THE EFFECT OF LONG-TERM BETA-CAROTENE AND VITAMIN-A ADMINISTRATION ONSERUM CONCENTRATIONS OF ALPHA-TOCOPHEROL

Many micronutrients are currently being tested for cancer prevention a ctivity. A short-term study recently suggested that two of these nutri ents, beta-carotene and alpha-tocopherol, may have an adverse interact ion, with beta-carotene supplementation leading to markedly decreased serum concentrations of alpha-tocopherol. We have analyzed the effect of beta-carotene supplementation on serum concentrations of alpha-toco pherol in 2319 participants enrolled in the Carotene and Retinol Effic acy Trial who have taken beta-carotene and vitamin A for up to 6 years . One thousand thirty-five participants enrolled in two pilot trials t o the Carotene and Retinol Efficacy Trial had serum collected at yearl y intervals; an additional 1284 recently recruited participants had se rum collected at biennial intervals. Using standard high pressure liqu id chromatography techniques, with attention to quality control, these samples were analyzed for beta-carotene and alpha-tocopherol. After u p to 6 years of supplementation with beta-carotene (30 mg/day) and vit amin A (25,000 international units/day) we found a small but statistic ally significant increase in the serum concentration of alpha-tocopher ol in participants taking the active agents. No evidence of a decrease was found in any of the subpopulations examined. We conclude that lon g-term supplementation with the combination of beta-carotene and vitam in A does not decrease serum concentrations of alpha-tocopherol. Our l ong-term trial validates results from several shorter trials conducted by others. The concept of adverse interactions between supplemental m icronutrients is important. All cancer prevention trials should closel y monitor serum concentrations of micronutrients, as well as the incid ence of other significant disease.