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

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; I2=9%, n=7 studies) for coronary heart disease, 0.88 (0.75 to 1.03; I2=56%, n=6) for stroke, and 0.78 (0.73 to 0.85; I2=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; I2=37%, n=6) for total cancer, 0.83 (0.77 to 0.90; I2=83%, n=11) for all causes, 0.78 (0.70 to 0.87; I2=0%, n=4) for respiratory disease, 0.49 (0.23 to 1.05; I2=85%, n=4) for diabetes, 0.74 (0.56 to 0.96; I2=0%, n=3) for infectious diseases, 1.15 (0.66 to 2.02; I2=79%, n=2) for diseases of the nervous system disease, and 0.78 (0.75 to 0.82; I2=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.

BMJ 2016;353:i2716

Alcohol consumption and cardiovascular disease, cancer, injury, admission to hospital, and mortality: a prospective cohort study


Alcohol consumption is proposed to be the third most important modifiable risk factor for death and disability. However, alcohol consumption has been associated with both benefits and harms, and previous studies were mostly done in high-income countries. We investigated associations between alcohol consumption and outcomes in a prospective cohort of countries at different economic levels in five continents.


We included information from 12 countries participating in the Prospective Urban Rural Epidemiological (PURE) study, a prospective cohort study of individuals aged 35–70 years. We used Cox proportional hazards regression to study associations with mortality (n=2723), cardiovascular disease (n=2742), myocardial infarction (n=979), stroke (n=817), alcohol-related cancer (n=764), injury (n=824), admission to hospital (n=8786), and for a composite of these outcomes (n=11 963).


We included 114 970 adults, of whom 12 904 (11%) were from high-income countries (HICs), 24 408 (21%) were from upper-middle-income countries (UMICs), 48 845 (43%) were from lower-middle-income countries (LMICs), and 28 813 (25%) were from low-income countries (LICs). Median follow-up was 4·3 years (IQR 3·0–6·0). Current drinking was reported by 36 030 (31%) individuals, and was associated with reduced myocardial infarction (hazard ratio [HR] 0·76 [95% CI 0·63–0·93]), but increased alcohol-related cancers (HR 1·51 [1·22–1·89]) and injury (HR 1·29 [1·04–1·61]). High intake was associated with increased mortality (HR 1·31 [1·04–1·66]). Compared with never drinkers, we identified significantly reduced hazards for the composite outcome for current drinkers in HICs and UMICs (HR 0·84 [0·77–0·92]), but not in LMICs and LICs, for which we identified no reductions in this outcome (HR 1·07 [0·95–1·21]; pinteraction<0·0001).


Current alcohol consumption had differing associations by clinical outcome, and differing associations by income region. However, we identified sufficient commonalities to support global health strategies and national initiatives to reduce harmful alcohol use.


Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, AstraZeneca (Canada), Sanofi-Aventis (France and Canada), Boehringer Ingelheim (Germany and Canada), Servier, GlaxoSmithKline, Novartis, King Pharma, and national or local organisations in participating countries.

Alcohol consumption and cardiovascular disease, cancer, injury, admission to hospital, and mortality: a prospective cohort study by Andrew Smyth et al.

Use of the English urgent referral pathway for suspected cancer and mortality in patients with cancer: cohort study

Objective To assess the overall effect of the English urgent referral pathway on cancer survival.

Setting 8049 general practices in England.

Design Cohort study. Linked information from the national Cancer Waiting Times database, NHS Exeter database, and National Cancer Register was used to estimate mortality in patients in relation to the propensity of their general practice to use the urgent referral pathway.

Participants 215,284 patients with cancer, diagnosed or first treated in England in 2009 and followed up to 2013.

Outcome measure Hazard ratios for death from any cause, as estimated from a Cox proportional hazards regression.

Results During four years of follow-up, 91,620 deaths occurred, of which 51,606 (56%) occurred within the first year after diagnosis. Two measures of the propensity to use urgent referral, the standardised referral ratio and the detection rate, were associated with reduced mortality. The hazard ratio for the combination of high referral ratio and high detection rate was 0.96 (95% confidence interval 0.94 to 0.99), applying to 16% (n=34,758) of the study population. Patients with cancer who were registered with general practices with the lowest use of urgent referral had an excess mortality (hazard ratio 1.07 (95% confidence interval 1.05 to 1.08); 37% (n=79,416) of the study population). The comparator group for these two hazard ratios was the remaining 47% (n=101,110) of the study population. This result in mortality was consistent for different types of cancer (apart from breast cancer) and with other stratifications of the dataset, and was not sensitive to adjustment for potential confounders and other details of the statistical model.

Conclusions Use of the urgent referral pathway could be efficacious. General practices that consistently have a low propensity to use urgent referrals could consider increasing the use of this pathway to improve the survival of their patients with cancer.

Use of the English urgent referral pathway for suspected cancer and mortality in patients with cancer: cohort study by Henrik Møller, et al. BMJ 2015; 351 :h5102 (Published 13 October 2015)

Light to moderate intake of alcohol, drinking patterns, and risk of cancer: results from two prospective US cohort studies

Objectives To quantify risk of overall cancer across all levels of alcohol consumption among women and men separately, with a focus on light to moderate drinking and never smokers; and assess the influence of drinking patterns on overall cancer risk.

Design Two prospective cohort studies. Setting Health professionals in the United States. Participants 88 084 women and 47 881 men participating in the Nurses’ Health Study (from 1980) and Health Professionals Follow-up Study (from 1986), followed until 2010.

Main outcomes and measures Relative risks of cancer.

Results 19 269 and 7571 (excluding non-advanced prostate cancers) incident cancers were documented among women and men, respectively, over 3 144 853 person years. Compared with non-drinkers, light to moderate drinkers had relative risks of total cancer of 1.02 (95% confidence interval 0.98 to 1.06) and 1.04 (1.00 to 1.09; Ptrend=0.12) for alcohol intake of 0.1-4.9 and 5-14.9 g/day among women, respectively. Corresponding values for men were 1.03 (0.96 to 1.11), 1.05 (0.97 to 1.12), and 1.06 (0.98 to 1.15; Ptrend=0.31) for alcohol intake of 0.1-4.9, 5-14.9, and 15-29.9 g/day, respectively. Associations for light to moderate drinking and total cancer were similar among ever or never smokers, although alcohol consumption above moderate levels (in particular ≥30 g/day) was more strongly associated with risk of total cancer among ever smokers than never smokers. For a priori defined alcohol related cancers in men, risk was not appreciably increased for light and moderate drinkers who never smoked (Ptrend=0.18). However, for women, even an alcohol consumption of 5-14.9 g/day was associated with increased risk of alcohol related cancer (relative risk 1.13 (95% confidence interval 1.06 to 1.20)), driven by breast cancer. More frequent and heavy episodic drinking was not further associated with risk of total cancer after adjusting for total alcohol intake.

Conclusion Light to moderate drinking is associated with minimally increased risk of overall cancer. For men who have never smoked, risk of alcohol related cancers is not appreciably increased for light and moderate drinking (up to two drinks per day). However, for women who have never smoked, risk of alcohol related cancers (mainly breast cancer) increases even within the range of up to one alcoholic drink a day.

Light to moderate intake of alcohol, drinking patterns, and risk of cancer: results from two prospective US cohort studies by Yin Cao et al. BMJ 2015; 351