"Creatine Update" How creatine increases muscle mass!

Creatine is back in the news as several studies show that creatine not only helps shape muscle cells and keep them alive and healthy, but can also be considered an anti-aging supplement. Recent studies are shedding light on exciting new mechanisms that show how creatine increases muscle mass and promotes muscle recovery. If I were stuck on a desert island, creatine would probably be the one supplement I'd like to have there.

Is creatine an antioxidant?
Italian scientists have published new research into the mechanisms by which creatine can improve muscle recovery and stimulate muscle growth, particularly in ageing people. Creatine has previously been shown to increase muscle growth by directly increasing IGF-1 levels and increasing the activation of satellite cells. IGF-1 is known to stimulate satellite cell activity, protein synthesis and increased muscle hypertrophy. IGF-1 is such a potent stimulator of muscle hypertrophy that local infusion of IFG-1 directly into muscle tissue has been shown to increase muscle mass (1).

It has also been reported that the addition of creatine to muscle cell cultures in the test tube results in increased expression of IGF-1 mRNA. This means that creatine increases muscle growth even when you're just lying around idle, but training increases this effect. Now you might be saying "Hey Robbie, I'm not a fucking test tube, give me the human studies.

Human studies have shown that creatine supplementation also increases mRNA IGF-1 activity. In a double-blind, cross-over design study, muscle biopsies were taken from the legs of weight-trained men who consumed creatine or protein/carbohydrate drinks for 5 days, at rest, and 3 and 24 hours after exercise. After creatine supplementation, mRNA IGF-1 expression was significantly increased (+30 percent). IGF-1 levels were increased three hours after exercise (+24%) and 24 hours after exercise (+29%), although this effect was not increased by creatine supplementation.

It is interesting to note that creatine increased mRNA IGF-1 activity without exercise in this study. The researchers concluded that the increase in lean muscle mass often reported with creatine supplementation may be mediated by signaling pathways related to the muscle mRNA IFG-1 (1). Now that we know that creatine increases IGF-1 levels, we should look at a new role of creatine: protection against damage at the cellular level.

Coming back to the new Italian study, it should be mentioned that the scientists found that creatine has a strong antioxidant effect at the cellular level. The scientists were able to show that creatine can prevent oxidative stress in skeletal muscle. Oxidative stress is the result of free radical-induced damage that causes massive damage to muscle cells, which can result in cellular mutations, tissue breakdown and reduced immune function.

You may now be asking what free radicals are? They are highly unstable molecules that react quickly and aggressively with other molecules in our body to create abnormal cells. They are able to penetrate a cell's DNA and damage its "blueprint", causing the cell to produce mutated cells that can replicate without normal controls.

Free radicals are unstable because they have unpaired electrons in their molecular structure. This causes them to react almost immediately with other substances within their reach. Oxidative stress has devastating effects on muscle growth as it impairs the ability of newly formed muscle fibers to develop into mature muscle fibers. An increase in oxidative stress combined with an inability of the cell to produce essential energy molecules such as ATP is a hallmark of cell aging and can be observed in many disease states.

Although this is an enormously complex issue, aging and the ultimate fate of a cell - which is directly related to our fate as human beings - depends on the cell's ability to prevent mitochondrial damage to DNA caused by reactive oxygen species and to counteract a concomitant decrease in ATP synthesis, which reduces body-wide ATP levels. It appears that maintaining antioxidant status (e.g. glutathione) and ATP levels is an essential combination in delaying the ageing process.

A new study published in the Journal of Molecular Nutrition and Food Research has shown that creatine protects muscle cells from oxidative stress (4). Thus, creatine protects muscles under stressful conditions and prevents oxidative stress caused by damage to the cell's mitochondria. Based on these studies, creatine should be considered an anti-aging supplement.

Creatine increases the ratio of DHT to testosterone
Testosterone can stimulate muscle growth by increasing the rate of protein synthesis and preventing muscle breakdown. Creatine has been shown to increase muscle mass, but there have been differing views on its effects on testosterone. In two studies, subjects who supplemented creatine in combination with branched-chain amino acids(BCAAs), taurine, caffeine and glucuronolactones showed increased growth hormone and testosterone responses immediately after training (5, 6). The question is, however, which of the supplemented compounds was responsible for this. Was it creatine or another compound?

Another study found increased testosterone levels in blood samples taken at rest after 10 weeks of resistance training in combination with creatine supplementation compared to a placebo and creatine/beta-alaninesupplementation (7). However, another study concluded that creatine had no effect on resting testosterone levels in trained subjects despite a seven-day loading phase (6). A third study concluded that creatine in combination with HMB did not increase testosterone levels (8). Does creatine increase testosterone levels - yes or no?

Twenty young men (aged 18 to 19) from a rugby academy near Stellenbosch University in South Africa took part in a study. The subjects were randomly divided into two groups for a placebo-controlled, cross-over, double-blind study. The subjects underwent a seven-day loading phase with creatine or a placebo, followed by 14 days of a maintenance dose (creatine or placebo). The creatine monohydrate was administered during the loading phase in combination with glucose (25 grams of creatine and 25 grams of glucose per day). During the maintenance phase, the members of the creatine group received 5 grams of creatine and 25 grams of glucose daily. The placebo group received only glucose during the loading and maintenance phases (50 grams during the loading phase and 30 grams during the maintenance phase.

This was the first study to report an increase in the dihydrotestosterone (DHT) to testosterone ratio in response to the loading phase - a response that was maintained for at least two weeks during the maintenance phase in young trained athletes. Testosterone can be converted to its more bioactive metabolite DHT by the 5-alpha reductase enzyme. In addition, biochemical studies of androgen receptor affinity show that DHT is 4 times more biologically active than testosterone (9).

Creatine supplementation may be beneficial for both older men and those just starting resistance training. Creatine supplementation has been shown to improve protein synthesis, increase cell hydration, increase growth hormone levels and lower elevated cholesterol levels.

In 1997, Italian researchers discovered that maintaining muscle mass is the most important determining factor when it comes to a healthier and longer life. Studies suggest that loss of muscle mass correlates with loss of brain function and loss of nervous system function.

References

1. Adams GR, & McCue SA (1998). Localized infusion of IGF-1 results in skeletal muscle hypertrophy in rats. Journal of Applied Physiology, 84(5),1716-1722
2. Deldicque L, Louis M, Theisen D, Nielesen H, Dehoux M, Thissen JP, Rennie MJ, Francaux M. Increased IGF mRNA in human skeletal muscle after creatine supplementation. Med Sci Sports Exerc, 2005 May; 37(5): 731-6
3. Louis M, Van Benden R, Dehoux M, Thissen JP, Francaux M. Creatine increases IGF-1 and myogenic regulatory factor mRNA in C(2)C(12) cells. FEBS Lett, 2004 Jan 16;557(1-3): 234-7
4. Sestili P, Barbieri E, Martinelli C, Battistelli M, Guescini M, Vallorani L, Casadei L, D'Emilio A, Falcieri E, Piccoli G, Agostini D, Annibalini G, Paolillo M, Gioacchini M, Stocchi V. Creatine supplementation prevents the inhibition of myogenic differentiation in oxidatively injuredC2C12 murine myoblasts. Mol Nutr Food Res, 2009 Sep;53(9): 1187-204
5. Hoffman JR, Ratamess NA, Ross R, et al. Effect of a pre-exercise energy supplement on the acute hormonal response to resistance exercise. J strength Cond Res, 2008;22: 874-882
6. Ratamess NA, Hoffman JR, Ross R, et al. Effect of an amino acid/creatine energy supplement on the acute hormonal response to resistance exercise. Int J Sport Nutr Exerc Metab, 2007; 17:608-623
7. Hoffman J, Ratamess N, Kang J, et al. Effect of creatine and beta-alanine supplementation on performance and endocrine responses in strength/power athletes. Int J Sport Nutr Exerc Metab, 2006; 16: 430-446
8. O'Connor DM, Crowe MJ. Effects of six weeks of beta-hydroxy-beta-methylbutyrate (HM) and HMB/Creatine supplementation on strength, power and anthropometry of highly trained athletes. J Strength Cond Res, 2007 May; 21(2): 419-23
9. Zhou ZX, Lane MV, Kemppainen JA, et al. Specifity of ligan-dependent androgen receptor stabilization: receptor domain interactions influence ligand dissociation and receptor stability. Mol Endocrinol, 1995; 9: 208-218