Metabolic and Behavioral Compensations in Response to Caloric Restriction: Implications for the Maintenance of Weight Loss

et al. (2009) Metabolic and Behavioral Compensations in Response to Caloric Restriction: Implications for the Maintenance of Weight Loss. PLoS ONE 4(2): e4377. doi:10.1371/journal.pone.0004377 Metabolic and Behavioral Compensations in Response to Caloric Restriction: Implications for the Maintenance of Weight Loss Leanne M. Redman 0 1 Leonie K. Heilbronn 0 1 Corby K. Martin 0 1 Lilian de Jonge 0 1 Donald A. Williamson 0 1 James P. Delany 0 1 Eric Ravussin 0 1 for the Pennington CALERIE team 0 1 Chenxi Wang, University of Louisville, United States of America 0 a Current address: Garvan Institute of Medical Research , Darlinghurst, New South Wales , Australia b Current address: Department of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania , United States of America 1 Pennington Biomedical Research Center , Baton Rouge, Louisiana , United States of America 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 (36.861.0 y), overweight (BMI 27.860.7 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 21.061.1% (Control), 210.460.9% (CR), 210.060.8% (CR+EX) and 213.960.8% (LCD). At M3, absolute TDEE was significantly reduced in CR (2454676 kcal/d) and LCD (2633666 kcal/d) but not in CR+EX or controls. At M6 the reduction in TDEE remained lower than baseline in CR (23166118 kcal/d) and LCD (23896124 kcal/d) but reached significance only when CR and LCD were combined (2351683 kcal/d). In response to caloric restriction (CR/LCD combined), TDEE adjusted for body composition, was significantly lower by 2431651 and 2240683 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 PLoS ONE | www.plosone.org - Funding: CALERIE (U01 AG20478), NCT00099151 (clinicaltrials.gov). This work was supported by U01 AG20478 (ER); National Health and Medical Research Council of Australia, Neil Hamilton-Fairley Training Fellowship (ID 349553) to LMR and NIH grant K23 DK068052-01A2 to CKM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Daily energy expenditure has three major components: resting metabolic rate, the thermic effect of food and the energy cost of physical activity. Respiratory chambers enable the measurement of sleeping metabolic rate, the energy cost of arousal, the thermic effect of food and the energy cost of spontaneous physical activity [1]. However the confined space within a respiratory chamber compromises the level of habitual and/or voluntary physical activity. Activity thermogenesis is the most variable component of daily energy expenditure and includes energy expended during both voluntary physical activity and all other non-exercise activities [2]. The latter, recently termed NEAT (non-exercise activity thermogenesis) includes the energy cost of sitting, fidgeting, maintaining posture, muscle tone and leisure activities such as playing guitar and shopping etc [3]. Caloric restriction (CR) is the most robust non-pharmacological intervention known to increase maximum lifespan. One of the most popular proposed theories by which CR promotes lifespan extension is the rate of living theory [4]. We hypothesized that caloric restriction will reduce energy metabolism in excess of the loss of metabolic mass (metabolic adaption) and therefore will reduce oxidative damage to tissues and organs by lowering the production rates of reactive oxygen species [5]. CR is indeed associated with robust decreases in energy metabolism, including a lowering of resting metabolic rate (or sleeping metabolic rate), reduced thermic effect of meals and a decrease in the energy cost and/or the level of physical activity. However, it is debated whether or not the decrease in total energy expenditure is proportional (or larger; metabolic adaptation) to the loss of metabolic tissues (fat-free and fat mass: FFM and FM). Furthermore, it is not clear if the metabolic adaptation persists once a new stable body weight is reached. Previously we reported that both 24-hour sedentary energy expenditure and sleeping metabolic rate measured in a respiratory chamber were reduced ,6% beyond what was expected for the loss of metabolic mass (FFM and FM) [6]. This metabolic adaptation was also observed in RMR measured by a ventilated hood indirect calorimeter [7]. A portion of the reduction in sedentary energy expenditure was due to the reduced energy intake itself (thermic effect of food), and a reduction in the energy cost of spontaneous physical activity. The majority however, was due to the decline in the size of the metabolizing mass and a lowering of the rate of metabolism per mass unit of tissues and organs. Essential to the study of the changes in energy expenditure with CR is an objective assessment of physical activity. Not only is the contribution of physical activity to daily energy expenditure quite variable, it is also likely that in an attempt to conserve energy during CR, individuals volitionally or non-volitionally decrease their level of physical activity [8]. In our study of 25% CR in overweight humans, we observed no change in spontaneous physical activity in a respiratory chamber [7] consistent with earlier reports of no alterations in spontaneous physical activity [9] or posture allocation in obese individuals following weight loss [10]. These findings are not surprising if the current hypothesis that spontaneous physical activity is biologically determined and not altered by perturbations in body weight, is true [2,10]. Combining the doubly labeled water method and indirect calorimetry allows us to (...truncated)