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Metabolic and behavioral compensations in response to caloric restriction: implications for the maintenance of weight loss
Redman LM, Heilbronn LK, Martin CK, de Jonge L, Williamson DA, Delany JP, Ravussin E, for the Pennington CALERIE Team
PLoS ONE 2009 Feb;4(2):e4377
clinical trial
4/10 [Eligibility criteria: No; Random allocation: Yes; Concealed allocation: No; Baseline comparability: No; Blind subjects: No; Blind therapists: No; Blind assessors: No; Adequate follow-up: Yes; Intention-to-treat analysis: No; Between-group comparisons: Yes; Point estimates and variability: Yes. Note: Eligibility criteria item does not contribute to total score] *This score has been confirmed*

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/m2) 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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