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.

Fig. 1

Effects of 1 year of calorie restriction (CR) on serum IGF-1 concentration and IGF-1 : IGFBP-3 ratio. Serum IGF-1 concentration (A) and the IGF-1 : IGFBP-3 ratio in response to 1 year of CR (n = 18), exercise-induced weight loss (Exercise; n = 18), and a healthy lifestyle control condition (HL; n = 10), as assessed during the randomized trail. Data are mean ± standard error. There were no significant differences within or among groups.

Fig. 2

Long-term effects of calorie restriction (CR) and protein restriction (PR) on serum IGF-1 concentration. Serum IGF-1 concentration (A), IGF-1 : IGFBP-3 ratio (B), and the serum concentrations of insulin (C) and C-reactive protein (D) from the cross-sectional comparison of individuals who were habitually consuming a low protein diet, a low calorie diet, or a typical Western diet. Data are mean ± standard error. *p ≤ 0.01 vs. the low calorie group. †p ≤ 0.01 vs. the Western diet group.