Tetrahydrobiopterin Improves Endothelial Function in Cardiovascular Disease: A Systematic Review

Background. Tetrahydrobiopterin (BH(4)) is a cofactor of nitric oxide synthase (NOS). Nitric oxide (NO) bioavailability is reduced during the early stage of vascular diseases, such as coronary artery disease, hypercholesterolemia, hypertension, and diabetic vasculopathy, and even throughout the entire progression of atherosclerosis. Methods. A literature search was performed using electronic databases (up to January 31, 2014), including MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL), using an established strategy. Results. Fourteen articles were selected with a total of 370 patients. Ten of the fourteen studies showed a significant improvement in the endothelial dysfunction of various cardiovascular disease groups with BH(4) supplementation compared with the control groups or placebos. Three studies showed no positive outcome, and one study showed that low-dose BH(4) had no effect but that high-dose BH(4) did have a significantly different result. Conclusions. This review concludes that supplementation with BH(4) and/or augmentation of the endogenous levels of BH(4) will be a novel approach to improve the endothelial dysfunction observed in various cardiovascular diseases. BH(4) might be considered to be a new therapeutic agent to prevent the initiation and progression of cardiovascular disease.