OBJECTIVE: To investigate the efficacy of the 3-carbon compounds pyruvate and dihydroxyacetone (PD) in inhibiting reaccumulation of body weight and fat with refeeding after weight loss. DESIGN: Longitudinal, in Clinical Research Center. After weight loss induced by hypoenergetic diet (1.3 MJ/d) for 3 weeks, refeeding with hyperenergetic diet (1.5 x resting energy expenditure) for 3 weeks. Refeeding diet randomized to contain PD or placebo (PL, polyglucose) as approximately 20% of energy intake. SUBJECTS: 17 obese healthy women (n = 8 in PL group, n = 9 in PD group) (age: 22-60 y, weight: 72.5-139.7 kg). MEASUREMENTS: Resting energy expenditure (REE), body composition (by bioelectrical impedance), nitrogen balance, serum proteins, biochemical profile, thyroid hormones, and insulin, before and after refeeding and weight and fat gain. RESULTS: Refeeding with a hyperenergetic diet, weight gain was significantly less in patients receiving PD compared to placebo (1.8 + 0.2 kg vs 2.9 +/- 0.1 kg, P < 0.01). Body fat regain was also less with feeding of PD (0.8 +/- 0.2 kg vs 1.8 +/- 0.2 kg, P < 0.01). Body protein metabolism, as measured by nitrogen balance, serum protein concentrations and fat free mass, was similar in subjects consuming either PD or PL. CONCLUSIONS: We conclude that 3-carbon compounds decrease weight gain and reaccumulation of body fat, without decreasing body protein gain, in obese subjects with hyperenergetic refeeding subsequent to weight loss.