Serum Metabolomic Response to Long-Term Supplementation with --Tocopheryl Acetate in a Randomized Controlled Trial.

. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a randomized controlled cancer prevention trial, showed a 32% reduction in prostate cancer incidence in response to vitamin E supplementation. Two other trials were not confirmatory, however. . We compared the change in serum metabolome of the ATBC Study participants randomized to receive vitamin E to those who were not by randomly selecting 50 men from each of the intervention groups (50 mg/day all---tocopheryl acetate (ATA), 20 mg/day -carotene, both, placebo). . Metabolomic profiling was conducted on baseline and follow-up fasting serum (Metabolon, Inc.). . After correction for multiple comparisons, five metabolites were statistically significantly altered ( is the change in metabolite level expressed as number of standard deviations on the log scale): -CEHC sulfate ( = 1.51, = 1.45 × 10), -CEHC glucuronide (β = 1.41, = 1.02 × 10), -tocopherol ( = 0.97, = 2.22 × 10), -tocopherol ( = -0.90, = 1.76 × 10), and -tocopherol ( = -0.73, = 9.40 × 10). Glutarylcarnitine, beta-alanine, ornithine, and N6-acetyllysine were also decreased by ATA supplementation ( range 0.40 to -0.36), but not statistically significantly. . Comparison of the observed metabolite alterations resulting from ATA supplementation to those in other vitamin E trials of different populations, dosages, or formulations may shed light on the apparently discordant vitamin E-prostate cancer risk findings.