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

S Nymo, S R Coutinho, J Jørgensen, J F Rehfeld, H Truby, B Kulseng, C Martins, S Nymo, S R Coutinho, J Jørgensen, J F Rehfeld, H Truby, B Kulseng, C Martins

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.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
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
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
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
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
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
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.

References

    1. WHO. Obesity and Overweight 2015. Available at accessed on 15 March 2016.
    1. Blackburn G. Effect of degree of weight loss on health benefits. Obes Res 1995;3 (Suppl 2): 211s–216s.
    1. Anderson JW, Konz EC, Frederich RC, Wood CL. Long-term weight-loss maintenance: a meta-analysis of US studies. Am J Clin Nutr 2001; 74: 579–584.
    1. Kraschnewski JL, Boan J, Esposito J, Sherwood NE, Lehman EB, Kephart DK et al. Long-term weight loss maintenance in the United States. Int J Obes 2010; 34: 1644–1654.
    1. Wing RR, Hill JO. Successful weight loss maintenance. Annu Rev Nutr 2001; 21: 323–341.
    1. Rosenbaum M, Leibel RL. Adaptive thermogenesis in humans. Int J Obes 2010; 34 (Suppl 1): S47–S55.
    1. Cornier MA. Is your brain to blame for weight regain? Physiol Behav 2011; 104: 608–612.
    1. Doucet E, Cameron J. Appetite control after weight loss: what is the role of bloodborne peptides? Appl Physiol Nutr Metab 2007; 32: 523–532.
    1. Maclean PS, Bergouignan A, Cornier MA, Jackman MR. Biology's response to dieting: the impetus for weight regain. Am J Physiol Regul Integr Comp Physiol 2011; 301: R581–R600.
    1. Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med 1995; 332: 621–628.
    1. Rosenbaum M, Vandenborne K, Goldsmith R, Simoneau JA, Heymsfield S, Joanisse DR et al. Effects of experimental weight perturbation on skeletal muscle work efficiency in human subjects. Am J Physiol Regul Integr Comp Physiol 2003; 285: R183–R192.
    1. Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A et al. Ketosis and appetite-mediating nutrients and hormones after weight loss. Eur J Clin Nutr 2013; 67: 759–764.
    1. Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med 2011; 365: 1597–1604.
    1. Fruhbeck G, Rotellar F, Hernandez-Lizoain JL, Gil MJ, Gomez-Ambrosi J, Salvador J et al. Fasting plasma ghrelin concentrations 6 months after gastric bypass are not determined by weight loss or changes in insulinemia. Obes Surg 2004; 14: 1208–1215.
    1. Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 2002; 346: 1623–1630.
    1. Adam TC, Jocken J, Westerterp-Plantenga MS. Decreased glucagon-like peptide 1 release after weight loss in overweight/obese subjects. Obes Res 2005; 13: 710–716.
    1. Essah PA, Levy JR, Sistrun SN, Kelly SM, Nestler JE. Effect of weight loss by a low-fat diet and a low-carbohydrate diet on peptide YY levels. Int J Obes 2010; 34: 1239–1242.
    1. Soenen S, Hochstenbach-Waelen A, Westerterp-Plantenga MS. Efficacy of alpha-lactalbumin and milk protein on weight loss and body composition during energy restriction. Obesity (Silver Spring) 2011; 19: 370–379.
    1. Chearskul S, Delbridge E, Shulkes A, Proietto J, Kriketos A. Effect of weight loss and ketosis on postprandial cholecystokinin and free fatty acid concentrations. Am J Clin Nutr 2008; 87: 1238–1246.
    1. Mars M, de Graaf C, de Groot LC, Kok FJ. Decreases in fasting leptin and insulin concentrations after acute energy restriction and subsequent compensation in food intake. Am J Clin Nutr 2005; 81: 570–577.
    1. Pasiakos SM, Caruso CM, Kellogg MD, Kramer FM, Lieberman HR. Appetite and endocrine regulators of energy balance after 2 days of energy restriction: insulin, leptin, ghrelin, and DHEA-S. Obesity (Silver Spring) 2011; 19: 1124–1130.
    1. Gibson AA, Seimon RV, Lee CM, Ayre J, Franklin J, Markovic TP et al. Do ketogenic diets really suppress appetite? A systematic review and meta-analysis. Obes Rev 2015; 16: 64–76.
    1. Brennan IM, Feltrin KL, Nair NS, Hausken T, Little TJ, Gentilcore D et al. Effects of the phases of the menstrual cycle on gastric emptying, glycemia, plasma GLP-1 and insulin, and energy intake in healthy lean women. Am J Physiol Gastrointest Liver Physiol 2009; 297: G602–G610.
    1. Nordic Nutrition Recommendations 2012: , 2014 Available at .
    1. Scheers T, Philippaerts R, Lefevre J. Patterns of physical activity and sedentary behavior in normal-weight, overweight and obese adults, as measured with a portable armband device and an electronic diary. Clin Nutr 2012; 31: 756–764.
    1. Stubbs RJ, Hughes DA, Johnstone AM, Rowley E, Reid C, Elia M et al. The use of visual analogue scales to assess motivation to eat in human subjects: a review of their reliability and validity with an evaluation of new hand-held computerized systems for temporal tracking of appetite ratings. Br J Nutr 2000; 84: 405–415.
    1. Rehfeld JF. Accurate measurement of cholecystokinin in plasma. Clin Chem 1998; 44: 991–1001.
    1. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc series B 1995; 57: 289–300.
    1. Clayton DJ, Creese M, Skidmore N, Stensel DJ, James LJ. No effect of 24h severe energy restriction on appetite regulation and ad libitum energy intake in overweight and obese males. Int J Obes 2016.
    1. Mars M, de Graaf C, de Groot CP, van Rossum CT, Kok FJ. Fasting leptin and appetite responses induced by a 4-day 65%-energy-restricted diet. Int J Obes 2006; 30: 122–128.
    1. Doucet E, Pomerleau M, Harper ME. Fasting and postprandial total ghrelin remain unchanged after short-term energy restriction. J Clin Endocrinol Metab 2004; 89: 1727–1732.
    1. Cameron JD, Goldfield GS, Riou ME, Finlayson GS, Blundell JE, Doucet E. Energy depletion by diet or aerobic exercise alone: impact of energy deficit modality on appetite parameters. Am J Clin Nutr 2016; 103: 1008–1016.
    1. Polidori D, Sanghvi A, Seeley RJ, Hall KD. How strongly does appetite counter weight loss? quantification of the feedback control of human energy intake. Obesity (Silver Spring) 2016; 24: 2289–2295.
    1. Hursel R, Westerterp-Plantenga MS. Green tea catechin plus caffeine supplementation to a high-protein diet has no additional effect on body weight maintenance after weight loss. Am J Clin Nutr 2009; 89: 822–830.
    1. Kovacs EM, Lejeune MP, Nijs I, Westerterp-Plantenga MS. Effects of green tea on weight maintenance after body-weight loss. Br J Nutr 2004; 91: 431–437.
    1. Lejeune MP, Kovacs EM, Westerterp-Plantenga MS. Effect of capsaicin on substrate oxidation and weight maintenance after modest body-weight loss in human subjects. Br J Nutr 2003; 90: 651–659.
    1. Lejeune MP, Kovacs EM, Westerterp-Plantenga MS. Additional protein intake limits weight regain after weight loss in humans. Br J Nutr 2005; 93: 281–289.
    1. Westerterp-Plantenga MS, Lejeune MP, Kovacs EM. Body weight loss and weight maintenance in relation to habitual caffeine intake and green tea supplementation. Obes Res 2005; 13: 1195–1204.
    1. Diepvens K, Soenen S, Steijns J, Arnold M, Westerterp-Plantenga M. Long-term effects of consumption of a novel fat emulsion in relation to body-weight management. Int J Obes 2007; 31: 942–949.
    1. Paoli A, Bosco G, Camporesi EM, Mangar D. Ketosis, ketogenic diet and food intake control: a complex relationship. Front Psychol 2015; 6: 27.
    1. Iepsen EW, Lundgren J, Holst JJ, Madsbad S, Torekov SS. Successful weight loss maintenance includes long-term increased meal responses of GLP-1 and PYY3-36. Eur J Endocrinol 2016; 174: 775–784.
    1. Burton-Freeman B, Davis PA, Schneeman BO. Plasma cholecystokinin is associated with subjective measures of satiety in women. Am J Clin Nutr 2002; 76: 659–667.
    1. Doucet E, Laviolette M, Imbeault P, Strychar I, Rabasa-Lhoret R, Prud'homme D. Total peptide YY is a correlate of postprandial energy expenditure but not of appetite or energy intake in healthy women. Metabolism 2008; 57: 1458–1464.
    1. Holt GM, Owen LJ, Till S, Cheng Y, Grant VA, Harden CJ et al. Systematic literature review shows that appetite rating does not predict energy intake. Crit Rev Food Sci Nutr 2016. Available at .
    1. Cornier MA, Salzberg AK, Endly DC, Bessesen DH, Tregellas JR. Sex-based differences in the behavioral and neuronal responses to food. Physiol Behav 2010; 99: 538–543.
    1. Gregersen NT, Moller BK, Raben A, Kristensen ST, Holm L, Flint A et al. Determinants of appetite ratings: the role of age, gender, BMI, physical activity, smoking habits, and diet/weight concern. Food Nutr Res 2011; 55: 1–10.

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