Endothelial dysfunction by acute hyperhomocyst(e)inaemia: restoration by folic acid.
Recent evidence demonstrates that hyperhomocyst(e)inaemia is a novel risk factor for cardiovascular diseases. In patients with chronic hyperhomocyst(e)inaemia, endothelial function is impaired. However, whether hyperhomocyst(e)inaemia per se is a cause or an epiphenomenon of endothelial dysfunction remains unknown. In this study, we examined the effects of methionine-induced acute hyperhomocyst(e)inaemia on human endothelial function. In healthy volunteers we administered methionine (0.1 g/kg body weight, per os), a substrate of homocyst(e)ine, with or without folic acid (20 mg, per os) and examined flow-mediated vasodilatation of the brachial artery by high-resolution ultrasonography as a non-invasive measure of endothelial function. We also measured plasma levels of homocyst(e)ine before and 3, 8 and 24 h after methionine loading. Methionine administration increased plasma levels of homocyst(e)ine by four times the basal level at 8 h (P<0.0001, ANOVA). The plasma levels returned to baseline at 24 h. Flow-mediated vasodilatation was significantly decreased to half of the baseline value at 8 h and returned to baseline at 24 h (P<0.0001, ANOVA), whereas endothelium-independent vasodilatation by glyceryl trinitrate was not affected by the methionine loading. Co-administration of folic acid did not attenuate methionine-induced hyperhomocyst(e)inaemia but completely prevented endothelial dysfunction. Our results suggest that in humans a methionine-rich diet may acutely impair endothelial function, which can be prevented by folic acid supplementation.
Department of Internal Medicine III, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011 Japan.
M
M
Usui
H
H
Matsuoka
H
H
Miyazaki
S
S
Ueda
S
S
Okuda
T
T
Imaizumi
D000208:Acute Disease; D000328:Adult; D001916:Brachial Artery / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005492:Folic Acid / Q000494:pharmacology*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008715:Methionine; D014664:Vasodilation / Q000187:drug effects
D005492:Folic Acid; D008715:Methionine