Serum Metabolomic Response to Long-Term Supplementation with<i>all-rac</i>-<i>α</i>-Tocopheryl Acetate in a Randomized Controlled Trial

Background. 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.Objective. 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-rac-α-tocopheryl acetate (ATA), 20 mg/dayβ-carotene, both, placebo).Methods. Metabolomic profiling was conducted on baseline and follow-up fasting serum (Metabolon, Inc.).Results. After correction for multiple comparisons, five metabolites were statistically significantly altered (βis the change in metabolite level expressed as number of standard deviations on the log scale):α-CEHC sulfate (β=1.51,p=1.45×10-38),α-CEHC glucuronide (β=1.41,p=1.02×10-31),α-tocopherol (β=0.97,p=2.22×10-13),γ-tocopherol (β=-0.90,p=1.76×10-11), andβ-tocopherol (β=-0.73,p=9.40×10-8). Glutarylcarnitine, beta-alanine, ornithine, and N6-acetyllysine were also decreased by ATA supplementation (βrange 0.40 to −0.36), but not sta