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.
Level 2 - randomized trial
Individual randomized controlled trial in humans
PubMed 26443692 · doi:10.1111/acel.12400
What was done
A multicenter randomized trial tested a 2-year 25% target calorie restriction (CR) intervention in 218 nonobese healthy adults (BMI 22–27.8 kg/m², aged 20–50 years). Achieved CR averaged 19.5 ± 0.8% in the first 6 months and 9.1 ± 0.7% over the subsequent 18 months. Circulating levels of IGF-1, IGFBP-1, IGFBP-3, cortisol, PDGF-AB, and TGFβ-1 were evaluated.
What was found
Weight loss averaged 7.6 ± 0.3 kg over 2 years, with 71% being fat mass loss (P < 0.0001). CR resulted in a 21% increase in serum IGFBP-1 and a 42% reduction in the IGF-1:IGFBP-1 ratio at 2 years (P < 0.008), with no change in total IGF-1 or the IGF-1:IGFBP-3 ratio. Serum cortisol was slightly increased at 1 year only (P = 0.003), with no sustained elevation at 2 years. CR had no effect on PDGF-AB or TGFβ-1 levels.
Why it matters
Unlike rodents, humans undergoing long-term calorie restriction do not experience sustained reductions in total circulating IGF-1 or persistent cortisol elevation, indicating distinct human endocrine adaptations primarily mediated by increased IGFBP-1.
Limits
Adherence declined substantially over time, with achieved restriction averaging ~9% rather than the 25% target in months 6–24. The sample was restricted to nonobese adults aged 20–50, limiting generalizability to older or obese populations, and tissue-level IGF-1 bioactivity was not directly measured.
Cited by
- supports In human caloric restriction studies by Fontana and colleagues, calorie restriction alone did not reduce IGF-1 levels until dietary protein was also restricted.