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Investigating physical performance and cognitive function through mild ketosis - Clarke Research — Physiology, Anatomy and Genetics

Clarke Research — Physiology, Anatomy and Genetics

Oxford University 

Investigating physical performance and cognitive function through mild ketosis


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.

In collaboration with the National Institutes of Health in the US, we created a diet containing ketone bodies, which caused mild ketosis. We are testing the metabolic mechanism underlying the effects of the ketone body diet during exercise, with and without ketosis. Endurance and cognitive function, tested in rats using treadmill exercise and a maze test, respectively, were found to be increased by the ketosis. We propose to further test the ketone diet during training, in a double-blind placebo-controlled cross-over trial. Exercise testing, cognitive function and skeletal and cardiac muscle energetics will be followed using physiological testing and non-invasive MRI of brain and muscle during exercise.

Should subjects on the ketone body diet have greater metabolic efficiency, and therefore better physical and cognitive function, during exercise and psychological stress than those on a normal diet, the diet could also be used to treat metabolic diseases, such as obesity, Alzheimer’s and Parkinson’s diseases.


Kieran Clarke