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Am J Clin Nutr. 2019 Jun 1;109(6):1511-1518. doi: 10.1093/ajcn/nqz002.

Investigating the effect of sex and ketosis on weight-loss-induced changes in appetite.

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Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Science, Norwegian University of Science and Technology Trondheim, Norway.
Centre for Obesity and Innovation (ObeCe), Clinic of Surgery, St. Olav University Hospital, Trondheim, Norway.
Nord-Trøndelag Hospital Trust, Clinic of Surgery, Namsos Hospital, Norway.
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Nutrition, Dietetics & Food, Monash University, Melbourne, Australia.



Diet-induced weight loss (WL) is usually accompanied by increased appetite, a response that seems to be absent when ketogenic diets are used. It remains unknown if sex modulates the appetite suppressant effect of ketosis.


The aim of this study was to examine if sex modulates the impact of WL-induced changes in appetite and if ketosis alters these responses.


Ninety-five individuals (55 females) with obesity (BMI [kg/m 2]: 37  ± 4) underwent 8 wk of a very-low-energy diet, followed by 4 wk of refeeding and weight stabilization. Body composition, plasma concentration of β-hydroxybutyrate (β-HB) and appetite-related hormones (active ghrelin, active glucagon-like peptide 1 [GLP-1], total peptide YY [PYY], cholecystokinin and insulin), and subjective feelings of appetite were measured at baseline, week 9 in ketosis, and week 13 out of ketosis.


The mean WL at week 9 was 17% for males and 15% for females, which was maintained at week 13. Weight, fat, and fat-free mass loss were greater in males (P < 0.001 for all) and the increase in β-HB at week 9 higher in females (1.174 ± 0.096 compared with 0.783 ± 0.112 mmol/L, P = 0.029). Basal and postprandial GLP-1 and postprandial PYY (all P < 0.05) were significantly different for males and females. There were no significant sex × time interactions for any other appetite-related hormones or subjective feelings of appetite. At week 9, basal GLP-1 was decreased only in males (P < 0.001), whereas postprandial GLP-1 was increased only in females (P < 0.001). No significant changes in postprandial PYY were observed over time for either sex.


Ketosis appears to have a greater beneficial impact on GLP-1 in females. However, sex does not seem to modulate the changes in the secretion of other appetite-related hormones, or subjective feelings of appetite, seen with WL, regardless of the ketotic state. This trial was registered at as NCT01834859.


cholecystokinin; fullness; ghrelin; glucagon-like peptide 1; hunger; ketosis; peptide YY; prospective food consumption; very-low-energy diet; weight loss

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