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Metabolic and Behavioral Compensations in Response to Caloric Restriction: Implications for the Maintenance of Weight Loss
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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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“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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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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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