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

J Nutr. 2013 Feb;143(2):142-7. doi: 10.3945/jn.112.169193. Epub 2012 Dec 12.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging*
  • Apoproteins / blood
  • Biomarkers / blood
  • Biomarkers / urine
  • Creatinine / urine
  • Cross-Sectional Studies
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Methylmalonic Acid / blood
  • Methylmalonic Acid / urine*
  • Nutritional Status*
  • Patient Compliance
  • Smoking / adverse effects
  • Time Factors
  • Transcobalamins / analysis
  • Vitamin B 12 / administration & dosage*
  • Vitamin B 12 / blood
  • Vitamin B 12 / therapeutic use
  • Vitamin B 12 Deficiency / blood
  • Vitamin B 12 Deficiency / diet therapy*
  • Vitamin B 12 Deficiency / physiopathology
  • Vitamin B 12 Deficiency / urine


  • Apoproteins
  • Biomarkers
  • Transcobalamins
  • Methylmalonic Acid
  • Creatinine
  • Vitamin B 12

Associated data

  • ISRCTN/ISRCTN92541398