Context The role of diet composition in response to overeating and energy dissipation in humans is unclear. Objective To evaluate the effects of overconsumption of low, normal, and high protein diets on weight gain, energy expenditure, and body composition. Design, Setting, and Participants A single-blind, randomized controlled trial of 25 US healthy, weight-stable male and female volunteers, aged 18 to 35 years with a body mass index between 19 and 30. The first participant was admitted to the inpatient metabolic unit in June 2005 and the last in October 2007. Intervention After consuming a weight-stabilizing diet for 13 to 25 days, participants were randomized to diets containing 5% of energy from protein (low protein), 15% (normal protein), or 25% (high protein), which they were overfed during the last 8 weeks of their 10- to 12-week stay in the inpatient metabolic unit. Compared with energy intake during the weight stabilization period, the protein diets provided approximately 40% more energy intake, which corresponds to 954 kcal/d (95% CI, 884–1022 kcal/d). Main Outcome Measures Body composition was measured by dual-energy x-ray absorptiometry biweekly, resting energy expenditure was measured weekly by ventilated hood, and total energy expenditure by doubly labeled water prior to the overeating and weight stabilization periods and at weeks 7 to 8. Results Overeating produced significantly less weight gain in the low protein diet group (3.16 kg; 95% CI, 1.88–4.44 kg) compared with the normal protein diet group (6.05 kg; 95% CI, 4.84–7.26 kg) or the high protein diet group (6.51 kg; 95% CI, 5.23–7.79 kg) (P=.002). Body fat increased similarly in all 3 protein diet groups and represented 50% to more than 90% of the excess stored calories. Resting energy expenditure, total energy expenditure, and body protein did not increase during overfeeding with the low protein diet. In contrast, resting energy expenditure (normal protein diet: 160 kcal/d [95% CI, 102–218 kcal/d]; high protein diet: 227 kcal/d [95% CI, 165–289 kcal/d]) and body protein (lean body mass) (normal protein diet: 2.87 kg [95% CI, 2.11–3.62 kg]; high protein diet: 3.18 kg [95% CI, 2.37–3.98 kg]) increased significantly with the normal and high protein diets. Conclusions Among persons living in a controlled setting, calories alone account for the increase in fat; protein affected energy expenditure and storage of lean body mass, but not body fat storage.

Background: Energy expenditure (EE) increases with overfeeding, but it is unclear how rapidly this is related to changes in body composition, increased body weight, or diet. Objective: The objective was to quantify the effects of excess energy from fat or protein on energy expenditure of men and women living in a metabolic chamber. Design: We conducted a randomized controlled trial in 25 participants who ate w40% excess energy for 56 d from 5%, 15%, or 25% protein diets. Twenty-four-hour EE (24EE) and sleeping EE (SleepEE) were measured on days 1, 14, and 56 of overfeeding and on day 57 while consuming the baseline diet (usually day 57). Metabolic and molecular markers of muscle metabolism were measured in skeletal muscle biopsy specimens. Results: In the low-protein diet group whose excess energy was fat, the 24EE and SleepEE did not increase during the first day of overfeeding. When extra energy contained protein, both 24EE and SleepEE increased in relation to protein intake (r = 0.50, P = 0.02). The 24EE over 8 wk in all 3 groups was correlated with protein intake (r = 0.60, P = 0.004) but not energy intake (r = 0.16; P = 0.70). SleepEE was unchanged by overfeeding in the low-protein diet group, and baseline surface area predicted increased 24EE in this group. Protein and fat oxidation were reciprocally related during overfeeding. Observed 24EE was higher than predicted on days 1 (P # 0.05), 14 (P = 0.0001), and 56 (P = 0.0007). There was no relation between change in fat mass and change in EE. Conclusions: Excess energy, as fat, does not acutely increase 24EE, which rises slowly as body weight increases. Excess energy as protein acutely stimulates 24EE and SleepEE. The strongest relation with change in 24EE was the change in energy expenditure in tissue other than muscle or fat-free mass. This trial was registered at clinicaltrials.gov as NCT00565149.Am J Clin Nutr 2015; 101:496-505.