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Updated: Jul 16, 2025

Assessing Energy Substrate Oxidation In Vitro with 14CO2 Trapping
Published on: March 23, 2022
High-fat ketogenic diets and ketone monoester supplements differentially affect substrate metabolism during aerobic
Lee M Margolis1, Stefan M Pasiakos2, Emily E Howard1
1Military Nutrition Division, US Army Research Institute of Environmental Medicine, Natick, Massachusetts, United States.
Abstract:
Chronically adhering to high-fat ketogenic diets or consuming ketone monoester supplements elicits ketosis. Resulting changes in substrate metabolism appear to be drastically different between ketogenic diets and ketone supplements. Consuming a ketogenic diet increases fatty acid oxidation with concomitant decreases in endogenous carbohydrate oxidation. Increased fat oxidation eventually results in an accumulation of circulating ketone bodies, which are metabolites of fatty acids that serve as an alternative source of fuel. Conversely, consuming ketone monoester supplements rapidly increases circulating ketone body concentrations that typically exceed those achieved by adhering to ketogenic diets. Rapid increases in ketone body concentrations with ketone monoester supplementation elicit a negative feedback inhibition that reduces fatty acid mobilization during aerobic exercise. Supplement-derived ketosis appears to have minimal impact on sparing of muscle glycogen or minimizing of carbohydrate oxidation during aerobic exercise. This review will discuss the substrate metabolic and associated aerobic performance responses to ketogenic diets and ketone supplements.
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