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

By Dr. Chinta SidharthanApr 12 2023Reviewed by Danielle Ellis, B.Sc.

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

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

Background 

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

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

About the study

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

Individuals who practiced alternative food habits such as veganism or vegetarianism, had chronic diseases, had food allergies, were on regular medications, smoked, had claustrophobia, were pregnant or lactating, had a high level of physical activity, had lost more than 5 kg in the last three months, or were currently on weight loss diets 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 the fat mass index. Indirect calorimetry was used to calculate the resting energy expenditure. Four interventions consisting of an isocaloric formula diet, total fasting, isocaloric ketogenic diet, and exogenous ketone salt supplements were conducted for 24 hours, with differing chronological orders of each intervention for the first and last four participants.

A bicycle ergometer was used to measure work and energy during three rounds of 20 minutes of exercise to maintain a physical activity level (PAL) of 1.65 during interventions. A controlled diet with a fixed composition of macronutrients was provided to all participants before beginning the interventions to establish equal baseline conditions. A whole-room indirect calorimeter was used to conduct the interventions and measure the energy requirements of each individual.

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

Results

The results reported that the total fasting and ketogenic diets resulted in significantly higher levels of ketone as compared to the isocaloric formula diet, and the exogenous ketone supplement diet resulted in slightly higher levels of ketones than the other three interventions. While the sleeping 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.

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

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

Conclusions

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