The healthy heart relies primarily upon the oxidation of fatty acids for energy, with the remaining coming from the oxidation of glucose and lactate. Changes in energy requirements are met by altering the balance of fuels depending upon the hormonal milieu as well as upon the availability of oxygen and substrates. The use of carbohydrates for fuel is metabolically more efficient and may improve the coupling between glycolysis and pyruvate oxidation. Therefore, promoting a shift in metabolic fuel substrate use during times of reduced oxygen availability may represent a cardioprotective strategy. Subsequently, there has been interest in pharmacologic strategies such insulin or drugs like ranolazine and dichloroacetate that stimulate carbohydrate oxidation either by enhancing oxidation at the pyruvate dehydrogenase complex or by limiting fatty acid oxidation. There is evidence that nutrients may also be able to stimulate carbohydrate oxidation. Previous studies by our group suggest that a combination of nutrients (carnitine, coenzyme Q10, and taurine) may work together, resulting in pleiotropic cardioprotective effects. Our current studies are investigating the potential of nutrients as both a preventative and adjunctive treatment before and after an ischemic event. These investigations will determine the role of nutritional supplementation in the care of patients with ischemic injury.