BACKGROUND & AIMS: Patients with anorexia nervosa (AN) have low serum IGF-I levels that may contribute to a lower bone mineral mass. We investigated the effects of a fermented, protein-fortified, dairy product on serum IGF-I levels in patients with AN during an in-hospital refeeding program. METHODS: In this multicenter, randomized, double-blind, placebo-controlled, clinical trial conducted at 3 university hospitals and 3 private clinics in France and Switzerland, 62 women recently admitted with confirmed AN and with a baseline low serum IGF-I level were randomized to 2 daily isocaloric fresh cheese pots containing either 15 g/150 g or 3 g/150 g (controls) of protein for 4 weeks. The primary outcome was the change in IGF-I levels. RESULTS: In the primary intention-to-treat analysis, mean serum IGF-I levels increased during the intervention phase from 22.9 +/- 1.5 to 28.6 +/- 1.3 nmol/L (means +/- SEM) (+20.2%) in the intervention group and from 20.2 +/- 1.2 to 25.7 +/- 1.5 nmol/L (+16.8%) in controls. In a preplanned analysis of covariance with repeated measures, the between-group difference was close to statistical significance (P = 0.071). In a post-hoc mixed-regression model analysis, the difference was statistically significant (4.9 nmol/l increase; P = 0.003), as was the change of the ratio IGF-I/IGF-BP3 (P=0.004). There was no between-group difference in biochemical markers of bone turnover (osteocalcin, P1NP, CTX) or in serum parathyroid hormone level. Serum calcium levels slightly increased during the intervention phase in the higher protein group (P = 0.02). IGF-BP2 decreased significantly more in the intervention group during the follow up period at week 4 after supplements cessation (P = 0.019). CONCLUSIONS: Intake of a fermented, protein-fortified, isocaloric dairy product during 4 weeks may slightly increase serum IGF-I levels in women with AN, without significant changes in bone turnover markers. CLINICAL TRIAL REGISTRATION NUMBER: NCT01823822