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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/day  β -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 ( β  is 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 ), and  β -tocopherol ( β  = −0.73,  p  = 9.40 × 10 −8 ). Glutarylcarnitine, beta-alanine, ornithine, and N6-acetyllysine were also decreased by ATA supplementation ( β  range 0.40 to −0.36), but not statistically significantly.  Conclusions . 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.

Serum Metabolomic Response to Long-Term Supplementation withall-rac-α-Tocopheryl Acetate in a Randomized Controlled Trial