24-hour ketogenic diet increases energy expenditure, ketone supplements show little effect

In a recent study published in the journal Clinical Nutrition ESPENThe researchers compared the effects of fasting, ketone salt supplementation, and a one-day isocaloric ketogenic diet on appetite perception and energy expenditure of healthy adults.

Randomized controlled trial: Impact of one-day fasting, ketogenic diet, or exogenous ketones on energy balance control in healthy participants.  Image Credit: Epine/ShutterstockRandom controlled experiment: Impact of one-day fasting, ketogenic diet, or exogenous ketones on energy balance control in healthy participants. Image Credit: Epine/Shutterstock


The ketogenic diet comprising high-fat, low-carb has become a successful and popular weight loss strategy, with the appetite-suppressing effects of the ketone bodies acetoacetate (AcAc) and beta-hydroxybutyrate ( BHB) and higher energy expenditure as possible explanations for its success. Furthermore, the low carbohydrate content of ketogenic diets also results in decreased insulin and blood sugar levels, and patients with type 2 diabetes and obesity have reported spontaneous weight loss within two weeks after following a ketogenic diet.

However, the high fat content of ketogenic diets poses some problems, such as an increase in low-density lipoprotein cholesterol due to the high fat content, and causes other health problems, such as gastrointestinal distress. In comparison, short-term diet options such as intermittent fasting and a 24-hour ketogenic diet are more beneficial. Furthermore, in recent years, exogenous ketones in the form of racemic ketone salts have been used to obtain ketosis.

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In the current study, researchers recruited eight adults between the ages of 25 and 30 who had body mass index (BMI) between 19 and 29 kilograms per square meter and had habitual levels of physical activity that ranged from low to normal. . The study group included four males and four females who were included only when they were using hormonal contraceptives continuously, as this would circumvent the influences of the menstrual cycle on energy expenditure.

Individuals who practiced alternative dietary habits such as veganism or vegetarianism, suffered from chronic illnesses, had food allergies, took regular medications, smoked, suffered from claustrophobia, were pregnant or nursing, had a high level of physical activity, had lost more of 5 kg in the past three months or were currently on a weight-loss diet were excluded from the study.

Height and body weight were measured at baseline, and air displacement plethysmography was used to assess fat mass, which was used to calculate fat mass index. Indirect calorimetry was used to calculate resting energy expenditure. Four interventions consisting of an isocaloric formula diet, total fasting, isocaloric ketogenic diet, and exogenous ketone salt supplements were conducted over 24 hours, with different chronological orders of each intervention for the first and last four participants.

A cycle ergometer was used to measure work and energy during three 20-minute cycles of exercise to maintain a physical activity level (PAL) of 1.65 throughout the interventions. All participants were provided with a controlled diet with a fixed composition of macronutrients before starting the interventions to establish an equal baseline. A full-room indirect calorimeter was used to conduct the interventions and measure the energy needs of each individual.

Blood and urine samples were taken postprandially at different time points to evaluate levels of BHB, AcAc, insulin, free fatty acids, C-peptide and dopamine. Appetite ratings were also assessed at various time points after a meal.


Results reported that total fasting and the ketogenic diets resulted in significantly higher ketone levels than the isocaloric formula diet, and the exogenous ketone supplement diet resulted in slightly higher ketone levels than the other three interventions. . While sleep and total energy expenditure did not vary between the isocaloric formula, total fasting, or exogenous ketone supplementation diets, the ketogenic diet increased both energy expenditures.

Carbohydrate oxidation was slightly lower in the exogenous ketone supplementation diet than in the isocaloric formula diet, which resulted in a positive carbohydrate balance. Furthermore, the absence of an increase in energy expenditure with exogenous ketone supplementation indicated that the metabolic switch from glucose utilization to ketone utilization cannot be achieved when ketones and glucose are both available to the body. .

The researchers believe that the increase in energy expenditure with the ketogenic diet could be explained by the upregulation of the energy-demanding pathways of the triglyceride fatty acid cycle and hepatic gluconeogenesis. Additionally, comparisons of cumulative energy expenditure between total fasting and ketogenic diets indicated that energy-demanding pathways only increased after about 16 hours on a ketogenic diet.


Overall, the results indicated that a 24-hour intermittent ketogenic diet could increase energy expenditure and help maintain energy balance. However, adding exogenous ketone salts as supplements to an isocaloric diet does not help regulate energy balance.

Magazine reference:

  • Hägele, FA, Dörner, R., Koop, J., Lübken, M., Seidel, U., Rimbach, G., Müller, MJ, & Bosy-Westphal, A. (2023). Impact of one-day fasting, ketogenic diet, or exogenous ketones on energy balance control in healthy participants. Clinical Nutrition ESPEN. https://doi.org/10.1016/j.clnesp.2023.03.025, https://www.sciencedirect.com/science/article/pii/S240545772300092X

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