Effects of 2-year calorie restriction on circulating levels of IGF-1, IGF-binding proteins and cortisol in nonobese men and women: a randomized clinical trial

Aging Cell. 2016 Feb;15(1):22-7. doi: 10.1111/acel.12400. Epub 2015 Oct 6.


Young-onset calorie restriction (CR) in rodents decreases serum IGF-1 concentration and increases serum corticosterone levels, which have been hypothesized to play major roles in mediating its anticancer and anti-aging effects. However, little is known on the effects of CR on the IGF-1 system and cortisol in humans. To test the sustained effects of CR on these key hormonal adaptations, we performed a multicenter randomized trial of a 2-year 25% CR intervention in 218 nonobese (body mass index between 22 and 27.8 kg m(-2) ) young and middle-aged (20-50 years age range) men and women. Average CR during the first 6 months was 19.5 ± 0.8% and 9.1 ± 0.7% over the next 18 months of the study. Weight loss averaged 7.6 ± 0.3 kg over the 2-years period of which 71% was fat mass loss (P < 0.0001). Average CR during the CR caused a significant 21% increase in serum IGFBP-1 and a 42% reduction in IGF-1:IGFBP-1 ratio at 2 years (P < 0.008), but did not change IGF-1 and IGF-1:IGFBP-3 ratio levels. Serum cortisol concentrations were slightly but significantly increased by CR at 1 year only (P = 0.003). Calorie restriction had no effect on serum concentrations of PDGF-AB and TGFβ-1. We conclude, on the basis of the present and previous findings, that, in contrast to rodents, humans do not respond to CR with a decrease in serum IGF-1 concentration or with a sustained and biological relevant increase in serum cortisol. However, long-term CR in humans significantly and persistently increases serum IGFBP-1 concentration.

Keywords: IGF-1; IGFBP-1; calorie restriction; cancer; cortisol; weight loss.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aging / physiology*
  • Blood Glucose / metabolism
  • Body Mass Index
  • Caloric Restriction*
  • Energy Intake / physiology*
  • Female
  • Humans
  • Hydrocortisone / metabolism*
  • Insulin-Like Growth Factor Binding Protein 1 / blood
  • Insulin-Like Growth Factor Binding Proteins / metabolism*
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Middle Aged
  • Sex Characteristics
  • Time Factors


  • Blood Glucose
  • IGF1 protein, human
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor I
  • Hydrocortisone