Reduction in blood homocysteine may not affect cardiovascular disease or cancer risk

Long-term reductions in blood homocysteine levels with vitamin B9 (folic acid) and vitamin B12 supplementation may not have beneficial effects on incidence of vascular disease or cancer, suggests a new UK study.

In the randomized controlled trial (‘SEARCH’ study), 12,064 individuals who had previously had heart attacks were allocated to receive either 2 mg vitamin B9 (folic acid) plus 1 mg vitamin B12 daily or placebo for an average of 6.7 years (1). The researchers assessed the effects of homocysteine -lowering with B vitamins on the incidence of vascular (coronary death, second heart attack, or stroke) and non-vascular (cancer) events. The results showed that although B vitamin supplementation reduced homocysteine concentrations by 28% (3.8 micromoles/L), it did not affect mortality and major morbidity. In particular, the researchers found that folic acid supplementation did not increase the risk of cancer, which had been speculated earlier.

One possible explanation for the lack of protective effect from a reduction in homocysteine levels could be that homocysteine is not a valid biomarker for cardiovascular risk, the scientists commented. Elevated homocysteine levels have been linked with increased risk of cardiovascular disease but it is not known yet if this association is causal. It has been shown that blood homocysteine levels are elevated by deficiencies in B vitamins and that supplementation with vitamin B9, B6 and B12 can reduce the concentration of homocysteine.

Consequently, the results of an earlier meta-analysis of prospective studies showed that lower homocysteine levels were associated with an 11% lower risk of coronary heart disease and 19% lower risk of stroke (2). In addition, a subgroup analysis of the ‘HOPE-2’ trial also found a protective effect of B vitamin supplementation (2.5mg folic acid, 50mg B6, and 1mg B12 for 5 years) on stroke (3).

Given that all 12,000 individuals previously had heart attacks, the SEARCH study certainly does not answer the question of whether B vitamins taken over time, and in combination with other healthy lifestyle habits, could help prevent cardiovascular disease, experts commented.

1. Armitage J. M. et al. Effects of homocysteine-lowering with folic acid plus vitamin B12 vs. placebo on mortality and major morbidity in myocardial infarction survivors. JAMA. 2010; 303(24):2486–2494.
2. Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA. 2002; 288(16):2015–2022.
3. Wang X, Qin X, Demirtas H; et al. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet. 2007; 369(9576):1876–1882.