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Clinical Trial
. 2002 Jan 1;105(1):22-6.
doi: 10.1161/hc0102.101388.

Folic acid improves endothelial function in coronary artery disease via mechanisms largely independent of homocysteine lowering

Sagar N Doshi  1 , Ian F W McDowell, Stuart J Moat, Nicola Payne, Hilary J Durrant, Malcolm J Lewis, Jonathan Goodfellow
Affiliations
Free article
Clinical Trial

Folic acid improves endothelial function in coronary artery disease via mechanisms largely independent of homocysteine lowering

Sagar N Doshi et al. Circulation. .
Free article

Abstract

Background: Homocysteine is a risk factor for coronary artery disease (CAD), although a causal relation remains to be proven. The importance of determining direct causality rests in the fact that plasma homocysteine can be safely and inexpensively reduced by 25% with folic acid. This reduction is maximally achieved by doses of 0.4 mg/d. High-dose folic acid (5 mg/d) improves endothelial function in CAD, although the mechanism is controversial. It has been proposed that improvement occurs through reduction in total (tHcy) or free (non-protein bound) homocysteine (fHcy). We investigated the effects of folic acid on endothelial function before a change in homocysteine in patients with CAD.

Methods and results: A randomized, placebo-controlled study of folic acid (5 mg/d) for 6 weeks was undertaken in 33 patients. Endothelial function, assessed by flow-mediated dilatation (FMD), was measured before, at 2 and 4 hours after the first dose of folic acid, and after 6 weeks of treatment. Plasma folate increased markedly by 1 hour (200 compared with 25.8 nmol/L; P<0.001). FMD improved at 2 hours (83 compared with 47 microm; P<0.001) and was largely complete by 4 hours (101 compared with 51 microm; P<0.001). tHcy did not significantly differ acutely (4-hour tHcy, 9.56 compared with 9.79 micromol/L; P=NS). fHcy did not differ at 3 hours but was slightly reduced at 4 hours (1.55 compared with 1.78 micromol/L; P=0.02). FMD improvement did not correlate with reductions in either fHcy or tHcy at any time.

Conclusions: These data suggest that folic acid improves endothelial function in CAD acutely by a mechanism largely independent of homocysteine.

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Comment in

  • Homocysteine and vascular diseases.
    Marasini B, Massarotti M, Biondi ML. Marasini B, et al. Circulation. 2002 Aug 13;106(7):e33. doi: 10.1161/01.cir.0000025826.01914.f5. Circulation. 2002. PMID: 12176969 No abstract available.

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