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Overweight and obesity affects more than 66% of the adult population and is associated with a variety of chronic diseases. Weight reduction reduces health risks associated with chronic diseases and is therefore encouraged by major health agencies. Guidelines of the National Heart, Lung, and Blood Institute (NHLBI) encourage a 10% reduction in weight, although considerable literature indicates reduction in health risk with 3% to 5% reduction in weight. Physical activity (PA) is recommended as a component of weight management for prevention of weight gain, for weight loss, and for prevention of weight regain after weight loss. In 2001, the American College of Sports Medicine (ACSM) published a Position Stand that recommended a minimum of 150 min·wk−1 of moderate-intensity PA for overweight and obese adults to improve health; however, 200-300 min·wk−1 was recommended for long-term weight loss. More recent evidence has supported this recommendation and has indicated more PA may be necessary to prevent weight regain after weight loss. To this end, we have reexamined the evidence from 1999 to determine whether there is a level at which PA is effective for prevention of weight gain, for weight loss, and prevention of weight regain. Evidence supports moderate-intensity PA between 150 and 250 min·wk−1 to be effective to prevent weight gain. Moderate-intensity PA between 150 and 250 min·wk−1 will provide only modest weight loss. Greater amounts of PA (>250 min·wk−1) have been associated with clinically significant weight loss. Moderate-intensity PA between 150 and 250 min·wk−1 will improve weight loss in studies that use moderate diet restriction but not severe diet restriction. Cross-sectional and prospective studies indicate that after weight loss, weight maintenance is improved with PA >250 min·wk−1. However, no evidence from well-designed randomized controlled trials exists to judge the effectiveness of PA for prevention of weight regain after weight loss. Resistance training does not enhance weight loss but may increase fat-free mass and increase loss of fat mass and is associated with reductions in health risk. Existing evidence indicates that endurance PA or resistance training without weight loss improves health risk. There is inadequate evidence to determine whether PA prevents or attenuates detrimental changes in chronic disease risk during weight gain.