Ketone metabolism in exercise and disease
Research in the Clarke group is focussed on the effects of mild ketosis on physical performance and cognitive function in health and disease. During periods of stress, elevated catecholamines, steroids and cytokines increase the metabolism of stored fat in the body. The increase in circulating free fatty acids causes insulin resistance, decreases skeletal and cardiac muscular efficiency and may decrease metabolic fuel for the brain, which cannot metabolize fat, but can metabolize ketones. Ketone bodies contain more recoverable metabolic energy than fatty acids and yield 28% more energy on combustion than glucose. We are testing whether the negative effects of elevated free fatty acids can be overcome by mild ketosis using a ketone ester drink, ΔG®. We found that endurance and cognitive function, tested in rats using treadmill exercise and a maze test, respectively, were increased by ΔG® in the diet. We have further tested the ketone drink during endurance exercise, in randomised, blinded placebo-controlled cross-over studies of rowing and cycling in elite athletes. We are currently testing the metabolic mechanism underlying the effects of exogenous ketones on exercise and in obesity, Parkinson’s and type 2 diabetes.
Our clinical and animal projects are closely interrelated in that we attempt to understand our human findings by studying cellular mechanisms in animal models of common metabolic diseases, including diabetes and heart failure. We use magnetic resonance (MR) techniques with biochemical, physiological and molecular techniques to detect energetic and functional changes in heart, brain and skeletal muscle and determine whether exogenous ketones can reverse the abnormalities.
We work in the Department of Physiology, Anatomy and Genetics and at the Oxford Centre for Clinical Magnetic Resonance Research (OCMR) at the John Radcliffe Hospital.
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