Dataset Information

Effects of α-tocopherol and β-carotene supplementation on liver cancer incidence and chronic liver disease mortality in the ATBC study.

ABSTRACT:

Background

Recent data suggest the possible benefits of α-tocopherol and β-carotene supplementation on liver cancer and chronic liver disease (CLD), but the long-term trial data are limited.

Methods

We evaluated the efficacy of supplemental 50 mg day(-1) α-tocopherol and 20 mg day(-1) β-carotene on incident liver cancer and CLD mortality in a randomised trial of 29,105 Finnish male smokers, who received supplementation for 5-8 years and were followed for 16 additional years for outcomes.

Results

Supplemental α-tocopherol, β-carotene, or both, relative to placebo, did not reduce the risk of liver cancer or CLD, either overall, during the intervention or during the post-intervention period.

Conclusions

Long-term supplemental α-tocopherol or β-carotene had no effect on liver cancer or CLD mortality over 24 years of follow-up.

SUBMITTER: Lai GY

PROVIDER: S-EPMC4264440 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Publications

Effects of α-tocopherol and β-carotene supplementation on liver cancer incidence and chronic liver disease mortality in the ATBC study.

Lai G Y GY Weinstein S J SJ Taylor P R PR McGlynn K A KA Virtamo J J Gail M H MH Albanes D D Freedman N D ND

British journal of cancer 20141014 12

<h4>Background</h4>Recent data suggest the possible benefits of α-tocopherol and β-carotene supplementation on liver cancer and chronic liver disease (CLD), but the long-term trial data are limited.<h4>Methods</h4>We evaluated the efficacy of supplemental 50 mg day(-1) α-tocopherol and 20 mg day(-1) β-carotene on incident liver cancer and CLD mortality in a randomised trial of 29,105 Finnish male smokers, who received supplementation for 5-8 years and were followed for 16 additional years for ou ...[more]

PMID: 25314069

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Project description:Background/objectivesThe role of vitamin E in chronic disease risk remains incompletely understood, particularly in an un-supplemented state, and evidence is sparse regarding the biological actions and pathways involved in its influence on health outcomes. Identifying vitamin-E-associated metabolites through agnostic metabolomics analyses can contribute to elucidating the specific associations and disease etiology. This study aims to investigate the association between circulating metabolites and serum α-tocopherol concentration in an un-supplemented state.Subjects/methodsMetabolomic analysis of 4,294 male participants was conducted based on pre-supplementation fasting serum in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The associations between 1,791 known metabolites measured by ultra-high-performance LC-MS/GC-MS and HPLC-determined α-tocopherol concentration were estimated using multivariable linear regression. Differences in metabolite levels per unit difference in α-tocopherol concentration were calculated as standardized β-coefficients and standard errors.ResultsA total of 252 metabolites were associated with serum α-tocopherol at the Bonferroni-corrected p value (p < 2.79 × 10-5). Most of these metabolites were of lipid and amino acid origin, with the respective subclasses of dicarboxylic fatty acids, and valine, leucine, and isoleucine metabolism, being highly represented. Among lipids, the strongest signals were observed for linoleoyl-arachidonoyl-glycerol (18:2/20:4)[2](β = 0.149; p = 8.65 × 10-146) and sphingomyelin (D18:2/18:1) (β = 0.035; p = 1.36 × 10-30). For amino acids, the strongest signals were aminoadipic acid (β = 0.021; p = 5.01 × 10-13) and l-leucine (β = 0.007; p = 1.05 × 10-12).ConclusionsThe large number of metabolites, particularly lipid and amino acid compounds associated with serum α-tocopherol provide leads regarding potential mechanisms through which vitamin E influences human health, including its role in cardiovascular disease and cancer.

Project description:Type 2 diabetes (T2D) is a complex chronic disease with substantial phenotypic heterogeneity affecting millions of individuals. Yet, its relevant metabolites and etiological pathways are not fully understood. The aim of this study is to assess a broad spectrum of metabolites related to T2D in a large population-based cohort. We conducted a metabolomic analysis of 4,281 male participants within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. The serum metabolomic analysis was performed using an LC-MS/GC-MS platform. Associations between 1,413 metabolites and T2D were examined using linear regression, controlling for important baseline risk factors. Standardized β-coefficients and standard errors (SEs) were computed to estimate the difference in metabolite concentrations. We identified 74 metabolites that were significantly associated with T2D based on the Bonferroni-corrected threshold (P < 3.5 × 10-5). The strongest signals associated with T2D were of carbohydrates origin, including glucose, 1,5-anhydroglucitol (1,5-AG), and mannose (β = 0.34, -0.91, and 0.41, respectively; all P < 10-75). We found several chemical class pathways that were significantly associated with T2D, including carbohydrates (P = 1.3 × 10-11), amino acids (P = 2.7 × 10-6), energy (P = 1.5 × 10-4), and xenobiotics (P = 1.2 × 10-3). The strongest subpathway associations were seen for fructose-mannose-galactose metabolism, glycolysis-gluconeogenesis-pyruvate metabolism, fatty acid metabolism (acyl choline), and leucine-isoleucine-valine metabolism (all P < 10-8). Our findings identified various metabolites and candidate chemical class pathways that can be characterized by glycolysis and gluconeogenesis metabolism, fructose-mannose-galactose metabolism, branched-chain amino acids, diacylglycerol, acyl cholines, fatty acid oxidation, and mitochondrial dysfunction.NEW & NOTEWORTHY These metabolomic patterns may provide new additional evidence and potential insights relevant to the molecular basis of insulin resistance and the etiology of T2D.

Dataset Information

Effects of α-tocopherol and β-carotene supplementation on liver cancer incidence and chronic liver disease mortality in the ATBC study.

Background

Methods

Results

Conclusions

Publications

Effects of α-tocopherol and β-carotene supplementation on liver cancer incidence and chronic liver disease mortality in the ATBC study.

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