Plasma levels of antioxidant vitamins in relation to ischemic heart disease and cancer.

Aggressive oxygen species (such as superoxide anion, hydroxyl radical, and singlet oxygen) have been implicated in carcinogenesis and arterial injury by ischemia followed by reoxygenation, arteriosclerosis, ionizing radiation, etc (1). Health hazards by these oxygen species can to some extent be prevented by the body’s multilevel defense system against free radicals, which comprises enzymes (eg, superoxide dismutase and glutathione peroxidase), endogenous nonessential antioxidants (eg, glutathione and uric acid), and last but not least antioxidant vitamins (1). Because the dietary supply of the principal essential antioxidants, ie, a-carotene and the vitamins A, C, and E, can vary considerably the body’s defense potential may in part be inversely related to the status ofantioxidant vitamins. This concept is in agreement with data from animals and human beings. In animals deficiency of vitamin A results in metaplasia whereas experimentally induced tumors can be diminished by /3-carotene and vitamins A, C, and E (2). Chronic marginal deficiency of vitamins C or E were reported to lead to arteriosclerosis-like lesions in rodents and piglets, and, interestingly, experimental scurvy in man also caused cardiomegaly, electrocardiographic abnormalities, and acute cardiac emergency in some subjects. In animal models ofarteriosclerosis, supplements of the vitamins A, C, or E have been shown to reduce the number oflesions (1). In the human there is abundant evidence from dietary surveys that the consumption of fresh fruits and leafy green-yellow vegetables as well as the calculated consumption of the above-mentioned essential antioxidants is inversely related to the incidence of cancers (36). The measurement of plasma antioxidants in previous prospective studies regarding the overall incidence ofcancers yielded mostly inconsistent results (2). This, however, could be due to imperfections of the protocol of the blood-bank type (eg, destruction ofplasma vitamins during storage in the deep freeze, analysis of plasma of a relatively low number of cases, and analysis ofa comparably low number of matched controls). In cross-sectional comparisons the vegetarian type of diet was also associated with a lower mortality from ischemic heart disease (IHD), and the standardized mortality for heart disease in England, Wales, Scotland, Norway, and Israel was reported to be inversely correlated with the calculated ascorbic acid intake from fresh fruits and green vegetables (1). However, a calculated commodity consumption is not conclusive for the in vivo status of a vitamin since food tables have an inherent inaccuracy, losses occurring during storage, cooking procedures are hard to account for, and the calculation ofone particular constituent of fruits/ vegetables does not prove that it is the responsible ingredient. Many of these arguments thus lead to the question: Does a poor plasma status of antioxidant vitamins really occur in westernized countries and, if so, is it associated with an increased risk of cancer and IHD? There are in principle three steps to an answer: first, cross-cultural epidemiology with the measurement of the plasma levels; second, corresponding prospective studies; and third, intervention trials. The presently available evidence regarding IHD is mainly based on cross-cultural comparisons whereas the hardest data on cancer were obtained by the prospective approach.