Abstract
It has been nearly 50 y since Mayer and coworkers hypothesized that the mechanisms controlling energy balance are accurate in persons with high levels of physical activity, but that in sedentary persons there is a threshold of physical activity below which these mechanisms become imprecise and that this leads to obesity. This hypothesis, however, was relatively untested in humans because of the difficulty of measuring total energy expenditure (TEE). The development of the doubly labeled water method has obviated this problem and we have now begun to test the Mayer hypothesis in humans. A review of cross-sectional data from doubly labeled water studies in adults provided support for the Mayer hypothesis in men but not in women. Men with TEE > approximately 1.75 times the resting metabolic rate (RMR) had lower body mass indexes than did those with lower expenditures. Further support for the hypothesis was obtained from a longitudinal study of previously obese women. Women with ratios of TEE to RMR > approximately 1.75 gained less weight than did those with lower energy expenditures. When a subset of the less active women was placed in an exercise program that increased TEE:RMR to 1.75, weight gain was arrested. Weight gain resumed when the exercise program ended. The doubly labeled water method now makes it possible to quantitatively and objectively test a hypothesis proposed almost 50 y ago. Results generally support the Mayer hypothesis of a threshold of physical activity that protects against weight gain.