Randomized, placebo-controlled trial of intramuscular vitamin B12 for the treatment of hyperhomocysteinaemia in dialysis patients

Intern Med J. 2003 Nov;33(11):489-94. doi: 10.1046/j.1445-5994.2003.00420.x.


Background: Plasma homocysteine is elevated in patients with end-stage renal disease (ESRD) and is a risk factor for cardiovascular disease. Folic acid has been shown to partially reduce homocysteine levels in dialysis patients. It is not known whether vitamin B12 reduces homocysteine independent of folic acid in patients who are not vitamin B12 deficient.

Aim: To determine whether 1 mg vitamin B12 lowers homocysteine in stable, chronic, haemodialysis patients independent of folic acid.

Methods: Twenty-eight haemodialysis patients were randomized to receive three doses of 1 mg vitamin B12 or 1 mL saline placebo in a double-blind fashion at 1-month intervals. Fasting plasma total homocysteine, folic acid, red-cell folate, vitamin B12 and haemoglobin levels were determined prior to each dose and 4 weeks after the final injection. The study was powered to detect a 30% reduction in homocysteine over the 3 months.

Results: Both the two groups were well matched with respect to total homocysteine levels, folic acid, red-cell folate and vitamin B12 levels. Serum vitamin B12 levels were significantly higher in the treatment group compared to placebo (217.7 pmol/L; 95% confidence interval (CI) 103.0-332.5; P < 0.001) at the end of the trial but homocysteine levels were not significantly different (3.08 micromol/L; 95% CI -4.44-10.61; P= 0.406).

Conclusions: The administration of intramuscular vitamin B12 over a 3-month period does not result in any reduction of plasma homocysteine levels in haemo-dialysis patients independent of folate status, however reductions of <30% cannot be excluded by the present study. High-dose folic acid remains the treatment of choice in reducing homocysteine, but whether this results in a reduction in cardiovascular events remains to be determined.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Double-Blind Method
  • Female
  • Folic Acid / blood
  • Homocysteine / blood
  • Humans
  • Hyperhomocysteinemia / drug therapy*
  • Injections, Intramuscular
  • Kidney Failure, Chronic / epidemiology
  • Male
  • Middle Aged
  • Prospective Studies
  • Renal Dialysis
  • Vitamin B 12 / administration & dosage*
  • Vitamin B 12 / blood


  • Homocysteine
  • Folic Acid
  • Vitamin B 12