Abstract
Objectives:We investigated whether lowering of fasting homocysteine concentrations, either with folic acid or with betaine supplementation, differentially affects vascular function, a surrogate marker for risk of cardiovascular disease, in healthy volunteers. As yet, it remains uncertain whether a high concentration of homocysteine itself or whether a low folate status—its main determinant—is involved in the pathogenesis of cardiovascular disease. To shed light on this issue, we performed this study.Design:This was a randomized, placebo-controlled, double-blind, crossover study.Setting:The study was performed at Wageningen University in Wageningen, the Netherlands.Participants:Participants were 39 apparently healthy men and women, aged 50–70 y.Interventions:Participants ingested 0.8 mg/d of folic acid, 6 g/d of betaine, and placebo for 6 wk each, with 6-wk washout in between.Outcome Measures:At the end of each supplementation period, plasma homocysteine concentrations and flow-mediated dilation (FMD) of the brachial artery were measured in duplicate.Results:Folic acid supplementation lowered fasting homocysteine by 20% (−2.0 μmol/l, 95% confidence interval [CI]: −2.3; −1.6), and betaine supplementation lowered fasting plasma homocysteine by 12% (−1.2 μmol/l; −1.6; −0.8) relative to placebo. Mean (± SD) FMD after placebo supplementation was 2.8 (± 1.8) FMD%. Supplementation with betaine or folic acid did not affect FMD relative to placebo; differences relative to placebo were −0.4 FMD% (95%CI, −1.2; 0.4) and −0.1 FMD% (−0.9; 0.7), respectively.Conclusions:Folic acid and betaine supplementation both did not improve vascular function in healthy volunteers, despite evident homocysteine lowering. This is in agreement with other studies in healthy participants, the majority of which also fail to find improved vascular function upon folic acid treatment. However, homocysteine or folate might of course affect cardiovascular disease risk through other mechanisms.
Highlights
High plasma total homocysteine concentrations may lead to cardiovascular disease [1,2], but proof that homocysteine lowering will prevent these diseases is currently lacking [3]
In an attempt to do so, we compared the effect of homocysteine lowering via folic acid supplementation and via betaine supplementation on vascular function
We investigated whether lowering of fasting homocysteine concentrations, either with folic acid or with betaine supplementation, differentially affects vascular function, a surrogate marker for risk of cardiovascular disease, in healthy volunteers
Summary
High plasma total homocysteine concentrations may lead to cardiovascular disease [1,2], but proof that homocysteine lowering will prevent these diseases is currently lacking [3]. In a trial of antihypertensive treatment, those with improved FMD had a more favorable prognosis than those without improved FMD, irrespective of blood pressure lowering [26] This supports the idea that FMD is a good surrogate marker to assess the risk of cardiovascular disease in intervention studies in low-risk populations. Supplementing the diet with B-vitamins lowers homocysteine levels, and large-scale trials are underway that will determine whether Bvitamin supplementation has an effect on cardiovascular outcomes, such as heart attacks and strokes These trials involve administration of folic acid as well as other B-vitamins. The researchers used a technique called flow-mediated dilation (FMD) to measure functioning of the main artery of the upper arm, as a surrogate for cardiovascular disease risk In this trial, both folic acid and betaine supplementation significantly lowered homocysteine levels over the 6-wk supplementation period. Both forms of supplementation failed to result in any significant change in functioning of the artery, as measured using FMD
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