Oral administration of 4.5 g of L-2-oxo-4-thiazolidine carboxylate significantly improved brachial artery flow-mediated dilation to 11.0% compared to 7.2% with placebo in patients with coronary artery disease.
RCT (n=48)
Double-blind
Randomized
No
Does oral L-2-oxo-4-thiazolidine carboxylate improve endothelium-dependent flow-mediated dilation in patients with coronary artery disease?
Augmenting cellular glutathione levels with oral L-2-oxo-4-thiazolidine carboxylate significantly improves endothelium-dependent flow-mediated dilation in patients with coronary artery disease.
Absolute Event Rate: 11% vs 7.2%
p-value: p=0.005
The effective action of endothelium-derived nitric oxide (EDNO) is impaired in patients with atherosclerosis. This impairment has been attributed in part to increased vascular oxidative stress. EDNO action is improved by administration of ascorbic acid, a water-soluble antioxidant. Ascorbic acid is a potent free-radical scavenger in plasma, and also regulates intracellular redox state in part by sparing cellular glutathione. We specifically investigated the role of intracellular redox state in EDNO action by examining the effect of L-2-oxo-4-thiazolidine carboxylate (OTC) on EDNO-dependent, flow-mediated dilation in a randomized double-blind placebo-controlled study of patients with angiographically proven coronary artery disease. OTC augments intracellular glutathione by providing substrate cysteine for glutathione synthesis. Brachial artery flow-mediated dilation was examined with high-resolution ultrasound before and after oral administration of 4.5 g of OTC or placebo in 48 subjects with angiographically documented coronary artery disease. Placebo treatment produced no change in flow-mediated dilation (7.0+/-3.9% vs. 7.2+/-3.7%), whereas OTC treatment was associated with a significant improvement in flow-mediated dilation (6.6+/-4.4% vs. 11.0+/-6.3%; P = 0.005). OTC had no effect on arterial dilation to nitroglycerin, systemic blood pressure, heart rate, or reactive hyperemia. These data suggest that augmenting cellular glutathione levels improves EDNO action in human atherosclerosis. Cellular redox state may be an important regulator of EDNO action, and is a potential target for therapy in patients with coronary artery disease.
Vita et al. (Sun,) conducted a rct in Coronary artery disease (n=48). L-2-oxo-4-thiazolidine carboxylate (OTC) vs. Placebo was evaluated on Brachial artery flow-mediated dilation at 4 hours (p=0.005). Oral administration of 4.5 g of L-2-oxo-4-thiazolidine carboxylate significantly improved brachial artery flow-mediated dilation to 11.0% compared to 7.2% with placebo in patients with coronary artery disease.