The role of folate, antioxidant vitamins and other constituents in fruit and vegetables in the prevention of cardiovascular disease: the epidemiological evidence.

Evidence that fruit and vegetables may protect against coronary heart disease is accumulating. It is unclear which constituents of fruit and vegetables are responsible for this protective effect. Folate as a co-substrate in homocysteine metabolism may be important. An intake of about 400 micrograms folate equivalents/day seems to be required to achieve stable low homocysteine blood levels. Five of eight epidemiologic studies show significant inverse associations between folate and cardiovascular disease. These associations could be confounded by antioxidant vitamins and/or other substances. In trials examining an association between folate and cardiovascular disease such confounding must be excluded, before specific recommendations can be given. Observational studies suggest that vitamin C plays a role in the aetiology of cardiovascular disease, but there are no completed intervention trials of this vitamin alone. With regard to vitamin E two cohort studies point to cardiovascular benefits with the long-term use of supplements of at least 100 IU/day, but the results of controlled trials are inconclusive. There is some evidence from observational studies of an inverse association between beta-carotene and cardiovascular disease, particularly in smokers. Intervention trials do not support this hypothesis, rather, they suggest a possible harmful effect of beta-carotene supplements in smokers. Nevertheless, protective effects of beta-carotene and vitamin E in different dosages, durations of administration, or different combinations are still possible. The last paragraph of this review discusses limitations of the present and priorities of future research.