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

Abstract

Background: 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.Objective: We evaluated the effect of a 2-y 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.Design: 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 mo 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.Results: The CR group achieved 11.9% ± 0.7% CR over 2-y 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 mo 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.Conclusions: 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. CALERIE was registered at clinicaltrials.gov as NCT00427193.

Keywords: body composition; calorie restriction; humans; long-term; nonobese.

© 2017 American Society for Nutrition.

Figures

FIGURE 1

Participant enrollment and retention, breakdown by sex. Study participant flow and reasons for attrition broken down by men and women within the ad libitum control group and CR. 1Reasons why the participants were withdrawn for safety: A BMD deficit in 1 participant and anemia in 2 other participants did not resolve, and they were permanently withdrawn from the intervention. Following intention-to-treat principles, their data were nevertheless included in the analysis dataset. BMD, bone mineral density; CR, calorie restriction.

FIGURE 2

Change in total, trunk and appendicular lean body mass at 24 mo in the CR group. Lean body mass, also the same as lean soft tissue mass, was calculated as fat-free mass minus bone mineral content. Absolute means (SEs in parentheses) are shown for the CR group only for trunk and appendicular (arms and legs) lean mass changes within men (n = 44) and women (n = 99) and the overall CR group (n = 143). CR, calorie restriction.

FIGURE 3

Body composition of the participants in the CR group (n = 143) at 24 mo compared with the AL group participants (n = 75). Participants in the CR group: men, n = 44; women, n = 99. Participants in the AL group: men, n = 22; women, n = 53. Percentage of fat mass and percentage of fat-free mass in the participants in the CR group at 24 mo were not only comparable to those of the men and women in the AL group, but they were significantly higher for percentage of fat-free mass and lower for percentage of fat mass (P < 0.01 for both men and women). AL, ad libitum control; CR, calorie restriction.