Impact of calorie restriction on energy metabolism in humans

Abstract

Calorie restriction (CR) is the most potent, non-pharmacological intervention to support metabolic health. The effects of calorie restriction exceed weight loss. Consistent throughout many studies, calorie restriction induces a reduction in energy expenditure that is larger than the loss of metabolic mass, i.e. fat-free mass and fat mass, can explain. Per prevailing theories of mammalian aging, this disproportionate reduction in metabolic rate, defined as metabolic adaptation, reduces oxidative damage and thereby delays age-associated declines in physiological function. The aim of this narrative review is to investigate the origins of CR-induced metabolic adaptation. From a physiological standpoint this likely relates to the composition of body weight loss, reductions in insulin secretion, thyroid and leptin concentrations, and increased mitochondrial energy efficiency. Behavioral factors including physical activity and eating behaviors likely also play a role, specifically to prevent weight regain. Future studies are required to understand the interindividual differences in the response to CR, e.g. by sex, physical activity, or mitochondrial capacity, and to assess the long-term implications of CR for weight regain.

Keywords: Adaptive thermogenesis; Calorie restriction; Energy efficiency; Energy requirements; Weight loss; Weight regain.

Fig. 1.

Simplified model of energy balance components during calorie restriction interventions. Calorie restriction (CR) is initiated at month 0 by prescribing 75% energy intake (EI) as compared to the baseline energy intake requirements (100%). Adherence to the CR regimen (‘Adhered EI’) is highest during the first 3 months (~21%), and declines to ~10% after 12 months. The compensatory decrease in total daily EE (TDEE) is smaller than the decrease in energy intake (EI), which induces an energy deficit (in grey) and weight loss (Phase 1 and 2). After 12 months, the CR daily energy intake approximates the total daily EE and weight is maintained on a 12% reduced level of energy balance, which defines CR during weight maintenance (Phase 3).

Fig. 2.

Models for reduction of energy intake requirements. In basal conditions, energy intake requirements are the sum of energy requirements for ATP generation and for heat production (column 1). Through CR, energy intake requirements for mass-adjusted metabolic rate, defined as metabolic adaptation, are reduced (column 2–4). Energy intake requirements can be reduced through reduction of ATP production, that is an attenuation of metabolic processes (column 2). Alternatively, or simultaneously (column 3 and 4) requirements can be reduced via reduced heat production which is achieved through improving mitochondrial coupling.