Do adaptive changes in metabolic rate favor weight regain in weight-reduced individuals? An examination of the set-point theory

Background: Obese persons generally regain lost weight, suggesting that ada ptive metabolic changes favor return to a preset weight. Objective: Our objective was to determine whether adaptive changes in resti ng metabolic rate (RMR) and thyroid hormones occur in weight-reduced person s, predisposing them to long term weight gain. Design: Twenty-four overweight, postmenopausal women were studied at a clin ical research center in four 10-d study phases: the overweight state (phase 1, energy balance; phase 2, 3350 kJ/d) and after reduction to a normal-wei ght state (phase 3, 3350 kJ/d; phase 3, energy balance). Weight-reduced wom en were matched with 24 never-overweight control subjects. After each study phase, assessments included RMR (by indirect calorimetry), body compositio n (by hydrostatic weighing), serum triiodothyronine (T-3), and reverse T-3 (rT(3)). Body weight was measured 4 y later, without intervention. Results: Body composition-adjusted RMR and T-3:rT(3) fell during acute (pha se 2) and chronic (phase 3) energy restriction (P < 0.01), but returned to baseline in the normal-weight, energy-balanced state (phase 4; mean weight loss: 12.9 +/- 2.0 kg). RMR among weight-reduced women (4771 +/- 414 kJ/d) was not significantly different from that in control subjects (4955 +/- 414 kJ/d; P = 0.14), and lower RMR did not predict greater 4-y weight regain ( r = 0.27, NS). Conclusions: Energy restriction produces a transient hypothyroid-hypometabo lic state that normalizes on return to energy-balanced conditions. Failure to establish energy balance after weight loss gives the misleading impressi on that weight-reduced persons are energy conservative and predisposed to w eight regain. Our findings do not provide evidence in support of adaptive m etabolic changes as an explanation for the tendency of weight-reduced perso ns to regain weight.