Creatine supplementation augments gains in lean body mass during resistance training, but exactly how it works remains unclear. This study had healthy men supplement with 15 g of creatine monohydrate or placebo per day for five days. After each supplementation period, subjects performed a bout of resistance exercise. Muscle was obtained from the leg using a biopsy needle before exercise, and 3 and 24 hours after exercise to measure the anabolic insulin-like growth factors (IGF) and some of the important signaling proteins they initiate that are involved in muscle hypertrophy. The study showed for the first time that five days of creatine supplementation significantly increased muscle IGF-I at rest (before exercise). Creatine supplementation also improved the signaling proteins that stimulate muscle hypertrophy 24 hours after exercise. These results provide some insights into the potential mechanism of the anabolic effects of creatine and suggest that upregulation of IGF-I may be involved.

Deldicque L, Louis M, Theisen D, et al. Increased IGF mRNA in human skeletal muscle after creatine supplementation. Med Sci Sport Exerc. 37(5)731-736, 2005.