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Metabolic and Behavioral Compensations in Response to Caloric Restriction: Implications for the Maintenance of Weight Loss
Open accessAbstract
BACKGROUND: Metabolic and behavioral adaptations to caloric restriction (CR) in free-living conditions have not yet been objectively measured. METHODOLOGY AND PRINCIPAL FINDINGS: Forty-eight (36.8+/-1.0 y), overweight (BMI 27.8+/-0.7 kg/m(2)) participants were randomized to four groups for 6-months; CONTROL: energy intake at 100% of energy requirements; CR: 25% calorie restriction; CR+EX: 12.5% CR plus 12.5% increase in energy expenditure by structured exercise; LCD: low calorie diet (890 kcal/d) until 15% weight reduction followed by weight maintenance. Body composition (DXA) and total daily energy expenditure (TDEE) over 14-days by doubly labeled water (DLW) and activity related energy activity (AREE) were measured after 3 (M3) and 6 (M6) months of intervention. Weight changes at M6 were -1.0+/-1.1% (CONTROL), -10.4+/-0.9% (CR), -10.0+/-0.8% (CR+EX) and -13.9+/-0.8% (LCD). At M3, absolute TDEE was significantly reduced in CR (-454+/-76 kcal/d) and LCD (-633+/-66 kcal/d) but not in CR+EX or controls. At M6 the reduction in TDEE remained lower than baseline in CR (-316+/-118 kcal/d) and LCD (-389+/-124 kcal/d) but reached significance only when CR and LCD were combined (-351+/-83 kcal/d). In response to caloric restriction (CR/LCD combined), TDEE adjusted for body composition, was significantly lower by -431+/-51 and -240+/-83 kcal/d at M3 and M6, respectively, indicating a metabolic adaptation. Likewise, physical activity (TDEE adjusted for sleeping metabolic rate) was significantly reduced from baseline at both time points. For control and CR+EX, adjusted TDEE (body composition or sleeping metabolic rate) was not changed at either M3 or M6. CONCLUSIONS: For the first time we show that in free-living conditions, CR results in a metabolic adaptation and a behavioral adaptation with decreased physical activity levels. These data also suggest potential mechanisms by which CR causes large inter-individual variability in the rates of weight loss and how exercise may influence weight loss and weight loss maintenance. TRIAL REGISTRATION: ClinicalTrials.gov NCT00099151.
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![Figure 1 Flow of participants through the Pennington Phase 1 CALERIE trial. The CONSORT diagram was published previously [6].](/paper-figures/0f00b8c15bba4b08ba358f228a186817/metabolic-and-behavioral-compensations-in-response-to-caloric-restriction-figure-1.jpg)


![Figure 4 The effect of caloric restriction (CR, n = 12) on all components of daily energy expenditure (Top Panel). Total daily energy expenditure (TDEE) is measured by doubly labeled water over a 2-week period whereas sedentary 24-h energy expenditure (24h-EE) is measured in a respiratory chamber. Spontaneous physical activity was calculated as previously reported [7] whereas the thermic effect of food (TEF) was calculated in the chamber as per Tataranni et al [38] and the same percentage of energy intake (9–12% across subjects) was assumed to assess the extra TEF in free living conditions. The changes in total daily energy expenditure after 3 and 6 months of CR (Bottom Panel) are shown and those representing a metabolic adaptation (larger than due to weight loss) are highlighted in grey.](/paper-figures/9bfa6a80a9784760ae049191cf2febbc/metabolic-and-behavioral-compensations-in-response-to-caloric-restriction-figure-4.jpg)
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“Even weight loss via caloric restriction faces difficulties, including an evolution-engendered guard against low fat mass [7, 31] and the propensity of the body to increase caloric efficiency during dieting [32, 33].”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [32]
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“Third, and probably most important, the body has homeostatic mechanisms such that weight loss produces an increase in caloric efficiency, i.e. a reduction in BMR, making further weight loss even more difficult 11,12.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [11]
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Cites
(1992) · PubMed · Cited by 33,716
The MOS 36-ltem Short-Form Health Survey (SF-36): I. Conceptual Framework and Item Selection
Ware, J. E., & Sherbourne, C. D. (1992) · Medical Care · doi:10.1097/00005650-199206000-00002 · Cited by 30,033
SF-36 health survey: Manual and interpretation guide
Ware, J. (2003) · Medical Entomology and Zoology · Cited by 11,424
Oxidative Stress, Caloric Restriction, and Aging
Sohal, R. S., & Weindruch, R. H. (1996) · Science · doi:10.1126/science.273.5271.59 · Cited by 3,133
THE BIOLOGY OF HUMAN STARVATION
Keys, A., BROŽEK, J., & Henschel, A. (1951) · The Medical Journal of Australia · doi:10.5694/j.1326-5377.1951.tb56499.x · Cited by 2,135
The Biology of Human Starvation: Volume I
KEYS, A., BROŽEK, J., HENSCHEL, A., MICKELSEN, O., & TAYLOR, H. L. (1950) · doi:10.5749/j.ctv9b2tqv · Cited by 2,039
Changes in Energy Expenditure Resulting from Altered Body Weight
Leibel, R. L., Rosenbaum, M., & Hirsch, J. (1995) · New England Journal of Medicine · doi:10.1056/nejm199503093321001 · Cited by 2,012
Handbook of the Biology of Aging
Finch, C. E., & Schneider, E. L. (1990) · DigitalGeorgetown (Georgetown University Library) · Cited by 1,210
Determinants of 24-hour energy expenditure in man. Methods and results using a respiratory chamber.
Ravussin, E., Lillioja, S., Anderson, T. E., Christin, L., & Bogardus, C. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112749 · Cited by 1,166
Role of Nonexercise Activity Thermogenesis in Resistance to Fat Gain in Humans
Levine, J. A., Eberhardt, N. L., & Jensen, M. D. (1999) · Science · doi:10.1126/science.283.5399.212 · Cited by 997
Heilbronn, L. K., de Jonge, L., Frisard, M. I., DeLany, J. P., Larson-Meyer, D. E., Rood, J., Nguyen, T., Martin, C. K., Volaufova, J., Most, M. M., et al. (2006) · JAMA · doi:10.1001/jama.295.13.1539 · Cited by 969
Interindividual variation in posture allocation: possible role in human obesity
Levine, J. A., Lanningham-Foster, L. M., McCrady, S. K., Krizan, A. C., Olson, L. R., Kane, P. H., Jensen, M. D., & Clark, M. M. (2005) · Science · doi:10.1126/science.1106561 · Cited by 705
Measurement of Energy Expenditure in Free-Living Humans by Using Doubly Labeled Water
Schoeller, D. A. (1988) · Journal of Nutrition · doi:10.1093/jn/118.11.1278 · Cited by 603
Rosenbaum, M., Hirsch, J., Gallagher, D. A., & Leibel, R. L. (2008) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/88.4.906 · Cited by 444
Exercise as an adjunct to weight loss and maintenance in moderately obese subjects.
Pavlou, K., Krey, S., & Steffee, W. (1989) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/49.5.1115 · Cited by 365
How much physical activity is needed to minimize weight gain in previously obese women?
Schoeller, D., Shay, K., & Kushner, R. (1997) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/66.3.551 · Cited by 342
Statistical considerations regarding the use of ratios to adjust data.
Allison, D. B., Paultre, F., Goran, M. I., Poehlman, É. T., & Heymsfield, S. B. (1995) · PubMed · Cited by 339
Relative dilution spaces of 2H- and 18O-labeled water in humans
Racette, S. B., Schoeller, D. A., Luke, A. H., Shay, K., Hnilicka, J. M., & Kushner, R. F. (1994) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1994.267.4.e585 · Cited by 316
Diminished energy requirements in reduced-obese patients
Leibel, R. L., & Hirsch, J. (1984) · Metabolism · doi:10.1016/0026-0495(84)90130-6 · Cited by 272
Effects of experimental weight perturbation on skeletal muscle work efficiency in human subjects
Rosenbaum, M., Vandenborne, K., Goldsmith, R., Simoneau, J.-A., Heymsfield, S., Joanisse, D. R., Hirsch, J., Murphy, E., Matthews, D., Segal, K. R., et al. (2003) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00474.2002 · Cited by 255 · cited 1×
“skeletal muscle or as also postulated, due to a reduction in physical activity with weight loss [28].”
BackgroundEffect of calorie restriction on resting metabolic rate and spontaneous physical activity.
Martin, C. K., Heilbronn, L. K., de Jonge, L., DeLany, J. P., Volaufova, J., Anton, S. D., Redman, L. M., Smith, S. R., & Ravussin, E. (2007) · Obesity · doi:10.1038/oby.2007.354 · Cited by 237
Self-citationKemnitz, J. W., Weindruch, R. H., Roecker, E. B., Crawford, K. S., Kaufman, P. L. P., & Ershler, W. B. (1993) · Journal of Gerontology · doi:10.1093/geronj/48.1.b17 · Cited by 224
Energy expenditure before and during energy restriction in obese patients
Ravussin, É., Burnand, B., Schutz, Y., & Jéquier, E. (1985) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/41.4.753 · Cited by 211
Weinsier, R. L., Nagy, T. R., Hunter, G. R., Darnell, B. E., Hensrud, D. D., & Weiss, H. L. (2000) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/72.5.1088 · Cited by 208 · cited 1×
“As an alternative hypothesis it would be reasonable to assume two metabolic phases occur in response to CR; an ‘adaptive phase’ when energy expenditure is adjusting to compensate for the reduced availability of energy sources, followed by a ‘maintenance phase’ when energy balance has been re-established and the metabo…”
BackgroundWeinsier, R. L., Hunter, G. R., Desmond, R. A., Byrne, N. M., Zuckerman, P. A., & Darnell, B. E. (2002) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/75.3.499 · Cited by 188
Spontaneous physical activity and obesity: cross-sectional and longitudinal studies in Pima Indians
ZURLO, F., Ferraro, R. T., Fontvielle, A. M., Rising, R., Bogardus, C., & Ravussin, É. (1992) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1992.263.2.e296 · Cited by 168
Field use of D2 18O to measure energy expenditure of soldiers at different energy intakes
DeLany, J. P., Schoeller, D. A., Hoyt, R. W., Askew, E. W., & Sharp, M. A. (1989) · Journal of Applied Physiology · doi:10.1152/jappl.1989.67.5.1922 · Cited by 140
Thermic effect of food in humans: methods and results from use of a respiratory chamber
Tataranni, P., Larson, D., Snitker, S., & Ravussin, É. (1995) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/61.5.1013 · Cited by 135
Energy expenditure of elite female runners measured by respiratory chamber and doubly labeled water
Schulz, L. O., Alger, S. A., Harper, I., Wilmore, J. H., & Ravussin, É. (1992) · Journal of Applied Physiology · doi:10.1152/jappl.1992.72.1.23 · Cited by 127
Thermic effect of food in humans: methods and results from use of a respiratory chamber.
Tataranni, P. A., Larson, D. E., Snitker, S., et al. (1995) · PubMed · doi:10.1093/ajcn/61.4.1013 · Cited by 113
A comparative study of different means of assessing long-term energy expenditure in humans
ROSENBAUM, M. S., Ravussin, É., Matthews, D. E., Gilker, C. D., Ferraro, R. T., Heymsfield, S. B., Hirsch, J., & Leibel, R. L. (1996) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1996.270.3.r496 · Cited by 74
Frisard, M. I., Fabre, J. M., Russell, R. D., King, C. M., DeLany, J. P., Wood, R. H., Ravussin, É., & Study, F. T. L. H. A. (2007) · The Journals of Gerontology Series A · doi:10.1093/gerona/62.7.783 · Cited by 66
Wierik, E. J. M. V.-T., Westerterp, K. R., & van den Berg, H. (1995) · PubMed · Cited by 65
Underfeeding and body weight regulation in normal-weight young men
Heyman, M. B., Young, V. R., Fuss, P., Tsay, R. H., Joseph, L. J., & Roberts, S. B. (1992) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1992.263.2.r250 · Cited by 57
Physiological Regulation of Body Weight and the Issue of Obesity
Keesey, R. E. (1989) · Medical Clinics of North America · doi:10.1016/s0025-7125(16)30689-7 · Cited by 51
Energy-metabolism adaptation in obese adults on a very-low-calorie diet
Fricker, J., Rozen, R., Melchior, J., & Apfelbaum, M. (1991) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/53.4.826 · Cited by 48
Nguyen, T., de Jonge, L., Smith, S. R., & Bray, G. A. (2003) · Medical and Biological Engineering and Computing · doi:10.1007/bf02345320 · Cited by 47
Metabolic adaptation and energy requirements in developing countries.
James, W. P. T., & Shetty, P. S. (1982) · PubMed · Cited by 44
Adaptation of energy metabolism of overweight women to alternating and continuous low energy intake
de Groot, C. P. G. M., van Es, A. J., van Raaij, J. M., Vogt, J. E., & HAUTVAST, J. G. A. J. (1989) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/50.6.1314 · Cited by 42
Vansant, G. A. A. M., Gaal, L. V., Acker, K. V., & Leeuw, I. D. (1989) · PubMed · Cited by 17
Research works printed but not linked: 1
- MI Frisard, 2007, Physical activity level and physical functionality in nonagenarians compared to individuals aged 60–74 years., J Gerontol A Biol Sci Med Sci, 62, 783, 10.1093/gerona/62.7.783 · DOI
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Sutton, E. F., Beyl, R., Early, K. S., Cefalu, W. T., Ravussin, E., & Peterson, C. M. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.04.010 · Cited by 1,531
Speakman, J. R., & Mitchell, S. E. (2011) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2011.07.001 · Cited by 797
Cellular bioenergetics as a target for obesity therapy
Tseng, Y.-H., Cypess, A. M., & Kahn, C. R. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3138 · Cited by 591
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Metadata
- Authors
- Redman, L. M., Heilbronn, L. K., Martin, C. K., de Jonge, L., Williamson, D. A., Delany, J. P., Ravussin, E., & for the Pennington CALERIE team
- Affiliations
- Pennington Biomedical Research Center (US)
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-02-09
- Volume
- 4
- Issue
- 2
- Pages
- e4377
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2634841
- OpenAlex
- W2037703570
- Cited by
- 355
- References
- 39
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 10 · 2023: 15 · 2022: 18 · 2021: 18 · 2020: 12 · 2019: 9 · 2018: 22 · 2017: 20 · 2016: 22 · 2015: 52 · 2014: 37 · 2013: 20 · 2012: 23
- FWCI
- 18.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health (5k23dk068052-04)
- Medical Research Council
- National Health and Medical Research Council
- National Institute on Aging (U01AG020478, U01-AG20478)
- National Institute of Diabetes and Digestive and Kidney Diseases (K23-DK-068052, K23 DK068052-01A2, P30DK072476)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Obesity, Physical Activity, Diet
- Keywords
- caloric restriction, weight loss maintenance, metabolic adaptation, total energy expenditure, physical activity, hypocaloric diet, body composition, energy expenditure, overweight adults, free-living conditions, behavioral adaptation, doubly labeled water, sleeping metabolic rate, obesity treatment, compensatory behavior
- MeSH terms
- Adult, Body Composition, Energy Intake, Energy Metabolism, Female, Humans, Male, Middle Aged, Weight Loss, Body Mass Index, Caloric Restriction, Behavior Control
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