No effect of B vitamins on ADMA levels in patients at increased cardiovascular risk

A M E Spoelstra-de Man, T Teerlink, C B Brouwer, J A Rauwerda, C D A Stehouwer, Y M Smulders

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OBJECTIVE: Asymmetric dimethylarginine (ADMA) is a recently identified potent cardiovascular risk factor. ADMA levels are increased in hyperhomocysteinaemia and the metabolism of ADMA is linked with that of homocysteine in several ways. Treatment with B vitamins effectively reduces homocysteine levels, but studies investigating the effect on ADMA levels are scarce and show conflicting results. In this study we evaluated the effect of treatment with B vitamins on ADMA levels in two high cardiovascular risk populations.

METHODS: In study I, 110 siblings of patients with clinical atherosclerotic disease and postmethionine hyperhomocysteinaemia were treated with 5 mg of folic acid and 250 mg of pyridoxine or placebo, and were analysed after 1 year. In study II, 41 patients with type 2 diabetes and mild hyperhomocysteinaemia were analysed after 6 months treatment with 5 mg of folic acid or placebo.

RESULTS: A correlation between baseline homocysteine and ADMA levels was found, which was partly due to confounding by renal function. Homocysteine levels decreased by 43% in study I and by 28% in study II. In both studies, treatment with B vitamins had no effect at all on ADMA, arginine/ADMA ratio and SDMA levels. This result was confirmed in multiple linear regression analyses with adjustment for baseline values and gender.

CONCLUSIONS: Our studies indicate that B vitamins, despite causing a substantial reduction in plasma homocysteine levels, have no beneficial effect on ADMA levels.

Original languageEnglish
Pages (from-to)495-501
Number of pages7
JournalClinical endocrinology
Issue number5
Publication statusPublished - May 2006


  • Adolescent
  • Adult
  • Arginine/analogs & derivatives
  • Atherosclerosis/blood
  • Cardiovascular Diseases/blood
  • Diabetes Mellitus, Type 2/blood
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Folic Acid/therapeutic use
  • Humans
  • Hyperhomocysteinemia/blood
  • Linear Models
  • Male
  • Middle Aged
  • Pyridoxine/therapeutic use
  • Risk Factors
  • Time Factors
  • Treatment Failure
  • Vitamin B Complex/therapeutic use

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