Insulin-like growth factor (IGF)-I is a biomarker that may have greater utility than other conventional nutritional biomarkers in assessing nutritional, health, and fitness status. We hypothesized that the IGF-I system would directionally track a short-term energy deficit and would be more related to changes in body composition than other nutritional biomarkers. Thirty-five healthy men (24 +/- 0.3 yr) underwent 8 days of exercise and energy imbalance. Total and free IGF-I, IGF binding proteins-1, -2, and -3, the acid labile subunit, transferrin, ferritin, retinol binding protein, prealbumin, testosterone, triiodothyronine, thyroxine, and leptin responses were measured. Dual-energy X-ray absorptiometry assessed changes in body mass and composition. Repeated-measures ANOVA, correlation analysis, and receiver operator characteristic curves were used for statistical analyses (P < or = 0.05). Body mass (-3.8%), fat-free mass (-2.2%), and fat mass (-12.9%) all decreased. Total and free IGF-I, IGF binding protein-3, and the acid labile subunit and prealbumin, but not transferrin, retinol-binding protein, and ferritin, directionally tracked the energy deficit and losses in body composition. The correlation (r = 0.43) between changes in free IGF-I and body and fat-free mass was the only significant association observed. Receiver operator characteristic curve analysis revealed that a baseline value < 1.67 for the molar volume ratio of IGF-I to acid labile subunit had an area under the curve of 0.745 and was a significant discriminator for those subjects losing >5% body mass. The IGF-I system is an important adjunct in the overall assessment of adaptation to stress imposed by high levels of physical activity superimposed on energy and sleep restriction and is more closely associated with losses in body mass and fat-free mass than other conventional nutritional biomarkers.