Timeline of changes in appetite during weight loss with a ketogenic diet

Abstract

Background/objective: Diet-induced weight loss (WL) leads to increased hunger and reduced fullness feelings, increased ghrelin and reduced satiety peptides concentration (glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK) and peptide YY (PYY)). Ketogenic diets seem to minimise or supress some of these responses. The aim of this study was to determine the timeline over which changes in appetite occur during progressive WL with a ketogenic very-low-energy diet (VLED).

Subjects/methods: Thirty-one sedentary adults (18 men), with obesity (body mass index: 37±4.5 kg m^-2) underwent 8 weeks (wks) of a VLED followed by 4 wks of weight maintenance. Body weight and composition, subjective feelings of appetite and appetite-related hormones (insulin, active ghrelin (AG), active GLP-1, total PYY and CCK) were measured in fasting and postprandially, at baseline, on day 3 of the diet, 5 and 10% WL, and at wks 9 and 13. Data are shown as mean±s.d.

Results: A significant increase in fasting hunger was observed by day 3 (2±1% WL), (P<0.01), 5% WL (12±8 days) (P<0.05) and wk 13 (17±2% WL) (P<0.05). Increased desire to eat was observed by day 3 (P<0.01) and 5% WL (P<0.05). Postprandial prospective food consumption was significantly reduced at wk 9 (16±2% WL) (P<0.01). Basal total PYY was significantly reduced at 10% WL (32±8 days) (P<0.05). Postprandial active GLP-1 was increased at 5% WL (P<0.01) and CCK reduced at 5 and 10% WL (P<0.01, for both) and wk 9 (P<0.001). Basal and postprandial AG were significantly increased at wk 13 (P<0.001, both).

Conclusions: WL with a ketogenic VLED transiently increases the drive to eat up to 3 weeks (5% WL). After that, and while participants are ketotic, a 10-17% WL is not associated with increased appetite. However, hunger feelings and AG concentrations increase significantly from baseline, once refeeding occurs.

Trial registration: ClinicalTrials.gov NCT01834859.

Figure 1

Basal plasma concentration of β-hydroxybutyric acid over time in all participants, males and females. Results presented as estimated marginal means±s.e.m. A significant main effect of time was found for β-hydroxybutyrate (P<0.001). Symbols denote significant differences from baseline in all participants ***P<0.001, males ^&&&P<0.001 and females ^###P<0.001. WL, weight loss

Figure 2

Changes in body weight (a) and body composition (b) over time in all participants, males and females. Results are presented as estimated marginal means±s.e.m. Symbols denote significant changes from baseline (all participants: ***P<0.001 for body weight and FM and ^###P<0.001 for FFM; males: ^&&&P<0.001 for FFM and ^∈∈∈P<0.001, and ^∈∈P<0.01 for FM and females: ^$$$P<0.001 and ^$P<0.05 for FM). FFM, fat-free mass; FM, fat mass; WL, weight loss.

Figure 3

Subjective feelings of appetite (a: hunger, b: fullness, c: desire to eat and d: PFC) in fasting, over time, in all participants, males and females. Results presented as estimated marginal means±s.e.m. Symbols denote significant differences from baseline in all participants: **P<0.01 and *P<0.05, males: ^&P<0.05 and females: ^##P<0.01 and ^#P<0.05. PFC, prospective food consumption; WL, weight loss.

Figure 4

AUC for subjective feelings of appetite (a: hunger, b: fullness, c: desire to eat and d: PFC) over time in all participants, males and females. Results presented as estimated marginal means±s.e.m. Symbols denote significant differences from baseline in all participants: **P<0.01 and females: ^#P<0.05. AUC, total area under the curve; PFC, prospective food consumption; WL, weight loss.

Figure 5

Basal plasma concentrations of appetite-related hormones (a: active ghrelin (AG), b: GLP-1, c: CCK, d: PYY and e: insulin) over time in all participants, males and females. Results presented as estimated marginal means±s.e.m. Symbols denote significant differences from baseline in all participants: ***P<0.001 and *P<0.05, males: ^&&&P<0.001, ^&&P<0.01 and ^&P<0.05, and females: ^###P<0.001 and ^#P<0.05. CCK, cholecystokinin; GLP-1, glucagon-like peptide-1; PYY, total peptide YY; WL, weight loss.

Figure 6

AUC for appetite-related hormones (a: active ghrelin (AG), b: GLP-1, c: CCK, d: PYY and e: insulin) over time in all participants, males and females. Results presented as estimated marginal means±s.e.m. Symbols denote significant differences from baseline in all participants: ***P<0.001, **P<0.01, males: ^&&&P<0.001, ^&&P<0.01 and ^&P<0.05 and females: ^#P<0.05. CCK, cholecystokinin; GLP-1, glucagon-like peptide-1; PYY, total peptide YY; tAUC, total area under the curve; WL, weight loss.