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      Whole grain consumption and risk of cardiovascular disease, cancer, and all cause and cause specific mortality: systematic review and dose-response meta-analysis of prospective studies

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          Abstract

          Objective To quantify the dose-response relation between consumption of whole grain and specific types of grains and the risk of cardiovascular disease, total cancer, and all cause and cause specific mortality.

          Data sources PubMed and Embase searched up to 3 April 2016.

          Study selection Prospective studies reporting adjusted relative risk estimates for the association between intake of whole grains or specific types of grains and cardiovascular disease, total cancer, all cause or cause specific mortality.

          Data synthesis Summary relative risks and 95% confidence intervals calculated with a random effects model.

          Results 45 studies (64 publications) were included. The summary relative risks per 90 g/day increase in whole grain intake (90 g is equivalent to three servings—for example, two slices of bread and one bowl of cereal or one and a half pieces of pita bread made from whole grains) was 0.81 (95% confidence interval 0.75 to 0.87; I 2=9%, n=7 studies) for coronary heart disease, 0.88 (0.75 to 1.03; I 2=56%, n=6) for stroke, and 0.78 (0.73 to 0.85; I 2=40%, n=10) for cardiovascular disease, with similar results when studies were stratified by whether the outcome was incidence or mortality. The relative risks for morality were 0.85 (0.80 to 0.91; I 2=37%, n=6) for total cancer, 0.83 (0.77 to 0.90; I 2=83%, n=11) for all causes, 0.78 (0.70 to 0.87; I 2=0%, n=4) for respiratory disease, 0.49 (0.23 to 1.05; I 2=85%, n=4) for diabetes, 0.74 (0.56 to 0.96; I 2=0%, n=3) for infectious diseases, 1.15 (0.66 to 2.02; I 2=79%, n=2) for diseases of the nervous system disease, and 0.78 (0.75 to 0.82; I 2=0%, n=5) for all non-cardiovascular, non-cancer causes. Reductions in risk were observed up to an intake of 210-225 g/day (seven to seven and a half servings per day) for most of the outcomes. Intakes of specific types of whole grains including whole grain bread, whole grain breakfast cereals, and added bran, as well as total bread and total breakfast cereals were also associated with reduced risks of cardiovascular disease and/or all cause mortality, but there was little evidence of an association with refined grains, white rice, total rice, or total grains.

          Conclusions This meta-analysis provides further evidence that whole grain intake is associated with a reduced risk of coronary heart disease, cardiovascular disease, and total cancer, and mortality from all causes, respiratory diseases, infectious diseases, diabetes, and all non-cardiovascular, non-cancer causes. These findings support dietary guidelines that recommend increased intake of whole grain to reduce the risk of chronic diseases and premature mortality.

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          Most cited references81

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          Gut microbiome composition is linked to whole grain-induced immunological improvements.

          The involvement of the gut microbiota in metabolic disorders, and the ability of whole grains to affect both host metabolism and gut microbial ecology, suggest that some benefits of whole grains are mediated through their effects on the gut microbiome. Nutritional studies that assess the effect of whole grains on both the gut microbiome and human physiology are needed. We conducted a randomized cross-over trial with four-week treatments in which 28 healthy humans consumed a daily dose of 60 g of whole-grain barley (WGB), brown rice (BR), or an equal mixture of the two (BR+WGB), and characterized their impact on fecal microbial ecology and blood markers of inflammation, glucose and lipid metabolism. All treatments increased microbial diversity, the Firmicutes/Bacteroidetes ratio, and the abundance of the genus Blautia in fecal samples. The inclusion of WGB enriched the genera Roseburia, Bifidobacterium and Dialister, and the species Eubacterium rectale, Roseburia faecis and Roseburia intestinalis. Whole grains, and especially the BR+WGB treatment, reduced plasma interleukin-6 (IL-6) and peak postprandial glucose. Shifts in the abundance of Eubacterium rectale were associated with changes in the glucose and insulin postprandial response. Interestingly, subjects with greater improvements in IL-6 levels harbored significantly higher proportions of Dialister and lower abundance of Coriobacteriaceae. In conclusion, this study revealed that a short-term intake of whole grains induced compositional alterations of the gut microbiota that coincided with improvements in host physiological measures related to metabolic dysfunctions in humans.
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            Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women.

            Dietary flavonoids may have beneficial cardiovascular effects in human populations, but epidemiologic study results have not been conclusive. We used flavonoid food composition data from 3 recently available US Department of Agriculture databases to improve estimates of dietary flavonoid intake and to evaluate the association between flavonoid intake and cardiovascular disease (CVD) mortality. Study participants were 34 489 postmenopausal women in the Iowa Women's Health Study who were free of CVD and had complete food-frequency questionnaire information at baseline. Intakes of total flavonoids and 7 subclasses were categorized into quintiles, and food sources were grouped into frequency categories. Proportional hazards rate ratios (RR) were computed for CVD, coronary heart disease (CHD), stroke, and total mortality after 16 y of follow-up. After multivariate adjustment, significant inverse associations were observed between anthocyanidins and CHD, CVD, and total mortality [RR (95% CI) for any versus no intake: 0.88 (0.78, 0.99), 0.91 (0.83, 0.99), and 0.90 (0.86, 0.95)]; between flavanones and CHD [RR for highest quintile versus lowest: 0.78 (0.65, 0.94)]; and between flavones and total mortality [RR for highest quintile versus lowest: 0.88 (0.82, 0.96)]. No association was found between flavonoid intake and stroke mortality. Individual flavonoid-rich foods associated with significant mortality reduction included bran (added to foods; associated with stroke and CVD); apples or pears or both and red wine (associated with CHD and CVD); grapefruit (associated with CHD); strawberries (associated with CVD); and chocolate (associated with CVD). Dietary intakes of flavanones, anthocyanidins, and certain foods rich in flavonoids were associated with reduced risk of death due to CHD, CVD, and all causes.
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              Diet and overall survival in elderly people.

              To assess the influence of a specific dietary pattern on overall survival. Cohort study. Three rural Greek villages, the data from which were collected as part of an international cross cultural study of food habits in later life. 182 elderly residents of the three villages. Overall mortality. Diet was assessed with a validated extensive semiquantitative questionnaire on food intake. A one unit increase in diet score, devised a priori on the basis of eight component characteristics of the traditional common diet in the Mediterranean region, was associated with a significant 17% reduction in overall mortality (95% confidence interval 1% to 31%). A diet meeting currently understood health criteria does predict survival among people.
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                Author and article information

                Contributors
                Role: PhD student
                Role: postdoctoral fellow
                Role: professor
                Role: postdoctoral researcher
                Role: professor
                Role: senior lecturer
                Role: head physician
                Role: professor
                Role: professor
                Role: senior research fellow
                Journal
                BMJ
                BMJ
                bmj
                The BMJ
                BMJ Publishing Group Ltd.
                0959-8138
                1756-1833
                2016
                14 June 2016
                : 353
                : i2716
                Affiliations
                [1 ]Department of Public Health and General Practice, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
                [2 ]Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
                [3 ]Department of Nutrition, Harvard T H Chan School of Public Health, Boston, MA, USA
                [4 ]Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, MA, USA
                [5 ]Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
                [6 ]Centre for International Health, Department of Global Public Health and Primary Care and Department of Clinical Dentistry, University of Bergen, Bergen, Norway
                [7 ]The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
                [8 ]Biostatistics Unit, Centre for Epidemiology and Biostatistics, University of Leeds, Leeds, UK
                [9 ]Section of Preventive Cardiology, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital Ullevål, Oslo, Norway
                Author notes
                Correspondence to: D Aune, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London W2 1PG, UK d.aune@ 123456imperial.ac.uk
                Article
                aund029745
                10.1136/bmj.i2716
                4908315
                27301975
                4e4063d9-e3ad-47e4-8616-f516fa63b0f2
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

                This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 3.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/3.0/.

                History
                : 06 May 2016
                Categories
                Research

                Medicine
                Medicine

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