title: A vitamin B-12 supplement of 500 μg/d for eight weeks does not normalize urinary methylmalonic acid or other biomarkers of vitamin B-12 status in elderly people with moderately poor vitamin B-12 status.
abstract: Plasma vitamin B-12 is the most commonly used biomarker of vitamin B-12 status, but the predictive value for low vitamin B-12 status is poor. The urinary methylmalonic acid (uMMA) concentration has potential as a functional biomarker of vitamin B-12 status, but the response to supplemental vitamin B-12 is uncertain. A study was conducted to investigate the responsiveness of uMMA to supplemental vitamin B-12 in comparison with other biomarkers of vitamin B-12 status [plasma vitamin B-12, serum holotranscobalamin (holoTC), plasma MMA] in elderly people with moderately poor vitamin B-12 status. A double-blind, placebo-controlled, randomized 8-wk intervention study was carried out using vitamin B-12 supplements (500 μg/d, 100 μg/d, and 10 μg/d cyanocobalamin) in 100 elderly people with a combined plasma vitamin B-12 <250 pmol/L and uMMA ratio (μmol MMA/mmol creatinine) >1.5. All biomarkers had a dose response to supplemental vitamin B-12. Improvements in plasma vitamin B-12 and serum holoTC were achieved at cobalamin supplements of 10 μg/d, but even 500 μg/d for 8 wk did not normalize plasma vitamin B-12 in 8% and serum holoTC in 12% of people. The response in uMMA was comparable with plasma MMA; 15-25% of people still showed evidence of metabolic deficiency after 500 μg/d cobalamin for 8 wk. There was a differential response in urinary and plasma MMA according to smoking behavior; the response was enhanced in ex-smokers compared with never-smokers. uMMA offers an alternative marker of metabolic vitamin-B12 status, obviating the need for blood sampling.
authors.affiliation: Human Nutrition Unit, Department of Oncology, Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield, UK.
authors.forename: Marilyn H
authors.initials: MH
authors.lastname: Hill
authors.forename: Janet E
authors.initials: JE
authors.lastname: Flatley
authors.forename: Margo E
authors.initials: ME
authors.lastname: Barker
authors.forename: Clare M
authors.initials: CM
authors.lastname: Garner
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Manning
authors.forename: Simon E
authors.initials: SE
authors.lastname: Olpin
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Moat
authors.forename: Jean
authors.initials: J
authors.lastname: Russell
authors.forename: Hilary J
authors.initials: HJ
authors.lastname: Powers
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001059:Apoproteins / Q000097:blood; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000652:urine; D003430:Cross-Sectional Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008764:Methylmalonic Acid / Q000097:blood / Q000652:urine*; D009752:Nutritional Status; D010349:Patient Compliance; D012907:Smoking / Q000009:adverse effects; D013997:Time Factors; D014155:Transcobalamins / Q000032:analysis; D014805:Vitamin B 12 / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000178:diet therapy* / Q000503:physiopathology / Q000652:urine
chemical_list: D001059:Apoproteins; D015415:Biomarkers; D014155:Transcobalamins; D008764:Methylmalonic Acid; D003404:Creatinine; D014805:Vitamin B 12