Dietary Antioxidant Micronutrients and All-Cause Mortality: The Japan Collaborative Cohort Study for Evaluation of Cancer Risk.

BACKGROUND: Oxidative stress, the imbalance between pro- and antioxidants, has been implicated in the etiology and pathophysiology of the incidence and mortality of many diseases. We aim to investigate the relations of dietary intakes of vitamin C and E and main carotenoids with all-cause mortality in Japanese men and women. METHODS: The Japan Collaborative Cohort Study for Evaluation of Cancer Risk had 22,795 men and 35,539 women, aged 40-79 years at baseline (1988-1990), who completed a valid food frequency questionnaire and were followed up to the end of 2009. RESULTS: There were 6,179 deaths in men and 5,355 deaths in women during the median follow-up of 18.9 years for men and 19.4 years for women. Multivariate hazard ratios for the highest versus lowest quintile intakes in women were 0.83 (95% confidence interval [CI], 0.76-0.90; P for trend < 0.0001) for vitamin C, 0.85 (95% CI, 0.78-0.93; P for trend < 0.0001) for vitamin E, 0.88 (95% CI, 0.81-0.96; P for trend = 0.0006) for ß-carotene, and 0.90 (95% CI, 0.82-0.98; P for trend = 0.0002) for ß-cryptoxanthin. The joint effect of any two of these highly correlated micronutrients showed significant 12-17% reductions in risk in the high-intake group compared with the low-intake group in women. These significant associations were also observed in the highest quintile intakes of vitamin C, vitamin E, and ß-carotene in female non-smokers but were not observed in female smokers, male smokers, and non-smokers. CONCLUSIONS: Higher dietary intakes of antioxidant vitamins may reduce the risk of all-cause mortality in middle-aged Japanese women, especially female non-smokers.