Long‐term effects of calorie or protein restriction on serum IGF‐1 and IGFBP‐3 concentration in humans

Abstract

Reduced function mutations in the insulin/IGF‐I signaling pathway increase maximal lifespan and health span in many species. Calorie restriction (CR) decreases serum IGF‐1 concentration by ~40%, protects against cancer and slows aging in rodents. However, the long‐term effects of CR with adequate nutrition on circulating IGF‐1 levels in humans are unknown. Here we report data from two long‐term CR studies (1 and 6 years) showing that severe CR without malnutrition did not change IGF‐1 and IGF‐1 : IGFBP‐3 ratio levels in humans. In contrast, total and free IGF‐1 concentrations were significantly lower in moderately protein‐restricted individuals. Reducing protein intake from an average of 1.67 g kg⁻¹ of body weight per day to 0.95 g kg⁻¹ of body weight per day for 3 weeks in six volunteers practicing CR resulted in a reduction in serum IGF‐1 from 194 ng mL⁻¹ to 152 ng mL⁻¹. These findings demonstrate that, unlike in rodents, long‐term severe CR does not reduce serum IGF‐1 concentration and IGF‐1 : IGFBP‐3 ratio in humans. In addition, our data provide evidence that protein intake is a key determinant of circulating IGF‐1 levels in humans, and suggest that reduced protein intake may become an important component of anticancer and anti‐aging dietary interventions.