Creatine Increase Muscle Hypertrophy

It has been reported that short-term Cr intake increases fat-free mass in strength-trained athletes^10,13. Accordingly, some in vitro (test tube) findings indicate Cr stimulates the biosynthesis of muscle myosin^11,12. In mice that are genetically engineered to be Cr deficient, the mice have increased muscle damage, decreased muscle mass, and reduced voluntary exercise capacity¹⁹. Decreased force developed per unit cross-sectional area by skeletal muscle of Cr deficient mice are due in part to decreased myofibrilliar and increased mitochondrial content, which may participate in muscle weakness. Indeed, a decrease in total myosin heavy chain of 25% in gastrocnemius and 45% in soleus was also described in Cr deficient engineered mice¹⁸.Cr is also being recognized as supplement to benefit patients with neurodegenerative and muscle wasting disorders¹⁴.  So how exactly is Cr increasing muscle hypertrophy?  At first, it was suggested that the increase in muscle mass after short-term Cr supplementation were due to fluid retention²⁰ but later studies over longer periods taking muscle biopsies documented true increases in muscle fiber area^15,25.  Cr has no effect on increasing muscle protein synthesis but reduced muscle protein breakdown was observed in men^{16, 17, 24.} New studies have recently been published which have shown that Cr does a whole lot more than just increase work capacity.

Creatine Increases IGF-1 mRNA Activity and Satellite Cell Activation.

New studies have been published which is turning new and novel mechanisms for Cr increases muscle mass.  One of the ways Cr may be increasing muscle hypertrophy is thru increasing IGF-1 mRNA.  Among the known growth factors, IGF-1 is known to stimulate satellite cell activity as well as protein synthesis, as well as increasing muscle hypertrophy. In fact, IGF-1 is such a potent stimulator of muscle hypertrophy that infusion of local IGF-1 directly to skeletal muscles has shown increases muscle mass²². It was earlier reported that when muscle cells were cultured in test tubes, the addition of Cr resulted in improved cell differentiation and increased expression of IGF-1 mRNA²¹. So what about human studies?  Human studies have also shown that Cr supplementation increases mRNA IGF-1 activity as well.  In a double-blind cross-over design, muscle biopsies were taken from the vastus lateralis of resistance trained men at rest and 3 and 24 hours post exercise who had taken Cr or a protein /carbohydrate drink for 5 days. After Cr supplementation, resting muscle expressed more mRNA for IGF-I (+30%). Exercise also caused an increase by 3 h postexercise in IGF-I (+24%) and by 24 h postexercise in IGF-I (+29%), but this effect was not increased by Cr supplementation. It's interesting that in the study, Cr increased mRNA IGF-1 activity without exercise, but taking Cr and exercise did not augment the response.  The researchers concluded that the increase in lean body mass often reported after Cr supplementation could be mediated by signaling pathway(s) involving muscle mRNA IGF-1²³.