CHAPTER 45: Homocysteine and Vascular Disease: A Review of the Published Results of 11 Trials involving 52 260 Individuals

Moderately elevated homocysteine has been suggested as a potentially modifiable risk factor for cardiovascular disease. Randomized trials of dietary supplementation with B vitamins were set up to assess whether lowering homocysteine levels could reduce the risk of coronary heart disease and stroke. A meta-analysis of 11 trials involving a total of 52 260 individuals provided comparisons for the effects of dietary supplementation with B vitamins to lower homocysteine levels on 4516 coronary heart disease (CHD) events, 2406 stroke events, 3010 incident cancer events and 6982 deaths. Taken together, these trials assessed the effects of lowering homocysteine levels on average by about 25% for about five5 years. Allocation to B vitamins had no beneficial effects on any cardiovascular events, with hazard ratios (95% confidence intervals, CI) of 1.03 (0.96–1.09) for CHD and 0.94 (0.86–1.02) for stroke. Importantly, allocation to B vitamins had no significant adverse effects on cancer (1.06; 0.98–1.14), or for death from any cause (1.02; 0.97–1.07). Thus, supplementation with B vitamins had no statistically significant beneficial effects on coronary heart disease or stroke and no statistically significant adverse effects on incident cancer or all-cause mortality. A previous meta-analysis based on individual participant data from eight trials involving 37 500 participants assessed the effects of lowering homocysteine levels on a broader range of outcomes, overall and in all relevant sub-groups and demonstrated no benefit in any of the pre-specified sub-groups. Hence, the available evidence does not support the routine use of B vitamins for the prevention of cardiovascular disease, overall or in any particular sub-set of the population.