One-day keto diet boosts energy expenditure, exogenous ketones have little effect

A high-fat ketogenic diet (KD) promotes higher total energy expenditure (TEE), which leads to weight loss. In addition, the appetite suppressant effects of acetoacetate (AcAc) and ketone bodies beta-hydroxybutyrate (BHB) promote weight loss. A previous study revealed that 14 days of KD caused spontaneous weight loss in obese and type 2 diabetic patients. However, there have been contradictory findings regarding the effect of a KD on TEE and appetite perception. 

Considering the contradictory results, a recent Clinical Nutrition ESPEN study compared the effects of a one-day ketogenic diet, fasting, and ketone salts (KS) supplementation with typical carbohydrates (CHO) on energy expenditure and appetite perception in healthy individuals.

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


Even though KD has many health benefits, including lowering glycemia and insulin levels, it has been associated with some ill effects, such as an increase in low-density lipoprotein cholesterol. In addition, long-term adherence to KD could be difficult due to restricted food choices and undesirable side effects, such as gastrointestinal problems. Recently, intermittent fasting or short-term diets have gained much popularity.

Total fasting decreases energy expenditure (EE) and increases appetite. Therefore, 24 hours of KD could be a favorable diet strategy to reduce weight. Currently, exogenous ketones (EXO) have become commercially available as racemic ketone salts (KS, D/L-BHB) or as ketone esters (KE, D-BHB), which can be used as supplements to achieve ketosis.

There have been mixed results regarding appetite suppressant effects of exogenous ketone supplementation. For instance, some studies revealed that KE mimics the appetite suppressant effect of a KD by decreasing the ghrelin levels. However, others have contradicted this result and revealed that oral consumption or intravenous administration of KS does not affect appetite suppression. 

About the Study

A total of 8 healthy adults, equally representative of men and women, were recruited into this randomized crossover study. All participants were 20 to 35 years old and had low to moderate regular physical activity. These participants were recruited from September 2020 to July 2021 at the University of Kiel, Germany.

All women needed to be on hormonal contraceptives to prevent EE's effects from the female cycle. In addition, participants with chronic diseases, pregnancy, alternative eating habits, food allergies, smoking, and high habitual physical activity, were excluded from this study. Finally, one participant was excluded from this study due to incorrect estimations linked to non-isocaloric energy intake with the ketogenic formula diet (KETO).

Study Findings

Compared to an isocaloric diet with a normal CHO content, one-day isocaloric KD led to a higher TEE and sleeping energy expenditure (SEE). Interestingly, a similar effect was observed in a whole room indirect calorimeter (WRIC) study, which involved shifting from a normal 50% CHO-based diet to an isocaloric KD with 5% CHO. SEE and TEE elevated by approximately þ100 kcal/ d with constant physical activity prescription and without alterations in the thermic effect of food (TEF).

Based on theoretical assumptions, a TEE of about 225 kcal/d was estimated due to the variations in CHO content between KETO and the isocaloric formula diet (ISO). However, such values were not achieved in the first 24 hours of KD intervention. A modest increase of about 100 kcal/d was observed in response to a KD. This could be due to the rise in energy-demanding pathways, such as hepatic gluconeogenesis (GNG) and the triglyceride fatty acid cycle.

Compared to total fasting (FAST), an increase in cumulative EE was associated with KETO intervention. This finding indicated that upregulation in the energy-demanding pathways occurs not before 16 hours of a ketogenic diet. There was no difference in total N-excretion and cumulative CHO oxidation between FAST and KETO. A higher EE with KETO could be attributed to an elevation in futile cycling of glucose and/or fatty acids instead of only GNG. Since the protein content of KETO is lower compared to EXO and ISO, it caused lower TEF.

Here, one-day KD was found to be effective as a weight maintenance strategy. This is because it caused a higher TEE, and ad libitum energy intake could be lower in the case of a habitual CHO-rich diet (highly processed food). However, these effects did not prevail when consuming a low-processed food diet with a lower energy density. 

Notably, FAST was seen to enhance GNG, ketogenesis, and ureagenesis. Therefore, resting energy expenditure (REE) was elevated during early fasting compared with ISO. Fasting was also linked with an increase in the sympathetic nervous system (SNS)-activity. Compared with ISO control, a reduction in CHO oxidation was found with KS supplementation. Consistent with the current study's findings, a previous study revealed that oral KS supplementation did not affect subjective appetite. The lack of appetite suppressant effect could be because one day of KD or fasting only causes a moderate increase in ketone levels.


The intra-individual cross-over design and the use of a highly standardized setting of a WRIC are key strengths of this study. However, the small sample size is the main shortcoming of this study. The study found that a 24-hour ketogenic diet increased energy expenditure and helped maintain a neutral balance of energy. However, adding exogenous ketone bodies to an isocaloric diet did not improve energy regulation. Subjective appetite ratings showed no differences between interventions. 

Journal reference:
Dr. Priyom Bose

Written by

Dr. Priyom Bose

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.


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