title: Serum Metabolomic Response to Long-Term Supplementation withall-rac-α-Tocopheryl Acetate in a Randomized Controlled Trial.
abstract: 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 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.
authors.affiliation: Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.
authors.forename: Alison M
authors.identifier: 0000-0002-8843-1416
authors.initials: AM
authors.lastname: Mondul
authors.affiliation: Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Nutritional Epidemiology Branch, Bethesda, MD, USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Moore
authors.affiliation: Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Nutritional Epidemiology Branch, Bethesda, MD, USA.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Weinstein
authors.affiliation: Metabolon, Inc., Durham, NC, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Evans
authors.affiliation: Metabolon, Inc., Durham, NC, USA.
authors.forename: Edward D
authors.initials: ED
authors.lastname: Karoly
authors.affiliation: Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Männistö
authors.affiliation: Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Biostatistics Branch, Bethesda, MD, USA.
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Sampson
authors.affiliation: Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Nutritional Epidemiology Branch, Bethesda, MD, USA.
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes