Effect of Folic Acid and B Vitamins on Risk of Cardiovascular Events and Total Mortality Among Women at High Risk for Cardiovascular Disease

Abstract

OMOCYSTEINE LEVELS HAVEbeen directly associated with cardiovascular risk in observational studies 1 ; and daily supplementation with folic acid, vitamin B 6 , vitamin B 12 , or a combination have been shown to reduce homocysteine levels to varying degrees in intervention studies. 2 Based on these data, several randomized trials were designed to test the hypothesis that supplementation with folic acid or B vitamins or both would prevent cardiovascular disease (CVD). However, published trials on patients with preexisting vascular disease have not demonstrated a benefit of folic acid or B vitamins on CVD risk. 3 Participants in observational studies were followed up for longer durations then participants in randomized trials 1 ; therefore, it is plausible that homocysteine lowering may have had a greater effect if participants were treated and observed for longer periods of time. Metaanalyses of randomized trials sug-For editorial comment see p 2086.

The effect of folate fortification on folic acid-based homocysteine-lowering intervention and stroke risk: a meta-analysis

“…The final fourteen RCT enrolled 39 420 patients. Among them, seven were included in the without folate fortification subgroup (28)(29)(30)(31)(32)(33)(34) , four were included in the with folate fortification subgroup (35)(36)(37)(38) and three were included in the partial folate fortification subgroup (39)(40)(41) . The screening process of potential articles is summarized in a flowchart (Fig.…”

Betaine supplementation decreases plasma homocysteine in healthy adult participants: a meta-analysis

“…33 More importantly, if homocysteine is elevated in response to a betaine insufficiency, it will not be corrected by folic acid supplementation alone; and this could help to explain why folic acid therapies do not lead to the expected reduction in vascular events. 34 Therefore, the elevated homocysteine concentrations in these studies could be an indication of betaine insufficiency; and hence, using folic acid supplementation to lower plasma homocysteine concentrations would not lead to a sufficient decrease in plasma homocysteine to ultimately reduce the incidence of cardiovascular disease. It is important that future studies in this area control for both the betaine and folic acid intakes with respect to their influence on reducing the incidence of cardiovascular disease so that the effects of one can be carefully identified in relation to the other.…”

Vitamin B6: a challenging link between nutrition and inflammation in CVD

“…Several large, prospective trials have been conducted in recent years with the principal aim of studying the effects of lowering serum homocysteine concentrations with the use of B vitamins, including vitamin B 6 , on cardiovascular events (60,61) . Overall, the most compelling data from vitamin supplementation studies have demonstrated that vitamin B 6 is not effective for preventing the recurrence of cardiovascular events, including CAD, peripheral vascular disease and stroke (54,62,63) .…”