Bettina Mittendorfer, Ph.D.
Project Overview:
Calorie restriction (CR) in overweight and obese subjects has many benefits; it increases insulin sensitivity and reduces cardiovascular (CVD) risk. Therefore, CR is the cornerstone of treatment to improve health in obese persons. CR also increases maximal lifespan in a variety of non-human species, so it is being promoted as a means to potentially increase lifespans in lean adults.
The effect of CR on health in lean human subjects is not clear. In healthy, lean individuals, CR could potentially be harmful because it is known to decrease muscle mass, bone mass and bone mineral density. This has minimal clinical implications in obese persons, because they have greater muscle mass and bone mineral density than lean people, and obese subjects lose less body protein during negative energy balance than do lean subjects. But in lean individuals, CR could cause sarcopenia, osteopenia/osteoporosis and impair physical function, which are predictors of frailty and disability and premature death, because of their relatively small baseline muscle and bone mass and bone mineral density.
This study will evaluate the effect of calorie restriction in lean older adults on metabolism, muscle and bone, and will test if additional protein intake can prevent the potential harmful effects of calorie restriction in lean subjects.
Final Report:
Calorie restriction (CR) in obese subjects has many benefits; it increases insulin sensitivity and reduces cardiovascular risk. Therefore, CR is the cornerstone of treatment to improve health in obese persons. In addition, it is being promoted to potentially increase lifespan in non-obese adults because CR increases maximal lifespan in a variety of non-human species. The effect of CR on health in non-obese human subjects is not clear. In fact, CR in healthy, non-obese individuals could potentially be harmful because it decreases muscle mass, bone mass and bone mineral density. This has minimal clinical implications in obese persons, because they have greater muscle mass and bone mineral density than lean people, and obese subjects lose less body protein during negative energy balance than do lean subjects. However, CR in non-obese individuals could cause sarcopenia, osteopenia/osteoporosis and impair physical function, which are predictors of frailty and disability and premature death, because of the relatively small baseline muscle and bone mass and bone mineral density. In addition, we have recently found that a group of lean men and women who have undergone self-imposed CR for years based on the belief that CR will extend their lifespan not only have low muscle mass and bone mass and bone mineral density but also have impaired oral glucose tolerance. CR in non-obese subjects could therefore have detrimental health consequences, but this issue has not been carefully studied in prospective, randomized controlled trials.
Accordingly, the overall purpose of this proposal was to provide a comprehensive evaluation of the effects of CR on metabolic health in healthy, non-obese, older adults. We found that CR in non-obese subjects leads to muscle loss and does not have the same beneficial effects as in obese subjects who experience significant improvements in insulin sensitivity after similar amount of weight loss. These results contrast those from non-obese non-human species (e.g., rodents, fish, flies, worms, and monkeys) in which CR delayed the onset of metabolic disease, prevented the age-associated loss of muscle mass, and increased both average and maximal life span.
