According to the “homocysteine hypothesis (Hcy),” elevated blood Hcy is a risk factor for cardiovascular disease (CVD). It is known that elevated homocysteine levels can be lowered by supplementation with folic acid and vitamin B12. In a recent meta-analysis, a 5μmol/L increase in Hcy was associated with a 9% increased risk of CVD among patients with end-stage renal disease (ESRD). The authors of the meta-analysis sought to further test this relationship in an RCT, the results of which have been published early online in Circulation.

The study conducted in 33 dialysis centres in north and east Germany between July 2002 and July 2008 involved 650 patients with ESRD undergoing haemodialysis, who were randomised to receive 2 post-dialysis treatments: 5 mg folic acid, 50 μg vitamin B12, and 20 mg vitamin B6 (active treatment) or 0.2 mg folic acid, 4 μg vitamin B12, and 1.0 mg vitamin B6 (low dose placebo group) given 3 times per week for an average of 2 years.

The primary outcome was total mortality and this occurred in 102 patients (31%) on active treatment and in 92 (28%) on placebo (hazard ratio, 1.13; 95% CI, 0.85 to 1.50; p = 0.51). The secondary outcome was fatal and nonfatal cardiovascular events and this occurred in 83 patients (25%) on active treatment and in 98 (30%) receiving placebo (0.80; 0.60 to 1.07; p = 0.13).

The researchers conclude from these findings that “increased intake of folic acid, vitamin B12, and vitamin B6 did not reduce total mortality and had no significant effect on the risk of cardiovascular events in patients with end-stage renal disease.”

An accompanying editorial discusses what these findings mean for the Hcy hypothesis and concludes that they “make an important contribution to the understanding of the effects of Hcy lowering in ESRD and adds further depth to a complex issue; however, no definitive conclusion can be drawn about the cardiovascular effects of Hcy lowering among patients with ESRD. Because of the relatively small numbers of CVD end points from this and other trials, larger RCTs, especially among patients with ESRD, are required to resolve this issue.”