Studies of the effect of dietary intakes of vitamin B12 on risk of stroke have not yielded consistent results. One study14
indicated that intakes of folate and vitamin B6, but not vitamin B12, were significantly associated with decreased cerebrovascular mortality, whereas intakes of folate and vitamin B12, but not vitamin B6, were inversely associated with the risk of ischemic stroke.15
Quinlivan and colleagues16
demonstrated that following supplementation with increasing doses of folic acid, the dependency of plasma homocysteine levels on folate diminished, and the main determinant of plasma homocysteine levels then became vitamin B12. These researchers suggested that fortification of food with both folic acid and vitamin B12 could lower homocysteine levels more effectively, providing a potential benefit in vascular disease risk reduction.
suggested that stroke type is important in determining the effect of blood vitamin levels on risk. Asian men younger than 50 years of age with ischemic stroke had elevated homocysteine levels only with large-artery strokes; vitamin B12 levels were significantly lower in cases compared with controls (P
< .001), but there were no significant differences in serum folate levels. The authors suggested that the proatherogenic effect of hyperhomocysteinemia might increase risk of stroke. Treatment of hyperhomocysteinemia with folic acid, vitamin B12, and vitamin B6 has been shown to reduce thrombin formation.18
Overall then, elevated homocysteine levels contribute to atherosclerosis, and optimum levels of folic acid and vitamins B12 and B6 might lower both homocysteine and the risk of clot formation.
With respect to heart disease and stroke, a more detailed understanding of the metabolism of homocysteine, particularly when homocysteine levels are elevated well above normal, is needed. Also, lowering homocysteine levels with vitamin supplementation has not been shown to affect secondary prevention as measured by recurrent myocardial infarction, stroke, or death due to cardiovascular causes.19,20
Dusitanond and colleagues note, in their study of the VITATOPS trial, that multivitamin therapy does not reduce blood levels of inflammatory biomarkers, endothelial dysfunction, or hypercoagulability; they suggest this might be because the biomarkers are not sensitive to decreases in homocysteine, because homocysteine might have different mechanisms of action, or because elevated homocysteine might be a marker for, but not a cause of, increased vascular risk.21
What is also not known is at what level the inflammatory process of atherosclerosis exceeds the ability of any supplement to reverse negative consequences. This, in fact, is the greatest difficulty researchers face when attempting to ascertain nutritional benefits in secondary prevention trials. Recent studies have shown that vitamin B12 with other B vitamins reduces insulin resistance in patients with metabolic syndrome22
and markers for oxidative stress and inflammation23,24
; however, 2 randomized clinical trials showed no effect of B vitamins on venous thrombosis,25,26
and a meta-analysis found no benefit regarding the progression of atherosclerosis.27