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.