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

Summary

This Aging Cell paper directly addressed a paradox: rodent studies of caloric restriction reliably show IGF-1 reductions and longevity benefits, but the few existing human CR studies had not replicated the IGF-1 effect. Why? Fontana and colleagues compared three groups of human subjects: 28 long-term Calorie Restriction Society members (about 30 percent CR for 5+ years, but maintaining typical Western protein percentages around 24 percent of energy), 28 age-matched moderately protein-restricted vegans (around 10 percent of energy from protein), and 28 sedentary controls. The headline finding overturned the assumption that calories drive the IGF-1 effect: the strict CR group had no significant reduction in IGF-1 versus controls, while the vegans (heavier than the CR group, with more body fat) had significantly lower total and free IGF-1. The paper's conclusion is unambiguous: in humans, low protein intake — not low calorie intake — is what suppresses IGF-1. This finding helped explain why CR-induced longevity benefits in mice have not translated cleanly to humans on standard Western protein intakes, even at low calorie levels.