by a search of PubMed and Scopus databases, and the Cochrane Library from inception to April 2019 with no restrictions. A random-effects model was used to calculate pooled RRs and their 95% CIs across studies for high compared with low categories of intake or circulating concentrations. We also performed a dose-response meta-analysis using the Greenland and Longnecker method and random-effects models. A total of 22 studies involving 516,740 adults were included in the meta-analysis. The pooled RRs of BC for the highest compared with the lowest category of carotenoid intake and circulating carotenoid concentrations were 0.88 (95% CI: 0.76, 1.03) and 0.36 (95% CI: 0.12, 1.07), respectively. The pooled RR of BC for the highest compared with lowest circulating lutein and zeaxanthin concentrations was 0.53 (95% CI: 0.33, 0.84). Dose-response analysis showed that BC risk decreased by 42% for every 1 mg increase in daily dietary β-cryptoxanthin intake (RR: 0.58; 95% CI: 0.36, 0.94); by 76% for every 1 μmol/L increase in circulating concentration of α-carotene (RR: 0.24; 95% CI: 0.08, 0.67); by 27% for every 1 μmol/L increase in circulating concentration of β-carotene (RR: 0.73; 95% CI: 0.57, 0.94); and by 56% for every 1 μmol/L increase in circulating concentrations of lutein and zeaxanthin (RR: 0.44; 95% CI: 0.28, 0.67). Dietary β-cryptoxanthin intake and circulating concentrations of α-carotene, β-carotene, and lutein and zeaxanthin were inversely associated with BC risk. KEYWORDS: bladder cancer; blood; carotenoids; diet; lutein; lycopene; zeaxanthin; α-carotene; β-carotene; β-cryptoxanthin Lifestyle Aspects As A Predictor Of Pain Among Oldest-Old Primary Care Patients - A Longitudinal Cohort Study. Mallon T, Eisele M, König HH, Brettschneider C, Röhr S, Pabst A, Weyerer S, Werle J, Mösch E, Weeg D, Fuchs A, Pentzek M, Heser K, Wiese B, Kleineidam L, Wagner M, Riedel-Heller S, Maier W, Scherer M. Clin Interv Aging. 2019 Nov 1;14:1881-1888. doi: 10.2147/CIA.S217431. eCollection 2019. PMID: 31802858 Abstract PURPOSE: Dealing with the high prevalence of pain among the oldest-old (+75) is becoming a major health issue. Therefore, the aim of the study was to uncover health-related lifestyle behaviors (HLB) and age-related comorbidities which may predict, influence and prevent pain in old age. PATIENTS AND METHODS: In this longitudinal cohort study, data were obtained initially from 3.327 individuals aged 75+ from over 138 general practitioners (GP) during structured clinical interviews in 2003. Nine follow-ups (FU) were assessed until 2017. Available data from 736 individuals scoring in FU3 and FU7 were included in this analysis. Data were assembled in an ambulatory setting at participant's homes. Associations were tested using a linear regression model (model 1) and ordered logistic regression model (model 2). RESULTS: Statistical analyses revealed increased likelihood to experience pain for participants with comorbidities such as peripheral arterial disease (PAD) (coef. 13.51, P>t = 0.00) or chronic back pain (CBP) (coef. 6.64, P>t = 0.003) or higher body mass index (BMI) (coef. 0.57, P>t = 0.015) and, female gender (coef. 6.00, SE 3.0, t = 2.02, P>t = 0.044). Participants with medium education and former smokers showed significantly lower pain rating (coef. -5.05, P>t = 0.026; coef. -5.27, P>t = 0.026). Suffering from chronic back pain (OR = 2.03), osteoarthritis (OR = 1.49) or depressive symptoms (OR = 1.10) raised the odds to experience impairments in daily living due to pain. Physical activity showed no significant results. CONCLUSION: Chronic conditions such as PAD, or CBP, female gender and higher BMI may increase the risk of experiencing more pain while successful smoking cessation can lower pain ratings at old age. Early and consistent support through GPs should be given to older patients in order to prevent pain at old age. KEYWORDS: chronic conditions; health-related aspects; longitudinal cohort study; oldest-old; pain prevention
  8. AlPater

    Al's CR updates

    Timing of Calorie Restriction in Mice Impacts Host Metabolic Phenotype with Correlative Changes in Gut Microbiota. Zhang L, Xue X, Zhai R, Yang X, Li H, Zhao L, Zhang C. mSystems. 2019 Dec 3;4(6). pii: e00348-19. doi: 10.1128/mSystems.00348-19. PMID: 31796564 https://msystems.asm.org/content/msys/4/6/e00348-19.full.pdf Abstract Calorie restriction (CR) is accompanied by self-imposed daily restriction of food intake and an extended fasting period between meals. The impact of restricting feeding to the dark or light phase on the effects of CR remains elusive. Here, light-fed CR mice showed physiological changes, such as muscle loss, concomitant with changes in the gut microbiota structure and composition. After switching to ad libitum access to food, light-fed mice had a period of food-craving behavior and short-lived physiological changes, while dark-fed mice displayed lasting changes in fat accumulation, glucose metabolism, intestinal barrier function, and systemic inflammatory markers. Moreover, the gut microbiota was modulated by when the food was consumed, and the most abundant Lactobacillus operational taxonomic unit (OTU) promoted by CR was enhanced in dark-fed mice. After switching to ad libitum feeding, the gut microbiota of dark-fed mice returned to the state resembling that of mice fed normal chow ad libitum, but that of light-fed mice was still significantly different from the other two groups. Together, these data indicate that for CR, restricting food consumption to the active phase brought better metabolic phenotype associated with potentially beneficial structural shifts in the gut microbiota.IMPORTANCE Aberrant feeding patterns whereby people eat more frequently throughout the day and with a bias toward late-night eating are prevalent in society today. However, whether restriction of food to daytime in comparison to nighttime, coupled with restricted calorie intake, can influence gut microbiota, metabolism, and overall health requires further investigation. We surveyed the effects of the shift in feeding time on gut microbiota and metabolic phenotype in calorie-restricted mice and found that avoiding eating during the rest period may generate more beneficial effects in mice. This work strengthens the evidence for using "when to eat" as an intervention to improve health during calorie restriction. KEYWORDS: anti-inflammation; calorie restriction; gut microbiota; shift of feeding time
  9. AlPater

    aging protein waves in blood

    The paper is in PubMed this morning: Undulating changes in human plasma proteome profiles across the lifespan. Lehallier B, Gate D, Schaum N, Nanasi T, Lee SE, Yousef H, Moran Losada P, Berdnik D, Keller A, Verghese J, Sathyan S, Franceschi C, Milman S, Barzilai N, Wyss-Coray T. Nat Med. 2019 Dec;25(12):1843-1850. doi: 10.1038/s41591-019-0673-2. Epub 2019 Dec 5. PMID: 31806903 https://www.biorxiv.org/content/biorxiv/early/2019/09/01/751115.full.pdf Abstract Aging is a predominant risk factor for several chronic diseases that limit healthspan1. Mechanisms of aging are thus increasingly recognized as potential therapeutic targets. Blood from young mice reverses aspects of aging and disease across multiple tissues2-10, which supports a hypothesis that age-related molecular changes in blood could provide new insights into age-related disease biology. We measured 2,925 plasma proteins from 4,263 young adults to nonagenarians (18-95 years old) and developed a new bioinformatics approach that uncovered marked non-linear alterations in the human plasma proteome with age. Waves of changes in the proteome in the fourth, seventh and eighth decades of life reflected distinct biological pathways and revealed differential associations with the genome and proteome of age-related diseases and phenotypic traits. This new approach to the study of aging led to the identification of unexpected signatures and pathways that might offer potential targets for age-related diseases.
  10. Stage 1 hypertension by the 2017 American College of Cardiology/American Heart Association hypertension guidelines and risk of cardiovascular disease events: systematic review, meta-analysis, and estimation of population etiologic fraction of prospective cohort studies. Han M, Chen Q, Liu L, Li Q, Ren Y, Zhao Y, Liu D, Zhang D, Liu F, Chen X, Cheng C, Guo C, Zhou Q, Tian G, Qie R, Huang S, Wu X, Liu Y, Li H, Sun X, Lu J, Hu D, Zhang M. J Hypertens. 2019 Nov 28. doi: 10.1097/HJH.0000000000002321. [Epub ahead of print] PMID: 31790053 Abstract BACKGROUND: Epidemiological studies reported an inconsistent association between stage 1 hypertension (SBP 130-139 mmHg or DBP 80-89 mmHg) defined by the 2017 American College of Cardiology/American Heart Association hypertension guidelines and cardiovascular disease (CVD) events. In addition, the proportion of CVD events that could be prevented with effective control of stage 1 hypertension is unknown. OBJECTIVES: To assess the association between stage 1 hypertension and CVD events and estimate the population etiologic fraction. METHODS: PubMed, Embase, and Web of Science databases were searched from 1 January 2017 to 22 September 2019. Normal BP was considered SBP less than 120 mmHg and DBP less than 80 mmHg. Hazard ratios and 95% confidence intervals (95% CIs) were pooled by using a random-effects model. RESULTS: We included 11 articles (16 studies including 3 212 447 participants and 65 945 events) in the analysis. Risk of CVD events was increased with stage 1 hypertension versus normal BP (hazard ratio 1.38, 95% CI 1.28-1.49). On subgroup analyses, stage 1 hypertension was associated with coronary heart disease (CHD) (hazard ratio 1.30, 95% CI 1.20-1.41), stroke (1.39, 1.27-1.52), CVD morbidity (1.42, 1.32-1.53), and CVD mortality (1.34, 1.05-1.71). The population etiologic fraction for the association of CVD events, CHD, stroke, CVD morbidity, and CVD mortality with stage 1 hypertension was 12.90, 10.48, 12.71, 14.03, and 11.69%, respectively. CONCLUSION: Stage 1 hypertension is associated with CVD events, CVD morbidity, CVD mortality, CHD, and stroke. Effective control of stage 1 hypertension could prevent more than 10% of CVD events. Dietary saturated fat intake and risk of stroke: Systematic review and dose-response meta-analysis of prospective cohort studies. Kang ZQ, Yang Y, Xiao B. Nutr Metab Cardiovasc Dis. 2019 Oct 1. pii: S0939-4753(19)30380-1. doi: 10.1016/j.numecd.2019.09.028. [Epub ahead of print] PMID: 31791641 Abstract BACKGROUND AND AIMS: Because of the conflicting research results, the association between saturated fatty acid (SFA) consumption and the risk of stroke remains controversial. We conducted a meta-analysis to evaluate potential dose-response relation between SFA intake and stroke. METHODS AND RESULTS: PubMed, Embase, the Cochrane Library Central Register of Controlled Trials, and Web of Science were searched. Summary relative risks (RRs) of the highest vs. the lowest category of SFA intake and their 95% confidence intervals (CIs) were pooled by random-effects models. Linear or nonlinear dose-response trend estimations were evaluated with data from categories of SFA consumption in each study. Fourteen studies involving a total of 598,435 participants were eligible for high vs. low meta-analysis, and 12 studies involving a total of 462,268 participants were eligible for the dose-response relation assessment. Higher dietary SFA intake was associated with a decreased overall risk for stroke (RR, 0.87; 95% CI, 0.78-0.96; I2 = 37.8%). A linear relation between SFA and stroke was explored (P = 0.01), the pooled RR of stroke per 10 g/day increase in SFA intake was 0.94 (95% CI, 0.89-0.98; P = 0.01). CONCLUSION: This meta-analysis further demonstrated that a higher consumption of dietary SFA is associated with a lower risk of stroke, and every 10 g/day increase in SFA intake is associated with a 6% relative risk reduction in the rate of stroke. Further research is needed to explore the influence of specific SFA types and different macronutrient replacement models of SFA on the stroke risk. KEYWORDS: Dietary saturated fat intake; Dose–response relation; Meta-analysis; Stroke risk
  11. AlPater

    Al's CR updates

    Protein Intake Greater than the RDA Differentially Influences Whole-Body Lean Mass Responses to Purposeful Catabolic and Anabolic Stressors: A Systematic Review and Meta-analysis. Hudson JL, Wang Y, Bergia Iii RE, Campbell WW. Adv Nutr. 2019 Dec 3. pii: nmz106. doi: 10.1093/advances/nmz106. [Epub ahead of print] PMID: 31794597 Abstract Under stressful conditions such as energy restriction (ER) and physical activity, the RDA for protein of 0.8 g · kg-1 · d-1 may no longer be an appropriate recommendation. Under catabolic or anabolic conditions, higher protein intakes are proposed to attenuate the loss or increase the gain of whole-body lean mass, respectively. No known published meta-analysis compares protein intakes greater than the RDA with intakes at the RDA. Therefore, we conducted a systematic review and meta-analysis to assess the effects of protein intakes greater than the RDA, compared with at the RDA, on changes in whole-body lean mass. Three researchers independently screened 1520 articles published through August 2018 using the PubMed, Scopus, CINAHL, and Cochrane databases, with additional articles identified in published systematic review articles. Randomized, controlled, parallel studies ≥6 wk long with apparently healthy adults (≥19 y) were eligible for inclusion. Data from 18 studies resulting in 22 comparisons of lean mass changes were included in the final overall analysis. Among all comparisons, protein intakes greater than the RDA benefitted changes in lean mass relative to consuming the RDA [weighted mean difference (95% CI): 0.32 (0.01, 0.64) kg, n = 22 comparisons]. In the subgroup analyses, protein intakes greater than the RDA attenuated lean mass loss after ER [0.36 (0.06, 0.67) kg, n = 14], increased lean mass after resistance training (RT) [0.77 (0.23, 1.31) kg, n = 3], but did not differentially affect changes in lean mass [0.08 (-0.59, 0.75) kg, n = 7] under nonstressed conditions (no ER + no RT). Protein intakes greater than the RDA beneficially influenced changes in lean mass when adults were purposefully stressed by the catabolic stressor of dietary ER with and without the anabolic stressor of RT. The RDA for protein is adequate to support lean mass in adults during nonstressed states. KEYWORDS: adults; body composition; exercise; fat-free mass; health; weight loss
  12. AlPater

    Al's CR updates

    Activation of Kappa Opioid Receptor Regulates the Hypothermic Response to Calorie Restriction and Limits Body Weight Loss. Cintron-Colon R, Johnson CW, Montenegro-Burke JR, Guijas C, Faulhaber L, Sanchez-Alavez M, Aguirre CA, Shankar K, Singh M, Galmozzi A, Siuzdak G, Saez E, Conti B. Curr Biol. 2019 Nov 5. pii: S0960-9822(19)31367-3. doi: 10.1016/j.cub.2019.10.027. [Epub ahead of print] PMID: 31786059 Abstract Mammals maintain a nearly constant core body temperature (Tb) by balancing heat production and heat dissipation. This comes at a high metabolic cost that is sustainable if adequate calorie intake is maintained. When nutrients are scarce or experimentally reduced such as during calorie restriction (CR), endotherms can reduce energy expenditure by lowering Tb [1-6]. This adaptive response conserves energy, limiting the loss of body weight due to low calorie intake [7-10]. Here we show that this response is regulated by the kappa opioid receptor (KOR). CR is associated with increased hypothalamic levels of the endogenous opioid Leu-enkephalin, which is derived from the KOR agonist precursor dynorphin [11]. Pharmacological inhibition of KOR, but not of the delta or the mu opioid receptor subtypes, fully blocked CR-induced hypothermia and increased weight loss during CR independent of calorie intake. Similar results were seen with DIO mice subjected to CR. In contrast, inhibiting KOR did not change Tb in animals fed ad libitum (AL). Chemogenetic inhibition of KOR neurons in the hypothalamic preoptic area reduced the CR-induced hypothermia, whereas chemogenetic activation of prodynorphin-expressing neurons in the arcuate or the parabrachial nucleus lowered Tb. These data indicate that KOR signaling is a pivotal regulator of energy homeostasis and can affect body weight during dieting by modulating Tb and energy expenditure. KEYWORDS: body temperature; body weight; calorie restriction; dieting; dynorphin; energy expenditure; energy homeostasis; hypothermia; kappa opioid receptor Negative genetic correlation between longevity and its hormetic extension by dietary restriction in Drosophila melanogaster. Gomez FH, Stazione L, Sambucetti P, Norry FM. Biogerontology. 2019 Nov 30. doi: 10.1007/s10522-019-09852-z. [Epub ahead of print] PMID: 31786681 Abstract Longevity is a highly malleable trait which is influenced by many genetic and environmental factors including nutrition. Mild stress of dietary restriction (DR) is often beneficial by extending longevity in many organisms. Here, DR-induced effects on longevity were tested for genetic variation in a set of recombinant inbred lines (RIL) in D. melanogaster. Genetic variability was significant in the longevity response following a DR-treatment across RIL, with detrimental effects in several RIL but beneficial effects in other RIL. One quantitative trait locus (QTL) was consistently significant in the middle of chromosome 2 for DR-induced changes in longevity, including hormesis (an increase in longevity by DR). Another QTL co-localized with a previously found QTL for starvation resistance in females. Several other QTL were also significant on most chromosomal arms. Longevity in controls was negatively correlated to DR effects across RIL for longevity in females, the sex showing higher DR-induced hormesis. This negative genetic correlation highlights the importance to further investigate the effects of genetic variation in the strength of DR-induced hormesis in longevity and its sex-specificity. KEYWORDS: Heat-induced hormesis; Hormesis; Quantitative trait loci; Sex-specificity; Starvation
  13. Association Between Beverage Intake and Incidence of Gastroesophageal Reflux Symptoms: Beverages and GER symptoms. Mehta RS, Song M, Staller K, Chan AT. Clin Gastroenterol Hepatol. 2019 Nov 28. pii: S1542-3565(19)31380-1. doi: 10.1016/j.cgh.2019.11.040. [Epub ahead of print] PMID: 31786327 Abstract BACKGROUND & AIMS: Patients are frequently advised to eliminate coffee, tea, and/or soda to reduce symptoms of gastroesophageal reflux (GER), such as heartburn or regurgitation. However, there are no data from prospective studies to support these recommendations. METHODS: We collected data from the prospective Nurses' Health Study II from 48,308 women, 42-62 years old, who were free of regular GER symptoms, without cancer, and not taking proton pump inhibitors or H2 receptor agonists. Multivariate Cox proportional hazards models were used to assess associations between beverage intake and risk for GER symptoms. RESULTS: During 262,641 person-years of follow up, we identified 7961 women who reported symptoms of GER once or more per week. After multivariable adjustment, hazard ratios (HRs) for women with the highest intake of each beverage (more than 6 servings/day) compared to women with the lowest intake (0 servings/day) were 1.34 for coffee (95% CI, 1.13-1.59; Ptrend<.0001), 1.26 for tea (95% CI, 1.03-1.55; Ptrend<.001), and 1.29 for soda (95% CI, 1.05-1.58; Ptrend<.0001). We obtained similar results when we stratified patients according to caffeine status. No association was observed between milk, water, or juice consumption and risk for GER symptoms. In a substitution analysis, replacement of 2 servings/day of coffee, tea, or soda with 2 servings of water was associated with reduced risk of GERD symptoms: coffee HR, 0.96 (95% CI, 0.92-1.00); tea HR, 0.96 (95% CI, 0.92-1.00); and soda HR, 0.92 (95% CI, 0.89- 0.96). CONCLUSIONS: In an analysis of data from the prospective Nurses' Health Study II, intake of coffee, tea, or soda was associated with an increased risk of GER symptoms. In contrast, consumption of water, juice, or milk were not associated with GER symptoms. Drinking water instead of coffee, tea, or soda reduced the risk of GER symptoms. KEYWORDS: GERD; NHS; PPI use; diet
  14. AlPater

    Al's CR updates

    Calorie restriction slows age-related microbiota changes in an Alzheimer's disease model in female mice. Cox LM, Schafer MJ, Sohn J, Vincentini J, Weiner HL, Ginsberg SD, Blaser MJ. Sci Rep. 2019 Nov 29;9(1):17904. doi: 10.1038/s41598-019-54187-x. PMID: 31784610 https://www.nature.com/articles/s41598-019-54187-x.pdf Abstract Alzheimer's disease (AD) affects an estimated 5.8 million Americans, and advanced age is the greatest risk factor. AD patients have altered intestinal microbiota. Accordingly, depleting intestinal microbiota in AD animal models reduces amyloid-beta (Aβ) plaque deposition. Age-related changes in the microbiota contribute to immunologic and physiologic decline. Translationally relevant dietary manipulations may be an effective approach to slow microbiota changes during aging. We previously showed that calorie restriction (CR) reduced brain Aβ deposition in the well-established Tg2576 mouse model of AD. Presently, we investigated whether CR alters the microbiome during aging. We found that female Tg2576 mice have more substantial age-related microbiome changes compared to wildtype (WT) mice, including an increase in Bacteroides, which were normalized by CR. Specific gut microbiota changes were linked to Aβ levels, with greater effects in females than in males. In the gut, Tg2576 female mice had an enhanced intestinal inflammatory transcriptional profile, which was reversed by CR. Furthermore, we demonstrate that Bacteroides colonization exacerbates Aβ deposition, which may be a mechanism whereby the gut impacts AD pathogenesis. These results suggest that long-term CR may alter the gut environment and prevent the expansion of microbes that contribute to age-related cognitive decline. xx
  15. Acute caffeine intake increases muscle oxygen saturation during a maximal incremental exercise test. Ruíz-Moreno C, Lara B, Brito de Souza D, Gutiérrez-Hellín J, Romero-Moraleda B, Cuéllar-Rayo Á, Del Coso J. Br J Clin Pharmacol. 2019 Nov 29. doi: 10.1111/bcp.14189. [Epub ahead of print] PMID: 31782534 Abstract AIMS: The main mechanism behind caffeine's ergogenicity lies in its tendency to bind to adenosine receptors although other mechanisms might be involved. The aim of this investigation was to analyze the effects of caffeine on muscle oxygen saturation during exercise of increasing intensity. METHODS: Thirteen healthy and active individuals volunteered to participate in a randomized, double blind, placebo-controlled crossover trial. During two different trials, participants either ingested a placebo (cellulose) or 3 mg/kg of caffeine. After waiting for 60 min to absorb the substances, participants underwent a maximal ramp cycle ergometer test (25 W/min). Near infrared spectrometers were positioned on each leg's vastus lateralis to monitor tissue O2 saturation. Blood lactate concentration was measured 1 min after the end of the exercise test. RESULTS: In comparison to the placebo, the ingestion of caffeine improved the maximal wattage (258±50 vs 271±54 W, respectively, P<0.001, effect size=0.27;0.14-0.35) and blood lactate concentration (11.9±3.8 vs 13.7±3.5 mmol/L, P=0.029, effect size=0.38;0.14-0.75) at the end of the test. Caffeine increased muscle oxygen saturation at several exercise workloads with a main effect found in respect to the placebo (F=6.28, P=0.029; effect sizes=from 0.30-to-0.54;0.01-0.78). Peak pulmonary ventilation (124±29 vs 129±23 L/min, P=0.035, effect size=0.25;0.07-0.40) and VO2 peak (3.18±0.70 vs 3.33±0.88 L/min, P=0.032, effect size=0.26;0.08-0.51) were also increased with caffeine. CONCLUSION: Acute ingestion of 3 mg/kg of caffeine improved peak aerobic performance and increased peak pulmonary ventilation. In addition, caffeine induced changes in muscle oxygen saturation during submaximal workloads, suggesting that this mechanism might also contribute to caffeine's ergogenic effect. KEYWORDS: VO2max; cycling; high intensity exercise; muscle oxygenation; near infrared spectroscopy Long-Term Trajectories of Body Weight, Diet, and Physical Activity From Midlife Through Late-Life and Subsequent Cognitive Decline in Women. Wagner M, Grodstein F, Proust-Lima C, Samieri C. Am J Epidemiol. 2019 Nov 29. pii: kwz262. doi: 10.1093/aje/kwz262. [Epub ahead of print] PMID: 31781745 Abstract Healthy lifestyle are promising targets for prevention of cognitive aging, yet the optimal time-windows for interventions remain unclear. We selected a case-control sample nested within the Nurses' Health Study (starting year 1976, mean age=51 years-old), including 14,956 women aged ≥70 years and free of both stroke and cognitive impairment at enrollment in a cognitive sub-study (1995-2001). Cases (n=1,496) were women with the 10% worst slopes of cognitive decline and controls (n=7,478) those with slopes better than the median. We compared the trajectories of body mass index, the alternate Mediterranean diet (A-MeDi) score, and physical activity between groups, from midlife through 1 year preceding the cognitive sub-study. In midlife, cases had higher body mass index (mean difference [MD] versus controls=0.59 [95% confidence interval [CI]:0.39,0.80] kg/m2), lower physical activity (MD=-1.41 [95%CI:-2.07,-0.71] metabolic-equivalent hours/week) and worse A-MeDi scores (MD=-0.16 [95%CI:-0.26,-0.06] point). From mid- through later-life, compared to controls, cases had consistently lower A-MeDi scores, but a deceleration of weight gain and a faster decrease of physical activity. In conclusion, maintaining healthy lifestyle since midlife may help reduce cognitive decline in aging. At older ages, both deceleration of weight gain and decrease in physical activity may reflect early signs of cognitive impairment. KEYWORDS: Mediterranean diet; body mass index; cognitive decline; physical activity; prospective cohort study Leading Determinants for Disease-Free Status in Community-Dwelling Middle-Aged Men and Women: A 9-Year Follow-Up Cohort Study. Shang X, Wang W, Keel S, Wu J, He M, Zhang L. Front Public Health. 2019 Nov 8;7:320. doi: 10.3389/fpubh.2019.00320. eCollection 2019. PMID: 31781526 Abstract Background: Identifying leading determinants for disease-free status may provide evidence for action priorities, which is imperative for public health with an expanding aged population worldwide. This study aimed to identify leading determinants, especially modifiable factors for disease-free status using machine learning methods. Methods: We included 52,036 participants aged 45-64 years from the 45 and Up Study who were free of 13 predefined chronic conditions at baseline (2006-2009). Disease-free status was defined as participants aging from 45-64 years at baseline to 55-75 years at the end of the follow-up (December 31, 2016) without developing any of the 13 chronic conditions. We used machine learning methods to evaluate the importance of 40 potential predictors and analyzed the association between the number of leading modifiable healthy factors and disease-free status. Results: Disease-free status was found in about half of both men and women during a mean 9-year follow-up. The five most common leading predictors were body mass index (6.4-9.5% of total variance), self-rated health (5.2-8.2%), self-rated quality of life (4.1-6.8%), red meat intake (4.5-6.5%), and chicken intake (4.5-5.9%) in both genders. Modifiable behavioral factors including body mass index, diets, smoking, alcohol consumption, and physical activity, contributed to 37.2-40.3% of total variance. Participants having six or more modifiable health factors were 1.63-8.76 times more likely to remain disease-free status and had 0.60-2.49 more disease-free years (out of 9-year follow-up) than those having two or fewer. Non-behavioral factors including low levels of education and income and high relative socioeconomic disadvantage, were leading risk factors for disease-free status. Conclusions: Body mass index, diets, smoking, alcohol consumption, and physical activity are key factors for disease-free status promotion. Individuals with low socioeconomic status are more in need of care. KEYWORDS: disease-free status; family history of chronic disease; healthy modifiable factors; leading predictors; psychological factors; socioeconomic status Association of supplemental calcium and dairy milk intake with all-cause and cause-specific mortality in the UK Biobank: a prospective cohort study. Stasinopoulos LC, Zhou A, Hyppönen E. Br J Nutr. 2019 Nov 29:1-19. doi: 10.1017/S0007114519003076. [Epub ahead of print] PMID: 31779733 https://www.cambridge.org/core/services/aop-cambridge-core/content/view/E33281873D8B17461CA9AF027F876A90/S0007114519003076a.pdf/div-class-title-association-of-supplemental-calcium-and-dairy-milk-intake-with-all-cause-and-cause-specific-mortality-in-the-uk-biobank-a-prospective-cohort-study-div.pdf Abstract Excessive calcium intakes have been proposed to associate with vascular calcification and a higher risk of prostate cancer. We investigated the associations of supplemental and dietary calcium intake with mortality using data from 497,828 UK Biobank participants. The average follow-up was 4.2 years and 14,255 participants died, 8,297 from cancer, 2,959 from cardiovascular diseases and 572 from respiratory disease. The use of calcium supplements and milk consumption were associated with differences in mortality in younger (≤65 years) but not in older participants (>65 years, Pinteraction≤0.04 for all comparisons). Among participants <65 years, there was an inverse association both between calcium supplementation (OR 0.91, 95% CI 0.83-0.99) and milk consumption (OR 0.93, 95% CI 0.86-1.00) with respect to all-cause mortality. In the same age group, milk drinkers had lower odds of cancer mortality (OR 0.89, 95% CI 0.80-0.98) but calcium supplement use was associated with increased odds of respiratory mortality (OR 1.69, 95% CI 1.16-2.74). All associations in participants aged ≥65 years were null after full adjustment. In sensitivity analyses stratifying by hormone replacement therapy, calcium supplement use associated with decreased odds of cancer mortality in users but increased risk in other women (OR 0.81, 95% CI 0.69-0.94 vs. OR 1.17, 95% CI 1.01-1.35, respectively). To conclude, we saw little evidence for harm with dietary or supplemental calcium. Further studies are required to confirm the proposed interaction with hormone replacement therapy and to exclude reverse causation as a determinant in the association between calcium supplements and increased risk of respiratory diseases. KEYWORDS: all-cause mortality; calcium supplements; cancer mortality; cardiovascular mortality; dairy milk; respiratory mortality. Associations of dairy intake with risk of mortality in women and men: three prospective cohort studies. Ding M, Li J, Qi L, Ellervik C, Zhang X, Manson JE, Stampfer M, Chavarro JE, Rexrode KM, Kraft P, Chasman D, Willett WC, Hu FB. BMJ. 2019 Nov 27;367:l6204. doi: 10.1136/bmj.l6204. PMID: 31776125 Abstract OBJECTIVE: To examine the association of consumption of dairy foods with risk of total and cause specific mortality in women and men. DESIGN: Three prospective cohort studies with repeated measures of diet and lifestyle factors. SETTING: Nurses' Health Study, Nurses' Health Study II, and the Health Professionals Follow-up Study, in the United States. PARTICIPANTS: 168 153 women and 49 602 men without cardiovascular disease or cancer at baseline. MAIN OUTCOME MEASURE: Death confirmed by state vital records, the national death index, or reported by families and the postal system. During up to 32 years of follow-up, 51 438 deaths were documented, including 12 143 cardiovascular deaths and 15 120 cancer deaths. Multivariable analysis further adjusted for family history of cardiovascular disease and cancer, physical activity, overall dietary pattern (alternate healthy eating index 2010), total energy intake, smoking status, alcohol consumption, menopausal status (women only), and postmenopausal hormone use (women only). RESULTS: Compared to the lowest category of total dairy consumption (average 0.8 servings/day), the multivariate pooled hazard ratio for total mortality was 0.98 (95% confidence interval 0.96 to 1.01) for the second category of dairy consumption (average 1.5 servings/day), 1.00 (0.97 to 1.03) for the third (average 2.0 servings/day), 1.02 (0.99 to 1.05) for the fourth (average 2.8 servings/day), and 1.07 (1.04 to 1.10) for highest category (average 4.2 servings/day; P for trend <0.001). For the highest compared to the lowest category of total dairy consumption, the hazard ratio was 1.02 (0.95 to 1.08) for cardiovascular mortality and 1.05 (0.99 to 1.11) for cancer mortality. For subtypes of dairy products, whole milk intake was significantly associated with higher risks of total mortality (hazard ratio per 0.5 additional serving/day 1.11, 1.09 to 1.14), cardiovascular mortality (1.09, 1.03 to 1.15), and cancer mortality (1.11, 1.06 to 1.17). In food substitution analyses, consumption of nuts, legumes, or whole grains instead of dairy foods was associated with a lower mortality, whereas consumption of red and processed meat instead of dairy foods was associated with higher mortality. CONCLUSION: These data from large cohorts do not support an inverse association between high amount of total dairy consumption and risk of mortality. The health effects of dairy could depend on the comparison foods used to replace dairy. Slightly higher cancer mortality was non-significantly associated with dairy consumption, but warrants further investigation. Modified alternate-day fasting vs. calorie restriction in the treatment of patients with metabolic syndrome: A randomized clinical trial. Parvaresh A, Razavi R, Abbasi B, Yaghoobloo K, Hassanzadeh A, Mohammadifard N, Safavi SM, Hadi A, Clark CCT. Complement Ther Med. 2019 Dec;47:102187. doi: 10.1016/j.ctim.2019.08.021. Epub 2019 Aug 28. PMID: 31779987 Abstract OBJECTIVE: The aim of present study was to compare the effect of calorie restriction and modified alternate-day fasting diet on treatment of adults with metabolic syndrome. DESIGN: This randomized clinical trial was conducted on 70 participants diagnosed with metabolic syndrome. SETTING: Patients were randomly allocated into 2 groups to follow either calorie restriction or a modified alternate-day fasting diet for 8 weeks. Diets was prescribed by dietitians and specialized for each participant. Anthropometric parameters, blood pressure, fasting plasma glucose, fasting insulin, HOMA-IR and lipid profile were measured at baseline and after trial conclusion. RESULTS: 69, out of 70, participants completed the study and were included in the final analysis. The results showed that, compared with calorie restriction, following the modified alternate-day fasting diet significantly reduced body weight (P = 0.003), waist circumference (P = 0.026), systolic blood pressure (P = 0.029) and fasting plasma glucose (P = 0.009). However, no significant difference was observed between the 2 groups in triglyceride (P = 0.614), total cholesterol (P = 0.759), LDL-C (P = 0.289), HDL-C (P = 0.909), diastolic blood pressure (P = 0.262), HOMA- IR (P = 0.425) and fasting insulin concentrations (P = 0.496). In addition, the participants did not report any complaint due to difficulties with diet adherence when following calorie restriction or modified alternate-day fasting diet. CONCLUSIONS: the present study suggests that modified alternate-day fasting diet may be a more effective option in managing body weight, waist circumference, systolic blood pressure, and fasting plasma glucose, compared with common calorie restriction. Further studies are needed to confirm the veracity of our results. KEYWORDS: Alternate-day fasting; Anthropometric; Energy restriction; Glycemic index; Metabolic syndrome x; Plasma lipids Naive extrapolations, overhyped claims and empty promises in ageing research and interventions need avoidance. Rattan SIS. Biogerontology. 2019 Nov 27. doi: 10.1007/s10522-019-09851-0. [Epub ahead of print] PMID: 31773357 https://sci-hub.tw/10.1007/s10522-019-09851-0 Abstract Most proclamations about another wonder breakthrough and another imminent miracle treatment of ageing are usually overhyped claims and empty promises. It is not that the experimental science behind those claims is totally wrong or fake. But it is often a case of being ahistorical and ignoring the cumulated knowledge and understanding of the evolutionary and biological principles of ageing and longevity. Furthermore, remaining stuck to the body-as-a-machine viewpoint reduces ageing and its associated health challenges to a mere problem of engineering and design. However, highly dynamic nature of the living systems with properties of interaction, interdependence, tolerance, adaptation and constant remodelling requires wholistic and interactive modes of understanding and maintaining health. The physiological relevance and significance of progressively accumulating molecular damage remains to be fully understood. As for ageing interventions, the three pillars of health-food, physical activity, and social and mental engagement-which actually show health-promoting effect, cannot simply be reduced to a single or a limited number of molecular targets with hopes of creating an exercise pill, a fasting pill, a happiness pill and so on. If we want to increase the credibility and socio-political-economic support of ageing research and interventions, we need to resist the temptation to overhype the claims or to make far-fetched promises, which undermine the theoretical and practical significance of new discoveries in biogerontology. KEYWORDS: Ageing; Anti-ageing; Holistic; Homeodynamics; Homeostasis; Longevity; Stress Life Expectancy and Mortality Rates in the United States, 1959-2017. Woolf SH, Schoomaker H. JAMA. 2019 Nov 26;322(20):1996-2016. doi: 10.1001/jama.2019.16932. PMID: 31769830 Abstract IMPORTANCE: US life expectancy has not kept pace with that of other wealthy countries and is now decreasing. OBJECTIVE: To examine vital statistics and review the history of changes in US life expectancy and increasing mortality rates; and to identify potential contributing factors, drawing insights from current literature and an analysis of state-level trends. EVIDENCE: Life expectancy data for 1959-2016 and cause-specific mortality rates for 1999-2017 were obtained from the US Mortality Database and CDC WONDER, respectively. The analysis focused on midlife deaths (ages 25-64 years), stratified by sex, race/ethnicity, socioeconomic status, and geography (including the 50 states). Published research from January 1990 through August 2019 that examined relevant mortality trends and potential contributory factors was examined. FINDINGS: Between 1959 and 2016, US life expectancy increased from 69.9 years to 78.9 years but declined for 3 consecutive years after 2014. The recent decrease in US life expectancy culminated a period of increasing cause-specific mortality among adults aged 25 to 64 years that began in the 1990s, ultimately producing an increase in all-cause mortality that began in 2010. During 2010-2017, midlife all-cause mortality rates increased from 328.5 deaths/100 000 to 348.2 deaths/100 000. By 2014, midlife mortality was increasing across all racial groups, caused by drug overdoses, alcohol abuse, suicides, and a diverse list of organ system diseases. The largest relative increases in midlife mortality rates occurred in New England (New Hampshire, 23.3%; Maine, 20.7%; Vermont, 19.9%) and the Ohio Valley (West Virginia, 23.0%; Ohio, 21.6%; Indiana, 14.8%; Kentucky, 14.7%). The increase in midlife mortality during 2010-2017 was associated with an estimated 33 307 excess US deaths, 32.8% of which occurred in 4 Ohio Valley states. CONCLUSIONS AND RELEVANCE: US life expectancy increased for most of the past 60 years, but the rate of increase slowed over time and life expectancy decreased after 2014. A major contributor has been an increase in mortality from specific causes (eg, drug overdoses, suicides, organ system diseases) among young and middle-aged adults of all racial groups, with an onset as early as the 1990s and with the largest relative increases occurring in the Ohio Valley and New England. The implications for public health and the economy are substantial, making it vital to understand the underlying causes. Pre- and post-diagnostic intake of whole grain and dairy products and breast cancer prognosis: the Danish Diet, Cancer and Health cohort. Andersen JLM, Hansen L, Thomsen BLR, Christiansen LR, Dragsted LO, Olsen A. Breast Cancer Res Treat. 2019 Nov 26. doi: 10.1007/s10549-019-05497-1. [Epub ahead of print] PMID: 31773360 Abstract PURPOSE: Fiber rich foods and dairy products have been suggested to be associated with breast cancer prognosis, though existing research is limited and either report on pre- or post-diagnostic dietary intake in relation to breast cancer prognosis. We investigated the associations between intake of whole grain (WG) and dairy products assessed both pre- and post-diagnostically in relation to breast cancer prognosis. METHODS: A total of 1965 women from the Diet, Cancer and Health cohort who were diagnosed with breast cancer between baseline (1993-1997) and December 2013 were included and followed for a median of 7 years after diagnosis. During follow-up, 309 women experienced breast cancer recurrence and 460 women died, of whom 301 died from breast cancer. Dietary assessment by food frequency questionnaires was obtained up to three times, pre- and post-diagnostic, over a period of 18 years. Cox proportional hazard models were used to estimate hazard ratios. RESULTS: No associations were observed between pre- or post-diagnostic intake of total WG or total dairy products and breast cancer prognosis. A high pre-diagnostic intake of oatmeal/muesli was associated with lower all-cause mortality (HR 0.76, 95% CI 0.59-0.99), whereas high post-diagnostic intake of rye bread was associated with higher breast cancer-specific mortality (HR 1.29, 95% CI 1.02-1.63). A generally high intake of cheese was associated with a higher recurrence rate. CONCLUSION: Pre-diagnostic intake of oatmeal/muesli was associated with lower all-cause mortality, and post-diagnostic intake of rye bread was associated with higher breast cancer specific mortality. KEYWORDS: Breast cancer prognosis; Cohort study; Dairy products; Epidemiology; Whole grains Mindfulness-Based Blood Pressure Reduction (MB-BP): Stage 1 single-arm clinical trial. Loucks EB, Nardi WR, Gutman R, Kronish IM, Saadeh FB, Li Y, Wentz AE, Webb J, Vago DR, Harrison A, Britton WB. PLoS One. 2019 Nov 27;14(11):e0223095. doi: 10.1371/journal.pone.0223095. eCollection 2019. PMID: 31774807 Abstract BACKGROUND AND OBJECTIVES: Impacts of mindfulness-based programs on blood pressure remain equivocal, possibly because the programs are not adapted to engage with determinants of hypertension, or due to floor effects. Primary objectives were to create a customized Mindfulness-Based Blood Pressure Reduction (MB-BP) program, and to evaluate acceptability, feasibility, and effects on hypothesized proximal self-regulation mechanisms. Secondary outcomes included modifiable determinants of blood pressure (BP), and clinic-assessed systolic blood pressure (SBP). METHODS: This was a Stage 1 single-arm trial with one year follow-up. Focus groups and in-depth interviews were performed to evaluate acceptability and feasibility. Self-regulation outcomes, and determinants of BP, were assessed using validated questionnaires or objective assessments. The MB-BP curriculum was adapted from Mindfulness-Based Stress Reduction to direct participants' mindfulness skills towards modifiable determinants of blood pressure. RESULTS: Acceptability and feasibility findings showed that of 53 eligible participants, 48 enrolled (91%). Of these, 43 (90%) attended at least 7 of the 10 MB-BP classes; 43 were followed to one year (90%). Focus groups (n = 19) and semi-structured interviews (n = 10) showed all participants viewed the delivery modality favorably, and identified logistic considerations concerning program access as barriers. A priori selected primary self-regulation outcomes showed improvements at one-year follow-up vs. baseline, including attention control (Sustained Attention to Response Task correct no-go score, p<0.001), emotion regulation (Difficulties in Emotion Regulation Score, p = 0.02), and self-awareness (Multidimensional Assessment of Interoceptive Awareness, p<0.001). Several determinants of hypertension were improved in participants not adhering to American Heart Association guidelines at baseline, including physical activity (p = 0.02), Dietary Approaches to Stop Hypertension-consistent diet (p<0.001), and alcohol consumption (p<0.001). Findings demonstrated mean 6.1 mmHg reduction in SBP (p = 0.008) at one year follow-up; effects were most pronounced in Stage 2 uncontrolled hypertensives (SBP≥140 mmHg), showing 15.1 mmHg reduction (p<0.001). CONCLUSION: MB-BP has good acceptability and feasibility, and may engage with self-regulation and behavioral determinants of hypertension.