Safety of antioxidant vitamins and beta-carotene

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Abstract
Epidemiologic evidence links high antioxidant status with low risk of degenerative disease. Optimal intakes of antioxidants may not be achievable by diet alone; supplements may be taken, particularly in subgroups of the population at high risk. It is thus necessary to ensure that antioxidant supplements are safe and free from side effects. The toxicity of vitamin E is low; no mutagenic, teratogenic, or carcinogenic effects are known and in double-blind studies in which large amounts of vitamin E were used in humans, no side effects occurred. High concentrations are contraindicated in subjects with vitamin K-associated blood coagulation disorders, and the toxicity in normal subjects ingesting large amounts of vitamin E over long periods requires additional investigation. Toxicity of beta-carotene also is low. Evidence from human toxicity trials is not available but there is much circumstantial evidence that 15-50 mg/d is without side effects except for hypercarotenemia in some subjects at high intakes. The findings of more lung cancer in subjects who smoked and who were given 20 mg beta-carotene/d than in those given a placebo could be influenced by the cancer being well advanced before beta-carotene administration. Massive anecdotal evidence exists that vitamin C (at > or = 1 g/d) is safe. Exhaustive literature searches have failed to reveal a controlled study of vitamin C toxicity in human subjects. Anxiety exists about oxalate stone formation, uricosuria, vitamin B-12 destruction, mutagenicity, and iron overload, but the consensus is that adverse effects do not occur in healthy subjects ingesting large amounts of vitamin C.