Body-composition changes in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: A 2-y randomized controlled trial of calorie restriction in nonobese humans

Authors: DAS, SAI - Tufts University; ROBERTS, SUSAN - Tufts University; BHAPKAR, MANJUSHRI - Duke Clinical Research Institute; VILLAREAL, DENNIS - Washington University School Of Medicine; FONTANA, LUIGI - Washington University School Of Medicine; MARTIN, CORBY - Pennington Biomedical Research Center; RACETTE, SUSAN - Washington University School Of Medicine; FUSS, PAUL - Tufts University; KRAUSS, WILLIAM - Duke University School Of Medicine; WONG, WILLIAM - Children'S Nutrition Research Center (CNRC); SALTZMAN, EDWARD - Tufts University; PIEPER, CARL - Duke University School Of Medicine; FIELDING, ROGER - Tufts University; SCHWARTZ, ANN - University Of California; RAVUSSIN, ERIC - Pennington Biomedical Research Center; REDMAN, LEANNE - Pennington Biomedical Research Center

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/19/2017
Publication Date: 2/22/2017
Citation: Das, S.K., Roberts, S.B., Bhapkar, M.V., Villareal, D.T., Fontana, L., Martin, C.K., Racette, S.B., Fuss, P.J., Krauss, W.E., Wong, W.W., Saltzman, E., Pieper, C.F., Fielding, R.A., Schwartz, A.V., Ravussin, E., Redman, L.M. 2017. Body-composition changes in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: A 2-y randomized controlled trial of calorie restriction in nonobese humans. American Journal of Clinical Nutrition. 105:913–927.

Interpretive Summary: Reducing caloric intake has been shown to slow down aging and increase life span in animals. The effects of reducing caloric intake on body tissues among humans are not clear. We looked at the effects of two years of reducing caloric intake on 143 nonobese humans and compared the results to 75 nonobese humans (control subjects) who took part in the two-year study but kept their usual caloric intakes. The study subjects were able to reduce their caloric intake by 12% over two years. When compared to the control subjects, the study subjects lost 7.6 kg of body weight, 6.2 cm in waist circumference, 5 kg of body fat, and 2 kg of muscle. With the loss in body weight, the study subjects who reduced their caloric intake actually had an increase in the percentage of muscle relative to body weight along with a decrease in the percentage of body fat at the end of the 2-year study. Therefore, reducing caloric intake over two years led to favorable proportion of muscle mass and body fat and could lead to favorable life span in humans.

Technical Abstract: Calorie restriction (CR) retards aging and increases longevity in many animal models. However, it is unclear whether CR can be implemented in humans without adverse effects on body composition. We evaluated the effect of a 2-year CR regimen on body composition including the influence of sex and body mass index (BMI; in kg/m2) among participants enrolled in CALERIE-2 (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), a multicenter, randomized controlled trial. Participants were 218 nonobese (BMI: 21.9-28.0) adults aged 21-51 y who were randomly assigned to 25% CR (CR, n=143) or ad libitum control (AL, n=75) in a 2:1 ratio. Measures at baseline and 12 and 24 months included body weight, waist circumference, fat mass (FM), fat-free mass (FFM), and appendicular mass by dual-energy X-ray absorptiometry; activity-related energy expenditure (AREE) by doubly labeled water; and dietary protein intake by self-report. Values are expressed as means +/- SDs. The CR group achieved 11.9% +/- 0.7% CR over 2-years and had significant decreases in weight (-7.6 +/- 0.3 compared with 0.4 +/- 0.5 kg), waist circumference (-6.2 +/- 0.4 compared with 0.9 +/- 0.5 cm), FM (-5.4 +/- 0.3 compared with 0.5 +/- 0.4 kg), and FFM (-2.0 +/- 0.2 compared with -0.0 +/- 0.2 kg) at 24 mo relative to the AL group (all between-group P<0.001). Moreover, FFM as a percentage of body weight at 24 months was higher, and percentage of FM was lower in the CR group than in the AL. AREE, but not protein intake, predicted preservation of FFM during CR (P<0.01). Men in the CR group lost significantly more trunk fat (P=0.03) and FFM expressed as a percentage of weight loss (P<0.001) than women in the CR group. Two years of CR had broadly favorable effects on both whole-body and regional adiposity that could facilitate health span in humans. The decrements in FFM were commensurate with the reduced body mass; although men in the CR group lost more FFM than the women did, the percentage of FFM in the men in the CR group was higher than at baseline.