The effect of a subnormal vitamin B-6 status on homocysteine metabolism

J Clin Invest. 1996 Jul 1;98(1):177-84. doi: 10.1172/JCI118763.


Homocysteine, an atherogenic amino acid, is either remethylated to methionine or metabolized to cysteine by the transsulfuration pathway. The biochemical conversion of homocysteine to cysteine is dependent upon two consecutive, vitamin B-6-dependent reactions. To study the effect of a selective vitamin B-6 deficiency on transsulfuration, we performed oral methionine load tests on 22 vitamin B-6-deficient asthma patients treated with theophylline (a vitamin B-6 antagonist) and 24 age- and sex-matched controls with a normal vitamin B-6 status. Both groups had normal circulating vitamin B-12 and folate concentrations. Methionine loading resulted in significantly higher increases in circulating total homocyst(e)ine (P < 0.01) and cystathionine (P < 0.05) concentrations in vitamin B-6-deficient patients compared with controls. 6 wk of vitamin B-6 supplementation (20 mg/d) significantly (P < 0.05) reduced post-methionine load increases in circulating total homocyst(e)ine concentrations in deficient subjects, but had no significant effect on the increase in total homocyst(e)ine concentrations in controls. The increases in post-methionine load circulating cystathionine concentrations were significantly (P < 0.01) reduced in both groups after vitamin supplementation. It is concluded that a vitamin B-6 deficiency may contribute to impaired transsulfuration and an abnormal methionine load test, which is associated with premature vascular disease.

MeSH terms

  • Administration, Oral
  • Adult
  • Asthma / drug therapy
  • Bronchodilator Agents / therapeutic use
  • Cystathionine / blood
  • Female
  • Homocysteine / blood*
  • Humans
  • Male
  • Methionine / administration & dosage
  • Methionine / metabolism*
  • Middle Aged
  • Pyridoxine / pharmacology*
  • Theophylline / therapeutic use
  • Vitamin B 6 Deficiency / chemically induced
  • Vitamin B 6 Deficiency / metabolism*


  • Bronchodilator Agents
  • Homocysteine
  • Cystathionine
  • Methionine
  • Theophylline
  • Pyridoxine