title: Metabolomics analysis of serum 25-hydroxy-vitamin D in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.
abstract: Vitamin D has been discussed in the context of cardiovascular disease, cancer, bone health and other outcomes. Epidemiological studies have reported on the importance of vitamin D in cancer prevention and treatment. The discovery of vitamin D-associated metabolites through agnostic metabolomics analyses offers a new approach for elucidating disease aetiology and health-related pathway identification.
  
  
  
  Baseline serum 25-hydroxy-vitamin D [25(OH)D] and 940 serum metabolites were measured in 392 men from eight nested cancer case-control studies in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish male smokers (aged 50-69 years). The metabolomic profiling was conducted using mass spectrometry. We used linear regression to estimate the standardized beta-coefficient as the effect metric for the associations between metabolites and 25(OH)D levels.
  
  
  
  A majority of the metabolites associated with 25(OH)D were of lipid origin, including 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) [beta-estimate 0.38 per 1 standard deviation (SD) increment], stearoyl-arachidonoyl-glycerophosphoethanolamine (GPPE) (-0.38 per SD) and two essential fatty acids: eicosapentaenoate (EPA; 0.17 per SD) and docosahexaenoate (DHA; 0.13 per SD). Each of these lipid metabolites was associated with 25(OH)D at the principal components corrected P-value of 3.09 × 10-4CONCLUSIONS: The large number of metabolites, particularly lipid compounds, found to be associated with serum 25(OH)D provide new biological clues relevant to the role of vitamin D status and human health outcomes. The present findings should be re-examined in other metabolomics studies of diverse populations.
authors.affiliation: Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA shakira.nelson@nih.gov.|Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Shakira M
authors.initials: SM
authors.lastname: Nelson
authors.affiliation: Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Orestis A
authors.initials: OA
authors.lastname: Panagiotou
authors.affiliation: Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Gabriella M
authors.initials: GM
authors.lastname: Anic
authors.affiliation: Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Mondul
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: Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Weinstein
authors.affiliation: Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
mesh_terms: D000368:Aged; D000596:Amino Acids / Q000097:blood*; D016022:Case-Control Studies; D019587:Dietary Supplements; D005227:Fatty Acids / Q000097:blood*; D005387:Finland; D005663:Furans / Q000097:blood*; D006801:Humans; D016014:Linear Models; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D015999:Multivariate Analysis; D009369:Neoplasms / Q000517:prevention & control; D011422:Propionates / Q000097:blood*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D012907:Smoking / Q000097:blood* / Q000453:epidemiology; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D024502:alpha-Tocopherol / Q000627:therapeutic use; D019207:beta Carotene / Q000627:therapeutic use
chemical_list: C468134:3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid; D000596:Amino Acids; D005227:Fatty Acids; D005663:Furans; D011422:Propionates; D019207:beta Carotene; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D024502:alpha-Tocopherol
keywords: 25-hydroxy-vitamin D; CMPF; amino acids; fatty acids; lipids; metabolomics; serum metabolites