The Effect of Long-Term /3-Carotene and Vitamin a Administration on Serum Concentrations of α-tocopherol

Many micronutrients are currently being tested for cancer prevention activity. A short-term study recently suggested that two of these nutrients, β-carotene and α-tocopherol, may have an adverse interaction, with β- carotene supplementation leading to markedly decreased serum concentrations of α-tocopherol. We have analyzed the effect of β-carotene supplementation on serum concentrations of α-tocopherol in 2319 participants enrolled in the Carotene and Retinol Efficacy Trial who have taken β-carotene and vitamin A for up to 6 years. One thousand thirty-five participants enrolled in two pilot trials to the Carotene and Retinol Efficacy Trial had serum collected at yearly intervals; an additional 1284 recently recruited participants had serum collected at biennial intervals. Using standard high pressure liquid chromatography techniques, with attention to quality control, these samples were analyzed for β-carotene and α-tocopherol. After up to 6 years of supplementation with β-carotene (30 mg/day) and vitamin A (25, 000 international units/day) we found a small but statistically significant increase in the serum concentration of α-tocopherol in participants taking the active agents. No evidence of a decrease was found in any of the subpopulations examined. We conclude that long-term supplementation with the combination of β- carotene and vitamin A does not decrease serum concentrations of α-tocopherol. Our long-term trial validates results from several shorter trials conducted by others. The concept of adverse interactions between supplemental micronutrients is important. All cancer prevention trials should closely monitor serum concentrations of micronutrients, as well as the incidence of other significant disease.