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Folate, homocysteine, endothelial function and cardiovascular disease
Stuart J Moat1, Derek Lang, Ian F W McDowell
1Cardiovascular Sciences Research Group, Wales Heart Research Institute, University of Wales College of Medicine, Cardiff, UK. moatsj@cardiff.ac.uk
Insights
Folic acid supplementation effectively lowers homocysteine levels and improves vascular function in cardiovascular disease (CVD) patients. Folate offers additional benefits beyond homocysteine reduction, potentially through increased nitric oxide production.
Area of Science:
- Cardiovascular Science
- Nutritional Biochemistry
- Vascular Biology
Background:
- Elevated plasma total homocysteine (tHcy) is linked to cardiovascular disease (CVD).
- Epidemiological studies show an inverse relationship between folate levels and cardiovascular events, independent of tHcy.
- Folic acid supplementation is a safe and cost-effective method to reduce tHcy.
Purpose of the Study:
- To investigate the effects of folic acid on endothelial dysfunction in CVD patients.
- To explore potential mechanisms of folate's vascular benefits beyond homocysteine lowering.
Main Methods:
- Review of clinical and epidemiological studies on homocysteine, folate, and CVD.
- Analysis of in vitro evidence regarding folate metabolites and vascular function.
Main Results:
- Folic acid supplementation lowers plasma tHcy concentrations.
- Folic acid reverses endothelial dysfunction in CVD patients, independent of tHcy reduction.
- In vitro studies suggest 5-methyltetrahydrofolate (5MeTHF) enhances nitric oxide production and scavenges superoxide radicals.
Conclusions:
- Folic acid has pleiotropic effects on the vasculature, extending beyond homocysteine metabolism.
- Folate may offer direct protective benefits to the vascular system.
- Further randomized controlled trials are investigating the role of folic acid in vascular disease.
Abstract:
Evidence reported from numerous clinical studies over the past decade has revealed an association between increased plasma total homocysteine (tHcy) concentrations and cardiovascular disease (CVD). In addition, epidemiological studies have identified an inverse association between blood folate concentrations, folate intake and cardiovascular endpoints, that are independent of homocysteine. Folic acid supplementation can lower plasma tHcy concentrations safely and inexpensively. Furthermore, folic acid can reverse endothelial dysfunction observed in patients with CVD. This reversal in endothelial dysfunction with folic acid has been shown to be independent of plasma tHcy lowering, suggesting that folate has pleiotropic effects on the vasculature other than homocysteine lowering. In vitro evidence demonstrates that 5-methyltetrahydrofolate (5MeTHF) the main circulating metabolite of folate, can increase nitric oxide production and can directly scavenge superoxide radicals. The potential beneficial role of folic acid supplements on vascular disease are currently being tested in randomized placebo controlled studies.
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