A Human Thrifty Phenotype Associated With Less Weight Loss During Caloric Restriction

Martin Reinhardt; Marie S. Thearle; Mostafa Ibrahim; Maximilian G. Hohenadel; Clifton Bogardus; Jonathan Krakoff; Susanne B. Votruba


Diabetes. 2015;64(8):2859-2867. 

In This Article

Abstract and Introduction


Successful weight loss is variable for reasons not fully elucidated. Whether effective weight loss results from smaller reductions in energy expenditure during caloric restriction is not known. We analyzed whether obese individuals with a "thrifty" phenotype, that is, greater reductions in 24-h energy expenditure during fasting and smaller increases with overfeeding, lose less weight during caloric restriction than those with a "spendthrift" phenotype. During a weight-maintaining period, 24-h energy expenditure responses to fasting and 200% overfeeding were measured in a whole-room indirect calorimeter. Volunteers then underwent 6 weeks of 50% caloric restriction. We calculated the daily energy deficit (kilocalories per day) during caloric restriction, incorporating energy intake and waste, energy expenditure, and daily activity. We found that a smaller reduction in 24-h energy expenditure during fasting and a larger response to overfeeding predicted more weight loss over 6 weeks, even after accounting for age, sex, race, and baseline weight, as well as a greater rate of energy deficit accumulation. The success of dietary weight loss efforts is influenced by the energy expenditure response to caloric restriction. Greater decreases in energy expenditure during caloric restriction predict less weight loss, indicating the presence of thrifty and spendthrift phenotypes in obese humans.


Whether greater weight loss is the result of a smaller reduction in energy expenditure with caloric restriction (CR) is not known. Resting energy expenditure and 24-h energy expenditure (24h-EE) vary substantially between individuals,[1,2] and relatively reduced rates of 24h-EE predict weight gain in some populations.[3,4] Obese individuals that lose at least 10% of their weight experience a decrease in 24h-EE and resting energy expenditure that is lower than predicted based on changes in body composition.[5] Most weight loss and overfeeding studies have found large individual variation in the amount of weight change,[6–9] and whether an individual's response to an intervention can be predicted is not clear. Measurements of 24h-EE response to fasting and overfeeding may help predict weight loss.

"Thrift" refers generically to the efficiency with which energy is used.[10] Some humans with a smaller increase in 24h-EE in response to short-term overfeeding have a correspondingly larger decrease in 24h-EE in response to fasting (thrifty) and vice versa (spendthrift)[11] (Fig. 1). This is true in lean and obese individuals and indicates an interindividual variability in the energy expenditure response to CR that might influence the ability to lose weight. The aim of this study was to define whether this variability in energy expenditure response to 24 h of fasting and overfeeding predicts weight changes during 6 weeks of controlled CR.

Figure 1.

Illustration of the concept of spendthrift and thrifty phenotypes, characterized by their individual 24h-EE response to overfeeding and fasting.