Metabolic and behavioral compensations in response to caloric restriction: implications for the maintenance of weight loss

Leanne M Redman, Leonie K Heilbronn, Corby K Martin, Lilian de Jonge, Donald A Williamson, James P Delany, Eric Ravussin, Pennington CALERIE Team, Leanne M Redman, Leonie K Heilbronn, Corby K Martin, Lilian de Jonge, Donald A Williamson, James P Delany, Eric Ravussin, Pennington CALERIE Team

Abstract

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Flow of participants through the…
Figure 1. Flow of participants through the Pennington Phase 1 CALERIE trial.
The CONSORT diagram was published previously .
Figure 2. Experimental design (A) and body…
Figure 2. Experimental design (A) and body weight and composition changes (B) at the completion of the study.
Figure 3. The effect of caloric restriction…
Figure 3. The effect of caloric restriction on AREE (change in TDEE at M3 and M6 after adjusting for SMR (a measure of sedentary energy expenditure).
* represents a significant change from baseline.
Figure 4. The effect of caloric restriction…
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 whereas the thermic effect of food (TEF) was calculated in the chamber as per Tataranni et al 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.

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