The Effects of Creatine and Related Compounds on Cardiovascular System: From Basic to Applied Studies

Beneficial effects of creatine were firstly shown in sport, where itself has been recognized as an ergogenic substance, increasing exercise endurancе, muscle strength and lean body mass. Creatine supplementation is very interesting, due to the fact that creatine supplementation have been reported to be beneficial for wide spectrum of diseases and conditions referring neuro-degenerative, rheumatic diseases, myopathies, cancer, type 2 diabetes. Creatine is a principle component of the creatine kinase/phosphagen system. In cardiomyocytes, it plays an important role in the buffering and transport of chemical energy to ensure that supply meets the dynamic demands of the heart. Studies in mice proved that elevated creatine protects the heart from ischemia-reperfusion injury. A natural precursor of creatine, guanidinoacetic acid (GAA), plays an important role as an energy carrier/mediator in the cell. GAA is formed in the first step of creatine synthesis. Supplementation with GAA might be of great significance in some circumstances where biosynthesis of GAA is limited like deficient diet, kidney failure, renal insufficiency, exercise-related GAA depletion. Betaine is a neutral compound in the form of zwitterion. Betaine supplementation is associated with improved cognition, neuroprotection, cardioprotection and exercise physiology. Betaine insufficiency represents increased risk for secondary heart failure and acute myocardial infarction. This mini-review outlines the evidence in support of creatine and creatine related compounds (GAA and betaine) elevation and examines the pharmacological approaches that are currently available. Since data from the available studies, regarding cardioprotection are inconsistent, this review might help clarifying the benefits of creatine, GAA and betaine supplementation on cardiovascular system.