A new study published in The Journal of Nutrition compared blood glucose utilization in response to two treatments – ketone plus carbohydrate supplementation and carbohydrate supplementation alone during exercise at a continuous, steady effort. Although the researchers found no differences between the two treatments in terms of rates of glucose utilization, ketone plus carbohydrate supplementation resulted in lower physical performance compared with carbohydrates alone.

Carbohydrate consumption during prolonged aerobic exercise is a common nutritional recommendation to maintain blood glucose concentrations and spare the body’s glycogen reserve. Therefore, glucose utilization as an energy source during physical performance may be optimized when a ketone supplement is consumed in combination with carbohydrate before and during exercise. Ketone supplementation rapidly increases circulating ketones, which subsequently can be utilized for energy production. These reported ergogenic effects have contributed to the growing popularity of ketone supplements in athletes and military populations. Although some studies report positive effects of ketone supplementation on physical performance and glucose metabolism, follow-up studies have shown that ketone supplementation may lower physical performance.

To bridge this knowledge gap, Howard, Margolis (United States Army Research Institute of Environmental Medicine) and colleagues conducted a study to determine the effect of ketone plus carbohydrate supplementation on glucose utilization during steady-state exercise and physical performance compared with carbohydrate alone. A randomly assigned, double-blind, placebo-controlled crossover study design that included 12 men was utilized. Each of the two testing trials, separated by a minimum 7-day washout, began by the completion of a 48-hour glycogen standardization period, followed by controlled feeding to ensure glycogen stores were similar at the start of testing. After an overnight fast, participants consumed a ketone plus carbohydrate supplement or carbohydrate alone, which was consumed before and during 90 minutes of steady-state treadmill exercise. Glucose utilization was determined using indirect calorimetry and stable isotopes. Physical performance was assessed using a time to exhaustion treadmill test after the 90-minute steady-state exercise, and a 6.4 km time trial the next day after participants consumed the supplement.

The primary findings from this study show that, while glucose utilization remained unchanged during steady-state exercise in the ketone plus carbohydrate testing trial, physical performance decreased compared with carbohydrate alone. Time to exhaustion decreased and treadmill time trial performance was slower in the ketone plus carbohydrate compared to the carbohydrate alone treatment. These findings collectively suggest that carbohydrate is a superior fuel choice compared with ketone plus carbohydrate for supporting moderate to higher intensity physical performance when consumed before and during exercise.

In a companion commentary, Gonzalez (University of Bath) underscores the need to further understand the impact of ketones during conditions that reflect sporting scenarios with higher carbohydrate intake requirements. It is also plausible that signaling effects of ketones may prove to be more important than their effects as a fuel source for exercise performance.


Howard EE, Allen JT, Coleman JL, Small SD, Karl JP, OFallon KS, Margolis LM. Ketone Monoester Plus Carbohydrate Supplementation Does Not Alter Exogenous and Plasma Glucose Oxidation or Metabolic Clearance Rate During Exercise in Men Compared with Carbohydrate Alone. The Journal of Nutrition, Volume 153, Issue 6, June 2023, Pages 1696-1709, doi.org/10.1016/j.tjnut.2023.01.003.

Gonzalez JT. Ketone Esters and Their Effects on Carbohydrate Metabolism During Exercise. The Journal of Nutrition, Volume 153, Issue 6, June 2023, Pages 1663-1664, doi.org/10.1016/j.tjnut.2023.04.003.

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