University of Oulu

Cathrine Horn Sommersten, Eirin Semb Gjerde, Johnny Laupsa-Borge, Amanda IO. Andersen, Laurence Lawrence-Archer, Adrian McCann, Patrik Hansson, Ghulam S. Raza, Karl Heinz Herzig, Gülen Arslan Lied, Catia Martins, Gunnar Mellgren, Jutta Dierkes, Simon N. Dankel, Relationship between Ketones, Ghrelin, and, Appetite on Isocaloric Diets with Varying Carbohydrate Quality and Amount: Results from a Randomized Controlled Trial in People with Obesity (CARBFUNC), The Journal of Nutrition, Volume 153, Issue 2, 2023, Pages 459-469, ISSN 0022-3166,

Relationship between ketones, ghrelin, and, appetite on isocaloric diets with varying carbohydrate quality and amount : results from a randomized controlled trial in people with obesity (CARBFUNC)

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Author: Sommersten, Cathrine Horn1,2; Gjerde, Eirin Semb1,2; Laupsa-Borge, Johnny1;
Organizations: 1Mohn Nutrition Research Laboratory, Centre for Nutrition, Department of Clinical Science, University of Bergen, Bergen, Norway
2Mohn Nutrition Research Laboratory, Centre for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen, Norway
3Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
4Bevital AS, Bergen, Norway
5Department of Clinical Medicine, Faculty of Health Sciences, the Arctic University of Norway, Tromsø, Norway
6Research Unit of Biomedicine, Faculty of Medicine, University of Oulu, Oulu, Finland
7Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Sciences and Technology, Trondheim, Norway
8Centre for Obesity and Innovation, Clinic of Surgery, St. Olav University Hospital, Trondheim, Norway
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.9 MB)
Persistent link:
Language: English
Published: Oxford University Press, 2023
Publish Date: 2023-11-07


Background: Low-carbohydrate high-fat (LCHF) diets may suppress the increase in appetite otherwise seen after diet-induced fat loss. However, studies of diets without severe energy restriction are lacking, and the effects of carbohydrate quality relative to quantity have not been directly compared.

Objectives: To evaluated short- (3 mo) and long-term (12 mo) changes in fasting plasma concentrations of total ghrelin, β-hydroxybutyrate (βHB), and subjective feelings of appetite on 3 isocaloric eating patterns within a moderate caloric range (2000–2500 kcal/d) and with varying carbohydrate quality or quantity.

Methods: We performed a randomized controlled trial of 193 adults with obesity, comparing eating patterns based on “acellular” carbohydrate sources (e.g., flour-based whole-grain products; comparator arm), “cellular” carbohydrate sources (minimally processed foods with intact cellular structures), or LCHF principles. Outcomes were compared by an intention-to-treat analysis using constrained linear mixed modeling. This trial was registered at as NCT03401970.

Results: Of the 193 adults, 118 (61%) and 57 (30%) completed 3 and 12 mo of follow-up. Throughout the intervention, intakes of protein and energy were similar with all 3 eating patterns, with comparable reductions in body weight (5%−7%) and visceral fat volume (12%−17%) after 12 mo. After 3 mo, ghrelin increased significantly with the acellular (mean: 46 pg/mL; 95% CI: 11, 81) and cellular (mean: 54 pg/mL; 95% CI: 21, 88) diets but not with the LCHF diet (mean: 11 pg/mL; 95% CI: −16, 38). Although βHB increased significantly more with the LCHF diet than with the acellular diet after 3 m (mean: 0.16 mmol/L; 95% CI: 0.09, 0.24), this did not correspond to a significant group difference in ghrelin (unless the 2 high-carbohydrate groups were combined [mean: −39.6 pg/mL; 95% CI: −76, −3.3]). No significant between-group differences were seen in feelings of hunger.

Conclusions: Modestly energy-restricted isocaloric diets differing in carbohydrate cellularity and amount showed no significant differences in fasting total ghrelin or subjective hunger feelings. An increase in ketones with the LCHF diet to 0.3–0.4 mmol/L was insufficient to substantially curb increases in fasting ghrelin during fat loss.

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Series: Journal of nutrition
ISSN: 0022-3166
ISSN-E: 1541-6100
ISSN-L: 0022-3166
Volume: 153
Issue: 2
Pages: 459 - 469
DOI: 10.1016/j.tjnut.2022.12.030
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Funding: This study was supported by grants from the Trond Mohn Foundation, Bergen, Norway; the University of Bergen, Bergen, Norway; and Kostfonden, Stockholm, Sweden.
Copyright information: © 2023 The Authors. Published by Elsevier Inc. on behalf of American Society for Nutrition. This is an open access article under the CC BY license (