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

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-y CR regimen on body composition including the influence of sex and body mass index (BMI; in kg/m) 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, = 143) or ad libitum control (AL, = 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. 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 < 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 ( < 0.01). Men in the CR group lost significantly more trunk fat ( = 0.03) and FFM expressed as a percentage of weight loss ( < 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. CALERIE was registered at clinicaltrials.gov as NCT00427193.

Significant improvement in cardiometabolic health in healthy nonobese individuals during caloric restriction-induced weight loss and weight loss maintenance

“…Of the lost body weight, importantly the loss of fat mass was larger than the loss of fat-free mass (70% FM vs. 30% FFM). Neither BMI at enrollment nor sex had a significant effect on weight change or changes in body composition outcomes (10), including the improvements in abdominal fat distribution, ectopic lipid, insulin resistance, and the 10-yr risk for CVD. Because adipose tissue depots differ in morphology, metabolism (24), and association with CVD (3), we quantified abdominal VAT and SAT depots using MRI.…”

Environmental risk factors and nonpharmacological and nonsurgical interventions for obesity: An umbrella review of meta‐analyses of cohort studies and randomized controlled trials

“…Although there is a wide consensus that multicomponent lifestyle interventions or behavioural modifications are core strategies in the management of obesity, this recommendation is derived mostly from RCTs, which were not properly blinded and that also enrolled overweight participants. For example, the look ahead trial enrolled participants who had type 2 diabetes and were overweight at trial inception, or the CALERIE trial that included nonobese subjects. Hence, while lifestyle and behavioural interventions have shown to consistently have some beneficial effects on metabolic and cardiovascular health of included participants (generally overweight), any extension to a population with obesity may require the inclusion of a more clearly defined sample of participants meeting consensus criteria for obesity.…”

Exceptional Human Longevity

“…108,109 The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy-2 study, a 2-year randomized controlled trial of calorie restriction in humans, randomized nonobese adults to 25% caloric restriction (11.7% restriction was achieved) or to maintenance of current diet for 2 years. [110][111][112] Biomarker data were applied to 2 biological age algorithms, both of which revealed that reduced caloric intake retarded aging independent of weight reduction. 113 Although reduced intake of calories in adults improves metabolic and hormonal profiles as well as functional capability, the specific reduction in caloric intake or the requisite body fat mass that improves human health and maximizes life span remains unknown.…”