Response of elevated methylmalonic acid to three dose levels of oral cobalamin in older adults

J Am Geriatr Soc. 2002 Nov;50(11):1789-95. doi: 10.1046/j.1532-5415.2002.50506.x.


Objectives: Because the effects of lower-dose oral cobalamin (Cbl) supplements on older people with cobalamin deficiency are not known, we determined whether oral Cbl supplements at three different dose levels would normalize elevated serum methylmalonic acid (MMA) and total homocysteine (tHcy) concentrations.

Design: Sequential nonrandomized intervention study of three dose levels.

Settings: Two university-based senior care clinics.

Participants: Twenty-three older adults (aged >/=65) with serum Cbl levels of 221 pmol/L (300 pg/mL) or lower and serum MMA greater than 271 nmol/L who had been enrolled in a previous screening study for Cbl deficiency (mean age 79 +/- 9; 17 male, 6 female; 17 white, 6 other).

Intervention: Sequential daily treatment with 25 microg oral cobalamin, followed by 100 microg and 1,000 microg cobalamin each for a 6-week period.

Measurements: Serum MMA, tHcy, and other metabolites at baseline and after each 6-week dosing interval.

Results: Treatment with 25 microg and 100 microg lowered but did not normalize MMA levels in most subjects. A dose of 1,000 microg/day proved to be the most effective in lowering MMA levels to within normal limits. Serum tHcy was normalized in six of 11 subjects who had elevated tHcy pretreatment with oral Cbl alone and in one subject in combination with a multivitamin.

Conclusions: Most Cbl-deficient older people require more than 100 microg of oral Cbl to normalize serum MMA, which is a larger dose than is available in most standard multivitamins and Cbl supplements.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Dose-Response Relationship, Drug
  • Female
  • Homocysteine / blood*
  • Humans
  • Male
  • Methylmalonic Acid / blood*
  • Pilot Projects
  • Time Factors
  • Vitamin B 12 / administration & dosage*
  • Vitamin B 12 / pharmacology
  • Vitamin B 12 / therapeutic use
  • Vitamin B 12 Deficiency / drug therapy


  • Homocysteine
  • Methylmalonic Acid
  • Vitamin B 12