Metabolic Damage: do Negative Metabolic Adaptations During Underfeeding Persist After Refeeding in Non-Obese Populations?

Main Article Content

Anastasia Zinchenko Menno Henselmans


Several researches have proposed that a prolonged period of caloric restriction (CR) may have a permanent, adverse effect on basal metabolism, fostering the development of obesity. This reported metabolic slowing has been associated with a reduction in resting metabolic rate (RMR) beyond what is predicted by the change in body composition, promoting the idea that metabolism can be permanently damaged. This systematic review investigates if prolonged CR exhibits a permanent, negative effect on basal metabolism.

Here we review the literature reporting weight loss and weight regain of individuals who were initially within a healthy weight range, such as the long-term Minnesota starvation experiment, in addition to research on chronically undernourished individuals, such as patients with anorexia nervosa, before and after recovery. Quantification of basal metabolism before and after prolonged CR revealed that body composition is the most critical factor in determining absolute RMR in neutral energy balance. Changes in energy balance induce a rapid yet reversible increase or decrease in RMR. Previous reports may have come to erroneous conclusions in favor of the metabolic damage hypothesis because they did not examine the full recovery period in the Minnesota experiment or neglected the influence of energy balance on RMR. Our findings indicate that the theory of permanent, diet-induced metabolic slowing in non-obese individuals is not supported by the current literature.

Article Details

How to Cite
ZINCHENKO, Anastasia; HENSELMANS, Menno. Metabolic Damage: do Negative Metabolic Adaptations During Underfeeding Persist After Refeeding in Non-Obese Populations?. Medical Research Archives, [S.l.], v. 4, n. 8, dec. 2016. ISSN 2375-1924. Available at: <>. Date accessed: 25 july 2024.
metabolic damage, metabolic slowing, weight regain, weight loss, weight cycling
Review Articles


Astrup, A., Gøtzsche, P. C., van de Werken, K., Ranneries, C., Toubro, S., Raben, A., & Buemann, B. (1999). Meta-analysis of resting metabolic rate in formerly obese subjects. The American Journal of Clinical Nutrition, 69, 1117–1122. Retrieved from

Bosy-Westphal, A., Braun, W., Schautz, B., & Müller, M. J. (2013). Issues in characterizing resting energy expenditure in obesity and after weight loss. Frontiers in Physiology, 4(March), 47.

Bosy-Westphal, A., Kahlhöfer, J., Lagerpusch, M., Skurk, T., & Müller, M. J. (2015). Deep body composition phenotyping during weight cycling: relevance to metabolic efficiency and metabolic risk. Obes Rev, 16(February), 36–44.

Bosy-Westphal, A., Müller, M. J., Boschmann, M., Klaus, S., Kreymann, G., Lührmann, P. M., … Steiniger, J. (2009). Grade of adiposity affects the impact of fat mass on resting energy expenditure in women. The British Journal of Nutrition, 101(4), 474–7.

Camps, S. G. J. A., Verhoef, S. P. M., & Westerterp, K. R. (2013). Weight loss, weight maintenance, and adaptive thermogenesis. The American Journal of Clinical Nutrition, 97(5), 990–4.

Dellava, J. E., Policastro, P., & Hoffman, D. J. (2009). Energy metabolism and body composition in long-term recovery from anorexia nervosa. The International Journal of Eating Disorders, 42(5), 415–21.

Diedrichs, P. C., Lee, C., & Kelly, M. (2011). Seeing the beauty in everyday people: a qualitative study of young Australians’ opinions on body image, the mass media and models. Body Image, 8(3), 259–66.

Doucet, E., St-Pierre, S., Almeras, N., Despres, J. P., Bouchard, C., & Tremblay, A. (2001). Evidence for the existence of adaptive thermogenesis during weight loss. Br J Nutr, 85(6), 715–723. [pii]

Dulloo, A. G., & Jacquet, J. (1998). Adaptive reduction in basal metabolic rate in response to food deprivation in humans: A role for feedback signals from fat stores. American Journal of Clinical Nutrition, 68, 599–606. Retrieved from

Dulloo, A. G., Jacquet, J., & Girardier, L. (1996). Autoregulation of body composition during weight recovery in human: the Minnesota Experiment revisited. International Journal of Obesity, 20, 393–405.

Dulloo, A. G., Jacquet, J., & Girardier, L. (1997). Poststarvation hyperphagia and body fat overshooting in humans: A role for feedback signals from lean and fat tissues. American Journal of Clinical Nutrition, 65(3), 717–723.

Dulloo, A. G., Jacquet, J., & Montani, J.-P. (2012). How dieting makes the lean fatter: from a perspective of human body composition autoregulation. Proceedings of the Nutrition Society, 71(3), 379–389.

Dulloo, A. G., Jacquet, J., Seydoux, J., & Montani, J.-P. (2006). The thrifty “catch-up fat” phenotype: its impact on insulin sensitivity during growth trajectories to obesity and metabolic syndrome. International Journal of Obesity, 30, S23–S35.

Ferro-Luzzi, A., Petracchi, C., Kuriyan, R., & Kurpad, A. V. (1997). Basal metabolism of weight-stable chronically undernourished men and women: lack of metabolic adaptation and ethnic differences. The American Journal of Clinical Nutrition, 66(5), 1086–93. Retrieved from

Fothergill, E., Guo, J., Howard, L., Kerns, J. C., Knuth, N. D., Brychta, R., … Hall, K. D. (2016). Persistent metabolic adaptation 6 years after “The Biggest Loser” competition. Obesity, 24(8), 1612–1619.

Grande, F., Anderson, J. T., & Keys, A. (1958). Changes of Basal Metabolic Rate in Man in Semistarvation und Refeeding. Journal of Applied Physiology, 12, 230–238. Retrieved from

Haas, V., Onur, S., Paul, T., Nutzinger, D. O., Bosy-Westphal, A., Hauer, M., … Muller, M. J. (2005). Leptin and body weight regulation in patients with anorexia nervosa before and during weight recovery. American Journal of Clinical Nutrition, 81(4), 889–896. [pii]

Hall, K. D. (2006). Computational model of in vivo human energy metabolism during semistarvation and refeeding. American Journal of Physiology-Endocrinology and Metabolism, 5621, 23–37.

Johannsen, D. L., Knuth, N. D., Huizenga, R., Rood, J. C., Ravussin, E., & Hall, K. D. (2012). Metabolic Slowing with Massive Weight Loss despite Preservation of Fat-Free Mass. The Journal of Clinical Endocrinology & Metabolism, 97(7), 2489–2496.

Johnstone, A. M., Murison, S. D., Duncan, J. S., Rance, K. A., & Speakman, J. R. (2005). Factors influencing variation in basal metabolic rate include fat-free mass, fat mass, age, and circulating thyroxine but not sex, circulating leptin, or triiodothyronine. American Journal of Clinical Nutrition, 82, 941–948. [pii]

Kenardy, J., Brown, W. J., & Vogt, E. (2001). Dieting and Health in Young Australian Women. European Eating Disorder Review, 4(9), 242–254. Retrieved from

Keys, A., Brozek, J., Henschel, A., Mickelsen, O., & Taylor, H. L. (1950). The Biology of Human Starvation. University of Minnesota Press, Minneapolis, MN.

Kosmiski, L., Schmiege, S. J., Mascolo, M., Gaudiani, J., & Mehler, P. S. (2014). Chronic starvation secondary to anorexia nervosa is associated with an adaptive suppression of resting energy expenditure. The Journal of Clinical Endocrinology & Metabolism, 99(3), 908–914.

Melby, C. L., Schmidt, W. D., & Corrigan, D. (1990). Resting metabolic rate in weight-cycling collegiate wrestlers compared with physically active, noncycling control subjects. American Journal of Clinical Nutrition, 52(3), 409–414. Retrieved from

Müller, M. J., & Bosy-Westphal, A. (2013). Adaptive thermogenesis with weight loss in humans. Obesity, 21(2), 218–228.

Müller, M. J., Enderle, J., Pourhassan, M., Braun, W., Eggeling, B., Lagerpusch, M., … Bosy-Westphal, A. (2015). Metabolic adaptation to caloric restrication and subsequent refeeding: the Minnesota Starvation Experiment revisited. American Journal of Clinical Nutrition, 102, 807–819.

Obarzanek, E., Lesem, M. D., & Jimerson, D. C. (1994). Resting metabolic rate of anorexia nervosa patients during weight gain. Am.J.Clin.Nutr., 60(5), 666–675. Retrieved from

Platte, P., Pirke, K. M., Trimborn, P., Pietsch, K., Krieg, J. C., & Fichter, M. M. (1994). Resting metabolic rate and total energy expenditure in acute and weight recovered patients with anorexia nervosa and in healthy young women. The International Journal of Eating Disorders, 16(1), 45–52. Retrieved from

Robinson, S. L., Lambeth-Mansell, A., Gillibrand, G., Smith-Ryan, A., & Bannock, L. (2015). A nutrition and conditioning intervention for natural bodybuilding contest preparation: case study. Journal of the International Society of Sports Nutrition, 12, 1–11.

Rosenbaum, M., Hirsch, J., Gallagher, D. A., & Leibel, R. L. (2008). Long-term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight. American Journal of Clinical Nutrition, 88(4), 906–912. [pii]

Rossow, L. M., Fukuda, D. H., Fahs, C. A., Loenneke, J. P., & Stout, J. R. (2013). Natural bodybuilding competition preparation and recovery: A 12-month case study. International Journal of Sports Physiology and Performance, 8(5), 582–592. [pii]

Russell, J., Baur, L., Beumont, P., Byrnes, S., & Zipfel, S. (1998). Refeeding of anorexics : wasteful not wilful. The Lancet, 352, 1445–1446.

Saarni, S. E., Rissanen, A., Sarna, S., Koskenvuo, M., & Kaprio, J. (2006). Weight cycling of athletes and subsequent weight gain in middleage. International Journal of Obesity, 30(11), 1639–44.

Shetty, P. S. (1999). Adaptation to low energy intakes: the responses and limits to low intakes in infants, children and adults. European Journal of Clinical Nutrition, 53, S14–S33.

Weyer, C., Walford, R. L., Harper, I. T., Milner, M., MacCallum, T., Tataranni, P. A., & Ravussin, E. (2000). Energy metabolism after 2 y of energy restriction: The Biosphere 2 experiment. American Journal of Clinical Nutrition, 72, 946–953. Retrieved from

Wymelbeke, V. Van, Brondel, L., Brun, J. M., & Rigaud, D. (2004). Factors associated with the increase in resting energy expenditure during refeeding in malnourished anorexia nervosa patients. American Journal of Clinical Nutrition, 80, 1469–1477. Retrieved from

Zipfel, S., Mack, I., Baur, L. A., Hebebrand, J., Touyz, S., Herzog, W., … Russell, J. (2013). Impact of exercise on energy metabolism in anorexia nervosa. J Eat Disord, 1(1), 37.