Aryan Namboodiri, Ph.D.; Use of glyceryltriacetate to reduce fatigue and improve physical performance

Use of glyceryltriacetate to reduce fatigue and improve physical performance Abstract Natural and synthetic products that can extend physical performance and/or delay fatigue would be of significant benefit to military members, particularly during deployments. Currently, many products are touted as performance enhancing, but to date few have an evidence base. One synthetic product that has not been considered or investigated in humans is glyceryltriacetate (GTA). This unique,hydrophobic, acetate source crosses membrane barriers easily, and has been used in animals and in babies with Canavan disease at concentrations ranging up to 10%. GTA, or Triacetin®, is a commonly used carrier for flavors and fragrances and was affirmed as a generally recognized as safe (GRAS) human food ingredient by the Food and Drug Administration (FDA); thus it can be used as a dietary supplement .Why would GTA be considered as a potential performance enhancer? The answer lies with the role of acetate in mitochondrial and non-mitochondrial ATP production, and we believe two mechanisms can be used to explain how GTA might enhance performance. First, we hypothesize that 1) providing GTA prior to exercise will overcome the acetyl group deficit at the onset of contraction to accelerate mitochondrial ATP synthesis and secondly, 2) providing an acetyl group will minimize the metabolic acidosis caused by a reliance on non-mitochondrial ATP turnover. We propose to perform preclinical studies to test effectiveness in a rat model and also to compare effectiveness with related molecules. Based on the results of the preclinical studies, studies in human volunteers will be performed to establish the usefulness of GTA. To accomplish these goals, Specific aim 1 is to test the effect of GTA supplementation on reducing fatigue and improving performance in different age groups of male and female rats using an endurance exercise model and to compare the GTA effect with that of related molecules such as ketone bodies. Specific aim 2 is to perform studies in human volunteers based on the results of the preclinical studies using appropriate tests to establish usefulness of GTA. The exploration of acetate supplementation with GTA as a method for improving human performance is highly innovative, and if we have positive results, GTA is likely to have widespread application among the senior citizens, in the military and in the world of sports. Additionally, it may be useful for persons with inborn errors of muscle metabolism, such as pyruvate dehydrogenase, phosphofructokinase or glycogen phosphorylase deficiency. Lastly, the simple, safe and less expensive nature of this approach makes it highly attractive for translational research and clinical trials.

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