Skip to main content

Successful and unsuccessful weight-loss maintainers: strategies to counteract metabolic compensation following weight loss

  • Louise D. Clamp (a1), David J. Hume (a1), Estelle V. Lambert (a1) and Jacolene Kroff (a1)

Adaptive thermogenesis and reduced fat oxidative capacity may accompany weight loss, continuing in weight maintenance. The present study aimed (1) to determine whether weight-reduced and weight-loss relapsed women are at greater metabolic risk for weight gain compared with BMI-matched controls with no weight-loss history, and (2) to identify protective strategies that might attenuate weight loss-associated adaptive thermogenesis and support successful weight-loss maintenance. Four groups of women were recruited: reduced-overweight/obese (RED, n 15), controls (low-weight stable weight; LSW, n 19) BMI <27 kg/m2; relapsed-overweight/obese (REL, n 11), controls (overweight/obese stable weight; OSW, n 11) BMI >27 kg/m2. Body composition (bioelectrical impedance), 75 g oral glucose tolerance test, fasting and postprandial metabolic rate (MR) and substrate utilisation (RER) and physical activity (accelerometer (7 d)) were measured. Sociobehavioural questionnaires and 3 × 24 h diet recalls were completed. Fasting and postprandial MR, RER and total daily energy intake (TDEI) were not different between RED and REL v. controls (P > 0·05). RED consumed less carbohydrate (44·8 (sd 10·3) v. 53·4 (sd 10·0) % TDEI, P = 0·020), more protein (19·2 (sd 6·0) v. 15·6 (sd 4·2) % TDEI, P = 0·049) and increased physical activity, but behaviourally reported greater dietary restraint (P = 0·002) compared with controls. TDEI, macronutrient intake and physical activity were similar between OSW and REL. REL reported higher subjective fasting and lower postprandial ratings of prospective food consumption compared with OSW. Weight-reduced women had similar RMR (adjusted for fat-free mass) compared with controls with no weight-loss history. Increased physical activity, higher protein intake and greater lean muscle mass may have counteracted weight loss-associated metabolic compensation and highlights their importance in weight-maintenance programmes.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Successful and unsuccessful weight-loss maintainers: strategies to counteract metabolic compensation following weight loss
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Successful and unsuccessful weight-loss maintainers: strategies to counteract metabolic compensation following weight loss
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Successful and unsuccessful weight-loss maintainers: strategies to counteract metabolic compensation following weight loss
      Available formats
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Corresponding author
*Corresponding author: Dr Jacolene Kroff, fax +27 21 6504561/+27 21 6867530, email
Hide All
1.Smith, GD (2016) A fatter, healthier but more unequal world. Lancet 387, 13491350.
2.Di Cesare, M, Bentham, J, Stevens, GA, et al. (2016) Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet 387, 13771396.
3.NCD Risk Factor Collaboration (NCD-RisC) – Africa Working Group (2017) Trends in obesity and diabetes across Africa from 1980 to 2014: an analysis of pooled population-based studies. Int J Epidemiol 46, 14211432.
4.Dietz, WH (2011) Reversing the tide of obesity. Lancet 378, 744746.
5.Mariman, ECM (2012) Human biology of weight maintenance after weight loss. J Nutrigenet Nutrigenomics 5, 1325.
6.Sumithran, P & Proietto, J (2013) The defence of body weight: a physiological basis for weight regain after weight loss. Clin Sci (Lond) 124, 231241.
7.Rosenbaum, M & Leibel, RL (2010) Adaptive thermogenesis in humans. Int J Obes (Lond) 34, Suppl. 1, S47S55.
8.Turk, MW, Yang, K, Hravnak, M, et al. (2009) Randomized clinical trials of weight loss maintenance: a review. J Cardiovasc Nurs 24, 5880.
9.Dombrowski, SU, Knittle, K, Avenell, A, et al. (2014) Long term maintenance of weight loss with non-surgical interventions in obese adults: systematic review and meta-analyses of randomised controlled trials. BMJ 348, g2646.
10.Klem, ML, Wing, RR, Lang, W, et al. (2000) Does weight loss maintenance become easier over time? Obes Res 8, 438444.
11.Wing, RR & Hill, JO (2001) Successful weight loss maintenance. Annu Rev Nutr 21, 323341.
12.Wing, RR & Phelan, S (2005) Long-term weight loss maintenance. Am J Clin Nutr 82, 222S2225.
13.Müller, MJ, Enderle, J, Pourhassan, M, et al. (2015) Metabolic adaptation to caloric restriction and subsequent refeeding: the Minnesota starvation experiment revisited. Am J Clin Nutr 102, 807819.
14.Müller, MJ, Enderle, J & Bosy-Westphal, A (2016) Changes in energy expenditure with weight gain and weight loss in humans. Curr Obes Rep 5, 413423.
15.Tremblay, A, Royer, MM, Chaput, JP, et al. (2012) Adaptive thermogenesis can make a difference in the ability of obese individuals to lose body weight. Int J Obes 37, 759764.
16.Carpentier, AC (2015) Acute adaptation of energy expenditure predicts diet-induced weight loss: revisiting the thrifty phenotype. Diabetes 64, 27142716.
17.Siervo, M, Faber, P, Lara, J, et al. (2015) Imposed rate and extent of weight loss in obese men and adaptive changes in resting and total energy expenditure. Metabolism 64, 896904.
18.Rosenbaum, M & Leibel, RL (2016) Models of energy homeostasis in response to maintenance of reduced body weight. Obesity 24, 16201629.
19.Buscemi, S, Verga, S, Caimi, G, et al. (2005) Low relative resting metabolic rate and body weight gain in adult Caucasian Italians. Int J Obes (Lond) 29, 287291.
20.Major, GC, Doucet, E, Trayhurn, P, et al. (2007) Clinical significance of adaptive thermogenesis. Int J Obes 31, 204212.
21.Cunningham, J (1991) Body composition as a determinant of energy expenditure: a synthetic review and a proposed general prediction equation. Am J Clin Nutr 54, 963969.
22.Vogels, N & Westerterp-Plantenga, MS (2007) Successful long-term weight maintenance: a 2-year follow-up. Obesity (Silver Spring) 15, 12581266.
23.Camps, SGJA, Verhoef, SPM & Westerterp, KR (2013) Weight loss, weight maintenance, and adaptive thermogenesis. Am J Clin Nutr 97, 990994.
24.Rosenbaum, M, Hirsch, J, Gallagher, DA, et al. (2008) Long-term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight. Am J Clin Nutr 88, 906912.
25.Galgani, JE, Moro, C & Ravussin, E (2008) Metabolic flexibility and insulin resistance. Am J Physiol Endocrinol Metab 295, E1009E1017.
26.Raben, A, Andersen, HB, Christensen, NJ, et al. (1994) Evidence for an abnormal postprandial response to a high-fat meal in women predisposed to obesity. Am J Physiol 267, E549E559.
27.Filozof, CM, Murúa, C, Sanchez, MP, et al. (2000) Low plasma leptin concentration and low rates of fat oxidation in weight-stable post-obese subjects. Obes Res 8, 205210.
28.Nelson, KM, Weinsier, RL, James, LD, et al. (1992) Effect of weight reduction on resting energy expenditure, substrate utilization, and the thermic effect of food in moderately obese women. Am J Clin Nutr 55, 924933.
29.Thyfault, JP, Kraus, RM, Hickner, RC, et al. (2004) Impaired plasma fatty acid oxidation in extremely obese women. Am J Physiol Endocrinol Metab 287, E1076E1081.
30.Ellis, AC, Hyatt, TC, Hunter, GR, et al. (2010) Respiratory quotient predicts fat mass gain in premenopausal women. Obesity (Silver Spring) 18, 22552259.
31.Ballor, DL, Harvey-Berino, JR, Ades, PA, et al. (1996) Decrease in fat oxidation following a meal in weight-reduced individuals: a possible mechanism for weight recidivism. Metabolism 45, 174178.
32.Seidell, JC, Muller, DC, Sorkin, JD, et al. (1992) Fasting respiratory exchange ratio and resting metabolic rate as predictors of weight gain: the Baltimore Longitudinal Study on Aging. Int J Obes Relat Metab Disord 16, 667674.
33.Zurlo, F, Lillioja, S, Esposito-Del Puente, A, et al. (1990) Low ratio of fat to carbohydrate oxidation as predictor of weight gain: study of 24-h RQ. Am J Physiol 259, 650657.
34.Jackman, MR, Steig, A, Higgins, JA, et al. (2008) Weight regain after sustained weight reduction is accompanied by suppressed oxidation of dietary fat and adipocyte hyperplasia. Am J Physiol Regul Integr Comp Physiol 294, R1117R1129.
35.Raynor, HA, Jeffery, RW, Phelan, S, et al. (2005) Amount of food group variety consumed in the diet and long-term weight loss maintenance. Obes Res 13, 883890.
36.Weinsier, RL, Hunter, GR, Desmond, RA, et al. (2002) Free-living activity energy expenditure in women successful and unsuccessful at maintaining a normal body weight. Am J Clin Nutr 75, 499504.
37.Stunkard, AJ & Messick, S (1985) The Three-Factor Eating Questionnaire to measure dietary restraint, disinhibition and hunger. J Psychosom Res 29, 7183.
38.Subar, AF, Kirkpatrick, SI, Mittl, B, et al. (2012) The Automated Self-administered 24-h Dietary Recall (ASA24): a resource for researchers, clinicians, and educators from the National Cancer Institute. J Acad Nutr Diet 112, 11341137.
39.Compher, C, Frankenfield, D, Keim, N, et al. (2006) Best practice methods to apply to measurement of resting metabolic rate in adults: a systematic review. J Am Diet Assoc 106, 881903.
40.De Weir, JB (1949) New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol 109, 19.
41.Frayn, KN (1983) Calculation of substrate oxidation rates in vivo from gaseous exchange rates. J Appl Physiol 55, 628634.
42.Ravn, AM, Gregersen, NT, Christensen, R, et al. (2013) Thermic effect of a meal and appetite in adults: an individual participant data meta-analysis of meal-test trials. Food Nutr Res 57, 10.3402/fnr.v57i0.19676.
43.Matthews, DR, Hosker, JP, Rudenski, AS, et al. (1985) Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412419.
44.Segal, KR, Chun, A, Coronel, P, et al. (1992) Reliability of the measurement of postprandial thermogenesis in men of three levels of body fatness. Metabolism 41, 754762.
45.Speechly, DP & Buffenstein, R (2000) Appetite dysfunction in obese males: evidence for role of hyperinsulinaemia in passive overconsumption with a high fat diet. Eur J Clin Nutr 54, 225233.
46.Cooling, J & Blundell, J (1998) Are high-fat and low-fat consumers distinct phenotypes? Differences in the subjective and behavioural response to energy and nutrient challenges. Eur J Clin Nutr 52, 193201.
47.Clamp, L, Hehir, APJ, Lambert, EV, et al. (2015) Lean and obese dietary phenotypes: differences in energy and substrate metabolism and appetite. Br J Nutr 114, 17241733.
48.Flint, A, Raben, A, Blundell, JE, et al. (2000) Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies. Int J Obes 24, 3848.
49.Kirkpatrick, SI, Subar, AF, Douglass, D, et al. (2014) Performance of the automated self-administered 24-h recall relative to a measure of true intakes and to an interviewer-administered 24-h recall. Am J Clin Nutr 100, 233240.
50.Matthews, CE, Ainsworth, BE, Thompson, RW, et al. (2002) Sources of variance in daily physical activity levels as measured by an accelerometer. Med Sci Sport Exerc 34, 13761381.
51.Mâsse, LC Fuemmeler, BF Anderson, CB, et al. (2005) Accelerometer data reduction: a comparison of four reduction algorithms on select outcome variables. Med Sci Sport Exerc 37, 11 Suppl., S544S554.
52.Matthews, C (2005) Calibration for accelerometer output for adults. Med Sci Sport Exerc 37, 11 Suppl., S512S522.
53.Black, AE, Coward, WA, Cole, TJ, et al. (1996) Human energy expenditure in affluent societies: an analysis of 574 doubly-labelled water measurements. Eur J Clin Nutr 50, 7292.
54.Bergouignan, A, Kealey, EH, Schmidt, SL, et al. (2014) Twenty-four hour total and dietary fat oxidation in lean, obese and reduced-obese adults with and without a bout of exercise. PLOS ONE 9, e94181.
55.Hill, JO, Peters, JC & Wyatt, HR (2009) Using the energy gap to address obesity: a commentary. J Am Diet Assoc 109, 18481853.
56.Stroebele, N, Hill, JO & Willich, SN (2011) Identifying the energy gap in the German population using results from representative national health surveys (1985–2002). Public Health Nutr 14, 4448.
57.Swinburn, BA, Sacks, G, Hall, KD, et al. (2011) The global obesity pandemic: shaped by global drivers and local environments. Lancet 378, 804814.
58.Redman, LM, Heilbronn, LK, Martin, CK, et al. (2009) Metabolic and behavioral compensations in response to caloric restriction: implications for the maintenance of weight loss. PLOS ONE 4, e4377.
59.Johannsen, DL, Knuth, ND, Huizenga, R, et al. (2012) Metabolic slowing with massive weight loss despite preservation of fat-free mass. J Clin Endocrinol Metab 97, 24892496.
60.Fothergill, E, Guo, J, Howard, L, et al. (2016) Persistent metabolic adaptation 6 years after “The Biggest Loser” competition. Obesity 24, 16121619.
61.Weinsier, RL, Nagy, TR, Hunter, GR, et al. (2000) Do adaptive changes in metabolic rate favor weight regain in weight-reduced individuals? An examination of the set-point theory. Am J Clin Nutr 72, 10881094.
62.Soenen, S, Martens, EAP, Hochstenbach-Waelen, A, et al. (2013) Normal protein intake is required for body weight loss and weight maintenance, and elevated protein intake for additional preservation of resting energy expenditure and fat free mass. J Nutr 143, 591596.
63.Lejeune, MPGM, Kovacs, EMR & Westerterp-Plantenga, MS (2005) Additional protein intake limits weight regain after weight loss in humans. Br J Nutr 93, 281289.
64.Ebbeling, CB, Swain, JF, Feldman, HA, et al. (2012) Effects of dietary composition on energy expenditure during weight-loss maintenance. JAMA 307, 26272634.
65.Sumithran, P, Prendergast, LA, Delbridge, E, et al. (2011) Long-term persistence of hormonal adaptations to weight loss. N Engl J Med 365, 15971604.
66.Wang, X, Lyles, MF, You, T, et al. (2008) Weight regain is related to decreases in physical activity during weight loss. Med Sci Sports Exerc 40, 17811788.
67.Camps, SG, Verhoef, SP & Westerterp, KR (2013) Weight loss-induced reduction in physical activity recovers during weight maintenance. Am J Clin Nutr 98, 917923.
68.Clamp, LD, Hume, DJ, Lambert, EV, et al. (2017) Enhanced insulin sensitivity in successful, long-term weight loss maintainers compared with matched controls with no weight loss history. Nutr Diabetes 7, e282.
69.Blaak, EE, Hul, G, Verdich, C, et al. (2006) Fat oxidation before and after a high fat load in the obese insulin-resistant state. J Clin Endocrinol Metab 91, 14621469.
70.Astrup, A, Buemann, B, Christensen, NJ, et al. (1992) 24-Hour energy expenditure and sympathetic activity in postobese women consuming a high-carbohydrate diet. Am J Physiol 262, E282E288.
71.Larson, DE, Ferraro, RT, Robertson, DS, et al. (1995) Energy metabolism in weight-stable postobese individuals. Am J Clin Nutr 62, 735739.
72.Faraj, M, Jones, P, Sniderman, AD, et al. (2001) Enhanced dietary fat clearance in postobese women. J Lipid Res 42, 571580.
73.Bosy-Westphal, A & Müller, MJ (2015) Impact of carbohydrates on weight regain. Curr Opin Clin Nutr Metab Care 18, 389394.
74.Foster-Schubert, KE, Overduin, J, Prudom, CE, et al. (2008) Acyl and total ghrelin are suppressed strongly by ingested proteins, weakly by lipids, and biphasically by carbohydrates. J Clin Endocrinol Metab 93, 19711979.
75.Brennan, IM, Luscombe-Marsh, ND, Seimon, RV, et al. (2012) Effects of fat, protein, and carbohydrate and protein load on appetite, plasma cholecystokinin, peptide YY, and ghrelin, and energy intake in lean and obese men. Am J Physiol Gastrointest Liver Physiol 303, G129G140.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Journal of Nutritional Science
  • ISSN: 2048-6790
  • EISSN: 2048-6790
  • URL: /core/journals/journal-of-nutritional-science
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score