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The Effect of ß-Carotene Supplementation on Serum Vitamin D Metabolite Concentrations¹

Divisions of Cancer Epidemiology and Genetics [D. M. F.] and Clinical Sciences [J. A. T., D. A.], National Cancer Institute, Bethesda, Maryland 20892, and National Public Health Institute, Helsinki, Finland [J. V.]

In the -Tocopherol, ß-Carotene Cancer Prevention (ATBC) study, a large randomized placebo-controlled trial designed to test the cancer prevention effects of -tocopherol (50 mg/day) and ß-carotene (20 mg/day), participants receiving supplemental ß-carotene had significantly higher rates of lung cancer than those not receiving ß-carotene. It has been hypothesized that the supplemental ß-carotene may have interfered with the synthesis of vitamin D and that the resulting lower concentrations of vitamin D contributed to the elevated cancer incidence. We evaluated whether supplementation with ß-carotene altered the serum concentrations of either 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D in the ATBC Study, by comparing on-study changes between baseline and follow-up serum samples among 20 randomly selected matched pairs of subjects from the ß-carotene and placebo groups. In a matched-pair analysis, the difference between the changes in both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in the ß-carotene supplement and placebo groups were small and statistically nonsignificant. These results provide no evidence that ß-carotene supplementation interferes with the endogenous production of 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D and suggest that it is unlikely that an interaction between supplemental ß-carotene and vitamin D metabolites contributed to the modest increase in lung cancer incidence observed in the ATBC Study.