No evidence of benefit was found with folic acid, vitamin B6, and vitamin B12 supplementation.
Epidemiologic studies have shown correlations between high homocysteine levels and cardiovascular (CV) disease, but in randomized trials, supplementation with folic acid and B vitamins has shown no reduction in cardiovascular events (Journal Watch Dec 28 2006). However, large trials have not been conducted in patients with chronic renal disease, many of whom have substantially elevated homocysteine levels.
In a multisite Veterans Affairs
trial, 2056 adults with advanced chronic renal disease (creatinine clearance 
30 mL/min) or end-stage renal disease
were randomized to daily supplementation with a capsule containing folic acid
(40 mg), vitamin B6 (100 mg), and vitamin B12 (2 mg), or
to placebo. All patients had plasma homocysteine levels of 15 µmol/L or higher;
at baseline, the median level was 22 µmol/L. Participants were followed for a
mean of 3.2 years.
Although homocysteine levels dropped in the intervention group by about 25%, there was no significant difference between the groups in death (hazard ratio, 1.04), myocardial infarction (HR, 0.86), stroke (HR, 0.90), or amputation (HR, 1.14), or in a composite of the four outcomes (HR, 0.99). Homocysteine-lowering therapy was ineffective among patients with the highest homocysteine levels (>25), and among patients who had not yet progressed to dialysis.
Comment: In this study, homocysteine lowering with B-vitamin supplementation was not beneficial among patients with chronic or end-stage renal disease. Thus, the findings echo the results of several large-scale trials in other high-risk populations. Editorialists suggest an eventual meta-analysis of prior and pending large-scale trials (12 total), which should reveal whether there are any patient populations in which B-vitamin supplementation reduces CV risk. In the meantime, there is no clinical basis for supplementation.
Published in Journal Watch General Medicine September 11, 2007
Jamison RL et al. Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease. JAMA 2007 Sep 12; 298:1163-70.