
Creatine Revisited
Creatine, to me, is still the single greatest find in supplement history. No supplement, prior or since, has such a record of both efficiency and safety as creatine. And today it still remains a favourite subject for research. Although I'm sure many will find creatine a boring subject by now, and I can't entirely disagree.
Over the past 5 or 6 years I have had to answer so many questions about it over and over again, it sometimes seems creatine is more of a curse than a blessing. But that doesn't change the fact that a few thousand money hungry supplement pioneers haven't managed to improve on this find. Sure, we now have prohormones, which are the first supplements to actually show notable increases in muscle mass in just a few weeks.
But their safety is very questionable, especially long term with regards to fertility and cardiovascular risk. And many have tried to cash in with the so-called second and third generation strategy, by claiming they have either augmented creatine delivery, or found a superior creatine analog.
The former only to jack up the price more than the increase in efficiency (adding sugar to creatine really doesn't cost an arm and a leg) and the latter only to see the error of their ways reflected in many disappointed customers. Creatine remains a safe and effective ergogenic supplement, with many benefits and above all, extremely affordable.
Creatine's effects on energy balance
I'm not going to stick a lot of studies beneath this subject, as I assume these features of creatine are already well-documented and I trust no one will dispute what is said here. Creatine's main use stems from its effect on rapidly repleting ATP stores. ATP is the energy currency in the body. Food is broken down to macronutrients, and macronutrients are oxidized in the mitochondria to create ATP, or adenosine tri-phosphate.
ATP releases its energy by breaking one of its high-energy phosphate bonds, and what remains is ADP or Adenosine Di-phosphate. ATP stores are depleted in a matter of seconds, after which we generally have to rely on other energy mechanisms to supply more, usually oxidative ones (via the Krebs cycle).
ATP Molecule
Creatine intake however increases the level of creatine phosphate, which can donate a phosphate to ADP and regenerate ATP. This increases our anaerobic ATP level by several seconds. The benefit being obvious to athletes that work predominantly anaerobic, such as powerlifters and bodybuilders.
However, creatine has also proven its benefits for other athletes as well. This may be, at least in part, due to the fact that it makes ATP generation more efficient by increasing citrate synthase activity, resulting in an almost 40% reduction in lactate output. Creatine supplementation also resulted in an increase in AMPK phosphorylation, which PPARgamma and Fatty acid synthase, potentially leaving more substrates available for long term oxidative energy production.
Ceddia R, Sweeney G. Creatine increases glucose oxidation and AMPK phosphorylation and reduces lactate production in L6 rat skeletal muscle cells. J Physiol. 2004 Jan 14
Creatine's effects on muscle growth
The most often discussed effect of creatine on muscle growth is the effect it has on cell swelling. Cell swelling has been demonstrated to be anabolic, leading to an increase in protein synthesis, independent of other factors. Creatine has been shown to increase the osmotic value of a cell, much like glycogen and glycerol, and therefore increase the water content of the cell, making it swell. Cell swelling by creatine has been shown to increase by as much as 2 or 3% (1).
But creatine may be much more versatile than that. It has been shown to affect the mitotic action of satellite cells. Satellite cells can be looked at as baby muscle cells. Under the influence of anabolic growth factors they can be incorporated into a muscle cell and donate a nucleus. Muscle cells are multi-nuclear, and the more nuclei the cell has, the more androgen receptors it has.
That means its more succeptible to muscle growth mediated by androgens, like testosterone. One such factor that melts satellite cells with muscle cells is IGF-1. Mitosis is the process of multiplication by division. Increased creatine content has been shown to enhance the multiplication of satellite cells (2).
Muscle Fiber
In and of itself that means nothing, but more recent research (3) has uncovered a more active role for creatine in muscle growth, namely the increasing of IGF-1 and MRF mRNA levels in muscle cells, leading to hypertrophy of the myotubes. Combined with the previous study that means not only does creatine increase the number of satellite cells, it can ACTIVELY promote their incorporation in muscle cells making them more responsive to hypertrophy.
That makes creatine a much more versatile and useful compound for muscle growth than we previously imagined. That makes the biggest find in supplement history, an even bigger find.
Ziegenfuss T, Lowery L, Lemon P. Acute Volume changes in men during three days of creatine supplementation. JEPonline Vol1 nr3, 1998
Dangott B, Schultz E, Mozdziak PE. Dietary creatine monohydrate supplementation increases satellite cell mitotic activity during compensatory hypertrophy. Int J Sports Med. 2000 Jan;21(1):13-6.
Louis M, Van Beneden R, Dehoux M, Thissen JP, Francaux M. Creatine increases IGF-I and myogenic regulatory factor mRNA in C(2)C(12) cells. FEBS Lett. 2004 Jan 16;557(1-3):243-7.
Other uses for creatine
For those interested, I suggest you check out some other uses of creatine pertaining to health. It has been implicated in the treatment of chronic fatigue, depression, fybromyalgia, etc. Supplementation seems to enhance brain phosphocreatine content (1), which leads to increases in mood and possibly cognition. So I expect the current list of valid treatment uses for creatine will no doubt become longer in the future, as we start to uncover the implications of this.
Some students even claim the increase in cognitive function helps them study, so creatine may be a powerful study aid as well for some of you younger iron enthusiasts. Creatine may even be a good anti-oxidant as well, since it seems to reduce homocysteine levels as well.
Lyoo IK, Kong SW, Sung SM, Hirashima F, Parow A, Hennen J, Cohen BM, Renshaw PF. Multinuclear magnetic resonance spectroscopy of high-energy phosphate metabolites in human brain following oral supplementation of creatine-monohydrate. Psychiatry Res. 2003 Jun 30;123(2):87-100.
Safety
Not only does creatine increase energy balance and muscle growth, its effective treatment in several health problems. But to totally understand how remarkable creatine is, we also have to look at the fact that creatine has no known side-effects. One of the leading creatine researchers, Prof Poortmans has demonstrated in a study lasting up to 5 years with doses almost 4 times what the normal bodybuilder would use, that creatine has absolutely no adverse effects.
Not on the heart, not on the liver, not on the kidneys. Any claims made by anyone that state otherwise are completely and utterly fictitious, and proven utterly wrong by a multitude of studies. Creatine, besides being one of the most effective dietary supplements used by athletes, is most likely also the safest.
This makes it continually harder to understand the stance some people, and in some cases even authorities take towards creatine. In France, creatine is banned by several athletic federations. The complete and utter stupidity of this continues to baffle me.
Poortmans JR, Francaux M. Adverse effects of creatine supplementation: fact or fiction? Sports Med. 2000 Sep;30(3):155-70.
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