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  1. A Meta-Analysis of 46 Studies Identified by the FDA Demonstrates that Soy Protein Decreases Circulating LDL and Total Cholesterol Concentrations in Adults. Blanco Mejia S, Messina M, Li SS, Viguiliouk E, Chiavaroli L, Khan TA, Srichaikul K, Mirrahimi A, Sievenpiper JL, Kris-Etherton P, Jenkins DJA. J Nutr. 2019 Apr 22. pii: nxz020. doi: 10.1093/jn/nxz020. [Epub ahead of print] PMID: 31006811 Abstract BACKGROUND: Certain plant foods (nuts and soy protein) and food components (viscous fibers and plant sterols) have been permitted by the FDA to carry a heart health claim based on their cholesterol-lowering ability. The FDA is currently considering revoking the heart health claim for soy protein due to a perceived lack of consistent LDL cholesterol reduction in randomized controlled trials. OBJECTIVE: We performed a meta-analysis of the 46 controlled trials on which the FDA will base its decision to revoke the heart health claim for soy protein. METHODS: We included the 46 trials on adult men and women, with baseline circulating LDL cholesterol concentrations ranging from 110 to 201 mg/dL, as identified by the FDA, that studied the effects of soy protein on LDL cholesterol and total cholesterol (TC) compared with non-soy protein. Two independent reviewers extracted relevant data. Data were pooled by the generic inverse variance method with a random effects model and expressed as mean differences with 95% CI. Heterogeneity was assessed and quantified. RESULTS: Of the 46 trials identified by the FDA, 43 provided data for meta-analyses. Of these, 41 provided data for LDL cholesterol, and all 43 provided data for TC. Soy protein at a median dose of 25 g/d during a median follow-up of 6 wk decreased LDL cholesterol by 4.76 mg/dL (95% CI: -6.71, -2.80 mg/dL, P < 0.0001; I2 = 55%, P < 0.0001) and decreased TC by 6.41 mg/dL (95% CI: -9.30, -3.52 mg/dL, P < 0.0001; I2 = 74%, P < 0.0001) compared with non-soy protein controls. There was no dose-response effect or evidence of publication bias for either outcome. Inspection of the individual trial estimates indicated most trials (∼75%) showed a reduction in LDL cholesterol (range: -0.77 to -58.60 mg/dL), although only a minority of these were individually statistically significant. CONCLUSIONS: Soy protein significantly reduced LDL cholesterol by approximately 3-4% in adults. Our data support the advice given to the general public internationally to increase plant protein intake. KEYWORDS: LDL cholesterol; cardiovascular disease prevention; lipids; meta-analysis; soy protein; total cholesterol Consumption of Meat, Fish, Dairy Products, Eggs and Risk of Ischemic Heart Disease: A Prospective Study of 7198 Incident Cases Among 409,885 Participants in the Pan-European EPIC Cohort. Key TJ, Appleby PN, Bradbury KE, Sweeting M, Wood A, Johansson I, Kühn T, Steur M, Weiderpass E, Wennberg M, Würtz AML, Agudo A, Andersson J, Arriola L, Boeing H, Boer JMA, Bonnet F, Boutron-Ruault MC, Cross AJ, Ericson U, Fagherazzi G, Ferrari P, Gunter M, Huerta JM, Katzke V, Khaw KT, Krogh V, La Vecchia C, Matullo G, Moreno-Iribas C, Naska A, Nilsson LM, Olsen A, Overvad K, Palli D, Panico S, Molina-Portillo E, Quirós JR, Skeie G, Sluijs I, Sonestedt E, Stepien M, Tjønneland A, Trichopoulou A, Tumino R, Tzoulaki I, van der Schouw YT, Verschuren WMM, Di Angelantonio E, Langenberg C, Forouhi N, Wareham N, Butterworth A, Riboli E, Danesh J. Circulation. 2019 Apr 22. doi: 10.1161/CIRCULATIONAHA.118.038813. [Epub ahead of print] PMID: 31006335 Abstract BACKGROUND: There is uncertainty about the relevance of animal foods to the etiology of ischemic heart disease (IHD). We examined meat, fish, dairy products and eggs and risk for IHD in the pan-European EPIC cohort. METHODS: A prospective study of 409,885 men and women in nine European countries. Diet was assessed using validated questionnaires, calibrated using 24-hour recalls. Lipids and blood pressure were measured in a subsample. During 12.6 years mean follow up, 7198 participants had a myocardial infarction or died from IHD. The relationships of animal foods with risk were examined using Cox regression with adjustment for other animal foods and relevant covariates. RESULTS: The hazard ratio (HR) for IHD was 1.19 (95% CI 1.06-1.33) for a 100 g/d increment in intake of red and processed meat, and this remained significant after excluding the first 4 years of follow-up (HR 1.25 [1.09-1.42]). Risk was inversely associated with intakes of yogurt (HR 0.93 [0.89-0.98] per 100 g/d increment), cheese (HR 0.92 [0.86-0.98] per 30 g/d increment) and eggs (HR 0.93 [0.88-0.99] per 20 g/d increment); the associations with yogurt and eggs were attenuated and non-significant after excluding the first 4 years of follow-up. Risk was not significantly associated with intakes of poultry, fish or milk. In analyses modelling dietary substitutions, replacement of 100 kcal/d from red and processed meat with 100 kcal/d from fatty fish, yogurt, cheese or eggs was associated with approximately 20% lower risk of IHD. Consumption of red and processed meat was positively associated with serum non-HDL cholesterol concentration and systolic blood pressure, and consumption of cheese was inversely associated with serum non-HDL cholesterol. CONCLUSIONS: Risk for IHD was positively associated with consumption of red and processed meat, and inversely associated with consumption of yogurt, cheese and eggs, although the associations with yogurt and eggs may be influenced by reverse causation bias. It is not clear whether the associations with red and processed meat and cheese reflect causality, but they were consistent with the associations of these foods with plasma non-HDL cholesterol, and for red and processed meat with systolic blood pressure, which could mediate such effects. KEYWORDS: dairy products; eggs; fish; meat Time of Exercise Specifies the Impact on Muscle Metabolic Pathways and Systemic Energy Homeostasis. Sato S, Basse AL, Schönke M, Chen S, Samad M, Altıntaş A, Laker RC, Dalbram E, Barrès R, Baldi P, Treebak JT, Zierath JR, Sassone-Corsi P. Cell Metab. 2019 Apr 12. pii: S1550-4131(19)30183-4. doi: 10.1016/j.cmet.2019.03.013. [Epub ahead of print] PMID: 31006592 https://sci-hub.tw/10.1016/j.cmet.2019.03.013 Abstract While the timing of food intake is important, it is unclear whether the effects of exercise on energy metabolism are restricted to unique time windows. As circadian regulation is key to controlling metabolism, understanding the impact of exercise performed at different times of the day is relevant for physiology and homeostasis. Using high-throughput transcriptomic and metabolomic approaches, we identify distinct responses of metabolic oscillations that characterize exercise in either the early rest phase or the early active phase in mice. Notably, glycolytic activation is specific to exercise at the active phase. At the molecular level, HIF1α, a central regulator of glycolysis during hypoxia, is selectively activated in a time-dependent manner upon exercise, resulting in carbohydrate exhaustion, usage of alternative energy sources, and adaptation of systemic energy expenditure. Our findings demonstrate that the time of day is a critical factor to amplify the beneficial impact of exercise on both metabolic pathways within skeletal muscle and systemic energy homeostasis. KEYWORDS: HIF1α; circadian rhythms; energy homeostasis; exercise metabolism; glycolysis; lipid oxidation; metabolomics; skeletal muscle; transcriptomics
  2. Habitual coffee consumption and risk of falls in 2 European cohorts of older adults. Machado-Fragua MD, Struijk EA, Ballesteros JM, Ortolá R, Rodriguez-Artalejo F, Lopez-Garcia E. Am J Clin Nutr. 2019 Apr 21. pii: nqy369. doi: 10.1093/ajcn/nqy369. [Epub ahead of print] PMID: 31005970 https://sci-hub.tw/10.1093/ajcn/nqy369 Abstract BACKGROUND: Habitual coffee consumption has been associated with lower risk of type 2 diabetes, cardiovascular disease, and sarcopenia, which are strong risk factors of falls. In addition, caffeine intake stimulates attention and vigilance, and reduces reaction time. Therefore, a protective effect of coffee on the risk of falling can be hypothesized. OBJECTIVES: The aim of this study was to examine the association between habitual coffee consumption and the risk of ≥1 falls, injurious falls, and falls with fracture in older people. METHODS: Data were taken from 2964 participants aged ≥60 y from the Seniors-ENRICA (Study on Nutrition and Cardiovascular Risk in Spain) cohort and 8999 participants aged ≥60 y from the UK Biobank cohort. In the Seniors-ENRICA study, habitual coffee consumption was assessed with a validated diet history in 2008-2010, and falls were ascertained up to 2015. In the UK Biobank study, coffee was measured with 3-5 multiple-pass 24-h food records starting in 2006, and falls were assessed up to 2016. RESULTS: A total of 793 individuals in Seniors-ENRICA and 199 in UK Biobank experienced ≥1 fall during follow-up. After multivariable adjustment for major lifestyle and dietary risk factors and compared with daily consumption of <1 cup of coffee, the pooled HR for ≥1 fall was 0.75 (95% CI: 0.52, 1.07) for total coffee consumption of 1 cup/d and 0.74 (95% CI: 0.62, 0.90) for ≥2 cups/d (P-trend = 0.001). The corresponding figures for caffeinated coffee were 0.67 (95% CI: 0.42, 1.07) and 0.70 (95% CI: 0.56, 0.87) (P-trend < 0.001). Decaffeinated coffee was not associated with risk of falling in the analyzed cohorts. In Seniors-ENRICA, there was a tendency to lower risk of injurious falls among those consuming caffeinated coffee (HR: 0.83; 95% CI: 0.68, 1.00 for 1 cup/d; HR: 0.83; 95% CI: 0.64, 1.09 for ≥2 cups/d; P-trend = 0.09). No association was observed between caffeinated or decaffeinated coffee consumption and risk of falls with fracture. CONCLUSIONS: Habitual coffee consumption was associated with lower risk of falling in older adults in Spain and the United Kingdom.
  3. Lower carbohydrate diets and all-cause and cause-specific mortality: a population-based cohort study and pooling of prospective studies. Mazidi M, Katsiki N, Mikhailidis DP, Sattar N, Banach M. Eur Heart J. 2019 Apr 19. pii: ehz174. doi: 10.1093/eurheartj/ehz174. [Epub ahead of print] PMID: 31004146 Abstract AIMS: Little is known about the long-term association between low-carbohydrate diets (LCDs) and mortality. We evaluated the link between LCD and overall or cause-specific mortality using both individual data and pooled prospective studies. METHODS AND RESULTS: Data on diets from the National Health and Nutrition Examination Survey (NHANES; 1999-2010) were analysed. Multivariable Cox proportional hazards were applied to determine the hazard ratios and 95% confidence intervals (CIs) for mortality for each quartile of the LCD score, with the lowest quartile (Q1-with the highest carbohydrates intake) used as reference. We used adjusted Cox regression to determine the risk ratio (RR) and 95% CI, as well as random effects models and generic inverse variance methods to synthesize quantitative and pooled data, followed by a leave-one-out method for sensitivity analysis. Overall, 24 825 participants from NHANES study were included (mean follow-up 6.4 years). After adjustment, participants with the lowest carbohydrates intake (quartile 4 of LCD) had the highest risk of overall (32%), cardiovascular disease (CVD) (50%), cerebrovascular (51%), and cancer (36%) mortality. In the same model, the association between LCD and overall mortality was stronger in the non-obese (48%) than in the obese (19%) participants. Findings on pooled data of nine prospective cohort studies with 462 934 participants (mean follow-up 16.1 years) indicated a positive association between LCD and overall (RR 1.22, 95% CI 1.06-1.39, P < 0.001, I2 = 8.6), CVD (RR 1.13, 95% CI 1.02-1.24, P < 0.001, I2 = 11.2), and cancer mortality (RR 1.08, 95% CI 1.01-1.14, P = 0.02, I2 = 10.3). These findings were robust in sensitivity analyses. CONCLUSION: Our study suggests a potentially unfavourable association of LCD with overall and cause-specific mortality, based on both new analyses of an established cohort and by pooling previous cohort studies. Given the nature of the study, causality cannot be proven; we cannot rule out residual bias. Nevertheless, further studies are needed to extend these important findings, which if confirmed, may suggest a need to rethink recommendations for LCD in clinical practice. KEYWORDS: Cancer; Cardiovascular; Low-carbohydrate diets; Mortality Meal Timing, Aging, and Metabolic Health. Kessler K, Pivovarova-Ramich O. Int J Mol Sci. 2019 Apr 18;20(8). pii: E1911. doi: 10.3390/ijms20081911. Review. PMID: 31003407 file:///C:/Users/Owner/Downloads/ijms-20-01911.pdf Abstract A growing body of evidence suggests that meal timing is an important factor for metabolic regulation and that the circadian clock tightly interacts with metabolic functions. The proper functioning of the circadian clock is critical for maintaining metabolic health. Therefore, chrononutrition, a novel discipline which investigates the relation between circadian rhythms, nutrition, and metabolism, has attracted increasing attention in recent years. Circadian rhythms are strongly affected by obesity, type 2 diabetes, and other dietary-induced metabolic diseases. With increasing age, the circadian system also undergoes significant changes which contribute to the dysregulation of metabolic rhythms. Metabolic diseases are a major health concern, particularly in light of a growing aging population, and effective approaches for their prevention and treatment are urgently needed. Recently, animal studies have impressively shown beneficial effects of several dietary patterns (e.g., caloric restriction or time-restricted feeding) on circadian rhythms and metabolic outcomes upon nutritional challenges. Whether these dietary patterns show the same beneficial effects in humans is, however, less well studied. As indicated by recent studies, dietary approaches might represent a promising, attractive, and easy-to-adapt strategy for the prevention and therapy of circadian and metabolic disturbances in humans of different age. KEYWORDS: aging; chrononutrition; circadian clock; meal timing; metabolic health Effect of a high-fat Mediterranean diet on bodyweight and waist circumference: a prespecified secondary outcomes analysis of the PREDIMED randomised controlled trial. Estruch R, Martínez-González MA, Corella D, Salas-Salvadó J, Fitó M, Chiva-Blanch G, Fiol M, Gómez-Gracia E, Arós F, Lapetra J, Serra-Majem L, Pintó X, Buil-Cosiales P, Sorlí JV, Muñoz MA, Basora-Gallisá J, Lamuela-Raventós RM, Serra-Mir M, Ros E; PREDIMED Study Investigators. Lancet Diabetes Endocrinol. 2019 May;7(5):e6-e17. doi: 10.1016/S2213-8587(19)30074-9. PMID: 31003626 Abstract BACKGROUND: Because of the high density of fat, high-fat diets are perceived as likely to lead to increased bodyweight, hence health-care providers are reluctant to recommend them to overweight or obese individuals. We assessed the long-term effects of ad libitum, high-fat, high-vegetable-fat Mediterranean diets on bodyweight and waist circumference in older people at risk of cardiovascular disease, most of whom were overweight or obese. METHODS: PREDIMED was a 5 year parallel-group, multicentre, randomised, controlled clinical trial done in primary care centres affiliated to 11 hospitals in Spain. 7447 asymptomatic men (aged 55-80 years) and women (aged 60-80 years) who had type 2 diabetes or three or more cardiovascular risk factors were randomly assigned (1:1:1) with a computer-generated number sequence to one of three interventions: Mediterranean diet supplemented with extra-virgin olive oil (n=2543); Mediterranean diet supplemented with nuts (n=2454); or a control diet (advice to reduce dietary fat; n=2450). Energy restriction was not advised, nor was physical activity promoted. In 2016, we reported the 5 year changes in bodyweight and waist circumference, but because of a subsequently identified protocol deviation (including enrolment of household members without randomisation, assignment to a study group without randomisation of some participants at one of 11 study sites, and apparent inconsistent use of randomisation tables at another site; 866 [11·6%] participants were affected in total), we have withdrawn our previously published report and now report revised effect estimates based on reanalyses that do not rely exclusively on the assumption that all the participants were randomly assigned. In this analysis of the trial, we measured bodyweight and waist circumference at baseline and yearly for 5 years in the intention-to-treat population. The PREDIMED trial is registered with ISRCTN.com, number ISRCTN35739639. FINDINGS: After a median 4·8 years (IQR 2·8-5·8) of follow-up, participants in all three groups had marginally reduced bodyweight and increased waist circumference. After multivariable adjustment, including adjustment for propensity scores and use of robust variance estimators, the difference in 5 year changes in bodyweight in the Mediterranean diet with olive oil group was -0·410 kg (95% CI -0·830 to 0·010; p=0·056) and in the nut group was -0·016 kg (-0·453 to 0·421; p=0·942), compared with the control group. The adjusted difference in 5 year changes in waist circumference was -0·466 cm (-1·109 to 0·176; p=0·154) in the Mediterranean diet with olive oil group and -0·923 cm (-1·604 to -0·241; p=0·008) in the nut group, compared with the control group. INTERPRETATION: A long-term intervention with an unrestricted-calorie, high-vegetable-fat Mediterranean diet was associated with no significant difference in bodyweight and some evidence of less gain in central adiposity compared with a control diet. These results lend support to advice not restricting intake of healthy fats for bodyweight maintenance. FUNDING: Spanish Government, CIBERobn, Instituto de Salud Carlos III, Hojiblanca, Patrimonio Comunal Olivarero, California Walnut Commission, Borges SA, and Morella Nuts.
  4. DHA Cycling Halves the DHA Supplementation Needed to Maintain Blood and Tissue Concentrations via Higher Synthesis from ALA in Long-Evans Rats. Metherel AH, Irfan M, Chouinard-Watkins R, Trépanier MO, Stark KD, Bazinet RP. J Nutr. 2019 Apr 1;149(4):586-595. doi: 10.1093/jn/nxy282. PMID: 30715388 Abstract BACKGROUND: Eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) recommendations are frequently stated at 500 mg/d; however, adherence to these recommendations would result in a large global commercial EPA/DHA production deficit. Previously, our laboratory demonstrated that acute DHA intake in rats can increase the capacity for synthesis-secretion of n-3 (ω-3) polyunsaturated fatty acids (PUFAs). OBJECTIVE: We aimed to investigate the utility of a dietary DHA cycling strategy that employs 2 wk of repeated DHA feeding for a total of 3 cycles over 12 wk. METHODS: Male Long-Evans rats were fed a 10% fat diet by weight comprised of either 1) a 2-wk, 2% α-linolenic acid (ALA, DHA-ALA group 18:3n-3) diet followed by a 2-wk, 2% DHA + 2% ALA diet over 3 consecutive 4-wk periods ("DHA cycling," DHA-ALA group); 2) a 2% DHA + 2% ALA diet (DHA group) for 12 wk; or 3) a 2% ALA-only diet (ALA group) for 12 wk. At 15 wk old, blood and tissue fatty acid concentrations and liver mRNA expression and 13C-DHA natural abundances were determined. RESULTS: DHA concentrations in plasma, erythrocytes, and whole blood between the DHA-ALA group and the DHA groups were not different (P ≥ 0.05), but were 72-110% higher (P < 0.05) than in the ALA group. Similarly, DHA concentrations in liver, heart, adipose, and brain were not different (P ≥ 0.05) between the DHA-fed groups, but were at least 62%, 72%, 320%, and 68% higher (P < 0.05) than in the ALA group in liver, heart, adipose, and skeletal muscle, respectively. Compound-specific isotope analysis indicated that 310% more liver DHA in the DHA-ALA group compared with the DHA group is derived from dietary ALA, and this was accompanied by a 123% and 93% higher expression of elongation of very long-chain (Elovl)2 and Elovl5, respectively, in the DHA-ALA group compared with the ALA group. CONCLUSIONS: DHA cycling requires half the dietary DHA while achieving equal blood and tissue DHA concentrations in rats. Implementation of such dietary strategies in humans could reduce the gap between global dietary n-3 PUFA recommendations and commercial production. KEYWORDS: DHA cycling; docosahexaenoic acid; lipids; nutrition; n–3 PUFA production deficit; n–3 polyunsaturated fatty acids Single nucleotide polymorphisms at the ADIPOQ gene locus rs1501299 interact with different type of dietary fatty acids in two hypocaloric diets. de Luis DA, Izaola O, Primo D, Aller R. Eur Rev Med Pharmacol Sci. 2019 Apr;23(7):2960-2970. doi: 10.26355/eurrev_201904_17577. PMID: 31002147 Abstract OBJECTIVE: Some adiponectin gene (ADIPOQ) and single nucleotide polymorphisms (SNPs) have been related to adiponectin levels and metabolic parameters. Few studies of interaction gene-nutrient have been realized in this topic area. The aim of our study was to analyze the effect of the rs1501299 ADIPOQ gene polymorphism, and the dietary intake on total adiponectin levels and the insulin resistance changes after an enriched-monounsaturated fat (Diet M) vs. an enriched-polyunsaturated fat hypocaloric diet (Diet P). PATIENTS AND METHODS: A Caucasian population of 363 obese patients was enrolled in a randomized clinical trial with two hypocaloric diets. Before and after 12 weeks on each hypocaloric diet, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were realized. The statistical analysis was performed for the combined GT and TT as a group (mutant) and GG as second group (wild). RESULTS: With both caloric restriction strategies, body weight, body mass index (BMI), fat mass, waist circumference, systolic blood pressure and leptin levels decreased. After Diet P, only subjects with GG genotype showed a significant improvement in the insulin levels (GG vs. GT±TT) (-3.2±1.0 mU/L vs. -0.6±0.4 mU/L: p=0.01) and in the homeostasis model assessment (HOMA-IR) (-1.1±0.2 units vs. -0.3±0.4 units: p=0.02). The same improvement in both parameters was reported after Diet M: insulin levels (-3.7±0.9 mU/L vs. -0.4±0.5 mU/L: p=0.01) and HOMA-IR (-1.0±0.2 units vs. -0.4±0.3 units: p=0.03). After weight loss with diet M, both genotypes (GG vs. GT±TT) showed similar decrease in total cholesterol and LDL-cholesterol. Only subjects with GG genotype showed a significant increase of the adiponectin levels after both diets: (Diet P: 9.3±3.0 ng/dl vs. Diet M: 8.2±2.9 ng/dl: p=0.38). CONCLUSIONS: The GG genotype of ADIPOQ gene variant (rs1501299) is associated to a significant improvement in the adiponectin levels and a decrease of insulin and HOMA-IR after two different hypocaloric diets with different profile of unsaturated dietary fats. Time-Restricted Feeding Improves Glucose Tolerance in Men at Risk for Type 2 Diabetes: A Randomized Crossover Trial. Hutchison AT, Regmi P, Manoogian ENC, Fleischer JG, Wittert GA, Panda S, Heilbronn LK. Obesity (Silver Spring). 2019 Apr 19. doi: 10.1002/oby.22449. [Epub ahead of print] PMID: 31002478 https://sci-hub.tw/10.1002/oby.22449 Abstract OBJECTIVE: This study aimed to assess the effects of 9-hour time-restricted feeding (TRF), early (TRFe) or delayed (TRFd), on glucose tolerance in men at risk for type 2 diabetes. METHODS: Fifteen men (age 55 ± 3 years, BMI 33.9 ± 0.8 kg/m2 ) wore a continuous glucose monitor for 7 days of baseline assessment and during two 7-day TRF conditions. Participants were randomized to TRFe (8 am to 5 pm) or TRFd (12 pm to 9 pm), separated by a 2-week washout phase. Glucose, insulin, triglycerides, nonesterified fatty acids, and gastrointestinal hormone incremental areas under the curve were calculated following a standard meal on days 0 and 7 at 8 am (TRFe) or 12 pm (TRFd). RESULTS: TRF improved glucose tolerance as assessed by a reduction in glucose incremental area under the curve (P = 0.001) and fasting triglycerides (P = 0.003) on day 7 versus day 0. However, there were no mealtime by TRF interactions in any of the variables examined. There was also no effect of TRF on fasting and postprandial insulin, nonesterified fatty acids, or gastrointestinal hormones. Mean fasting glucose by continuous glucose monitor was lower in TRFe (P = 0.02) but not TRFd (P = 0.17) versus baseline, but there was no difference between TRF conditions. CONCLUSIONS: While only TRFe lowered mean fasting glucose, TRF improved glycemic responses to a test meal in men at risk for type 2 diabetes regardless of the clock time that TRF was initiated. SIRT6 Is Responsible for More Efficient DNA Double-Strand Break Repair in Long-Lived Species. Tian X, Firsanov D, Zhang Z, Cheng Y, Luo L, Tombline G, Tan R, Simon M, Henderson S, Steffan J, Goldfarb A, Tam J, Zheng K, Cornwell A, Johnson A, Yang JN, Mao Z, Manta B, Dang W, Zhang Z, Vijg J, Wolfe A, Moody K, Kennedy BK, Bohmann D, Gladyshev VN, Seluanov A, Gorbunova V. Cell. 2019 Apr 18;177(3):622-638.e22. doi: 10.1016/j.cell.2019.03.043. PMID: 31002797 Abstract DNA repair has been hypothesized to be a longevity determinant, but the evidence for it is based largely on accelerated aging phenotypes of DNA repair mutants. Here, using a panel of 18 rodent species with diverse lifespans, we show that more robust DNA double-strand break (DSB) repair, but not nucleotide excision repair (NER), coevolves with longevity. Evolution of NER, unlike DSB, is shaped primarily by sunlight exposure. We further show that the capacity of the SIRT6 protein to promote DSB repair accounts for a major part of the variation in DSB repair efficacy between short- and long-lived species. We dissected the molecular differences between a weak (mouse) and a strong (beaver) SIRT6 protein and identified five amino acid residues that are fully responsible for their differential activities. Our findings demonstrate that DSB repair and SIRT6 have been optimized during the evolution of longevity, which provides new targets for anti-aging interventions. KEYWORDS: DNA DSB repair; DNA repair; NER; SIRT6; aging; longevity Risk factors for gestational diabetes: An umbrella review of meta-analyses of observational studies. Giannakou K, Evangelou E, Yiallouros P, Christophi CA, Middleton N, Papatheodorou E, Papatheodorou SI. PLoS One. 2019 Apr 19;14(4):e0215372. doi: 10.1371/journal.pone.0215372. eCollection 2019. PMID: 31002708 https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0215372&type=printable Abstract BACKGROUND/OBJECTIVE: Gestational diabetes mellitus (GDM) is a common pregnancy complication, with complex disease mechanisms, and several risk factors may contribute to its onset. We performed an umbrella review to summarize the evidence from meta-analyses of observational studies on risk factors associated with GDM, evaluate whether there are indications of biases in this literature and identify which of the previously reported associations are supported by convincing evidence. METHODS: We searched PubMed and ISI Web of Science from inception to December 2018 to identify meta-analyses examining associations between putative risk factors for GDM. For each meta-analysis we estimated the summary effect size, the 95% confidence interval, the 95% prediction interval, the between-study heterogeneity, evidence of small-study effects, and evidence of excess-significance bias. RESULTS: Thirty eligible meta-analyses were identified, providing data on 61 associations. Fifty (82%) associations had nominally statistically significant findings (P<0.05), while only 15 (25%) were significant at P<10-6 under the random-effects model. Only four risk factors presented convincing evidence:, low vs. normal BMI (cohort studies), BMI ~30-35 kg/m2 vs. normal BMI, BMI >35 kg/m2 vs. normal BMI, and hypothyroidism. CONCLUSIONS: The compilation of results from synthesis of observational studies suggests that increased BMI and hypothyroidism show the strongest consistent evidence for an association with GDM. Diet and lifestyle modifications in pregnancy should be tested in large randomized trials. Our findings suggest that women with known thyroid disease may be offered screening for GDM earlier in pregnancy.
  5. AlPater

    Al's CR updates

    Effects of Calorie Restriction and Voluntary Exercise on Doxorubicin-Induced Cardiotoxicity. Hall SE, Smuder AJ, Hayward R. Integr Cancer Ther. 2019 Jan-Dec;18:1534735419843999. doi: 10.1177/1534735419843999. PMID: 30999765 https://journals.sagepub.com/doi/pdf/10.1177/1534735419843999 Abstract INTRODUCTION: Doxorubicin (DOX) is a widely used chemotherapeutic agent with known cardiotoxic properties, while calorie restriction (CR) and exercise have well-documented cardioprotective effects. No studies have investigated the effects of CR alone or the combined effects of CR and exercise on DOX cardiotoxicity. METHODS: Rats were divided into 4 groups based on their food intake (ad libitum or CR) and activity (sedentary or voluntary wheel running [WR]). After completing a 16-week treatment, animals received either DOX (15 mg/kg) or saline (SAL) and cardiac function was measured 5 days after treatment. Chromatography was used to quantify left ventricular DOX accumulation. RESULTS: Left ventricular developed pressure (LVDP), end systolic pressure (ESP), and left ventricular maximal rate of pressure development (dP/dtmax) were significantly higher in the CR + DOX group when compared with DOX. Fractional shortening, LVDP, ESP, dP/dtmax, and dP/dtmin were significantly higher in the CR + WR + DOX group compared with the DOX group. In addition, the CR + WR + DOX group showed significantly higher LVDP and ESP compared with the WR + DOX group. DOX accumulation in the heart was 5-fold lower ( P < .05) in the CR + WR + DOX group compared with the DOX group. CONCLUSION: This is the first study to demonstrate that CR can reduce cardiac DOX accumulation, and confirms the protective role of CR against DOX-induced cardiac dysfunction. Our data also show that combining a known cardioprotective intervention, exercise training, with CR results in additive benefits in the protection against DOX cardiotoxicity. KEYWORDS: calorie restriction; cardiotoxicity; doxorubicin; exercise
  6. Onion (Allium cepa L.) is potentially a good source of important antioxidants. Sidhu JS, Ali M, Al-Rashdan A, Ahmed N. J Food Sci Technol. 2019 Apr;56(4):1811-1819. doi: 10.1007/s13197-019-03625-9. Epub 2019 Feb 13. PMID: 30996417 https://sci-hub.tw/10.1007/s13197-019-03625-9 Abstract Six different cultivars of onions available in the Kuwaiti market were analyzed for various physic-chemical properties, such as, moisture content, sugar composition, TBARS as malondialdehyde, total phenolic content, as well as trolox equivalent antioxidant capacity, these cultivars comprised of US onions white, US onions yellow, Indian onions red, Egyptian onions red, New Zealand onions golden and Saudi onions white. Layers from each onion bulb were manually cut and separated into three nearly equal portions, i.e., outer layers, middle layers and the inner layers. The outermost layers of the bulb showed the highest concentration of antioxidant compounds and a distinct decreasing trend was observed towards the innermost layers in all types of onion samples. The onion samples studied showed variations in carbohydrate contents (glucose, fructose and sucrose), which would have important implications in affecting the flavor (sweetness and pungency) and the suitability of these onions for processing. An important observation is about the distribution of antioxidant compounds with the highest contents in the outmost layers of the onions than in their middle and inner layers. Unfortunately, these outer layers are generally discarded by the consumers thus depriving them of the important health-promoting phytochemicals. KEYWORDS: Allium cepa; Antioxidant capacity; Free radical scavenging activity; Sugars; Total phenolics
  7. Diet and colorectal cancer in UK Biobank: a prospective study. Bradbury KE, Murphy N, Key TJ. Int J Epidemiol. 2019 Apr 17. pii: dyz064. doi: 10.1093/ije/dyz064. [Epub ahead of print] PMID: 30993317 Abstract BACKGROUND: Most of the previous studies on diet and colorectal cancer were based on diets consumed during the 1990s. METHODS: We used Cox-regression models to estimate adjusted hazard ratios for colorectal cancer by dietary factors in the UK Biobank study. Men and women aged 40-69 years at recruitment (2006-10) reported their diet on a short food-frequency questionnaire (n = 475 581). Dietary intakes were re-measured in a large sub-sample (n = 175 402) who completed an online 24-hour dietary assessment during follow-up. Trends in risk across the baseline categories were calculated by assigning re-measured intakes to allow for measurement error and changes in intake over time. RESULTS: During an average of 5.7 years of follow-up, 2609 cases of colorectal cancer occurred. Participants who reported consuming an average of 76 g/day of red and processed meat compared with 21 g/day had a 20% [95% confidence interval (CI): 4-37] higher risk of colorectal cancer. Participants in the highest fifth of intake of fibre from bread and breakfast cereals had a 14% (95% CI: 2-24) lower risk of colorectal cancer. Alcohol was associated with an 8% (95% CI: 4-12) higher risk per 10 g/day higher intake. Fish, poultry, cheese, fruit, vegetables, tea and coffee were not associated with colorectal-cancer risk. CONCLUSIONS: Consumption of red and processed meat at an average level of 76 g/d that meets the current UK government recommendation (≤90 g/day) was associated with an increased risk of colorectal cancer. Alcohol was also associated with an increased risk of colorectal cancer, whereas fibre from bread and breakfast cereals was associated with a reduced risk. KEYWORDS: Diet; UK Biobank; colorectal cancer; processed meat; prospective study; red meat Association between consumption of fruit or processed fruit and chronic diseases and their risk factors: a systematic review of meta-analyses. Fardet A, Richonnet C, Mazur A. Nutr Rev. 2019 Apr 17. pii: nuz004. doi: 10.1093/nutrit/nuz004. [Epub ahead of print] PMID: 30995309 https://sci-hub.tw/10.1093/nutrit/nuz004 Abstract CONTEXT: The degree of fruit processing is rarely considered in epidemiological studies of fruit consumption. OBJECTIVE: Pooled analyses and meta-analyses of cohort studies and randomized controlled trials that linked fruit consumption with the risk of chronic disease and metabolic deregulation were reviewed systematically to examine the effects of fruit processing. DATA SOURCES: The Web of Science and Cochrane Library databases were searched until June 2018. Search terms, querying the article title only, were based on multiple combinations and included the following: type of publication, fruit products, and chronic diseases and their risk factors. STUDY SELECTION: The selection of studies and the systematic review were carried out in accordance with the PRISMA statement. DATA EXTRACTION: The literature search identified 189 pooled analyses and meta-analyses, 10 of which met the inclusion criteria. RESULTS: The results showed that the degree of processing influences the health effects of fruit-based products. Fresh and dried fruits appeared to have a neutral or protective effect on health, 100% fruit juices had intermediary effects, and high consumption of canned fruit and sweetened fruit juice was positively associated with the risk of all-cause mortality and type 2 diabetes, respectively. CONCLUSIONS: The results support the need to consider the degree of food processing in future epidemiological studies and randomized controlled trials in order to adjust official recommendations for fruit consumption. KEYWORDS: chronic diseases; fruit; meta-analyses; pooled; processing; systematic review
  8. Humor: Local germaphobe/health guru dies grisly, unsanitary death after contracting infection from soap dispenser at vegan cooking retreat BENJAMIN PORTER— BBPORTER@UCDAVIS.EDU Photo Credits: CAITLYN SAMPLEY / AGGIE https://theaggie.org/2019/04/14/humor-local-germaphobe-health-guru-dies-grisly-unsanitary-death-after-contracting-infection-from-soap-dispenser-at-vegan-cooking-retreat/ Avert your eyes, and anything else that can contract infection D. Finn Kumquat was quite successful as an avocado — f***ing hell, excuse me, I’m sorry — was quite successful as an advocate of the health food movement. He spent decades serving the local community from his private practice as a “licensed” diet, health, wellness, motivation and primary personal companion plant positivity consulting professional. It is with heavy hearts that we relay the sad news that D. Kumquat passed away this past weekend after an unlikely series of freak coincidences, none of which were preventable by his healthy lifestyle and extreme germaphobic tendencies. For six months, D. Kumquat had been living in virtual isolation with several other health food aficionados at a vegan cooking retreat at a Freeganist grass-fed, cage-free, free-range, GMO-free, pesticide-free, certified transitional cooperative farm on the California coast. A few Meatless Mondays ago, during an artisanal probiotic juicing class, D. Kumquat accidentally sliced his hand while cleaning the blade of his spiralizer. He lost concentration because a classmate, Annie Yocksidance, tripped over the compost bin, spilling a bowl of passion fruit, açaí berries and other superfoods all over the room while Teacher Quinua Aquafaba answered questions on differences between the Whole 30, keto, paleo, vegan, gluten-free, raw-food, vegetarian, fruitarian, flexitarian, pescatarian and pesca-pescatarian diets. D. Kumquat immediately ran to the restroom to clean the wound, taking every precaution to prevent infection. This was his fatal mistake. Cole Estheral had just left the restroom after a mud bath, leaving grime on the soap dispenser, and out of habit D. Kumquat began furiously pumping the soap dispenser with his injured hand, allowing germs to enter the wound. A lifetime of germaphobic habits had left him with a weak immune system that allowed the infection to fester. For the next week, he did a detox cleanse, engaging in some much needed LTC, using essential oils for aromatherapy and maintaining his CR by eating only an AI of GRAS foods, like kombucha and ACV dressing, all while tracking his BMI, ADME, calories and CALERIE. Alas, the infection prevailed, taking a gruesome toll on his overly purified and sanitized body. While D. Kumquat never introduced himself as “Dr. Kumquat,” most people came to believe that the “D” did indeed stand for “Dr.” and that he just went by “D” to demonstrate his great humility. Unfortunately, the secret of whether or not he actually was a qualified doctor will go with him to the grave — well, actually, to his biodegradable burial pod that will eventually turn his body into a tree (unfortunately there was a mix-up and he will instead become a persimmon tree rather than a kumquat tree, as he requested). Nonetheless, we will always have confidence in his medical competence because of the giant inflatable carrot on his office roof, the neon “HEALTH GURU” window sign and the official-looking framed documents on his wall that were possibly diplomas from some prestigious online university. *Acronym and Abbreviation Guide for those persons actively disengaged from engagement in Earth-positive personal dietary practices: GMO (Genetically Modified Organisms); LTC (long-term care); CR (Caloric Restriction); AI (Adequate Intake); GRAS (Generally Recognized as Safe); ACV (Apple Cider Vinegar); BMI (Body Mass Index); ADME (Absorption, Distribution, Metabolism, Excretion); CALERIE (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy); D (Doctor). Written by: Benjamin Porter— bbporter@ucdavis.edu (This article is humor and/or satire, and its content is purely fictional. The story and the names of “sources” are fictionalized.)
  9. Beverage intake during alternate-day fasting: Relationship to energy intake and body weight. Kalam F, Kroeger CM, Trepanowski JF, Gabel K, Song JH, Cienfuegos S, Varady KA. Nutr Health. 2019 Apr 14:260106019841452. doi: 10.1177/0260106019841452. [Epub ahead of print] PMID: 30983506 Abstract BACKGROUND: Alternate-day fasting (ADF) involves a 'famine day' (25% energy intake) and a 'feast day' (ad libitum intake). This secondary analysis examined changes in beverage intake in relation to energy intake and body weight during 12 months of ADF versus daily calorie restriction (CR). METHODS: Obese subjects ( n = 100 enrolled, n = 69 completers) were randomized to one of three groups for 12 months: (a) ADF; (b) CR; or (c) control. RESULTS: At baseline, intakes of diet soda, caffeinated beverages, sugar-sweetened soda, alcohol, juice, and milk were similar between groups. There were no statistically significant changes in the intake of these beverages by month 6 or 12 between ADF (feast or famine day), CR, or control groups. Beverage intake was not related to energy intake or body weight at month 6 or 12 in any group. CONCLUSION: These pilot findings suggest that intermittent fasting does not impact beverage intake in a way that affects energy intake or body weight. KEYWORDS: Beverage intake; alcohol; alternate-day fasting; body weight; caffeine; calorie restriction; obese adults; soda Dietary choline and betaine intakes and risk of total and lethal prostate cancer in the Atherosclerosis Risk in Communities (ARIC) Study. Han P, Bidulescu A, Barber JR, Zeisel SH, Joshu CE, Prizment AE, Vitolins MZ, Platz EA. Cancer Causes Control. 2019 Apr;30(4):343-354. doi: 10.1007/s10552-019-01148-4. Epub 2019 Mar 1. PMID: 30825046 Abstract PURPOSE: Two prior cohort studies suggested that choline, but not betaine intake, is associated with an increased risk of advanced prostate cancer (PCa). Given that evidence remains limited, we evaluated whether intakes of choline and derivative betaine are associated with total and lethal PCa risk and PCa death in men with PCa. METHODS: We included 6,528 men (24.4% African American) without a cancer diagnosis at baseline (1987-1989) followed through 2012. Dietary intake was assessed using a food frequency questionnaire coupled with a nutrient database. We used Cox proportional hazards regression to estimate hazards ratios (HRs) and 95% confidence intervals (CIs) of total and lethal PCa risk overall and by race. RESULTS: Choline intake was not associated with total (n = 811) or lethal (n = 95) PCa risk overall or by race. Betaine intake was inversely associated with lethal (tertile 3 vs 1, HR 0.59, 95% CI 0.35-1.00, p trend = 0.04), but not total PCa risk; patterns for lethal PCa were similar by race. Neither nutrient was associated with PCa death in men with PCa. CONCLUSIONS: Choline intake was not associated with total or lethal PCa or with PCa death in men with PCa. Betaine intake was inversely associated with lethal, but not total PCa risk or with PCa death in men with PCa. Our results do not support the hypothesis that higher choline intake increases lethal PCa risk, but do suggest that higher betaine intake may be associated with lower lethal PCa risk. Further investigation with a larger number of lethal cases is needed. KEYWORDS: Case-fatality; Choline; Incidence; Lethal prostate cancer; Race
  10. 'Is red meat good or bad?' Researchers say that's the wrong question In assessing heart health from diets without red meat, pay attention to what's substituted in its place CBC News · Posted: Apr 15, 2019 https://www.cbc.ca/news/health/red-meat-meta-analysis-1.5096917 >>>>>>>>>>>>>>>>>>>>>>>>> Meta-Analysis of Randomized Controlled Trials of Red Meat Consumption in Comparison With Various Comparison Diets on Cardiovascular Risk Factors. Guasch-Ferré M, Satija A, Blondin SA, Janiszewski M, Emlen E, O'Connor LE, Campbell WW, Hu FB, Willett WC, Stampfer MJ. Circulation. 2019 Apr 9;139(15):1828-1845. doi: 10.1161/CIRCULATIONAHA.118.035225. PMID: 30958719 https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.118.035225 Abstract BACKGROUND: Findings among randomized controlled trials evaluating the effect of red meat on cardiovascular disease risk factors are inconsistent. We provide an updated meta-analysis of randomized controlled trials on red meat and cardiovascular risk factors and determine whether the relationship depends on the composition of the comparison diet, hypothesizing that plant sources would be relatively beneficial. METHODS: We conducted a systematic PubMed search of randomized controlled trials published up until July 2017 comparing diets with red meat with diets that replaced red meat with a variety of foods. We stratified comparison diets into high-quality plant protein sources (legumes, soy, nuts); chicken/poultry/fish; fish only; poultry only; mixed animal protein sources (including dairy); carbohydrates (low-quality refined grains and simple sugars, such as white bread, pasta, rice, cookies/biscuits); or usual diet. We performed random-effects meta-analyses comparing differences in changes of blood lipids, apolipoproteins, and blood pressure for all studies combined and stratified by specific comparison diets. RESULTS: Thirty-six studies totaling 1803 participants were included. There were no significant differences between red meat and all comparison diets combined for changes in blood concentrations of total, low-density lipoprotein, or high-density lipoprotein cholesterol, apolipoproteins A1 and B, or blood pressure. Relative to the comparison diets combined, red meat resulted in lesser decreases in triglycerides (weighted mean difference [WMD], 0.065 mmol/L; 95% CI, 0.000-0.129; P for heterogeneity <0.01). When analyzed by specific comparison diets, relative to high-quality plant protein sources, red meat yielded lesser decreases in total cholesterol (WMD, 0.264 mmol/L; 95% CI, 0.144-0.383; P<0.001) and low-density lipoprotein (WMD, 0.198 mmol/L; 95% CI, 0.065-0.330; P=0.003). In comparison with fish, red meat yielded greater decreases in low-density lipoprotein (WMD, -0.173 mmol/L; 95% CI, -0.260 to -0.086; P<0.001) and high-density lipoprotein (WMD, -0.065 mmol/L; 95% CI, -0.109 to -0.020; P=0.004). In comparison with carbohydrates, red meat yielded greater decreases in triglycerides (WMD, -0.181 mmol/L; 95% CI, -0.349 to -0.013). CONCLUSIONS: Inconsistencies regarding the effects of red meat on cardiovascular disease risk factors are attributable, in part, to the composition of the comparison diet. Substituting red meat with high-quality plant protein sources, but not with fish or low-quality carbohydrates, leads to more favorable changes in blood lipids and lipoproteins. KEYWORDS: apolipoproteins; blood pressure; diet; lipids; meat; red meat Dietary-fat effect of the rs10830963 polymorphism in MTNR1B on insulin resistance in response to 3 months weight-loss diets. de Luis DA, Izaola O, Primo D, Aller R. Endocrinol Diabetes Nutr. 2019 Apr 10. pii: S2530-0164(19)30062-X. doi: 10.1016/j.endinu.2019.02.007. [Epub ahead of print] English, Spanish. PMID: 30981681 Abstract BACKGROUND & AIMS: The risk allele (G) of rs10830963 in the melatonin receptor 1 B (MTNR1B) gene presents an association with obesity. We study the effect of this SNP on cardiovascular risk factors and weight loss secondary to 2hypocaloric diets. METHODS: 361 obese subjects were randomly allocated during 3 months (Diet M - high monounsaturated fat hypocaloric diet vs. Diet P - high polyunsaturated fat hypocaloric diet). Anthropometric parameters, fasting blood glucose, C-reactive protein (CRP), insulin concentration, insulin resistance (HOMA-IR), lipid profile and adipocytokines levels were measured. Genotype of MTNR1B gene polymorphism (rs10830963) was evaluated. RESULTS: All anthropometric parameters, systolic blood pressure and leptin levels decreased in all subjects after both diets. This improvement of anthropometric parameters was higher in non G allele carriers than G allele carriers. After dietary intervention with Diet M, (CC vs. CG + GG); total cholesterol (delta: -10.4 ± 2.1mg/dl vs. -6.4 ± 1.2mg/dl: P <.05), LDL-cholesterol (delta:-7.1 ± 0.9mg/dl vs. -2.8 ± 0.8mg/dl: P <.05), insulin (delta:-3.0 ± 0.8 UI/L vs. -2.0 ± 1.0 UI/L: P<.05) and HOMA-IR (delta:-3.4 ± 1.0 units vs. -2.9 ± 0.9 units: P<.05) improved in no G allele carriers. After Diet P, in the group of subjects without G allele CC, insulin levels (delta: -2.9 ± 1.0 UI/L vs. -0.6 ± 0.2 UI/L: P <.05) and HOMA-IR (delta (CC vs. CG + GG): -0.8 ± 0.2 units vs. -0.4 ± 0.3 units: P <.05) decreased, too. CONCLUSIONS: Our study detected a relationship of rs10830963 MTNR1B SNP with body weight loss and insulin resistance modification induced by 2different hypocaloric. Only monounsaturated enriched hypocaloric diet and in no-G allele carriers showed a significant effect on lipoproteins. KEYWORDS: Dieta hipocalórica; Dietary fat; Grasa de la dieta; Hypocaloric diet; MTNR1B; rs10830963 Whole grain, bran and cereal fibre consumption and CVD: a systematic review. Barrett EM, Batterham MJ, Ray S, Beck EJ. Br J Nutr. 2019 Apr;121(8):914-937. doi: 10.1017/S000711451900031X. Epub 2019 Feb 14. PMID: 30761962 https://sci-hub.tw/10.1017/S000711451900031X Abstract Whole grain intake is associated with lower CVD risk in epidemiological studies. It is unclear to what extent cereal fibre, located primarily within the bran, is responsible. This review aimed to evaluate association between intake of whole grain, cereal fibre and bran and CVD risk. Academic databases were searched for human studies published before March 2018. Observational studies reporting whole grain and cereal fibre or bran intake in association with any CVD-related outcome were included. Studies were separated into those defining whole grain using a recognised definition (containing the bran, germ and endosperm in their natural proportions) (three studies, seven publications) and those using an alternative definition, such as including added bran as a whole grain source (eight additional studies, thirteen publications). Intake of whole grain, cereal fibre and bran were similarly associated with lower risk of CVD-related outcomes. Within the initial analysis, where studies used the recognised whole grain definition, results were less likely to show attenuation after adjustment for cereal fibre content. The fibre component of grain foods appears to play an important role in protective effects of whole grains. Adjusting for fibre content, associations remained, suggesting that additional components within the whole grain, and the bran component, may contribute to cardio-protective association. The limited studies and considerable discrepancy in defining and calculating whole grain intake limit conclusions. Future research should utilise a consistent definition and methodical approach of calculating whole grain intake to contribute to a greater body of consistent evidence surrounding whole grains. KEYWORDS: ; CRP C-reactive protein; HPFS Health Professionals Follow-up Study; HR hazard ratio; NHS Nurses’Health Study; RR relative risk; T2DM type 2 diabetes mellitus; Bran; CVD; Fibre; Systematic reviews; Whole grains Insulin-like growth factor I, binding proteins -1 and -3, risk of type 2 diabetes and macronutrient intakes in men. Similä ME, Kontto JP, Virtamo J, Hätönen KA, Valsta LM, Sundvall J, Männistö S. Br J Nutr. 2019 Apr;121(8):938-944. doi: 10.1017/S0007114519000321. Epub 2019 Mar 22. PMID: 30898176 Abstract The insulin-like growth factor (IGF) axis may be involved in the development of type 2 diabetes. We examined the associations of IGF-I and IGF binding proteins (IGFBP)-1 and -3 with diabetes risk and evaluated macronutrient intakes related to the observed associations. In a nested case-control study of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish male smokers aged 50-69 years, the IGF variables were measured from baseline serum samples for a random sample of 310 men with diabetes diagnosed during a 12-year follow-up and for 310 controls matched by age, recruitment day and intervention group. Diet at baseline was assessed using a validated FFQ. The associations of IGF proteins with diabetes risk were estimated using conditional logistic regression and the associations with macronutrient intakes using linear regression. IGF-I and IGFBP-3 were not associated with the incidence of diabetes. Higher IGFBP-1 was associated with lower diabetes risk in an unadjusted crude model (OR 0·25; 95 % CI 0·15, 0·42 in the highest quartile compared with the lowest), but not after adjustment for BMI (corresponding OR 0·76; 95 % CI 0·41, 1·40). Intakes of carbohydrates, plant protein and milk protein associated positively and intake of meat protein and fat negatively with IGFBP-1 (P&lt;0·005). IGFBP-1 was inversely associated with diabetes risk, but the association was substantially dependent on BMI. The associations between macronutrient intakes and IGFBP-1 may reflect influences of nutrients or foods on insulin concentrations. KEYWORDS: ATBC Alpha-Tocopherol; Beta-Carotene Cancer Prevention; IGF insulin-like growth factor; IGFBP insulin-like growth factor binding protein; Binding protein; Insulin-like growth factor; Insulin-like growth factor binding proteins; Macronutrients; Type 2 diabetes
  11. Does ginger supplementation lower blood pressure? A systematic review and meta-analysis of clinical trials. Hasani H, Arab A, Hadi A, Pourmasoumi M, Ghavami A, Miraghajani M. Phytother Res. 2019 Apr 11. doi: 10.1002/ptr.6362. [Epub ahead of print] Review. PMID: 30972845 Abstract The aim of the present systematic review and meta-analysis was to determine the efficacy of ginger supplementation on blood pressure (BP). PubMed, Scopus, ISI Web of Science, Cochrane Library, and Google Scholar were comprehensively searched until September 2018. Human clinical trials, which reported the effect of ginger supplementation on aortic and/or brachial BP, were included. Mean differences were pooled using a random effects model. Standard methods were used for assessment of heterogeneity, sensitivity analysis, and publication bias. Total of six randomized clinical trials (345 participants) were included in the meta-analysis. Pooled analysis suggested that ginger supplementation can reduced systolic BP (MD: -6.36 mmHg, 95% confidence interval [-11.27, -1.46]; I2 = 89.8%; P = .011) and diastolic BP (MD: -2.12 mmHg, 95% confidence interval [-3.92, -0.31]; I2 = 73.4%; P = .002). When studies were categorized based on participants' mean age, ginger dosage and duration of intervention, systolic BP and diastolic BP were significantly decreased only in the subset of studies with mean age ≤ 50 years, follow-up duration of ≤8 weeks and ginger doses ≥3 g/d. Our findings revealed that ginger supplementation has favorable effects on BP. Nonetheless, further studies are warranted before definitive conclusions may be reached. KEYWORDS: blood pressure; ginger; meta-analysis; systematic review Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies. Marklund M, Wu JHY, Imamura F, Del Gobbo LC, Fretts A, de Goede J, Shi P, Tintle N, Wennberg M, Aslibekyan S, Chen TA, de Oliveira Otto MC, Hirakawa Y, Eriksen HH, Kröger J, Laguzzi F, Lankinen M, Murphy RA, Prem K, Samieri C, Virtanen J, Wood AC, Wong K, Yang WS, Zhou X, Baylin A, Boer JMA, Brouwer IA, Campos H, Chaves PHM, Chien KL, de Faire U, Djoussé L, Eiriksdottir G, El-Abbadi N, Forouhi NG, Gaziano JM, Geleijnse JM, Gigante B, Giles G, Guallar E, Gudnason V, Harris T, Harris WS, Helmer C, Hellénius ML, Hodge A, Hu FB, Jacques PF, Jansson JH, Kalsbeek A, Khaw KT, Koh WP, Laakso M, Leander K, Lin HJ, Lind L, Luben R, Luo J, McKnight B, Mursu J, Ninomiya T, Overvad K, Psaty BM, Rimm E, Schulze MB, Siscovick D, Skjelbo Nielsen M, Smith AV, Steffen BT, Steffen L, Sun Q, Sundström J, Tsai MY, Tunstall-Pedoe H, Uusitupa MIJ, van Dam RM, Veenstra J, Verschuren WMM, Wareham N, Willett W, Woodward M, Yuan JM, Micha R, Lemaitre RN, Mozaffarian D, Risérus U; Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCE). Circulation. 2019 Apr 11. doi: 10.1161/CIRCULATIONAHA.118.038908. [Epub ahead of print] PMID: 30971107 Abstract BACKGROUND: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies. METHODS: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease (CHD), ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytical plan. Levels of LA and AA, measured as % of total fatty acids, were evaluated linearly according to their interquintile range (i.e., the range between the mid-point of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available). RESULTS: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15,198 incident cardiovascular events occurred among 68,659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI: 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower CHD risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; comparing extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships. CONCLUSIONS: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention. KEYWORDS: Arachidonic acid; Linoleic acid; Pooled analysis; diet and nutrition
  12. AlPater

    Al's CR updates

    The effect of caloric restriction on working memory in healthy non-obese adults. Leclerc E, Trevizol AP, Grigolon RB, Subramaniapillai M, McIntyre RS, Brietzke E, Mansur RB. CNS Spectr. 2019 Apr 10:1-7. doi: 10.1017/S1092852918001566. [Epub ahead of print] PMID: 30968820 https://sci-hub.tw/10.1017/S1092852918001566 Abstract OBJECTIVE: We aim to evaluate the effect of caloric restriction (CR) in cognition by comparing performance in neuropsychological tests for working memory between a group of non-obese healthy subjects doing CR for 2 years with another consuming ad libitum diet (AL). METHODS: This study was part of a larger multicenter trial called CALERIE that consisted of a randomized clinical trial with parallel-group comparing 2 years of 25% CR and AL in 220 volunteers with a BMI between 22 and 28 kg/m2, across 3 sites. The cognitive tests used were the Cambridge Neuropsychological Tests Automated Battery (CANTAB) for Spatial Working Memory (SWM) including the total number of errors (SWMTE) and strategy (SWMS). Included as possible moderators were sleep quality, mood states, perceived stress, and energy expenditure. Analyses were performed at baseline and months 12 and 24. RESULTS: After adjustments, there was a significantly greater improvement in working memory assessed by the SWM for CR individuals, compared to AL. At month 24, it was related mostly to lower protein intake, compared to other macronutrients. Changes in SWM were moderated by changes in sleep quality, physical activity, and energy expenditure. CONCLUSION: On the long term, CR in healthy individuals seems to have a slightly positive effect on working memory. The study of brain CR targets opens new possibilities to prevent and treat cognitive deficits. KEYWORDS: Clinical trial; cognition; diet; mental health; nonpharmacological interventions
  13. Hepatic arginase 2 (Arg2) is sufficient to convey the therapeutic metabolic effects of fasting. Zhang Y, Higgins CB, Fortune HM, Chen P, Stothard AI, Mayer AL, Swarts BM, DeBosch BJ. Nat Commun. 2019 Apr 8;10(1):1587. doi: 10.1038/s41467-019-09642-8. PMID: 30962478 https://www.nature.com/articles/s41467-019-09642-8.pdf Abstract Caloric restriction and intermittent fasting are emerging therapeutic strategies against obesity, insulin resistance and their complications. However, the effectors that drive this response are not completely defined. Here we identify arginase 2 (Arg2) as a fasting-induced hepatocyte factor that protects against hepatic and peripheral fat accumulation, hepatic inflammatory responses, and insulin and glucose intolerance in obese murine models. Arg2 is upregulated in fasting conditions and upon treatment with the hepatocyte glucose transporter inhibitor trehalose. Hepatocyte-specific Arg2 overexpression enhances basal thermogenesis, and protects from weight gain, insulin resistance, glucose intolerance, hepatic steatosis and hepatic inflammation in diabetic mouse models. Arg2 suppresses expression of the regulator of G-protein signalling (RGS) 16, and genetic RGS16 reconstitution reverses the effects of Arg2 overexpression. We conclude that hepatocyte Arg2 is a critical effector of the hepatic glucose fasting response and define a therapeutic target to mitigate the complications of obesity and non-alcoholic fatty liver disease. Short-Term Dietary Intervention with Cooked but Not Raw Brassica Leafy Vegetables Increases Telomerase Activity in CD8+ Lymphocytes in a Randomized Human Trial. Tran HTT, Schreiner M, Schlotz N, Lamy E. Nutrients. 2019 Apr 5;11(4). pii: E786. doi: 10.3390/nu11040786. PMID: 30959753 https://www.mdpi.com/2072-6643/11/4/786/htm Abstract Telomerase in T lymphocytes is dynamic and limited evidence from epidemiological studies indicates that the enzyme can be modulated in peripheral lymphocytes by dietary and lifestyle factors. The differential effect of dietary intervention on T cell subsets has not been investigated so far. Brassica vegetables are known for their multiple beneficial effects on human health, and here, the effect of a five-day short-term intervention with raw or cooked leaves of Brassica carinata on telomerase activity in CD4+ and CD8+ T cells from 22 healthy volunteers was investigated in a randomized single-blind, controlled crossover study. Blood samples were collected before and after intervention, and CD4+/CD8+ T lymphocytes were isolated. Telomerase activity was quantified using the TRAP-ELISA assay. Intervention with both preparations led to a marginal increase in telomerase activity of CD4+ cells compared to the baseline level. In CD8+ cells, a significant increase in telomerase activity (25%, p < 0.05) was seen after intervention with the cooked material. An increase in telomerase activity in CD8+ cells of healthy volunteers could be regarded as beneficial in terms of helping with the cell-mediated immune response. Whether a Brassica intervention has long-term effects on telomere extension in specific T cell subsets needs to be determined. KEYWORDS: Brassica; T lymphocytes; food intervention; isothiocyanates; polyphenols; telomerase activity Relationship between carbohydrate and dietary fibre intake and the risk of cardiovascular disease mortality in Japanese: 24-year follow-up of NIPPON DATA80. Miyazawa I, Miura K, Miyagawa N, Kondo K, Kadota A, Okuda N, Fujiyoshi A, Chihara I, Nakamura Y, Hozawa A, Nakamura Y, Kita Y, Yoshita K, Okamura T, Okayama A, Ueshima H; NIPPON DATA80 Research group. Eur J Clin Nutr. 2019 Apr 8. doi: 10.1038/s41430-019-0424-y. [Epub ahead of print] PMID: 30962516 https://sci-hub.tw/10.1038/s41430-019-0424-y Abstract BACKGROUND/OBJECTIVES: The association between carbohydrate intake and cardiovascular disease (CVD) risk has been investigated, but whether the quality of carbohydrate is more important than its amount is not known. We examined the associations between intake of dietary fibre (DF), carbohydrate, available carbohydrate, and starch with long-term CVD mortality in a Japanese population. SUBJECTS/METHODS: We prospectively followed 8925 participants (3916 men and 5009 women) aged 30-79 years without CVD at baseline who participated in the National Nutrition Survey in Japan. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs) for CVD mortality by quartiles of exposure variables. RESULTS: During 24 years of follow-up, 823 CVD deaths were observed. In men, the multivariable-adjusted HR for CVD mortality was lower in the highest quartile of DF intake (HR: 0.64; 95% CI: 0.47-0.87; Ptrend = 0.007) compared with the lowest quartile. This association was not significant in women. Multivariable-adjusted HR for total stroke mortality was lower in the highest quartile of DF intake (HR: 0.61, 95% CI: 0.38-0.98) compared with the lowest quartile in women. Carbohydrate, available carbohydrate, and starch intake were not associated with CVD mortality. CONCLUSIONS: Higher intake of DF was associated significantly with a lower risk of CVD mortality in men and lower risk of stroke mortality in women. Intake of carbohydrate, available carbohydrate, and starch were not associated with the risk of CVD mortality in men or women.
  14. Vegetarian diet and risk of gout in two separate prospective cohort studies. Chiu THT, Liu CH, Chang CC, Lin MN, Lin CL. Clin Nutr. 2019 Mar 27. pii: S0261-5614(19)30129-3. doi: 10.1016/j.clnu.2019.03.016. [Epub ahead of print] PMID: 30955983 https://sci-hub.tw/10.1016/j.clnu.2019.03.016 Abstract BACKGROUNDS & AIMS: Plant-based diets may target multiple pathways in gout pathogenesis (uric acid reduction and anti-inflammation) while improving gout associated cardiometabolic comorbidities. We aim to prospectively examine the relationship between a vegetarian diet and gout, and to explore if this relationship is independent of hyperuricemia. METHODS: We followed 4903 participants in the Tzu Chi Health Study (Cohort1, recruited in 2007-2009) and 9032 participants in the Tzu Chi Vegetarian Study (Cohort2, recruited in 2005) until end of 2014. Baseline serum uric acid was measured in Cohort1. Vegetarian status was assessed through a diet questionnaire that includes dietary habits and a food frequency questionnaire. Incidence of gout was ascertained by linkage to the National Health Insurance Database. Hazard Ratio of gout in vegetarians versus nonvegetarians was assessed by Cox regression, adjusted for age, sex, lifestyle and metabolic risk factors. Hyperuricemia was additionally adjusted in Cohort1. RESULTS: In Cohort1, lacto-ovo vegetarians had the lowest uric acid concentration, followed by vegans, then nonvegetarians (men: 6.05, 6.19, 6.32 mg/dL, respectively; women: 4.92, 4.96, 5.11 mg/dL, respectively); 65 gout cases occurred in the 29,673 person-years of follow-up; vegetarians experienced a lower risk of gout (without adjustment for hyperuricemia: HR: 0.33; 95% CI: 0.14, 0.79; with adjustment for hyperuricemia: HR: 0.40; 95% CI: 0.17, 0.97). In Cohort2, 161 gout cases occurred in the 83,019 person-years follow-up, and vegetarians also experienced a lower risk of gout (HR: 0.61; 95% CI: 0.41, 0.88). CONCLUSION: Taiwanese vegetarian diet is associated with lower risk of gout. This protective association may be independent of baseline hyperuricemia. STUDY REGISTERED: URL: https://www.clinicaltrials.gov. Unique Identifier: NCT03470584. KEYWORDS: Dietary patterns; Gout incidence; Uric acid; Vegetarian diet Association Among Dietary Supplement Use, Nutrient Intake, and Mortality Among U.S. Adults: A Cohort Study. Chen F, Du M, Blumberg JB, Ho Chui KK, Ruan M, Rogers G, Shan Z, Zeng L, Zhang FF. Ann Intern Med. 2019 Apr 9. doi: 10.7326/M18-2478. [Epub ahead of print] PMID: 30959527 Abstract BACKGROUND: The health benefits and risks of dietary supplement use are controversial. OBJECTIVE: To evaluate the association among dietary supplement use, levels of nutrient intake from foods and supplements, and mortality among U.S. adults. DESIGN: Prospective cohort study. SETTING: NHANES (National Health and Nutrition Examination Survey) data from 1999 to 2010, linked to National Death Index mortality data. PARTICIPANTS: 30 899 U.S. adults aged 20 years or older who answered questions on dietary supplement use. MEASUREMENTS: Dietary supplement use in the previous 30 days and nutrient intake from foods and supplements. Outcomes included mortality from all causes, cardiovascular disease (CVD), and cancer. RESULTS: During a median follow-up of 6.1 years, 3613 deaths occurred, including 945 CVD deaths and 805 cancer deaths. Ever-use of dietary supplements was not associated with mortality outcomes. Adequate intake (at or above the Estimated Average Requirement or the Adequate Intake level) of vitamin A, vitamin K, magnesium, zinc, and copper was associated with reduced all-cause or CVD mortality, but the associations were restricted to nutrient intake from foods. Excess intake of calcium was associated with increased risk for cancer death (above vs. at or below the Tolerable Upper Intake Level: multivariable-adjusted rate ratio, 1.62 [95% CI, 1.07 to 2.45]; multivariable-adjusted rate difference, 1.7 [CI, -0.1 to 3.5] deaths per 1000 person-years), and the association seemed to be related to calcium intake from supplements (≥1000 mg/d vs. no use: multivariable-adjusted rate ratio, 1.53 [CI, 1.04 to 2.25]; multivariable-adjusted rate difference, 1.5 [CI, -0.1 to 3.1] deaths per 1000 person-years) rather than foods. LIMITATIONS: Results from observational data may be affected by residual confounding. Reporting of dietary supplement use is subject to recall bias. CONCLUSION: Use of dietary supplements is not associated with mortality benefits among U.S. adults.
  15. Longevity and cause of death in male Wistar rats fed lifelong diets based on virgin olive oil, sunflower oil or fish oil. Ramirez-Tortosa CL, Varela-López A, Navarro-Hortal MD, Ramos-Pleguezuelos FM, Márquez-Lobo B, Ramirez-Tortosa MC, Ochoa JJ, Battino M, Quiles JL. J Gerontol A Biol Sci Med Sci. 2019 Apr 6. pii: glz091. doi: 10.1093/gerona/glz091. [Epub ahead of print] PMID: 30953048 https://sci-hub.tw/10.1093/gerona/glz091 Abstract Extending life by delaying the aging process have proven to be the most effective way to fight multiple chronic diseases in elderly adults. Evidence suggests that longevity is inversely related to unsaturation of membrane phospholipids. The present study investigated how different unsaturated dietary fats affect lifespan and cause death in male Wistar rats fed diets based on virgin olive oil (V), sunflower oil (S) or fish oil (F), which were supplemented or not with Coenzyme Q10 (CoQ10). Previous results suggest that individual longevity and survival probability at different ages may be modulated by an appropriate dietary fat treatment. Lifelong feeding with V or F diets would reduce death probability compared to feeding with S diet at certain ages, although the effects of V diet would be maintained for most of life. Furthermore, the addition of lower amounts of CoQ10 reduced mortality associated with S diet, but CoQ10 had no effect on survival when combined with virgin olive oil or fish oil. Supplementation with low doses of CoQ10 failed to increase the maximum lifespan potential of rats fed a V or F diet. No clear evidence showing that MUFA, n-3 PUFA or CoQ10 exerted the observed effects by modulating the rate of aging has been found.