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Do adaptive changes in metabolic rate favor weight regain in weight-reduced individuals? An examination of the set-point theory^1,2,3

¹ From the Departments of Nutrition Sciences and Human Studies, the General Clinical Research Center, and the Medical Statistics Section, University of Alabama at Birmingham, and the Mayo Clinic, Rochester, MN.

Background: Obese persons generally regain lost weight, suggesting that adaptive metabolic changes favor return to a preset weight.

Objective: Our objective was to determine whether adaptive changes in resting metabolic rate (RMR) and thyroid hormones occur in weight-reduced persons, predisposing them to long-term weight gain.

Design: Twenty-four overweight, postmenopausal women were studied at a clinical 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-weight state (phase 3, 3350 kJ/d; phase 4, energy balance). Weight-reduced women were matched with 24 never-overweight control subjects. After each study phase, assessments included RMR (by indirect calorimetry), body composition (by hydrostatic weighing), serum triiodothyronine (T₃), and reverse T₃ (rT₃). Body weight was measured 4 y later, without intervention.

Results: Body composition–adjusted RMR and T₃:rT₃ fell during acute (phase 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-hypometabolic state that normalizes on return to energy-balanced conditions. Failure to establish energy balance after weight loss gives the misleading impression that weight-reduced persons are energy conservative and predisposed to weight regain. Our findings do not provide evidence in support of adaptive metabolic changes as an explanation for the tendency of weight-reduced persons to regain weight.

Key Words: Overweight • obesity • weight loss • body composition • thyroid hormones • energy expenditure • metabolic rate • set-point theory • postmenopausal women

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