Reduction of plasma homocysteine and serum methylmalonate concentrations in apparently healthy elderly subjects after treatment with folic acid, vitamin B12 and vitamin B6: a randomised trial

Eur J Clin Nutr. 2003 Nov;57(11):1426-36. doi: 10.1038/sj.ejcn.1601707.


Objectives: To investigate, in an elderly population: (1) the effects of oral B-vitamin therapy on P-tHcys, S-MMA and Hb/MCV, (2) the appropriate decision limit for 'high' metabolite concentrations and (3) the estimated prevalence of vitamin B(12)/folate deficiency on the basis of different decision limits.

Design: Double-blind placebo-controlled intervention study.

Setting: Outpatient clinic.

Subjects: A total of 209 community-dwelling subjects, median age 76 y (range 70-93) y.

Intervention: Four months of oral daily supplementation with 0.5 mg cyanocobalamin, 0.8 mg folic acid and 3 mg vitamin B(6).

Results: High P- tHcys was found in 64% of men and 45% of women, high S-MMA in 11% of both. Vitamin B(12) deficiency was observed in 7.2% and folate deficiency in 11% of all subjects. Health-related upper reference limits for the metabolites at the start were higher than the laboratory's upper reference limits. The latter were, however, similar to those of the vitamin replete group. There was a significant decrease in P-tHcys (P<0.001) and S-MMA (P=0.009) after 4 months of vitamin treatment. In a multivariate analysis, the P-Hcys change correlated positively with baseline P-tHcys and inversely with baseline P-folate and transferrin saturation (Fe/TIBC ratio). The S-MMA change correlated with baseline S-MMA and inversely with baseline vitamin B(12) and age.

Conclusions: Suboptimal vitamin status is an important cause of elevated P-tHcys and S-MMA in apparently healthy elderly subjects. Oral B-vitamin therapy is an effective and convenient way to normalise P-tHcys and S-MMA.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Double-Blind Method
  • Female
  • Folic Acid / administration & dosage*
  • Folic Acid / blood
  • Folic Acid Deficiency / blood
  • Folic Acid Deficiency / drug therapy*
  • Folic Acid Deficiency / epidemiology
  • Homocysteine / blood*
  • Humans
  • Male
  • Methylmalonic Acid / blood*
  • Reference Values
  • Vitamin B 12 / administration & dosage*
  • Vitamin B 12 / blood
  • Vitamin B 12 Deficiency / blood
  • Vitamin B 12 Deficiency / drug therapy*
  • Vitamin B 12 Deficiency / epidemiology
  • Vitamin B 6 / administration & dosage*
  • Vitamin B 6 / blood


  • Homocysteine
  • Vitamin B 6
  • Methylmalonic Acid
  • Folic Acid
  • Vitamin B 12