Endothelial dysfunction caused by increases in vascular
oxidant stress that decrease bioavailable
nitric oxide (NO) plays a critical role in the vascular pathobiology of
hyperhomocysteinemia. Boosting cellular
glutathione levels or increasing the activity of cellular
glutathione peroxidase can compensate for
homocysteine's effects on endothelial function. Aged garlic extract (AGE) contains water- and oil-soluble
sulfur compounds that modify the intracellular
thiol and redox state, minimize intracellular
oxidant stress, and stimulate NO generation in endothelial cells and animals. We performed a placebo-controlled, blinded, crossover trial to examine whether AGE reduces macro- and microvascular endothelial dysfunction during acute
hyperhomocysteinemia induced by an oral
methionine challenge in healthy subjects. Acute
hyperhomocysteinemia leads to a significant decrease in flow-mediated vasodilation of the brachial artery as determined by vascular ultrasound, indicative of macrovascular endothelial dysfunction. In addition, acute
hyperhomocysteinemia leads to a decrease in
acetylcholine-stimulated skin perfusion as measured by
laser-Doppler flowmetry. This indicates microvascular endothelial dysfunction, which is presumably a result of impairment of the endothelium-derived hyperpolarizing factor pathway. Pretreatment with AGE for 6 wk significantly diminished the adverse effects of acute
hyperhomocysteinemia in both vascular territories. We conclude that AGE may at least partly prevent a decrease in bioavailable NO and endothelium-derived hyperpolarizing factor during acute
hyperhomocysteinemia. This pilot study warrants further investigations on the effects of AGE on endothelial dysfunction in patients with other cardiovascular risk factors or established
vascular disease and on the clinical outcome of patients with
cardiovascular disease.