Changes in basal and postmethionine load concentrations of total homocysteine and cystathionine after B vitamin intervention

Am J Clin Nutr. 2004 Sep;80(3):641-8. doi: 10.1093/ajcn/80.3.641.


Background: Vitamin B-6 is necessary for the metabolism of homocysteine and is often used in combination with folic acid and vitamin B-12 in clinical trials that investigate whether the lowering of plasma total homocysteine (tHcy) can prevent vascular disease.

Objective: We compared the effects of vitamin B-6 with the effects of folic acid and vitamin B-12, as used in the Western Norway B-vitamin Intervention Trial (WENBIT), on basal and postmethionine load (PML) tHcy and cystathionine concentrations.

Design: Ninety patients with suspected coronary artery disease were randomly assigned to 1 of 4 groups to receive daily oral treatment with 1) 0.8 mg folic acid, 0.4 mg vitamin B-12, and 40 mg vitamin B-6 (group A); 2) 0.8 mg folic acid and 0.4 mg vitamin B-12 (group B); 3) 40 mg vitamin B-6 (group C); or 4) placebo (group D). For the first 2 wk, groups A and B received additional folic acid (5 mg/d). A methionine-loading test was performed at baseline and after 3 mo.

Results: Treatment with folic acid and vitamin B-12 caused a rapid and significant lowering of basal (31%) and PML tHcy concentrations (22%), with no effect on cystathionine. Vitamin B-6 did not change basal tHcy and had a significant but limited effect on PML tHcy concentrations. However, vitamin B-6 treatment markedly lowered basal and PML cystathionine by 31% and 42%, respectively.

Conclusion: The folic acid and vitamin B-12 combination applied in WENBIT provides rapid, substantial, and long-term tHcy-lowering effects, whereas the effect of vitamin B-6 on tHcy was relatively small and confined to PML tHcy. However, vitamin B-6 treatment caused a marked reduction in plasma cystathionine. Cystathionine could be a useful marker for assessment of the vitamin B-6 effect and should, together with tHcy, be related to clinical outcome in ongoing trials.

Publication types

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

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control
  • Cystathionine / blood*
  • Double-Blind Method
  • Drug Synergism
  • Drug Therapy, Combination
  • Female
  • Folic Acid / administration & dosage*
  • Homocysteine / blood*
  • Humans
  • Hyperhomocysteinemia / blood
  • Hyperhomocysteinemia / complications
  • Hyperhomocysteinemia / drug therapy
  • Male
  • Methionine / administration & dosage*
  • Methionine / metabolism
  • Middle Aged
  • Norway
  • Prospective Studies
  • Vitamin B 12 / administration & dosage*
  • Vitamin B 6 / administration & dosage*


  • Homocysteine
  • Cystathionine
  • Vitamin B 6
  • Folic Acid
  • Methionine
  • Vitamin B 12