Fontana · Aging cell 2008 · Cohort comparison and uncontrolled before-after intervention · n=? (n=6 in prospective protein restriction sub-study)

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

Cited 395 times in the scientific literature.

Level 3 - non-randomized controlled study

Non-randomized comparative cohort studies and an uncontrolled before-and-after dietary intervention.

PubMed 18843793 · doi:10.1111/j.1474-9726.2008.00417.x · record verified 2026-08-30

What was done

Evaluated serum IGF-1 concentrations and IGF-1:IGFBP-3 ratios across two long-term calorie restriction (CR) studies (1 and 6 years) in humans practicing severe CR without malnutrition. In addition, total and free IGF-1 were examined in moderately protein-restricted individuals, and a 3-week intervention lowering protein intake from 1.67 g/kg/day to 0.95 g/kg/day was conducted in 6 volunteers already practicing CR.

What was found

Severe long-term CR for 1 and 6 years did not change serum IGF-1 levels or the IGF-1:IGFBP-3 ratio (no numerical values reported in the abstract). Moderately protein-restricted individuals had significantly lower total and free IGF-1 concentrations. In the 6 CR volunteers, reducing protein intake for 3 weeks lowered mean serum IGF-1 from 194 ng/mL to 152 ng/mL.

Why it matters

Unlike rodent models where calorie restriction robustly lowers IGF-1, circulating IGF-1 in humans appears largely unresponsive to calorie restriction alone unless protein intake is concurrently reduced.

Limits

The abstract does not report sample sizes, baseline demographics, or quantitative data for the 1- and 6-year CR cohorts. The prospective protein restriction trial was very small (n=6), short (3 weeks), and uncontrolled. Clinical endpoints such as disease incidence or lifespan were not measured.

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