Research

Hormonal

Long-term calorie restriction (25% reduction for 2 years) in nonobese humans does not reduce serum IGF-1 levels, but significantly increases IGFBP-1 and decreases the IGF-1:IGFBP-1 ratio, thereby reducing bioavailable IGF-1.

If you are practicing long-term calorie restriction to optimize longevity markers, do not expect your total IGF-1 levels to drop significantly unless you also restrict protein. Instead, you will see a beneficial reduction in bioavailable (free) IGF-1 due to increased IGFBP-1. This suggests that the mechanism of action for CR in humans may differ from rodents, relying more on binding proteins than total hormone suppression.

StrongQualifiesHIGH confidence
long-term CR results in a significant and persistent increase in serum IGFBP-1 and decrease in IGF-1:IGFBP-1 ratio levels, which should translate into lower circulating levels of free IGF-1 and inhibition of IGF-1 activity in humans.
Luigi Fontana et al. · Aging Cell · 2015

Why this rating

Large, multicenter, randomized controlled trial (CALERIE) with 218 participants and 2-year duration.

Source

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

Luigi Fontana et al. · Aging Cell · 2015

DOI 10.1111/acel.12400

rct · n=218Cited 172×
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DOI resolved against Crossref · corpus check 2026-06-10

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