title: Ratios of One-Carbon Metabolites Are Functional Markers of B-Vitamin Status in a Norwegian Coronary Angiography Screening Cohort.
abstract: Background:Functional (metabolic) markers of B-vitamin status, including plasma total homocysteine (tHcy) for folate and plasma methylmalonic acid (MMA) for vitamin B-12, suffer from moderate sensitivity and poor specificity. Ratios of metabolites belonging to the same pathway may have better performance characteristics.Objective:We evaluated the ratios of tHcy to total cysteine (tCys; Hcy:Cys), tHcy to creatinine (Hcy:Cre), and tHcy to tCys to creatinine (Hcy:Cys:Cre) as functional markers of B-vitamin status represented by a summary score composed of folate, cobalamin, betaine, pyridoxal 5'-phosphate (PLP), and riboflavin concentrations measured in plasma.Methods:Cross-sectional data were obtained from a cohort of patients with stable angina pectoris (2994 men and 1167 women) aged 21-88 y. The relative contribution of the B-vitamin score, age, sex, smoking, body mass index, and markers of renal function and inflammation to the variance of the functional B-vitamin markers was calculated by using multiple linear regression.Results:Compared with tHcy alone, Hcy:Cys, Hcy:Cre, and Hcy:Cys:Cre all showed improved sensitivity and specificity for detecting plasma B-vitamin status. Improvements in overall performance ranged from 4-fold for Hcy:Cys to ∼8-fold for Hcy:Cys:Cre and were particularly strong in subjects with the common 5,10-methylenetetrahydrofolate reductase (MTHFR) 677CC genotype.Conclusions:Ratios of tHcy to tCys and/or creatinine showed a severalfold improvement over tHcy alone as functional markers of B-vitamin status in Norwegian coronary angiography screenees. The biological rationale for these ratios is discussed in terms of known properties of enzymes involved in the catabolism of homocysteine and synthesis of creatine and creatinine.
authors.affiliation: Bevital AS, Bergen, Norway; arve.ulvik@farm.uib.no.
authors.forename: Arve
authors.initials: A
authors.lastname: Ulvik
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Steinar
authors.initials: S
authors.lastname: Hustad
authors.affiliation: Bevital AS, Bergen, Norway.
authors.forename: Adrian
authors.initials: A
authors.lastname: McCann
authors.affiliation: Bevital AS, Bergen, Norway.
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Midttun
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Heart Disease, Haukeland University Hospital, Bergen, Norway; and.
authors.forename: Ottar K
authors.initials: OK
authors.lastname: Nygård
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway.|Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.
authors.forename: Per M
authors.initials: PM
authors.lastname: Ueland
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000787:Angina Pectoris / Q000097:blood* / Q000201:enzymology / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D002244:Carbon / Q000378:metabolism*; D003404:Creatinine / Q000097:blood*; D003430:Cross-Sectional Studies; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D003545:Cysteine / Q000097:blood*; D005260:Female; D014644:Genetic Variation; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009664:Norway; D009752:Nutritional Status; D014805:Vitamin B 12 / Q000097:blood; D014803:Vitamin B Complex / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006710:Homocysteine; D014803:Vitamin B Complex; D002244:Carbon; D003404:Creatinine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D003541:Cystathionine beta-Synthase; D003545:Cysteine; D014805:Vitamin B 12
keywords: B-vitamins; functional markers; inflammation; one-carbon metabolites; renal function