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Serum Metabolomic Response to Vitamin E Supplementation in a Controlled Cancer Prevention Trial
Author(s) -
Albanes Demetrius,
Moore Steven,
Weinstein Stephanie,
Mondul Alison
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.389.5
Subject(s) - tocopherol , vitamin e , metabolomics , cancer prevention , chemistry , metabolite , carotene , medicine , pharmacology , cancer , biochemistry , antioxidant , food science , chromatography
The Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study found that vitamin E supplementation led to 32% lower prostate cancer incidence, but two subsequent trials were not confirmatory. To increase our understanding of the effects of α‐tocopherol supplementation on cancer risk by searching for novel biochemical signatures, we examined the on‐study change in serum metabolomic profiles of men randomized to receive the ATBC α‐tocopherol supplement. Fifty men were randomly selected from each of the four trial groups: α‐tocopherol (as all‐ rac ‐α‐tocopheryl acetate), ß‐carotene, both supplements, and placebo. Metabolomic profiling of baseline and follow‐up fasting serum was conducted at Metabolon, Inc. (Durham, NC) using ultrahigh‐performance liquid chromatography/mass spectroscopy and gas chromatography/mass spectroscopy. Of the 500 metabolites we identified, 24 changed in response to supplementation with α‐tocopherol at p<0.05. After correction for multiple comparisons with a threshold of p<0.00021, the top five metabolite signals were for α‐CEHC sulfate (β=1.512, p=1.5x10 ‐38 ), α‐CEHC glucuronide (β=1.412, p=1.0x10 ‐31 ), α‐tocopherol (β=0.974, p=2.2x10 ‐13 ), γ‐tocopherol (β=‐0.902, p=1.8x10 ‐11 ), and β‐tocopherol (β=‐0.731, p=9.4x10 ‐8 ). Interestingly, three amino acids were also altered by the α‐tocopherol supplementation, but below the Bonferroni level of statistical significance: beta‐alanine, ornithine, and N6‐acetyllysine (β=‐0.4, p=10 ‐2 ‐10 –3 ). Comparison of the metabolomic profile found here to those in other vitamin E prevention trials may shed light on their apparently discordant findings. Research support: Intramural Research Program of the National Cancer Institute, NIH.