Dietary intake and blood concentrations of antioxidants and the risk of cardiovascular disease, total cancer, and all-cause mortality: a systematic review and dose-response meta-analysis of prospective studies

Background: High dietary intake or blood concentrations (as biomarkers of dietary intake) of vitamin C, carotenoids and vitamin E have been associated with reduced risk of cardiovascular disease, cancer and mortality, but these associations have not been systematically assessed.

Objective: We conducted a systematic review and meta-analysis of prospective studies of dietary intake and blood concentrations of vitamin C, carotenoids, and vitamin E in relation to these outcomes.

Design: We searched PubMed and Embase up to 16th of February 2017. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random effects models.

Results: Sixty six prospective studies (95 publications) were included. The summary RR per 100 mg/d increment of dietary vitamin C intake was 0.87 (95% CI, 0.79-0.95, I2=23%, n=10) for coronary heart disease, 0.93 (95% CI, 0.87-0.99, I2=60%, n=11) for stroke, 0.92 (95% CI, 0.88-0.97, I2=0%, n=6) for cardiovascular disease, 0.93 (95% CI, 0.86-1.01, I2=51%, n=6) for total cancer, and 0.90 (95% CI, 0.85-0.95, I2=77%, n=12) for all-cause mortality. Corresponding RRs per 50 μmol/L increase in blood concentrations of vitamin C were 0.74 (95% CI, 0.65-0.83, I2=0%, n=4), 0.72 (95% CI, 0.62-0.82, I2=0%, n=4), 0.76 (95% CI, 0.65-0.87, I2=56%, n=6), 0.74 (95% CI, 0.66-0.82, I2=0%, n=5), and 0.72 (95% CI, 0.66-0.79, I2=0%, n=8). Dietary intake and/or blood concentrations of carotenoids (total, beta-carotene, alpha-carotene, beta-cryptoxanthin, lycopene) and alpha-tocopherol, but not dietary vitamin E, were similarly inversely associated with coronary heart disease, stroke, cardiovascular disease, cancer and/or all-cause mortality.

Conclusions: Higher dietary intake and/or blood concentrations of vitamin C, carotenoids, and alpha-tocopherol (as markers of fruit, vegetable and nut intake) were associated with reduced risk of cardiovascular disease, total cancer and all-cause mortality. These results support dietary recommendations to increase fruit and vegetable intake for chronic disease prevention, although antioxidant supplement use may not have these same benefits.