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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.

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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

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'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

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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

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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.)

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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

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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

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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.

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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.

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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.

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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

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Habitual Meat Consumption and Changes in Sleep Duration and Quality in Older Adults.
Lana A, Struijk EA, Arias-Fernandez L, Graciani A, Mesas AE, Rodriguez-Artalejo F, Lopez-Garcia E.
Aging Dis. 2019 Apr 1;10(2):267-277. doi: 10.14336/AD.2018.0503. eCollection 2019 Apr.
PMID: 31011478
Abstract
Dietary proteins are sources of some amino acid precursors of two neurotransmitters relevant for biological rhythms, serotonin and melatonin, which are involved in sleep and alertness. Meat is the main source of proteins in many countries. Furthermore, meat consumption is of special interest because it provides high-quality protein as well as saturated and trans fatty acids. However, its effect on sleep patterns is unclear. Thereby, the aim was to examine the association of habitual meat consumption with changes in sleep duration and with sleep quality in older adults. We used data from 1,341 participants in the Seniors-ENRICA cohort aged ≥60 years, followed from 2012 through 2015. Habitual meat consumption was assessed at baseline with a validated diet history. Sleep duration and quality were ascertained both in 2012 and 2015. Analyses were performed with logistic regression and adjusted for socio-demographic variables, lifestyle, morbidity, sleep duration and poor sleep indicators at baseline. During follow-up, 9.0% of individuals increased and 7.9% decreased their sleep duration by ≥2 hours/night. Compared with individuals in the lowest tertile of meat consumption (<87 g/d), those in the highest tertile (≥128 g/d) showed increased incidence of a large decrease (≥2 h) in sleep duration (OR: 1.93; 95% CI:1.01-3.72; p-trend:0.04). Higher consumption of meat was also associated with incidence of snoring (OR:2.06; 95% CI:1.17-3.60; p-trend:0.01) and poor general sleep quality (OR:1.71; 95% CI:1.04-2.82; p-trend:0.03). Each 100 g/d increment in meat intake was associated with a 60% higher risk of both large sleep duration changes and poor sleep quality (OR:1.60; 95% CI:1.07-2.40). Results were in the same direction for red and processed meat and for white meat separately, and among individuals with physical impairment. Higher meat consumption (≥128 g/d) was associated with changes in sleep duration and with poor sleep in older adults.
KEYWORDS:
aging; cohort study; diet; meat; sleep

Prepregnancy Habitual Intakes of Total, Supplemental, and Food Folate and Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study.
Li M, Li S, Chavarro JE, Gaskins AJ, Ley SH, Hinkle SN, Wang X, Ding M, Bell G, Bjerregaard AA, Olsen SF, Mills JL, Hu FB, Zhang C.
Diabetes Care. 2019 Apr 22. pii: dc182198. doi: 10.2337/dc18-2198. [Epub ahead of print]
PMID: 31010874
Abstract
OBJECTIVE:
To identify novel modifiable risk factors of gestational diabetes mellitus (GDM) by examining the association between prepregnancy habitual folate intake and GDM risk.
RESEARCH DESIGN AND METHODS:
The study included 14,553 women in the Nurses' Health Study II who reported at least one singleton pregnancy between the 1991 and 2001 questionnaires. Prepregnancy intakes of total folate, supplemental folate, and food folate were assessed using a food frequency questionnaire administered every 4 years. Incident GDM was ascertained from a self-reported physician diagnosis. Relative risks (RRs) of GDM were estimated using log-binomial models, with adjustment for demographic, lifestyle, and dietary factors.
RESULTS:
Over the study follow-up, 824 incident GDM cases were reported among 20,199 pregnancies. Women with adequate total folate intake (≥400 μg/day) had an RR of GDM of 0.83 (95% CI 0.72, 0,95, P = 0.007) compared with women with inadequate intake (<400 μg/day). This association was entirely driven by supplemental folate intake. The RRs of GDM for 1-399, 400-599, and ≥600 μg/day of supplemental folate intake were 0.83, 0.77, and 0.70, respectively, compared with no supplemental folate intake (P trend = 0.002). The association between supplemental folate intake and GDM risk largely persisted after additional adjustment for intake of multivitamins and other micronutrients, as well as among women who likely planned for the pregnancy.
CONCLUSIONS:
Higher habitual intakes of supplemental folate before pregnancy were significantly associated with lower GDM risk. If confirmed, these findings indicate that prepregnancy folic acid supplementation could offer a novel and low-cost avenue to reduce GDM risk.

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Elevated Triglycerides to High-Density Lipoprotein Cholesterol (TG/HDL-C) Ratio Predicts Long-Term Mortality in High-Risk Patients.
Sultani R, Tong DC, Peverelle M, Lee YS, Baradi A, Wilson AM.
Heart Lung Circ. 2019 Apr 16. pii: S1443-9506(19)30334-8. doi: 10.1016/j.hlc.2019.03.019. [Epub ahead of print]
PMID: 31014557
Abstract
BACKGROUND:
Elevated triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been utilised as a predictor of outcomes in patients with adverse cardiometabolic risk profiles. In this study, we examined the prognostic value of elevated TG/HDL-C level in an Australian population of patients with high clinical suspicion of coronary artery disease (CAD) presenting for coronary angiography.
METHODS:
Follow-up data was collected for 482 patients who underwent coronary angiography in a prospective cohort study. The primary endpoint was all-cause mortality and the secondary endpoint was a major adverse cardiac event (MACE). Patients were stratified into two groups according to their baseline TG/HDL-C ratio, using a TG/HDL-C ratio cut point of 2.5.
RESULTS:
The mean follow-up period was 5.1 ± 1.2 years, with 49 all-cause deaths. Coronary artery disease on coronary angiography was more prevalent in patients with TG/HDL-C ratio ≥2.5 (83.6% vs. 69.4%, p = 0.03). On the Kaplan-Meier analysis, patients with TG/HDL-C ratio ≥2.5 had worse long-term prognosis (p = 0.04). On multivariate Cox regression adjusting for established cardiovascular risk factors and CAD on coronary angiography, TG/HDL-C ratio ≥2.5 was an independent predictor of long-term all-cause mortality (hazard ratio {HR} 2.10, 95% confidence interval [CI] 1.04-4.20, p = 0.04). On multivariate logistic regression adjusting for known cardiovascular risk factors and CAD on coronary angiography, TG/HDL-C ratio ≥2.5 was strongly associated with an increased risk of long-term MACE (odds ratio [OR] 2.72, 95% CI 1.42-5.20, p = 0.002).
CONCLUSIONS:
Elevated TG/HDL-C ratio is an independent predictor of long-term all-cause mortality and is strongly associated with an increased risk of MACE.
KEYWORDS:
All-cause mortality; Coronary; Coronary artery disease; Major adverse cardiovascular events; Triglycerides to high-density lipoprotein cholesterol ratio; angiography

Hemoglobin A1c and 10-year information processing speed in Japanese community dwellers.
Otsuka R, Nishita Y, Tange C, Tomida M, Ando F, Shimokata H.
Environ Health Prev Med. 2019 Apr 23;24(1):24. doi: 10.1186/s12199-019-0778-8.
PMID: 31014232
https://environhealthprevmed.biomedcentral.com/track/pdf/10.1186/s12199-019-0778-8
Abstract
BACKGROUND:
Hyperglycemia is believed to be a risk factor for cognitive decline, but the longitudinal relationship between hyperglycemia and cognitive decline in the Japanese population is unclear. The present study aimed to clarify the association between blood glucose levels and information processing ability in middle-aged and older adults.
METHODS:
The subjects were 866 men and 815 women aged 40-79 years not taking medication for diabetes who participated in the first study wave (1997-2000) and then participated at least once in the subsequent six study waves (2000-2012) of the National Institute for Longevity Sciences-Longitudinal Study of Aging, Japan. Hemoglobin A1c (HbA1c) levels were categorized into four groups (< 5.6, 5.6 to < 6.0, 6.0 to < 6.5, ≥ 6.5%), and a mixed-effects model was used to evaluate the effects of the HbA1c level (four groups) on repeated measures of information processing speed. The models also included baseline age, body mass index, ethanol intake, smoking status, educational level, family income, and history of stroke, hypertension, heart disease, and dyslipidemia as covariates.
RESULTS:
Mean (standard deviation) HbA1c and follow-up time in participants were 5.2 (0.5) % and 10.0 (3.6) years, respectively. A linear mixed model showed that the main effect of the four HbA1c groups on information processing ability was not significant in either men or women, but the interaction of HbA1c and time with information processing speed in the higher HbA1c level groups (≥ 6.5% group in men, 6.0 to < 6.5% and ≥ 6.5% groups in women) was significant compared to the lower HbA1c level (< 5.6%) group (P < 0.05). When the slope of information processing speed by HbA1c level at baseline was examined, the slope of information processing speed in the higher HbA1c level (≥ 6.5%) group was higher than in the lower HbA1c level (< 5.6%) group, both in men (- 0.31/year) and in women (- 0.30/year), as well as in women with an HbA1c level of 6.0 to < 6.5% (- 0.40/year).
CONCLUSIONS:
Higher baseline HbA1c was associated with greater subsequent decline in information processing ability in Japanese community dwellers, even with the pre-clinical HbA1c level (6.0 to < 6.5%) in women. The results suggest that good glycemic control or prevention of hyperglycemia may contribute to maintaining information processing ability.
KEYWORDS:
Community dwellers; Hemoglobin A1c; Information processing speed; Japanese; Longitudinal study

Edited by AlPater

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Low-Carbohydrate Diets and Risk of Incident Atrial Fibrillation: A Prospective Cohort Study.
Zhang S, Zhuang X, Lin X, Zhong X, Zhou H, Sun X, Xiong Z, Huang Y, Fan Y, Guo Y, Du Z, Liao X.
J Am Heart Assoc. 2019 May 7;8(9):e011955. doi: 10.1161/JAHA.119.011955.
PMID: 31020911
https://www.ahajournals.org/doi/pdf/10.1161/JAHA.119.011955
Abstract
Background The influences of low-carbohydrate diets in cardiovascular disease are controversial. Few studies have examined the relationship of carbohydrate intake and risk of incident atrial fibrillation ( AF ). We aimed to evaluate the association between carbohydrate intake and the risk of incident AF in the ARIC (Atherosclerosis Risk in Communities) Study. Methods and Results We included 13 385 participants (age, 54.2±5.8 years; 45.1% men and 74.7% white) who completed a dietary questionnaire at baseline (1987-1989) in the ARIC Study. The primary outcome was incident AF , which was identified by ECG performed during study examinations, hospital discharge codes, and death certificates. We used multivariable Cox hazard regression models to assess the association between carbohydrate intake and incident AF . We further explored the effects of specific food source (animal versus plant based) used to replace carbohydrate intake in the low-carbohydrate intake setting. During a median follow-up of 22.4 years, 1808 cases (13.5%) of AF occurred. The hazard ratio for incident AF associated with a 1- SD (9.4%) increase in carbohydrate intake as a percentage of energy intake was 0.82 (95% CI , 0.72-0.94), after adjustment for traditional AF risk factors and other diets factors. Results were similar when individuals were categorized by carbohydrate intake quartiles (hazard ratio, 0.64; 95% CI , 0.49-0.84; comparing extreme quartiles). No association was found between the type of protein or fat used to replace the carbohydrate and risk of incident AF . Conclusions Low-carbohydrate diets were associated with increased risk of incident AF , regardless of the type of protein or fat used to replace the carbohydrate.
KEYWORDS:
atrial fibrillation; diet; epidemiology; risk factor

Association between coffee intake and the risk of oral cavity cancer: a meta-analysis of observational studies.
He T, Guo X, Li X, Liao C, Yin W.
Eur J Cancer Prev. 2019 Apr 23. doi: 10.1097/CEJ.0000000000000515. [Epub ahead of print]
PMID: 31021885
Abstract
The association between coffee intake and the risk of oral cavity cancer has been inconsistent in previous studies. Therefore, we conducted a meta-analysis to summarize the evidence regarding the strength of association between coffee intake and oral cavity cancer. PubMed, Embase, and Cochrane Library were searched to select studies on the relationship between coffee intake and oral cavity cancer conducted up to September 2018. Case-control or cohort studies and those that have reported about the effect estimates with 95% confidence intervals (CIs) of oral cavity cancer according to the different categories of coffee intake were included. The odds ratio (OR) and its corresponding 95% CI were calculated using the random-effects model. Fourteen case-control and five cohort studies that recruited 6456 patients with oral cavity cancer were included in the final quantitative meta-analysis. High versus low coffee intake was associated with a reduced risk of oral cavity cancer (OR: 0.68; 95% CI: 0.56-0.82; P<0.001) in case-control studies (OR: 0.70; 95% CI: 0.55-0.90; P=0.006) and cohort studies (OR: 0.65; 95% CI: 0.48-0.87; P=0.004). Moreover, intermediate coffee intake was significantly associated with a reduced risk of oral cavity cancer (OR: 0.85; 95% CI: 0.77-0.94; P=0.002), and such associations were mainly observed in case-control studies (OR: 0.86; 95% CI: 0.76-0.98; P=0.021) but not in cohort studies (OR: 0.83; 95% CI: 0.67-1.02; P=0.071). High or intermediate coffee intake might have protective effects against oral cavity cancer. However, the underlying mechanisms must be further evaluated in large-scale prospective cohort studies.

Dose-dependent associations between prenatal caffeine consumption and small for gestational age, preterm birth, and reduced birthweight in the Japan Environment and Children's Study.
Kobayashi S, Sata F, Murata K, Saijo Y, Araki A, Miyashita C, Itoh S, Minatoya M, Yamazaki K, Ait Bamai Y, Kishi R; Japan Environment and Children's Study Group.
Paediatr Perinat Epidemiol. 2019 Apr 24. doi: 10.1111/ppe.12551. [Epub ahead of print]
PMID: 31020683
Abstract
BACKGROUND:
Few previous studies have investigated the association between prenatal caffeine intake and birth size (small for gestational age [SGA], preterm birth, and birthweight Z-score) in Japan.
OBJECTIVES:
We examined the dose-dependency of this association (prenatal caffeine consumption and birth size) as part of the Japan Environment and Children's Study.
METHODS:
A prospective birth cohort included 94 876 fetuses in Japan. Participants were enrolled between January 2011 and March 2014. Adjusted multiple linear regression and Cox regression models were used to examine the association between prenatal caffeine levels and infant birth size.
RESULTS:
The median estimated caffeine consumption during pregnancy was 125.5 mg/day, as determined by self-administered questionnaires. There were 7252 SGA infants (7.6%) and 4281 preterm birth infants (4.5%). Compared with infants of mothers whose caffeine consumption during pregnancy was in the lowest quartile (4.2 to <86.4 mg/day), infants of mothers whose caffeine consumption was in the highest quartile 4 (205.5-5080.0 mg/day) were at an increased risk of SGA (relative risk [RR] 1.18, 95% confidence interval [CI] 1.10, 1.27), and at an increased risk of preterm birth at the second trimester of gestation (RR 1.94, 95% CI 1.12, 3.37), with a 0.32-day reduction in gestational age (95% CI -0.52, -0.12) and with a 0.07 reduction in birthweight Z-score observed (95% CI -0.09, -0.05).
CONCLUSIONS:
Prenatal caffeine consumption was associated with birth size. However, as the association between prenatal caffeine consumption and birth size was likely confounded by unpredicted potential factors, our confidence in the true causality of the association is moderate.
KEYWORDS:
birthweight; caffeine; pregnancy; preterm birth; small for gestational age; the Japan Environment and Children's Study

The short-chain fatty acid propionate increases glucagon and FABP4 production, impairing insulin action in mice and humans.
Tirosh A, Calay ES, Tuncman G, Claiborn KC, Inouye KE, Eguchi K, Alcala M, Rathaus M, Hollander KS, Ron I, Livne R, Heianza Y, Qi L, Shai I, Garg R, Hotamisligil GS.
Sci Transl Med. 2019 Apr 24;11(489). pii: eaav0120. doi: 10.1126/scitranslmed.aav0120.
PMID: 31019023
https://stm.sciencemag.org/content/scitransmed/11/489/eaav0120.full.pdf
Abstract
The short-chain fatty acid propionate is a potent inhibitor of molds that is widely used as a food preservative and endogenously produced by gut microbiota. Although generally recognized as safe by the U.S. Food and Drug Administration, the metabolic effects of propionate consumption in humans are unclear. Here, we report that propionate stimulates glycogenolysis and hyperglycemia in mice by increasing plasma concentrations of glucagon and fatty acid-binding protein 4 (FABP4). Fabp4-deficient mice and mice lacking liver glucagon receptor were protected from the effects of propionate. Although propionate did not directly promote glucagon or FABP4 secretion in ex vivo rodent pancreatic islets and adipose tissue models, respectively, it activated the sympathetic nervous system in mice, leading to secretion of these hormones in vivo. This effect could be blocked by the pharmacological inhibition of norepinephrine, which prevented propionate-induced hyperglycemia in mice. In a randomized, double-blind, placebo-controlled study in humans, consumption of a propionate-containing mixed meal resulted in a postprandial increase in plasma glucagon, FABP4, and norepinephrine, leading to insulin resistance and compensatory hyperinsulinemia. Chronic exposure of mice to a propionate dose equivalent to that used for food preservation resulted in gradual weight gain. In humans, plasma propionate decreased with weight loss in the Dietary Intervention Randomized Controlled Trial (DIRECT) and served as an independent predictor of improved insulin sensitivity. Thus, propionate may activate a catecholamine-mediated increase in insulin counter-regulatory signals, leading to insulin resistance and hyperinsulinemia, which, over time, may promote adiposity and metabolic abnormalities. Further evaluation of the metabolic consequences of propionate consumption is warranted.

Baseline serum folate, vitamin B12 and the risk of prostate and breast cancer using data from the Swedish AMORIS cohort.
Essén A, Santaolalla A, Garmo H, Hammar N, Walldius G, Jungner I, Malmström H, Holmberg L, Van Hemelrijck M.
Cancer Causes Control. 2019 Apr 24. doi: 10.1007/s10552-019-01170-6. [Epub ahead of print]
PMID: 31020446
https://link.springer.com/content/pdf/10.1007%2Fs10552-019-01170-6.pdf
Abstract
PURPOSE:
The roles of folate and vitamin B12 in prostate cancer (PCa) or breast cancer (BC) development are unclear. We investigated their roles using the prospective Swedish Apolipoprotein MOrtality RISk (AMORIS) study.
METHODS:
8,783 men and 19,775 women with vitamin B12 and folate serum measurements were included. Their associations with PCa and BC risk categories were evaluated using Cox proportional hazards regression.
RESULTS:
During mean follow-up of 13 years, 703 men developed PCa. There was an inverse association between folate > 32 nmol/L and high-risk PCa [hazard ratio (HR) 0.12, 95% confidence interval (CI) 0.02-0.90], and a positive association between folate < 5 nmol/L and metastatic PCa (HR 5.25, 95% CI 1.29-21.41), compared with folate 5-32 nmol/L. No associations with vitamin B12 were found. 795 women developed BC during mean follow-up of 14 years. When restricting to the fasting population, there was a positive association between folate > 32 nmol/L and BC (HR 1.47, 95% CI 1.06-2.04).
CONCLUSION:
High folate levels may protect against PCa and low folate levels may increase risk of metastatic PCa. High fasting folate levels may be associated with an increased BC risk. Vitamin B12 was not found to be linked with risk of PCa or BC. Longitudinal studies with serum and dietary information could help define new prevention targets and add information on the role of folate fortification.
KEYWORDS:
Breast cancer (BC); Folate; Prostate cancer (PCa); Severity; Vitamin B12

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Association of Skipping Breakfast With Cardiovascular and All-Cause Mortality.
Rong S, Snetselaar LG, Xu G, Sun Y, Liu B, Wallace RB, Bao W.
J Am Coll Cardiol. 2019 Apr 30;73(16):2025-2032. doi: 10.1016/j.jacc.2019.01.065.
PMID: 31023424
Abstract
BACKGROUND:
Skipping breakfast is common among U.S. adults. Limited evidence suggests that skipping breakfast is associated with atherosclerosis and cardiovascular disease.
OBJECTIVES:
The authors sought to examine the association of skipping breakfast with cardiovascular and all-cause mortality.
METHODS:
This is a prospective cohort study of a nationally representative sample of 6,550 adults 40 to 75 years of age who participated in the National Health and Nutrition Examination Survey III 1988 to 1994. Frequency of breakfast eating was reported during an in-house interview. Death and underlying causes of death were ascertained by linkage to death records through December 31, 2011. The associations between breakfast consumption frequency and cardiovascular and all-cause mortality were investigated by using weighted Cox proportional hazards regression models.
RESULTS:
Among the 6,550 participants (mean age 53.2 years; 48.0% male) in this study, 5.1% never consumed breakfast, 10.9% rarely consumed breakfast, 25.0% consumed breakfast some days, and 59.0% consumed breakfast every day. During 112,148 person-years of follow-up, 2,318 deaths occurred including 619 deaths from cardiovascular disease. After adjustment for age, sex, race/ethnicity, socioeconomic status, dietary and lifestyle factors, body mass index, and cardiovascular risk factors, participants who never consumed breakfast compared with those consuming breakfast everyday had hazard ratios of 1.87 (95% confidence interval: 1.14 to 3.04) for cardiovascular mortality and 1.19 (95% confidence interval: 0.99 to 1.42) for all-cause mortality.
CONCLUSIONS:
In a nationally representative cohort with 17 to 23 years of follow-up, skipping breakfast was associated with a significantly increased risk of mortality from cardiovascular disease. Our study supports the benefits of eating breakfast in promoting cardiovascular health.
KEYWORDS:
all-cause mortality; cardiovascular mortality; skipping breakfast

Association of Exposure to Persistent Organic Pollutants With Mortality Risk: An Analysis of Data From the Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS) Study.
Lind PM, Salihovic S, Stubleski J, Kärrman A, Lind L.
JAMA Netw Open. 2019 Apr 5;2(4):e193070. doi: 10.1001/jamanetworkopen.2019.3070.
Abstract
IMPORTANCE:
It has been suggested that persistent organic pollutants (POPs) are harmful to human health.
OBJECTIVE:
To investigate if POP levels in plasma are associated with future mortality.
DESIGN, SETTING, AND PARTICIPANTS:
Cohort study using data from the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, collected between May 2001 and June 2004 when participants reached age 70 years. Participants were followed up for 5 years after the first examination. Mortality was tracked from age 70 to 80 years. Data analysis was conducted in January and February 2018.
EXPOSURES:
Eighteen POPs identified by the Stockholm Convention, including polychlorinated biphenyls (PCBs), organochlorine pesticides, and a brominated flame retardant, were measured in plasma levels by gas chromatography-mass spectrometry.
MAIN OUTCOMES AND MEASURES:
All-cause mortality.
RESULTS:
The study sample initially included 992 individuals (497 [50.1%] men) aged 70 years, who were examined between 2001 and 2004. At the second examination 5 years later, 814 individuals (82.1%; 412 [50.7%] women) completed follow-up. During a follow-up period of 10.0 years, 158 deaths occurred. When updated information on POP levels at ages 70 and 75 years was associated with all-cause mortality using Cox proportional hazard analyses, a significant association was found between hexa-chloro- through octa-chloro-substituted (highly chlorinated) PCBs and all-cause mortality (except PCB 194). The most significant association was observed for PCB 206 (hazard ratio {HR} for 1-SD higher natural log-transformed circulating PCB 206 levels, 1.55; 95% CI, 1.26-1.91; P < .001). Following adjustment for hypertension, diabetes, smoking, body mass index, and cardiovascular disease at baseline, most associations were no longer statistically significant, but PCBs 206, 189, 170, and 209 were still significantly associated with all-cause mortality (PCB 206: adjusted HR, 1.47; 95% CI, 1.19-1.81; PCB 189: adjusted HR, 1.29; 95% CI, 1.08-1.55; PCB 170: adjusted HR, 1.24; 95% CI, 1.02-1.52; PCB 209: adjusted HR, 1.29; 95% CI, 1.04-1.60). In a secondary analysis, these associations were mainly because of death from cardiovascular diseases rather than noncardiovascular diseases. Three organochlorine pesticides, including dichlorodiphenyldichloroethylene, and the brominated flame retardant diphenyl ether 47 were also evaluated but did not show any significant associations with all-cause mortality.
CONCLUSIONS AND RELEVANCE:
Higher levels of highly chlorinated PCBs were associated with an increased mortality risk, especially from cardiovascular diseases. These results suggest that public health actions should be undertaken to minimize exposure to highly chlorinated PCBs.

Alcohol Intake and Risk of Lethal Prostate Cancer in the Health Professionals Follow-Up Study.
Downer MK, Kenfield SA, Stampfer MJ, Wilson KM, Dickerman BA, Giovannucci EL, Rimm EB, Wang M, Mucci LA, Willett WC, Chan JM, Van Blarigan EL.
J Clin Oncol. 2019 Apr 26:JCO1802462. doi: 10.1200/JCO.18.02462. [Epub ahead of print]
PMID: 31026211
Abstract
PURPOSE:
It is unknown whether alcohol intake is associated with the risk of lethal (metastatic or fatal) prostate cancer. We examine (1) whether alcohol intake among men at risk of prostate cancer is associated with diagnosis of lethal prostate cancer and (2) whether intake among men with nonmetastatic prostate cancer is associated with metastasis or death.
METHODS:
This prospective cohort study uses the Health Professionals Follow-Up Study (1986 to 2012). Our analysis of alcohol intake among men at risk of prostate cancer included 47,568 cancer-free men. Our analysis of alcohol intake among men with prostate cancer was restricted to 5,182 men diagnosed with nonmetastatic prostate cancer during follow-up. We examine the association of total alcohol, red and white wine, beer, and liquor with lethal prostate cancer and death. Multivariate Cox proportional hazards regression estimated hazard ratios (HRs) and 95% CIs.
RESULTS:
Alcohol drinkers had a lower risk of lethal prostate cancer (any v none: HR, 0.84 [95% CI, 0.71 to 0.99]) without a dose-response relationship. Total alcohol intake among patients with prostate cancer was not associated with progression to lethal prostate cancer (any v none: HR, 0.99 [95% CI, 0.57 to 1.72]), whereas moderate red wine intake was associated with a lower risk (any v none: HR, 0.50 [95% CI, 0.29 to 0.86]; P trend = .05). Compared with none, 15 to 30 g/d of total alcohol after prostate cancer diagnosis was associated with a lower risk of death (HR, 0.71 [95% CI, 0.50 to 1.00]), as was red wine (any v none: HR, 0.74 [95% CI, 0.57 to 0.97]; P trend = .007).
CONCLUSION:
Cancer-free men who consumed alcohol had a slightly lower risk of lethal prostate cancer compared with abstainers. Among men with prostate cancer, red wine was associated with a lower risk of progression to lethal disease. These observed associations merit additional study but provide assurance that moderate alcohol consumption is safe for patients with prostate cancer.

Edited by AlPater

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Socioeconomic status and risk of cardiovascular disease in 20 low-income, middle-income, and high-income countries: the Prospective Urban Rural Epidemiologic (PURE) study.
Rosengren A, Smyth A, Rangarajan S, Ramasundarahettige C, Bangdiwala SI, AlHabib KF, Avezum A, Bengtsson Boström K, Chifamba J, Gulec S, Gupta R, Igumbor EU, Iqbal R, Ismail N, Joseph P, Kaur M, Khatib R, Kruger IM, Lamelas P, Lanas F, Lear SA, Li W, Wang C, Quiang D, Wang Y, Lopez-Jaramillo P, Mohammadifard N, Mohan V, Mony PK, Poirier P, Srilatha S, Szuba A, Teo K, Wielgosz A, Yeates KE, Yusoff K, Yusuf R, Yusufali AH, Attaei MW, McKee M, Yusuf S.
Lancet Glob Health. 2019 Apr 23. pii: S2214-109X(19)30045-2. doi: 10.1016/S2214-109X(19)30045-2. [Epub ahead of print]
PMID: 31028013
https://www.thelancet.com/pdfs/journals/langlo/PIIS2214-109X(19)30045-2.pdf
Abstract
BACKGROUND:
Socioeconomic status is associated with differences in risk factors for cardiovascular disease incidence and outcomes, including mortality. However, it is unclear whether the associations between cardiovascular disease and common measures of socioeconomic status-wealth and education-differ among high-income, middle-income, and low-income countries, and, if so, why these differences exist. We explored the association between education and household wealth and cardiovascular disease and mortality to assess which marker is the stronger predictor of outcomes, and examined whether any differences in cardiovascular disease by socioeconomic status parallel differences in risk factor levels or differences in management.
METHODS:
In this large-scale prospective cohort study, we recruited adults aged between 35 years and 70 years from 367 urban and 302 rural communities in 20 countries. We collected data on families and households in two questionnaires, and data on cardiovascular risk factors in a third questionnaire, which was supplemented with physical examination. We assessed socioeconomic status using education and a household wealth index. Education was categorised as no or primary school education only, secondary school education, or higher education, defined as completion of trade school, college, or university. Household wealth, calculated at the household level and with household data, was defined by an index on the basis of ownership of assets and housing characteristics. Primary outcomes were major cardiovascular disease (a composite of cardiovascular deaths, strokes, myocardial infarction, and heart failure), cardiovascular mortality, and all-cause mortality. Information on specific events was obtained from participants or their family.
FINDINGS:
Recruitment to the study began on Jan 12, 2001, with most participants enrolled between Jan 6, 2005, and Dec 4, 2014. 160 299 (87·9%) of 182 375 participants with baseline data had available follow-up event data and were eligible for inclusion. After exclusion of 6130 (3·8%) participants without complete baseline or follow-up data, 154 169 individuals remained for analysis, from five low-income, 11 middle-income, and four high-income countries. Participants were followed-up for a mean of 7·5 years. Major cardiovascular events were more common among those with low levels of education in all types of country studied, but much more so in low-income countries. After adjustment for wealth and other factors, the HR (low level of education vs high level of education) was 1·23 (95% CI 0·96-1·58) for high-income countries, 1·59 (1·42-1·78) in middle-income countries, and 2·23 (1·79-2·77) in low-income countries (pinteraction<0·0001). We observed similar results for all-cause mortality, with HRs of 1·50 (1·14-1·98) for high-income countries, 1·80 (1·58-2·06) in middle-income countries, and 2·76 (2·29-3·31) in low-income countries (pinteraction<0·0001). By contrast, we found no or weak associations between wealth and these two outcomes. Differences in outcomes between educational groups were not explained by differences in risk factors, which decreased as the level of education increased in high-income countries, but increased as the level of education increased in low-income countries (pinteraction<0·0001). Medical care (eg, management of hypertension, diabetes, and secondary prevention) seemed to play an important part in adverse cardiovascular disease outcomes because such care is likely to be poorer in people with the lowest levels of education compared to those with higher levels of education in low-income countries; however, we observed less marked differences in care based on level of education in middle-income countries and no or minor differences in high-income countries.
INTERPRETATION:
Although people with a lower level of education in low-income and middle-income countries have higher incidence of and mortality from cardiovascular disease, they have better overall risk factor profiles. However, these individuals have markedly poorer health care. Policies to reduce health inequities globally must include strategies to overcome barriers to care, especially for those with lower levels of education.

Randomized study of the effects of cocoa-rich chocolate on the ventricle-arterial coupling and vascular function of young, healthy adults.
Pereira T, Bergqvist J, Vieira C, Grüner Sveälv B, Castanheira J, Conde J.
Nutrition. 2019 Feb 27;63-64:175-183. doi: 10.1016/j.nut.2019.02.017. [Epub ahead of print]
PMID: 31029045
Abstract
OBJECTIVES:
The aim of this study was to evaluate and explore the benefits of long-term dark chocolate intake in young, healthy adults by measuring cardiovascular function.
METHODS:
A randomized study was conducted with 30 healthy participants ages 18 to 27 y. Half of the participants ingested a 20-g dose of lower cocoa chocolate (LCC; ∼55%; 12.6 ± 1.4 mg equivalent of epicatechin/g) and the others ingested a daily dose of 20 g of higher cocoa chocolate (HCC; ∼90%; 18.2 ± 2.6 mg equivalent of epicatechin/g). A baseline evaluation was performed before the participants started ingesting the assigned chocolate for a 30-d period, after which a final evaluation was performed. Each evaluation included heart ultrasonography, carotid-femoral pulse wave velocity (PWV) and carotid pulse wave analysis, flow-mediated slowing (FMS), and an analysis of the ventricular-arterial coupling (VAC), which reflects the matching between the aorta and the left ventricle (ratio of arterial elastance to left ventricle elastance).
RESULTS:
The baseline evaluation presented similar values within normal range in both groups. The positive vascular effects were overall more distinct in the group eating the HCC. No structural modifications on the heart were found after the intervention, notwithstanding cardiac function was improved on certain functional parameters in the HCC group only. A statistically significant improvement was depicted over the brachial and central systolic and pulse pressures in the HCC group, and a trend for improvement in the reflected waves component (Aix) and the FMS was also observed in the HCC, but not in the LCC group. VAC parameters were similar at baseline between groups, but showed a significant improvement in the HCC group after intervention, increasing from 0.674 to 0.719 (P = 0.004), so that the post-intervention VAC was significantly higher in the HCC group than in the LCC group (P < 0.05). In addition, significant variation was observed in both groups regarding arterial and left ventricle elastances, stroke work, and potential energy, with greater mean differences identified in the HCC group.
CONCLUSION:
This study demonstrated that regular consumption of HCC has beneficial effects on the cardiovascular system in young, healthy adults, improving vascular function by reducing central brachial artery pressures and promoting vascular relaxation, and thus enhancing the matching of the arterial system with the left ventricle.
KEYWORDS:
Arterial stiffness; Cocoa; Flavanols; Ventricle–arterial coupling

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Relationship Between Poor Olfaction and Mortality Among Community-Dwelling Older Adults: A Cohort Study.
Liu B, Luo Z, Pinto JM, Shiroma EJ, Tranah GJ, Wirdefeldt K, Fang F, Harris TB, Chen H.
Ann Intern Med. 2019 Apr 30. doi: 10.7326/M18-0775. [Epub ahead of print]
PMID: 31035288
Abstract
BACKGROUND:
Poor olfaction is common among older adults and has been linked to higher mortality. However, most studies have had a relatively short follow-up and have not explored potential explanations.
OBJECTIVE:
To assess poor olfaction in relation to mortality in older adults and to investigate potential explanations.
DESIGN:
Community-based prospective cohort study.
SETTING:
2 U.S. communities.
PARTICIPANTS:
2289 adults aged 71 to 82 years at baseline (37.7% black persons and 51.9% women).
MEASUREMENTS:
Brief Smell Identification Test in 1999 or 2000 (baseline) and all-cause and cause-specific mortality at 3, 5, 10, and 13 years after baseline.
RESULTS:
During follow-up, 1211 participants died by year 13. Compared with participants with good olfaction, those with poor olfaction had a 46% higher cumulative risk for death at year 10 (risk ratio, 1.46 [95% CI, 1.27 to 1.67]) and a 30% higher risk at year 13 (risk ratio, 1.30 [CI, 1.18 to 1.42]). Similar associations were found in men and women and in white and black persons. However, the association was evident among participants who reported excellent to good health at baseline (for example, 10-year mortality risk ratio, 1.62 [CI, 1.37 to 1.90]) but not among those who reported fair to poor health (10-year mortality risk ratio, 1.06 [CI, 0.82 to 1.37]). In analyses of cause-specific mortality, poor olfaction was associated with higher mortality from neurodegenerative and cardiovascular diseases. Mediation analyses showed that neurodegenerative diseases explained 22% and weight loss explained 6% of the higher 10-year mortality among participants with poor olfaction.
LIMITATION:
No data were collected on change in olfaction and its relationship to mortality.
CONCLUSION:
Poor olfaction is associated with higher long-term mortality among older adults, particularly those with excellent to good health at baseline. Neurodegenerative diseases and weight loss explain only part of the increased mortality.

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Social Integration, Social Support, and All-Cause, Cardiovascular Disease and Cause-Specific Mortality: A Prospective Cohort Study.
Tan J, Wang Y.
Int J Environ Res Public Health. 2019 Apr 27;16(9). pii: E1498. doi: 10.3390/ijerph16091498.
PMID: 31035622
https://www.mdpi.com/1660-4601/16/9/1498/htm
Abstract
Social relationships are associated with all-cause mortality. Substantial uncertainties remain, however, for the associations of social relationships with mortality from subtypes of cardiovascular disease (CVD) and major non-vascular diseases. This prospective cohort study estimated mortality risks according to social support and social integration utilizing a nationally representative sample of 29,179 adults ages 18 years and older. Cox proportional hazards regression models were employed. Social integration, but not social support was associated with all-cause mortality risk. For CVD mortality, social integration predicted a 33% lower risk (HR = 0.67, 95% CI = 0.53-0.86). The results were similar in magnitude for heart disease mortality. Participants with the highest social integration level had a 53%, 30%, and 47% decreased mortality risk of diabetes, Alzheimer's disease, and chronic lower respiratory diseases (CLRD) than those with the lowest level. These social integration associations were linear and consistent across baseline age, sex and socioeconomic status. We did not observe an association of social integration with the risk of cancer mortality. Our findings support the linear association of social integration but not social support with mortality from a range of major chronic diseases in the US adult population, independent of socioeconomic status (SES), behavioral risk factors, and health status.
KEYWORDS:
cardiovascular disease; cohort; mortality; social integration; social support

Dietary fibre intake and the risk of diverticular disease: a systematic review and meta-analysis of prospective studies.
Aune D, Sen A, Norat T, Riboli E.
Eur J Nutr. 2019 Apr 29. doi: 10.1007/s00394-019-01967-w. [Epub ahead of print] Review.
PMID: 31037341
Abstract
BACKGROUND:
A high intake of dietary fibre has been associated with a reduced risk of diverticular disease in several studies; however, the dose-response relationship between fibre intake and diverticular disease risk has varied, and the available studies have not been summarised in a meta-analysis. We conducted a systematic review and meta-analysis of prospective cohort studies to clarify the association between dietary fibre intake, fibre subtypes, and the risk of diverticular disease.
METHODS:
PubMed and Embase databases were searched up to August 9th 2018. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model and nonlinear associations were modelled using fractional polynomial models.
RESULTS:
Five prospective cohort studies with 19,282 cases and 865,829 participants were included in the analysis of dietary fibre and diverticular disease risk. The summary RR was 0.74 (95% CI 0.71-0.78, I2 = 0%) per 10 g/day. There was no evidence of a nonlinear association between dietary fibre intake and diverticular disease risk, pnonlinearity = 0.35, and there was a 23%, 41% and 58% reduction in risk for an intake of 20, 30, and 40 g/day, respectively, compared to 7.5 g/day. There was no evidence of publication bias with Egger's test, p = 0.58 and the association persisted in subgroup and sensitivity analyses. The summary RR per 10 g/day was 0.74 (95% CI 0.67-0.81, I2 = 60%, n = 4) for cereal fibre, 0.56 (95% CI 0.37-0.84, I2 = 73%, n = 2) for fruit fibre, and 0.80 (95% CI 0.45-1.44, I2 = 87%, n = 2) for vegetable fibre.
CONCLUSIONS:
These results suggest that a high fibre intake may reduce the risk of diverticular disease and individuals consuming 30 g of fibre per day have a 41% reduction in risk compared to persons with a low fibre intake. Further studies are needed on fibre types and risk of diverticular disease and diverticulitis.
KEYWORDS:
Diverticular disease; Fibre; Meta-analysis; Systematic review

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Dietary macronutrient content, age-specific mortality and lifespan.
Senior AM, Solon-Biet SM, Cogger VC, Le Couteur DG, Nakagawa S, Raubenheimer D, Simpson SJ.
Proc Biol Sci. 2019 May 15;286(1902):20190393. doi: 10.1098/rspb.2019.0393.
PMID: 31039722
https://royalsocietypublishing.org/doi/pdf/10.1098/rspb.2019.0393
Abstract
Protein and calorie restrictions extend median lifespan in many organisms. However, studies suggest that among-individual variation in the age at death is also affected. Ultimately, both of these outcomes must be caused by effects of nutrition on underlying patterns of age-specific mortality (ASM). Using model life tables, we tested for effects of dietary macronutrients on ASM in mice ( Mus musculus). High concentrations of protein and fat relative to carbohydrates were associated with low life expectancy and high variation in the age at death, a result caused predominantly by high mortality prior to middle age. A lifelong diet comprising the ratio of macronutrients self-selected by mouse (in early adulthood) was associated with low mortality up until middle age, but higher late-life mortality. This pattern results in reasonably high life expectancy, but very low variation in the age at death. Our analyses also indicate that it may be possible to minimize ASM across life by altering the ratio of dietary protein to carbohydrate in the approach to old age. Mortality in early and middle life was minimized at around one-part protein to two-parts carbohydrate, whereas in later life slightly greater than equal parts protein to carbohydrate reduced mortality.
KEYWORDS:
ageing; calorie; demography; life history; nutrition; standard deviation

Association of High Birth Weight With Incident Heart Failure in the ARIC Study.
Rashid A, Agarwala A, Novak E, Brown DL.
J Am Heart Assoc. 2019 May 7;8(9):e011524. doi: 10.1161/JAHA.118.011524.
PMID: 31041881
https://www.ahajournals.org/doi/pdf/10.1161/JAHA.118.011524
Abstract
Background Traditional risk factors for heart failure--coronary heart disease, hypertension, diabetes mellitus, obesity, and smoking--only account for about 50% of cases. Thus, the identification of novel risk factors is of significant public health importance. As high birth weight infants are at increased risk for obesity and diabetes mellitus later in life, which are both risk factors for the development of heart failure, we sought to assess the association of high birth weight with incident heart failure in the ARIC (Atherosclerosis Risk in Communities) study. Methods and Results The ARIC study is a biracial prospective community-based investigation of 15 792 individuals aged 45 to 64 years at baseline. Study participants who were born premature or born a twin were excluded from this analysis, resulting in 9820 participants who provided either their birth weight category (low, medium, high) or exact birth weight. After adjusting for differences in demographics, risk factors, and comorbidities, compared with medium birth weight, those with high birth weight had a significantly increased risk of incident heart failure (hazard ratio, 1.27; 95% CI , 1.05-1.54 [ P=0.014]). The hazard for all-cause mortality for high birth weight compared with medium birth weight was 1.16 (95% CI , 0.99-1.34; P=0.06). There was no association of high birth weight with myocardial infarction (hazard ratio, 1.06; 95% CI , 0.84-1.34 [ P=0.6]). Conclusions High birth weight was associated with a significantly increased hazard of incident heart failure independent of traditional risk factors and a trend toward an increased hazard of death. A history of high birth weight should be ascertained in young adults for primordial prevention of heart failure and in older adults for primary prevention.
KEYWORDS:
heart failure; obesity; pregnancy; prevention; risk factor

A prospective study of nut consumption and risk of primary hepatocellular carcinoma in the U.S. women and men.
Sui J, Yang W, Ma Y, Li TY, Simon TG, Meyerhardt JA, Liang G, Giovannucci EL, Chan AT, Zhang X.
Cancer Prev Res (Phila). 2019 Apr 30. pii: canprevres.0511.2019. doi: 10.1158/1940-6207.CAPR-18-0511. [Epub ahead of print]
PMID: 31040153
https://sci-hub.tw/http://cancerpreventionresearch.aacrjournals.org/content/early/2019/04/30/1940-6207.CAPR-18-0511
bstract
Although increasing evidence suggests a potential beneficial effect of nut consumption on various diseases, no epidemiologic study has yet examined the association between nut consumption and risk of hepatocellular carcinoma (HCC). We prospectively examined this association in 88,783 women from the Nurses' Health Study and 51,492 men from the Health Professionals Follow-up Study. Nut consumption was assessed every 4 years using validated food frequency questionnaires. Multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards regression models after adjusting for HCC risk factors. After an average of 27.9 years of follow-up, we identified a total of 162 incident HCC cases. Higher total nut consumption was not significantly associated with HCC risk (the highest vs. lowest tertile intake, HR=0.84, 95% CI: 0.56-1.26). For the same comparison, higher tree nut consumption was associated with a lower HCC risk (HR=0.64, 95% CI: 0.43-0.95). We found non-significant inverse associations with consumption of walnuts, peanuts, and peanut butter. Overall, nut consumption was not strongly associated with HCC risk. There was a suggestive inverse association with tree nut consumption. Future studies should carefully consider hepatitis B or C virus infections and examine these associations in other racial/ethnic groups.

Effect of whey protein supplementation during resistance training sessions on body mass and muscular strength: a meta-analysis.
Li M, Liu F.
Food Funct. 2019 May 1. doi: 10.1039/c9fo00182d. [Epub ahead of print]
PMID: 31041966
Abstract
This study evaluates the effect of whey protein (WP) supplementation with resistance training (RT) on body mass and muscular strength through randomized controlled trials (RCTs). A literature survey was conducted using electronic databases, and study selection was based on predetermined eligibility criteria. Meta-analyses of mean differences (MD) in lean/fat mass or standardized MD (SMD) in muscular strength between WP-RT and placebo-RT groups were conducted along with sensitivity and subgroup analyses. Metaregression analyses were performed to identify factors affecting the change in lean/fat mass. Data were used from 21 RCTs in which 837 participants attended 13.1 weeks [95% CI 10.5, 15.7] of RT. In comparison with the placebo-RT group, WP-RT exhibited improved lean mass (MD 0.46 kg [-0.02, 0.94]; p = 0.01), fat mass (MD -0.62 kg [-1.05, -0.19]; p = 0.004) and muscular strength (SMD 0.25 [0.11, 0.38]; p = 0.0003) in healthy individuals but not in individuals with a pathological condition. Moreover, in comparison with the placebo-RT group, the WP-RT group showed improved lean mass (MD 0.38 kg [-0.03, 0.79]; p = 0.07), fat mass (MD -0.75 kg [-1.09, -0.41]; p < 0.00001) and muscular strength (SMD 0.30 [0.13, 0.47]; p = 0.005) in younger (<40 years age) individuals only. The change in lean mass was inversely associated with age in the overall population. The RT duration was positively associated with the improvement in lean mass in healthy individuals. The improvement in fat mass was positively associated with the body height of individuals. WP supplementation during RT sessions was found to improve lean mass, fat mass and muscular strength in healthy and younger individuals.

A Diet Rich in Vegetables and Fruit and Incident CKD: A Community-Based Prospective Cohort Study.
Jhee JH, Kee YK, Park JT, Chang TI, Kang EW, Yoo TH, Kang SW, Han SH.
Am J Kidney Dis. 2019 Apr 27. pii: S0272-6386(19)30662-6. doi: 10.1053/j.ajkd.2019.02.023. [Epub ahead of print]
PMID: 31040089
Abstract
RATIONALE & OBJECTIVE:
A diet rich in vegetables and fruit can lower blood pressure and may reduce cardiovascular risk. However, the association between this dietary pattern and incident chronic kidney disease in the general population is unknown.
STUDY DESIGN:
A community-based prospective cohort study.
SETTING & PARTICIPANTS:
9,229 study participants with normal kidney function from the Korean Genome and Epidemiology Study database.
PREDICTORS:
Daily consumption of nonfermented and fermented vegetables and fruit classified into tertiles based on a validated semiquantitative food-frequency questionnaire.
OUTCOMES:
Incident occurrence of estimated glomerular filtration rate (eGFR) < 60mL/min/1.73m2, incident proteinuria (≥1+ by dipstick test), and repeated measures of estimated net endogenous acid production.
ANALYTICAL APPROACH:
Multivariable cause-specific hazards model to assess the association of vegetable and fruit intake with incident chronic kidney disease.
RESULTS:
During a mean follow-up of 8.2 years, 1,741 (21.9/1,000 person-years [PY]) participants developed eGFRs < 60mL/min/1.73m2. Incident eGFR < 60mL/min/1.73m2 occurred less frequently with higher intake of nonfermented vegetables, occurring at rates of 22.8/1,000 PY, 22.7/1,000 PY, and 20.1/1,000 PY for the lowest, middle, and highest tertiles, respectively; P for trend < 0.001. The incidence of proteinuria was also lower in the middle and highest tertiles. In a multivariable cause-specific hazards model, the highest tertile of nonfermented vegetable intake was associated with 14% lower risk for incident eGFR < 60mL/min/1.73m2 than the lowest tertile. The highest tertile was also associated with 32% lower risk for proteinuria than the lowest tertile. There were no associations of fermented vegetable and fruit intake with incidence of eGFR < 60mL/min/1.73m2. However, the highest tertiles of both fermented vegetable and fruit intake were associated with 14% and 45% lower risks for incident proteinuria compared with the lowest tertiles (both P < 0.001). During follow-up, estimated net endogenous acid production increased in the lowest tertile of intake of nonfermented or fermented vegetables and fruit, whereas it decreased in the highest tertile.
LIMITATIONS:
Self-reported dietary intake, single ethnicity population.
CONCLUSIONS:
A diet rich in vegetables and fruit may reduce the risk for kidney disease.
KEYWORDS:
Vegetable; chronic kidney disease (CKD); diet; eating patterns; estimated glomerular filtration rate (eGFR); fermented vegetable; food choices; fruit; incident CKD; modifiable risk factor; non-fermented vegetable; proteinuria; reduced eGFR

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Dietary intake of fiber, whole grains and risk of colorectal cancer: an updated analysis according to food sources, tumor location and molecular subtypes in two large US cohorts.
He X, Wu K, Zhang X, Nishihara R, Cao Y, Fuchs CS, Giovannucci EL, Ogino S, Chan AT, Song M.
Int J Cancer. 2019 May 1. doi: 10.1002/ijc.32382. [Epub ahead of print]
PMID: 31044426
https://sci-hub.tw/10.1002/ijc.32382
Abstract
Epidemiologic evidence relating fiber intake to colorectal cancer (CRC) remains inconclusive and data are limited on different food sources of fiber and heterogeneity by tumor subsite and molecular profile. We prospectively followed for CRC incidence 90,869 women from the Nurses' Health Study (1980-2012) and 47,924 men from the Health Professionals Follow-up Study (1986-2012), who completed a validated food frequency questionnaire every four years. Cox proportional hazards regression was used to examine the associations with CRC risk for total, cereal, fruit, and vegetable fiber, and whole grains. We also assessed the associations according to tumor subsites (proximal colon, distal colon, and rectum) and molecular markers (microsatellite instability, BRAF mutation, CpG island methylator phenotype, and KRAS mutation). We documented 3,178 CRC cases during 3,685,903 person-years of follow-up in the NHS and HPFS. Intake of total dietary fiber was not associated with CRC risk after multivariable adjustment in either women (Hazard Ratio {HR} comparing extreme deciles, 1.17; 95% CI, 0.92-1.48, Ptrend =0.55) or men (HR, 0.90; 95% CI, 0.67-1.21, Ptrend =0.47). Higher intake of cereal fiber and whole grains was associated with lower CRC risk in men with an HR of 0.75 (95% CI, 0.57-1.00) and 0.72 (95% CI, 0.54-0.96), respectively. No heterogeneity was detected by tumor subsite or molecular markers (Pheterogeneity >0.05). Higher intake of total dietary fiber within the range of a typical American diet is unlikely to substantially reduce colorectal cancer risk. The potential benefit of cereal fiber and whole grains in men warrants further confirmation.
KEYWORDS:
colorectal cancer; fiber; molecular epidemiology; whole grains

Intake of cocoa products and risk of type-2 diabetes: the multiethnic cohort.
Maskarinec G, Jacobs S, Shvetsov Y, Boushey CJ, Setiawan VW, Kolonel LN, Haiman CA, Le Marchand L.
Eur J Clin Nutr. 2018 May 24. doi: 10.1038/s41430-018-0188-9. [Epub ahead of print]
PMID: 29795238
https://sci-hub.tw/10.1038/s41430-018-0188-9
Abstract
BACKGROUND/OBJECTIVES:
As cocoa products may be protective against chronic disease due to their polyphenol content, the current study determined the association of chocolate consumption and flavanol intake with type-2 diabetes (T2D) incidence in the Multiethnic Cohort (MEC) Study.
SUBJECTS/METHODS:
The analysis included 151,691 participants of Native Hawaiian, Japanese American, Latino, African American, and white ancestry with 8487 incident T2D cases after 7.8 ± 3.5 years of follow-up. T2D status was based on three self-reports and confirmed by at least one of three administrative data sources. Dietary intake was assessed using a validated quantitative food frequency questionnaire, and flavanols from cocoa products were estimated from self-reported consumption of chocolate candy and drinks. Cox hazard regression, adjusted for potential confounders was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI).
RESULTS:
For chocolate candy, both the highest vs. lowest (≥10 vs. <1 g/day) consumption (HR = 0.90; 95% CI, 0.83-0.97; ptrend = 0.01) and the frequency (≥4/week vs. <1/month) of intake (HR = 0.81; 95% CI, 0.72-0.91; ptrend = 0.0002) were inversely associated with T2D. The estimated flavanol intake from cocoa products (≥3 vs. <1 mg/day) also showed an inverse association with T2D risk (HR = 0.93; 95% CI, 0.88-0.99; ptrend = 0.02). Significant interaction terms indicated that the inverse relation was limited to Japanese Americans, normal-weight individuals, and to those without comorbidities.
CONCLUSIONS:
The current study confirms previous reports that participants with high intake of chocolate products and cocoa-derived flavanols experience a reduced risk of developing T2D even after controlling for sugar intake, diet quality, and other aspects of the diet.

Edited by AlPater

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FEV1 and total Cardiovascular mortality and morbidity over an 18 years follow-up Population-Based Prospective EPIC-NORFOLK Study.
Ching SM, Chia YC, Lentjes MAH, Luben R, Wareham N, Khaw KT.
BMC Public Health. 2019 May 3;19(1):501. doi: 10.1186/s12889-019-6818-x.
PMID: 31053065
BACKGROUND:
Our study aimed to determine the association between forced expiratory volume in one second (FEV1) and subsequent fatal and non-fatal events in a general population.
METHODS:
The Norfolk (UK) based European Prospective Investigation into Cancer (EPIC-Norfolk) recruited 25,639 participants between 1993 and 1997. FEV1 measured by portable spirometry, was categorized into sex-specific quintiles. Mortality and morbidity from all causes, cardiovascular disease (CVD) and respiratory disease were collected from 1997 up to 2015. Cox proportional hazard regression analysis was used with adjustment for socio-economic factors, physical activity and co-morbidities.
RESULTS:
Mean age of the population was 58.7 ± 9.3 years, mean FEV1 for men was 294± 74 cL/s and 214± 52 cL/s for women. The adjusted hazard ratios for all-cause mortality for participants in the highest fifth of the FEV1 category was 0.63 (0.52, 0.76) for men and 0.62 (0.51, 0.76) for women compared to the lowest quintile. Adjusted HRs for every 70 cL/s increase in FEV1 among men and women were 0.77 (p < 0.001) and 0.68 (p < 0.001) for total mortality, 0.85 (p<0.001) and 0.77 (p<0.001) for CVD and 0.52 (p <0.001) and 0.42 (p <0.001) for respiratory disease.
CONCLUSIONS:
Participants with higher FEV1 levels had a lower risk of CVD and all-cause mortality. Measuring the FEV1 with a portable handheld spirometry measurement may be used as a surrogate marker for cardiovascular risk. Every effort should be made to identify those with poorer lung function even in the absence of cardiovascular disease as they are at greater risk of total and CV mortality.
KEYWORDS:
Cardiovascular; EPIC-NORFOLK; FEV1; Population-Based; Prospective; Respiratory disease; morbidity; mortality

Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and risk of total and cause-specific mortality: results from the Golestan Cohort Study.
Mokhtari Z, Sharafkhah M, Poustchi H, Sepanlou SG, Khoshnia M, Gharavi A, Sohrabpour AA, Sotoudeh M, Dawsey SM, Boffetta P, Abnet CC, Kamangar F, Etemadi A, Pourshams A, FazeltabarMalekshah A, Islami F, Brennan P, Malekzadeh R, Hekmatdoost A.
Int J Epidemiol. 2019 May 5. pii: dyz079. doi: 10.1093/ije/dyz079. [Epub ahead of print]
PMID: 31056682
Abstract
OBJECTIVE:
To evaluate the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and overall and cause-specific mortality in the Golestan Cohort Study (GCS).
METHODS:
A total of 50 045 participants aged 40 years or older were recruited from Golestan Province, Iran, from 2004 to 2008 and followed for a mean of 10.64 years. The DASH diet score was calculated for each individual based on food groups. The primary outcome measure was death from any cause.
RESULTS:
During 517 326 person-years of follow-up, 6763 deaths were reported. After adjustment for potential confounders, DASH diet score was inversely associated with risk of death from all causes and cancers [hazard ratio (HR): 0.86; 95% confidence interval (CI): 0.75, 0.98; and HR: 0.65; 95% CI: 0.47, 0.90, respectively]. A higher DASH diet score was associated with lower risk of gastrointestinal cancer mortality in men (HR: 0.55; 95% CI: 0.30, 0.99). A greater adherence to DASH diet was also associated with lower other-cancer mortality in women (HR: 0.50; 95% CI: 0.24, 0.99). No association between DASH diet score and cardiovascular disease mortality was observed, except that those dying of cardiovascular disease were younger than 50 years of age and smokers.
CONCLUSIONS:
Our findings suggest that maintaining a diet similar to the DASH diet is independently associated with reducing the risk of total death, cancers, and especially gastrointestinal cancers in men.
KEYWORDS:
Diet; DASH; cancer; cardiovascular disease; dietary approaches to stop hypertension; mortality

Vegetable dietary pattern associated with low risk of preeclampsia possibly through reducing proteinuria.
Mi B, Wen X, Li S, Liu D, Lei F, Liu R, Shen Y, Chen Y, Zeng L, Liu X, Dang S, Yan H.
Pregnancy Hypertens. 2019 Apr;16:131-138. doi: 10.1016/j.preghy.2019.04.001. Epub 2019 Apr 8.
PMID: 31056148
Abstract
BACKGROUND:
Evidence on the potential roles that dietary patterns play in the risk of preeclampsia remains limited.
OBJECTIVE:
To examine the associations between dietary patterns during pregnancy and the risk of preeclampsia.
STUDY DESIGN:
We analyzed data from a cluster randomized controlled trial among 987 healthy pregnant women in three rural counties in northwestern China. Maternal diet during the whole pregnancy was assessed using a 107-item food frequency questionnaire with proportion size administered before delivery. Principal component factor analysis with varimax rotation was used to identify common dietary patterns. Preeclampsia was diagnosed by trained clinicians and recorded in delivery records.
RESULTS:
Nineteen participants (1.9%) were diagnosed with preeclampsia. Gestational hypertension and proteinuria were only weakly correlated with each other (Kappa = 0.06): 10.7% participants with gestational hypertension only, 8.8% with proteinuria only, 1.9% with both, and 78.6% with neither. Five common dietary patterns were identified: vegetable, meat, fruit, snack, and wheat staple patterns. After adjusting for calories, other dietary pattern scores and baseline blood pressure, a higher vegetable pattern scores was associated with lower risk of preeclampsia (P for trend = 0.041; the highest vs lowest quartile, adjusted relative risk = 0.20 [95% confidence interval, 0.04-0.98]). A similar association was also observed for the risk of proteinuria (P for trend = 0.015): the highest vs lowest quartiles of the vegetable pattern score, adjusted relative risk = 0.44 (95% confidence interval, 0.24-0.80). The other four pattern scores were not associated with preeclampsia.
CONCLUSIONS:
Adherence to vegetable dietary pattern may be associated with the lower risk of preeclampsia, possibly through reducing development of proteinuria. The original full study was registered at clinicaltrials.gov as NCT02537392.
KEYWORDS:
Dietary pattern; Gestational hypertension; Preeclampsia; Proteinuria; Relative risk; Vegetable

Protein intake and the incidence of pre-diabetes and diabetes in 4 population-based studies: the PREVIEW project.
Sluik D, Brouwer-Brolsma EM, Berendsen AAM, Mikkilä V, Poppitt SD, Silvestre MP, Tremblay A, Pérusse L, Bouchard C, Raben A, Feskens EJM.
Am J Clin Nutr. 2019 May 1;109(5):1310-1318. doi: 10.1093/ajcn/nqy388.
PMID: 31051510
https://sci-hub.tw/10.1093/ajcn/nqy388
Abstract
BACKGROUND:
Data on the relationship between protein intake and the risk of type 2 diabetes are conflicting.
OBJECTIVE:
We studied prospective associations between the intake of total, plant-based, and animal protein and the risk of pre-diabetes and diabetes in 4 population-based studies included in the PREVIEW project.
METHODS:
Analyses were conducted with the use of data from 3 European cohorts and 1 Canadian cohort, including 78,851 participants. Protein intake was assessed through the use of harmonized data from food-frequency questionnaires or 3-d dietary records. Cohort-specific incidence ratios (IRs) were estimated for pre-diabetes and diabetes, adjusting for general characteristics, lifestyle and dietary factors, disease history, and body mass index (BMI) and waist circumference; results were pooled based on a random-effects meta-analysis.
RESULTS:
Higher total protein intake (g · kg-1 · d-1) was associated with lower incidences of pre-diabetes and diabetes (pooled IRs: 0.84; 95% CI: 0.82, 0.87 and 0.49; 95% CI: 0.28, 0.83, respectively); plant-based protein intake was the main determinant (pooled IRs: 0.83; 95% CI: 0.81, 0.86 and 0.53; 95% CI: 0.36, 0.76, respectively). Substituting 2 energy percentage (E%) protein at the expense of carbohydrates revealed increased risks of pre-diabetes and diabetes (pooled IRs: 1.04; 95% CI: 1.01, 1.07 and 1.09; 95% CI: 1.01, 1.18, respectively). Except for the associations between intakes of total protein and plant-based protein (g · kg-1 · d-1) and diabetes, all other associations became nonsignificant after adjustment for BMI and waist circumference.
CONCLUSIONS:
Higher protein intake (g · kg-1 · d-1) was associated with a lower risk of pre-diabetes and diabetes. Associations were substantially attenuated after adjustments for BMI and waist circumference, which demonstrates a crucial role for adiposity and may account for previous conflicting findings. 
KEYWORDS:
diabetes; epidemiology; impaired glucose metabolism; observational studies; protein intake

Dose-response relation between dietary sodium and blood pressure: a meta-regression analysis of 133 randomized controlled trials.
Graudal N, Hubeck-Graudal T, Jürgens G, Taylor RS.
Am J Clin Nutr. 2019 May 1;109(5):1273-1278. doi: 10.1093/ajcn/nqy384.
PMID: 31051506
Abstract
BACKGROUND:
The projected reduced mortality effect of reduced sodium intake in model-based studies conflicts with the observed increased mortality associated with low sodium intake in population studies. This may reflect an overestimation of the dose-response relation between sodium reduction (SR) and blood pressure (BP) used in mortality modeling studies.
OBJECTIVES:
The present meta-regression analysis sought to estimate the dose-response relations between SR and BP in study groups with mean BP above or below the 75th percentile of the general population.
METHODS:
Based on a literature search from 1 January 1946 to 11 April 2018, we identified 133 randomized controlled trials allocating healthy or hypertensive individuals to SR or usual sodium intake. Multivariable regression analyses of the mean SR versus the mean blood pressure effect adjusted for effect modifiers were performed.
RESULTS:
In study groups with mean BP above the 75th percentile [131/78 mm Hg systolic BP (SBP)/diastolic BP (DBP)], there was strong evidence of a linear dose-response relation between SR and BP. For SBP, the dose-response relation was -7.7 mm Hg/100 mmol SR (95% CI: -10.4, -5.0), and for DBP it was -3.0 mm Hg/100 mmol SR (95% CI: -4.6, -1.4). In study groups with mean BP ≤ 131/78 mm Hg, the relation between SR and BP was weak. For SBP it was -1.46 mm Hg/100 mmol SR (95% CI: -2.7, -0.20) and for DBP it was: -0.07 mm Hg/100 mmol SR (95% CI: -1.5, 1.4).
CONCLUSIONS:
Only study groups with a BP in the highest 25th percentile of the population showed a clinically significant drop in BP with SR. The policy of lowering dietary sodium intake in the general population may need to be reframed to target patients with hypertension.
KEYWORDS:
diet; meta-analysis; meta-regression; mortality; randomized controlled trial; salt; sodium

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Dietary Habits Bursting into the Complex Pathogenesis of Autoimmune Diseases: The Emerging Role of Salt from Experimental and Clinical Studies.
Scrivo R, Perricone C, Altobelli A, Castellani C, Tinti L, Conti F, Valesini G.
Nutrients. 2019 May 5;11(5). pii: E1013. doi: 10.3390/nu11051013.
PMID: 31060286
Abstract
The incidence and prevalence of autoimmune diseases have increased in Western countries over the last years. The pathogenesis of these disorders is multifactorial, with a combination of genetic and environmental factors involved. Since the epidemiological changes cannot be related to genetic background, which did not change significantly in that time, the role of environmental factors has been reconsidered. Among these, dietary habits, and especially an excessive salt, typical of processed foods, has been implicated in the development of autoimmune diseases. In this review, we summarize current evidence, deriving both from experimental models and clinical studies, on the capability of excessive salt intake to exacerbate proinflammatory responses affecting the pathogenesis of immune-mediated diseases. Data on several diseases are presented, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and Crohn's disease, with many of them supporting a proinflammatory effect of salt. Likewise, a hypertonic microenvironment showed similar effects in experimental models both in vivo and in vitro. However, murine models of spontaneous autoimmune polyneuropathy exposed to high salt diet suggest opposite outcomes. These results dictate the need to further analyse the role of cooking salt in the treatment and prevention of autoimmune diseases, trying to shape a fine tuning between the possible advantages of a restricted salt intake and the changes in circulating metabolites, mediators, and hormones which come along salt consumption and could in turn influence autoimmunity.
KEYWORDS:
Th17 cells; Treg cells; autoimmunity; environmental factors; inflammatory bowel disease; multiple sclerosis; rheumatoid arthritis; salt; sodium chloride; systemic lupus erythematosus

Potato consumption and the risk of overall and cause specific mortality in the NIH-AARP study.
Hashemian M, Murphy G, Etemadi A, Liao LM, Dawsey SM, Malekzadeh R, Abnet CC.
PLoS One. 2019 May 7;14(5):e0216348. doi: 10.1371/journal.pone.0216348. eCollection 2019.
PMID: 3106348
https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0216348&type=printable
Abstract
BACKGROUND:
Potato consumption has been hypothesized to be associated with higher risk of hypertension, diabetes, and colorectal cancer.
OBJECTIVE:
The aim of this study was to examine the association between potato consumption and the risk of overall and cause specific mortality in the large prospective National Institutes of Health-AARP (NIH-AARP) Study.
DESIGN:
The NIH-AARP study recruited 566,407 persons, aged 50-72 years in 1995-1996. We excluded subjects that reported a history of chronic disease at baseline. Potato consumption data from a validated food frequency questionnaire completed at baseline was used in Cox proportional hazard models to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for overall and cause specific mortality. Final models were adjusted for potential risk factors for mortality.
RESULTS:
Among 410,701 participants included in this analysis, 76,921 persons died during the 15.6 years of follow-up. Eating baked, boiled, or mashed potatoes, French fries or potato salad seven or more times per week was associated with higher risk of overall mortality, in models adjusted only for age and sex (HR C4 vs C1 = 1.17, 95%CI = 1.13, 1.21). These results were attenuated in fully adjusted models (HR C4 vs C1 = 1.02, 95%CI = 0.97, 1.06). Potato consumption was not associated with risk of mortality caused by cancer (HR C4 vs C1 = 1.04, 95%CI = 0.97, 1.11), heart disease (HR C4 vs C1 = 1.00, 95%CI = 0.93, 1.09), respiratory disease (HR C4 vs C1 = 1.16, 95%CI = 0.99, 1.37), or diabetes (HR C4 vs C1 = 0.91, 95%CI = 0.71, 1.19). We tested for an association with different preparation methods and found limited evidence for differences by preparation method. The only statistically significant association was that for French fry consumption with cancer-related mortality (HR C4 vs C1 = 1.27, 95%CI = 1.02, 1.59), a finding for which uncontrolled confounding could not be ruled out.
CONCLUSION:
We find little evidence that potato consumption is associated with all-cause or cause-specific mortality.

Important food sources of fructose-containing sugars and incident gout: a systematic review and meta-analysis of prospective cohort studies.
Ayoub-Charette S, Liu Q, Khan TA, Au-Yeung F, Blanco Mejia S, de Souza RJ, Wolever TM, Leiter LA, Kendall C, Sievenpiper JL.
BMJ Open. 2019 May 5;9(5):e024171. doi: 10.1136/bmjopen-2018-024171.
PMID: 31061018
https://bmjopen.bmj.com/content/bmjopen/9/5/e024171.full.pdf
Abstract
OBJECTIVE:
Sugar-sweetened beverages (SSBs) are associated with hyperuricaemia and gout. Whether other important food sources of fructose-containing sugars share this association is unclear.
DESIGN:
To assess the relation of important food sources of fructose-containing sugars with incident gout and hyperuricaemia, we conducted a systematic review and meta-analysis of prospective cohort studies.
METHODS:
We searched MEDLINE, Embase and the Cochrane Library (through 13 September 2017). We included prospective cohort studies that investigated the relationship between food sources of sugar and incident gout or hyperuricaemia. Two independent reviewers extracted relevant data and assessed the risk of bias. We pooled natural-log transformed risk ratios (RRs) using the generic inverse variance method with random effects model and expressed as RR with 95% confidence intervals (CIs). The overall certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation system.
RESULTS:
We identified three studies (1 54 289 participants, 1761 cases of gout), comparing the highest with the lowest level of exposure for SSBs, fruit juices and fruits. No reports were found reporting incident hyperuricaemia. Fruit juice and SSB intake showed an adverse association (fruit juice: RR=1.77, 95% CI 1.20 to 2.61; SSB: RR=2.08, 95% CI 1.40 to 3.08), when comparing the highest to lowest intake of the most adjusted models. There was no significant association between fruit intake and gout (RR 0.85, 95% CI 0.63 to 1.14). The strongest evidence was for the adverse association with SSB intake (moderate certainty), and the weakest evidence was for the adverse association with fruit juice intake (very low certainty) and lack of association with fruit intake (very low certainty).
CONCLUSION:
There is an adverse association of SSB and fruit juice intake with incident gout, which does not appear to extend to fruit intake. Further research is needed to improve our estimates.
KEYWORDS:
food sources of fructose containing sugars; fructose; gout; sugars; systematic review and meta-analysis; uric acid

Habitual coffee intake reduces all-cause mortality by decreasing heart rate.
Nohara-Shitama Y, Adachi H, Enomoto M, Fukami A, Nakamura S, Kono S, Morikawa N, Sakaue A, Hamamura H, Toyomasu K, Fukumoto Y.
Heart Vessels. 2019 May 6. doi: 10.1007/s00380-019-01422-0. [Epub ahead of print]
PMID: 31062117
Abstract
It is well known that subjects with metabolic syndrome show an elevated resting heart rate. We previously reported that elevated heart rate was significantly related to all-cause mortality, and that coffee consumption was inversely associated with metabolic syndrome. We hypothesized that higher coffee consumption may decrease all-cause mortality by reducing resting heart rate. We performed a longitudinal epidemiological study in Tanushimaru (a cohort of the Seven Countries Study). A total of 1920 residents aged over 40 years received health checkups in 1999. We measured components of metabolic syndrome, and eating and drinking patterns were evaluated by a food frequency questionnaire. We followed up the participants annually for 15 years. During the follow-up period, 343 of the participants died. Of these, 102 subjects died of cancer, 48 of cerebro-cardiovascular diseases, and 44 of infectious diseases. Multivariate analyses revealed that higher coffee consumption was inversely associated with resting heart rate. Kaplan-Meier curves found lower mortality rates in the higher coffee consumption groups. In the lower coffee consumption groups, elevated hazard ratios of all-cause death were observed in the increased heart rate quintiles, whereas heart rate was not associated with all-cause death in the higher coffee consumption groups. These significant associations remained after further adjustment for confounders. This prospective study suggests that higher coffee consumption may have a protective effect against all-cause death due to reducing resting heart rate.
KEYWORDS:
Coffee intake; Epidemiology; Heart rate; Mortality; Prospective study

Maternal nut intake in pregnancy and child neuropsychological development up to 8 years old: a population-based cohort study in Spain.
Gignac F, Romaguera D, Fernández-Barrés S, Phillipat C, Garcia Esteban R, López-Vicente M, Vioque J, Fernández-Somoano A, Tardón A, Iñiguez C, Lopez-Espinosa MJ, García de la Hera M, Amiano P, Ibarluzea J, Guxens M, Sunyer J, Julvez J.
Eur J Epidemiol. 2019 May 7. doi: 10.1007/s10654-019-00521-6. [Epub ahead of print]
PMID: 31062119
Abstract
There is scientific evidence on the protective effects of nut intake against cognitive decline in the elderly; however, this effect has been less explored in child neurodevelopment and no studies have explored the potential longitudinal association with nut intake during pregnancy. We aimed to analyze the association of maternal nut intake during pregnancy with child neuropsychological outcomes. We included 2208 mother-child pairs from a population-based birth cohort in four regions of Spain. The follow up settings were during pregnancy (first and third trimesters), birth, 1.5, 5 and 8 years. Neuropsychological examinations were based on Bayley Scales of Infant Development (1.5 years), McCarthy scales of Children's Abilities (5 year), Attention Network Test (ANT, 8 year) and N-Back test (8 year). Nut intake in pregnancy was reported through a validated food frequency questionnaire during the first and the third trimester. Multivariable regressions analyzed associations after controlling for priori selected confounders notably maternal education, social class, body mass index, energy intake, fish intake, omega-3 supplements, alcohol consumption and smoking habits during pregnancy. Children within the highest tertile of maternal nut consumption during first pregnancy trimester (> 32 g/week) had a decrease of 13.82 ms [95% confidence interval (CI) - 23.40, - 4.23] in the ANT-hit reaction time standard error, compared to the first tertile (median 0 g/w). A similar protective association pattern was observed with the other cognitive scores at the different child ages. After correcting for multiple testing using Bonferroni familywise error rate (FWER), Hochberg FWER and Simes false discovery rate, ANT-hit reaction time standard error remained significant. Final model estimates by inverse probability weighting did not change results. Third pregnancy trimester nut intake showed weaker associations. These data indicate that nut intake during early pregnancy is associated with long-term child neuropsychological development. Future cohort studies and randomized clinical trials are needed to confirm this association pattern in order to further extend nutrition guidelines among pregnant women.
KEYWORDS:
Children; Maternal diet; Neurodevelopment; Nut; Population-based cohort

Dietary Fat Intake and Cognitive Function among Older Populations: A Systematic Review and Meta-Analysis.
Cao GY, Li M, Han L, Tayie F, Yao SS, Huang Z, Ai P, Liu YZ, Hu YH, Xu B.
J Prev Alzheimers Dis. 2019;6(3):204-211. doi: 10.14283/jpad.2019.9.
PMID: 31062836
https://sci-hub.tw/10.14283/jpad.2019.9
Abstract
OBJECTIVE:
The associations between dietary fat intake and cognitive function are inconsistent and inconclusive. This study aimed to provide a quantitative synthesis of prospective cohort studies on the relationship between dietary fat intake and cognitive function among older adults.
METHODS:
PubMed, EMBASE, PsycINFO and Web of Science databases were searched for prospective cohort studies published in English before March 2018 reporting cognitive outcomes in relation to dietary fat intake. Four binary incident outcomes included were mild cognitive impairment (MCI), dementia, Alzheimer disease (AD) and cognitive impairment. The categories of dietary fat intake were based on fat consumption or the percentage of energy from fat consumption, including dichotomies, tertiles, quartiles and quintiles. The relative risk (RR) with the corresponding 95% confidence intervals (CIs) was pooled using a random effects model.
RESULTS:
Nine studies covering a total of 23,402 participants were included. Compared with the lowest category of consumption, the highest category of saturated fat intake was associated with an increased risk of cognitive impairment (RR = 1.40; 95% CI: 1.02-1.91) and AD (RR: 1.87, 95% CI: 1.09-3.20). The total and unsaturated fat intake was not statistically associated with cognitive outcomes with significant between-study heterogeneity.
CONCLUSION:
This study reported a detrimental association between saturated fat intake and cognitive impairment and mixed results between unsaturated fat intake and selected cognitive outcomes. Given the substantial heterogeneity in the sample size and methodology used across studies, the evidence presented here should be interpreted with caution.
KEYWORDS:
Alzheimer’s disease; High-fat diet; cognitive function; dementia; mild cognitive impairment

Association of Gestational Weight Gain With Adverse Maternal and Infant Outcomes.
LifeCycle Project-Maternal Obesity and Childhood Outcomes Study Group, Voerman E, Santos S, Inskip H, Amiano P, Barros H, Charles MA, Chatzi L, Chrousos GP, Corpeleijn E, Crozier S, Doyon M, Eggesbø M, Fantini MP, Farchi S, Forastiere F, Georgiu V, Gori D, Hanke W, Hertz-Picciotto I, Heude B, Hivert MF, Hryhorczuk D, Iñiguez C, Karvonen AM, Küpers LK, Lagström H, Lawlor DA, Lehmann I, Magnus P, Majewska R, Mäkelä J, Manios Y, Mommers M, Morgen CS, Moschonis G, Nohr EA, Nybo Andersen AM, Oken E, Pac A, Papadopoulou E, Pekkanen J, Pizzi C, Polanska K, Porta D, Richiardi L, Rifas-Shiman SL, Roeleveld N, Ronfani L, Santos AC, Standl M, Stigum H, Stoltenberg C, Thiering E, Thijs C, Torrent M, Trnovec T, van Gelder MMHJ, van Rossem L, von Berg A, Vrijheid M, Wijga A, Zvinchuk O, Sørensen TIA, Godfrey K, Jaddoe VWV, Gaillard R.
JAMA. 2019 May 7;321(17):1702-1715. doi: 10.1001/jama.2019.3820.
PMID: 31063572
Abstract
IMPORTANCE:
Both low and high gestational weight gain have been associated with adverse maternal and infant outcomes, but optimal gestational weight gain remains uncertain and not well defined for all prepregnancy weight ranges.
OBJECTIVES:
To examine the association of ranges of gestational weight gain with risk of adverse maternal and infant outcomes and estimate optimal gestational weight gain ranges across prepregnancy body mass index categories.
DESIGN, SETTING, AND PARTICIPANTS:
Individual participant-level meta-analysis using data from 196 670 participants within 25 cohort studies from Europe and North America (main study sample). Optimal gestational weight gain ranges were estimated for each prepregnancy body mass index (BMI) category by selecting the range of gestational weight gain that was associated with lower risk for any adverse outcome. Individual participant-level data from 3505 participants within 4 separate hospital-based cohorts were used as a validation sample. Data were collected between 1989 and 2015. The final date of follow-up was December 2015.
EXPOSURES:
Gestational weight gain.
MAIN OUTCOMES AND MEASURES:
The main outcome termed any adverse outcome was defined as the presence of 1 or more of the following outcomes: preeclampsia, gestational hypertension, gestational diabetes, cesarean delivery, preterm birth, and small or large size for gestational age at birth.
RESULTS:
Of the 196 670 women (median age, 30.0 years [quartile 1 and 3, 27.0 and 33.0 years] and 40 937 were white) included in the main sample, 7809 (4.0%) were categorized at baseline as underweight (BMI <18.5); 133 788 (68.0%), normal weight (BMI, 18.5-24.9); 38 828 (19.7%), overweight (BMI, 25.0-29.9); 11 992 (6.1%), obesity grade 1 (BMI, 30.0-34.9); 3284 (1.7%), obesity grade 2 (BMI, 35.0-39.9); and 969 (0.5%), obesity grade 3 (BMI, ≥40.0). Overall, any adverse outcome occurred in 37.2% (n = 73 161) of women, ranging from 34.7% (2706 of 7809) among women categorized as underweight to 61.1% (592 of 969) among women categorized as obesity grade 3. Optimal gestational weight gain ranges were 14.0 kg to less than 16.0 kg for women categorized as underweight; 10.0 kg to less than 18.0 kg for normal weight; 2.0 kg to less than 16.0 kg for overweight; 2.0 kg to less than 6.0 kg for obesity grade 1; weight loss or gain of 0 kg to less than 4.0 kg for obesity grade 2; and weight gain of 0 kg to less than 6.0 kg for obesity grade 3. These gestational weight gain ranges were associated with low to moderate discrimination between those with and those without adverse outcomes (range for area under the receiver operating characteristic curve, 0.55-0.76). Results for discriminative performance in the validation sample were similar to the corresponding results in the main study sample (range for area under the receiver operating characteristic curve, 0.51-0.79).
CONCLUSIONS AND RELEVANCE:
In this meta-analysis of pooled individual participant data from 25 cohort studies, the risk for adverse maternal and infant outcomes varied by gestational weight gain and across the range of prepregnancy weights. The estimates of optimal gestational weight gain may inform prenatal counseling; however, the optimal gestational weight gain ranges had limited predictive value for the outcomes assessed.

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Higher protein intake is associated with a lower likelihood of frailty among older women, Kuopio OSTPRE-Fracture Prevention Study.
Isanejad M, Sirola J, Rikkonen T, Mursu J, Kröger H, Qazi SL, Tuppurainen M, Erkkilä AT.
Eur J Nutr. 2019 May 7. doi: 10.1007/s00394-019-01978-7. [Epub ahead of print]
PMID: 31065844
https://link.springer.com/content/pdf/10.1007%2Fs00394-019-01978-7.pdf
Abstract
PURPOSE:
Nordic nutrition recommendations (2012) suggest protein intake ≥ 1.1 g/kg body weight (BW) to preserve physical function in Nordic older adults. However, no published study has used this cut-off to evaluate the association between protein intake and frailty. This study examined associations between protein intake, and sources of protein intake, with frailty status at the 3-year follow-up.
METHODS:
Participants were 440 women aged 65─72 years enrolled in the Osteoporosis Risk Factor and Prevention-Fracture Prevention Study. Protein intake g/kg BW and g/d was calculated using a 3-day food record at baseline 2003─4. At the 3-year follow-up (2006─7), frailty phenotype was defined as the presence of three or more, and prefrailty as the presence of one or two, of the Fried criteria: low grip strength adjusted for body mass index, low walking speed, low physical activity, exhaustion was defined using a low life-satisfaction score, and weight loss > 5% of BW. The association between protein intake, animal protein and plant protein, and frailty status was examined by multinomial regression analysis adjusting for demographics, chronic conditions, and total energy intake.
RESULTS:
At the 3-year follow-up, 36 women were frail and 206 women were prefrail. Higher protein intake ≥ 1.1 g/kg BW was associated with a lower likelihood of prefrailty (OR = 0.45 and 95% confidence interval (CI) = 0.01-0.73) and frailty (OR = 0.09 and CI = 0.01-0.75) when compared to protein intake < 1.1 g/kg BW at the 3-year follow-up. Women in the higher tertile of animal protein intake, but not plant protein, had a lower prevalence of frailty (P for trend = 0.04).
CONCLUSIONS:
Protein intake ≥ 1.1 g/kg BW and higher intake of animal protein may be beneficial to prevent the onset of frailty in older women.
KEYWORDS:
Animal protein; Frailty; Older women; Plant protein; Protein intake

4 in 10 Canadian cancer cases could be prevented by not smoking, keeping active, making other choices
Avoiding smoking, keeping physical activity, nutritious diet and sun safety are keys to reducing cancer rate
The Canadian Press · Posted: May 08, 2019
https://www.cbc.ca/news/health/canada-cancer-prevention-policy-smoking-activity-1.5127786
>>>>>>>>>>>>>>>>>>>>
Media backgrounder: ComPARe study
08 May 2019
https://www.cancer.ca/en/about-us/for-media/media-releases/national/2019/compare-general-backgrounder/?region=qc
The Canadian Population Attributable Risk of Cancer (ComPARe) study, published today in Preventive Medicine, was the result of a partnership between the Canadian Cancer Society (CCS) and a pan-Canadian team of experts in epidemiology, biostatistics, cancer risk factors, cancer prevention and knowledge translation. The study provides estimates of the number and percentage of more than 30 cancer types in Canada due to more than 20 modifiable lifestyle, environmental and infectious agents risk factors using cancer incidence data from 2015.

Interethnic differences in pancreatic cancer incidence and risk factors: The Multiethnic Cohort.
Huang BZ, Stram DO, Le Marchand L, Haiman CA, Wilkens LR, Pandol SJ, Zhang ZF, Monroe KR, Setiawan VW.
Cancer Med. 2019 May 8. doi: 10.1002/cam4.2209. [Epub ahead of print]
PMID: 31066497
Abstract
While disparity in pancreatic cancer incidence between blacks and whites has been observed, few studies have examined disparity in other ethnic minorities. We evaluated variations in pancreatic cancer incidence and assessed the extent to which known risk factors account for differences in pancreatic cancer risk among African Americans, Native Hawaiians, Japanese Americans, Latino Americans, and European Americans in the Multiethnic Cohort Study. Risk factor data were obtained from the baseline questionnaire. Cox regression was used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for pancreatic cancer associated with risk factors and ethnicity. During an average 16.9-year follow-up, 1,532 incident pancreatic cancer cases were identified among 184,559 at-risk participants. Family history of pancreatic cancer (RR 1.97, 95% CI 1.50-2.58), diabetes (RR 1.32, 95% CI 1.14-1.54), body mass index ≥30 kg/m2 (RR 1.25, 95% CI 1.08-1.46), current smoking (<20 pack-years RR 1.43, 95% CI 1.19-1.73; ≥20 pack-years RR 1.76, 95% CI 1.46-2.12), and red meat intake (RR 1.17, 95% CI 1.00-1.36) were associated with pancreatic cancer. After adjustment for these risk factors, Native Hawaiians (RR 1.60, 95% CI 1.30-1.98), Japanese Americans (RR 1.33, 95% CI 1.15-1.54), and African Americans (RR 1.20, 95% CI 1.01-1.42), but not Latino Americans (RR 0.90, 95% CI 0.76-1.07), had a higher risk of pancreatic cancer compared to European Americans. Interethnic differences in pancreatic cancer risk are not fully explained by differences in the distribution of known risk factors. The greater risks in Native Hawaiians and Japanese Americans are new findings and elucidating the causes of these high rates may improve our understanding and prevention of pancreatic cancer.
KEYWORDS:
cohort; epidemiology; ethnicity; incidence; minority; pancreatic cancer

Urinary Sodium Excretion, Blood Pressure, and Risk of Future Cardiovascular Disease and Mortality in Subjects Without Prior Cardiovascular Disease.
Welsh CE, Welsh P, Jhund P, Delles C, Celis-Morales C, Lewsey JD, Gray S, Lyall D, Iliodromiti S, Gill JMR, Sattar N, Mark PB.
Hypertension. 2019 Jun;73(6):1202-1209. doi: 10.1161/HYPERTENSIONAHA.119.12726.
PMID: 31067194
https://sci-hub.tw/10.1161/HYPERTENSIONAHA.119.12726
Abstract
Hypertension is a risk factor for cardiovascular disease. Increased urinary sodium excretion, representing dietary sodium intake, is associated with hypertension. Low sodium intake has been associated with increased mortality in observational studies. Further studies should assess whether confounding relationships explain associations between sodium intake and outcomes. We studied UK Biobank participants (n=457 484; mean age, 56.3 years; 44.7% men) with urinary electrolytes and blood pressure data. Estimated daily urinary sodium excretion was calculated using Kawasaki formulae. We analyzed associations between sodium excretion and blood pressure in subjects without cardiovascular disease, treated hypertension, or diabetes mellitus at baseline (n=322 624). We tested relationships between sodium excretion, incidence of fatal and nonfatal cardiovascular disease, heart failure, and mortality. Subjects in higher quintiles of sodium excretion were younger, with more men and higher body mass index. There was a linear relationship between increasing urinary sodium excretion and blood pressure. During median follow-up of 6.99 years, there were 11 932 deaths (1125 cardiovascular deaths) with 10 717 nonfatal cardiovascular events. There was no relationship between quintile of sodium excretion and outcomes. These relationships were unchanged after adjustment for comorbidity or excluding subjects with events during the first 2 years follow-up. No differing risk of incident heart failure (1174 events) existed across sodium excretion quintiles. Urinary sodium excretion correlates with elevated blood pressure in subjects at low cardiovascular risk. No pattern of increased cardiovascular disease, heart failure, or mortality risk was demonstrated with either high or low sodium intake.
KEYWORDS:
blood pressure; cardiovascular diseases; diet; heart failure; sodium

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Dietary Nitrate Supplementation Improves Exercise Tolerance by Reducing Muscle Fatigue and Perceptual Responses.
Husmann F, Bruhn S, Mittlmeier T, Zschorlich V, Behrens M.
Front Physiol. 2019 Apr 24;10:404. doi: 10.3389/fphys.2019.00404. eCollection 2019.
PMID: 31068827
Abstract
The present study was designed to provide further insight into the mechanistic basis for the improved exercise tolerance following dietary nitrate supplementation. In a randomized, double-blind, crossover design, twelve recreationally active males completed a dynamic time-to-exhaustion test of the knee extensors after 5 days of consuming both nitrate-rich (NITRATE) and nitrate-depleted beetroot juice (PLACEBO). Participants who improved their time-to-exhaustion following NITRATE performed a time-matched trial corresponding to the PLACEBO exercise duration with another 5 days of dietary nitrate supplementation. This procedure was performed to obtain time-matched exercise trials with (NITRATEtm) and without dietary nitrate supplementation (PLACEBO). Neuromuscular tests were performed before and after each time-matched condition. Muscle fatigue was quantified as percentage change in maximal voluntary torque from pre- to post-exercise (ΔMVT). Changes in voluntary activation (ΔVA) and quadriceps twitch torque (ΔPS100) were used to quantify central and peripheral factors of muscle fatigue, respectively. Muscle oxygen saturation, quadriceps muscle activity as well as perceptual data (i.e., perception of effort and leg muscle pain) were recorded during exercise. Time-to-exhaustion was improved with NITRATE (12:41 ± 07:18 min) compared to PLACEBO (09:03 ± 04:18 min; P = 0.010). NITRATEtm resulted in both lower ΔMVT and ΔPS100 compared to PLACEBO (P = 0.002; P = 0.001, respectively). ΔVA was not different between conditions (P = 0.308). NITRATEtm resulted in reduced perception of effort and leg muscle pain. Our findings extend the mechanistic basis for the improved exercise tolerance by showing that dietary nitrate supplementation (i) attenuated the development of muscle fatigue by reducing the exercise-induced impairments in contractile muscle function; and (ii) lowered the perception of both effort and leg muscle pain during exercise.
KEYWORDS:
beetroot juice; central fatigue; contractile function; muscle pain; performance fatigability; peripheral fatigue

Helicobacter pylori Seropositivity: Prevalence, Associations, and the Impact on Incident Metabolic Diseases/Risk Factors in the Population-Based KORA Study.
Wawro N, Amann U, Butt J, Meisinger C, Akmatov MK, Pessler F, Peters A, Rathmann W, Kääb S, Waterboer T, Linseisen J.
Front Public Health. 2019 Apr 24;7:96. doi: 10.3389/fpubh.2019.00096. eCollection 2019.
PMID: 31069210
https://www.frontiersin.org/articles/10.3389/fpubh.2019.00096/full
Abstract
Introduction: Helicobacter pylori (H. pylori) is a common infection and known risk factor for gastric cancer. We assessed cross-sectional and longitudinal associations to study the impact of H. pylori seropositivity on metabolic diseases. Methods: Helicobacter pylori seropositivity in serum samples of the KORA study was analyzed by multiplex serology. We calculated sex-specific prevalence of H. pylori seropositivity for the year 2007 based on the first follow-up survey (termed F4) of the KORA study S4. We identified factors associated with H. pylori seropositivity in the F4 survey. Further, we assessed relative risks of incident metabolic diseases/risk factors at the time of the second follow-up survey of S4 (termed FF4) and H. pylori seropositivity at the F4 survey as a determinant. Models were adjusted for age, sex, overweight status, physical activity, smoking status, education level, alcohol intake, and other metabolic diseases. Results: Based on 3,037 persons aged 32 to 82 years, the H. pylori prevalence for 2007 was 30.2% in men (n = 1,465) and 28.1% in women (n = 1,572). Increasing age, current smoking, low education and no alcohol intake were significantly associated with H. pylori seropositivity in the F4 survey. However, no association between H. pylori seropositivity and BMI, metabolic diseases (type 2 diabetes, hypertension and dyslipidemia, gout or increased uric acid) and gastrointestinal diseases (gastritis, inflammatory bowel disease, and gastric or duodenal ulcer) was observed. No significant associations between H. pylori seropositivity and one of the five investigated incident metabolic diseases/risk factors were detected in the longitudinal analysis. Conclusion: We identified associations between age, smoking, education and alcohol intake and H. pylori seropositivity but no impact of H. pylori seropositivity on incident metabolic diseases/risk factors.
KEYWORDS:
Helicobacter pylori; infection; metabolic diseases; multiplex serology; prevalence

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Aspects of Dietary Diversity Differ in Their Association with Atherosclerotic Cardiovascular Risk in a Racially Diverse US Adult Population.
Fanelli Kuczmarski M, Brewer BC, Rawal R, Pohlig RT, Zonderman AB, Evans MK.
Nutrients. 2019 May 8;11(5). pii: E1034. doi: 10.3390/nu11051034.
PMID: 31072009
Abstract
The study objectives were to measure dietary diversity (DD) of an urban US population and to determine if associations of 10 year atherosclerotic cardiovascular (ASCVD) risk with DD were independent of dietary quality. Participants were drawn from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, wave 4 (n = 2066, 1259 African Americans (AA), 807 Whites (W). Three DD measures were derived from 2 days of 24 h recall data collected with the USDA automated-multiple-pass-method. Count was based on consumption of at least half an equivalent of food from 21 subgroups. Evenness was calculated using Berry Index (BI) and BI-adjusted by food health values. Dissimilarity was calculated by Mahalanobis Distance. Diet quality was assessed by Mean Nutrient Adequacy (MAR) and DASH scores. Associations of DD and quality with ASCVD risk, calculated using 2013 American College of Cardiology and American Heart Association guidelines, were assessed with multivariable regression. Covariates included income, education, food security, and energy/kg weight. Count and MAR were positively associated whereas dissimilarity was negatively associated with ASCVD risk. There was no evidence that evenness contributed to cardiovascular health. The findings suggest more diversity in food attributes and diets rich in micronutrients rather than increased count support cardiovascular health.
KEYWORDS:
DASH; MAR; cardiovascular disease risk; diet diversity; diet quality

Postponement of Death by Statin Use: a Systematic Review and Meta-analysis of Randomized Clinical Trials.
Hansen MR, Hróbjartsson A, Pottegård A, Damkier P, Larsen KS, Madsen KG, dePont Christensen R, Kristensen MEL, Christensen PM, Hallas J.
J Gen Intern Med. 2019 May 9. doi: 10.1007/s11606-019-05024-4. [Epub ahead of print]
PMID: 31073857
Abstract
BACKGROUND:
The average postponement of the outcome (gain in time to event) has been proposed as a measure to convey the effect of preventive medications. Among its advantages over number needed to treat and relative risk reduction is a better intuitive understanding among lay persons.
OBJECTIVES:
To develop a novel approach for modeling outcome postponement achieved within a trial's duration, based on published trial data and to present a formalized meta-analysis of modeled outcome postponement for all-cause mortality in statin trials.
METHODS:
The outcome postponement was modeled on the basis of the hazard ratio or relative risk, the mortality rate in the placebo group and the trial's duration. Outcome postponement was subjected to a meta-analysis. We also estimated the average outcome postponement as the area between Kaplan-Meier curves. Statin trials were identified through a systematic review.
RESULTS:
The median modeled outcome postponement was 10.0 days (interquartile range, 2.9-19.5 days). Meta-analysis of 16 trials provided a summary estimate of outcome postponement for all-cause mortality of 12.6 days, with a 95% postponement interval (PI) of 7.1-18.0. For primary, secondary, and mixed prevention trials, respectively, outcome postponements were 10.2 days (PI, 4.0-16.3), 17.4 days (PI, 6.0-28.8), and 8.5 days (PI, 1.9-15.0).
CONCLUSIONS:
The modeled outcome postponement is amenable to meta-analysis and may be a useful approach for presenting the benefits of preventive interventions. Statin treatment results in a small increase of average survival within the duration of a trial.

Sex-specific Association of Circulating Ferritin Levels and Risk of Type 2 Diabetes: A Dose-response Meta-analysis of Prospective Studies.
Jiang L, Wang K, Lo K, Zhong Y, Yang A, Fang X, Akezhuoli H, Song Z, Chen L, An P, Xu M, Min J, Wang F.
J Clin Endocrinol Metab. 2019 May 10. pii: jc.2019-00495. doi: 10.1210/jc.2019-00495. [Epub ahead of print]
PMID: 31074789
Abstract
CONTEXT:
Although the role of iron in the development of type 2 Diabetes (T2D) has long been concerned, prospective studies directly linking body iron stores to T2D risk in sex-dependent context still inconsistent.
OBJECTIVE:
A systematic meta-analysis was conducted to explore the sex-specific association of circulating ferritin with T2D risk among men and women.
DATA SOURCES:
We searched PubMed, Web of Science, and EMBASE databases to identify available prospective studies through 1 August 2018.
RESULTS:
Fifteen prospective studies comprising a total of 77,352 participants and 18,404 T2D cases aged 20 to 80 years with approximately 3 to 17 years' follow-up durations was identified. In highest vs lowest category, combined participants had a 54% increased risk of T2D associated with ferritin levels (RR=1.54, 95% CI 1.32-1.79). For each 100 μg/L increment in ferritin levels, T2D risk increased by 22% (RR=1.22, 95% CI, 1.14-1.31). Notably, significant heterogeneities by sex were identified in that increased ferritin levels appeared to have a greater impact on T2D risk in women (RR=1.53, 95% CI, 1.29-1.82) than in men (RR=1.21, 95% CI 1.15-1.27) after excluding a study with high heterogeneity (41,512 men and 6,974 women for sex-specific analyses, P = 0.020 for sex difference). Further restricted cubic spline analysis between circulating ferritin and T2D risk also showed sex- dimorphic association in that T2D risk for women were twice as strong in magnitude than that of men at the same ferritin level.
CONCLUSIONS:
Greater circulating ferritin levels were independently associated with increased T2D risk, which appeared stronger among women than men. Our findings provide prospective evidence for further testing the utility of circulating ferritin levels as a predicator for T2D risk in a sex-specific manner.

Dairy consumption and risk of functional disability in an elderly Japanese population: the Hisayama Study.
Yoshida D, Ohara T, Hata J, Shibata M, Hirakawa Y, Honda T, Uchida K, Takasugi S, Kitazono T, Kiyohara Y, Ninomiya T.
Am J Clin Nutr. 2019 May 10. pii: nqz040. doi: 10.1093/ajcn/nqz040. [Epub ahead of print]
PMID: 31075788
https://sci-hub.tw/10.1093/ajcn/nqz040
Abstract
BACKGROUND:
Little is known about the association between dairy intake and risk of functional disability in the elderly.
OBJECTIVES:
We examined the influence of dairy intake on the development of declining functional capacity and activities of daily living (ADL) in a prospective cohort study of an elderly population.
METHODS:
A total of 859 community-dwelling Japanese residents, aged ≥65 y without functional disability, were followed up for 7 y. Functional capacity impairment was defined as a Tokyo Metropolitan Institute of Gerontology Index of Competence score of ≤12, and ADL disability was defined as a Barthel Index score of ≤95. Dairy intake was evaluated using a 150-item semiquantitative food frequency questionnaire, grouped into quartiles. The RR of dairy intake on incident functional disability was computed using a Poisson regression model.
RESULTS:
The multivariable-adjusted RR of impaired functional capacity decreased significantly with increasing dairy intake levels (RR [95% CI]: quartile 1, 1.00 [reference]; quartile 2, 0.85 [0.71, 1.02]; quartile 3, 0.81 [0.68, 0.98]; and quartile 4, 0.74 [0.61, 0.90]; P-trend = 0.001). Regarding the three subscales of functional capacity, the inverse association between dairy intake and risk for impairment of intellectual activity and social role remained significant (P-trend = 0.0009 and 0.02, respectively), but such an association was not observed for instrumental ADL. The multivariable-adjusted risk of ADL disability also decreased weakly but significantly with elevating dairy intake (P-trend = 0.04). A similar association was seen for severity of functional disability (P-trend = 0.002). However, the magnitude of these associations was attenuated after further adjustment for protein intake.
CONCLUSION:
Our findings suggest that higher dairy intake is associated with a lower risk of functional disability and its progression in the elderly, probably via an increase in protein intake.
KEYWORDS:
Japanese; cohort studies; dairy intake; disability; elderly; functional capacity impairment; functional disability

Association of High Intakes of Vitamins B6 and B12 From Food and Supplements With Risk of Hip Fracture Among Postmenopausal Women in the Nurses' Health Study.
Meyer HE, Willett WC, Fung TT, Holvik K, Feskanich D.
JAMA Netw Open. 2019 May 3;2(5):e193591. doi: 10.1001/jamanetworkopen.2019.3591.
PMID: 31074816
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2733176
Abstract
IMPORTANCE:
Vitamin supplementation far exceeding recommended doses is popular in segments of the population. However, adverse effects can occur. In a previous secondary analysis of combined data from 2 double-blind randomized clinical trials (RCTs), an unexpected increased risk of hip fracture was found among those treated with high doses of vitamin B6 in combination with vitamin B12.
OBJECTIVES:
To study if high intakes of vitamins B6 and B12 from food and supplements were associated with a risk of hip fracture in the Nurses' Health Study and to investigate whether combined high intakes of both vitamins conferred a particularly increased fracture risk.
DESIGN, SETTING, AND PARTICIPANTS:
In this prospective cohort study, 75 864 postmenopausal women in the United States were followed up from June 1984 through May 2014. The dates of analysis were July 2016 to June 2018. Information on hip fracture and a wide range of potential confounders was collected at baseline and with biennial follow-up questionnaires. Extensive dietary information was collected approximately every 4 years with a semiquantitative food frequency questionnaire. Relative risks (RRs) were calculated by Cox proportional hazards regression, with cumulative average intakes of vitamins B6 and B12 as main exposures, adjusting for potential confounders.
MAIN OUTCOME AND MEASURE:
Hip fracture.
RESULTS:
During follow-up, 2304 of 75 864 women had a hip fracture. Among the women with hip fractures, the median (range) age at hip fracture was 75.8 (46.7-93.0) years and the mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 24.3 (4.6). Median (interquartile range) cumulative average intakes of total vitamins B6 and B12 were 3.6 (4.8) mg/d and 12.1 (11.7) μg/d, respectively. Both vitamin B6 (RR, 1.29; 95% CI, 1.04-1.59 for an intake of ≥35 vs <2 mg/d; P = .06 for linear trend) and vitamin B12 (RR, 1.25; 95% CI, 0.98-1.58 for an intake of ≥30 vs <5 μg/d; P = .02 for linear trend) were associated with increased fracture risk. Risk was highest in women with a combined high intake of both vitamins (B6 ≥35 mg/d and B12 ≥20 μg/d), exhibiting an almost 50% increased risk of hip fracture (RR, 1.47; 95% CI, 1.15-1.89) compared with women with a low intake of both vitamins (B6 <2 mg/d and B12 <10 μg/d).
CONCLUSIONS AND RELEVANCE:
In this cohort study, a combined high intake of vitamins B6 and B12 was associated with an increased risk of hip fracture. The intakes were far higher than the recommended dietary allowances. These findings add to previous studies suggesting that vitamin supplements should be used cautiously because adverse effects can occur.

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