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What is Creatine?

Research into Creatine

What is Creatine?

Creatine a natural substance is a nitrogenous organic acid that occurs in all vertebrates and helps to supply energy to muscle cells. Creatine was discovered in 1832 by Michel Eugène Chevreul who identified it as a component of skeletal muscle which he called creatine after the Greek word for flesh, Kreas. Creatine functions as part of a system based on arginine/phosphoarginine that operates in many invertebrates. The presence of this energy shuttle keeps the ATP/ADP ratio high, which ensures that the free energy of ATP remains high and minimizes the loss of adenosine nucleotides, which would cause cellular dysfunction. Creatine is sold in both powders & tablet form. Sometimes it is mixed in with other compounds to increase the efficiency of the delivery of the product to the body system. It is also available in different forms such as Monohydrate ( the most common often sold in powder form) Kre-Alkalyn ( normally found in purple capsules ) and Creatine Ethyl Ester ( used as the basis for the more powerful versions).


In the human body, creatine is synthesized mainly in the liver by the use of parts from three different amino acids - arginine, glycine, and methionine. 95% of it is later stored in the skeletal muscles, with the rest in the brain, heart, and testes.
The enzyme GATM (Guanidinoacetate N-methyltransferase, also known as L-arginine:glycine amidinotransferase (AGAT), EC 2.1.4.1), is a mitchondrial enzyme responsible for catalyzing the first rate-limiting step of creatine biosynthesis, and is primarily expressed in the kidneys.The second enzyme in the pathway (GAMT, guanidinoacetate N-methyltransferase, EC:2.1.1.2) is primarily expressed in the liver. Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects.


In humans, typically 50% of stored creatine originates from food (mainly from meat and fish). However, endogenous synthesis of creatine in the liver is sufficient for normal activities. This is evidenced by the fact that even though vegetables do not contain creatine, vegetarians do not suffer from creatine deficiency. Addition of creatine to the vegetarian diet has been shown to improve athletic performance [1] . Vegetarian creatine can be obtained via chemical synthesis using plant-derived amino acids.

Creatine supplementation has been, and continues to be, investigated as a therapeutic approach for the treatment of many things including -  muscular, neurological and neuromuscular diseases (arthritis, congestive heart failure, disuse atrophy, gyrate atrophy, McArdle's disease, Huntington's disease, miscellaneous neuromuscular diseases, mitochondrial diseases, muscular dystrophy, neuroprotection, etc.).

Two scientific studies have indicated that creatine may be beneficial for neuromuscular disorders. First, a study (Klivenyi et al. 1999) by MDA-funded researcher M. Flint Beal of Cornell University Medical Center demonstrated that creatine was twice as effective as the prescription drug riluzole in extending the lives of mice with the degenerative neural disease amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease). Beal suspects that the neuroprotective effects of creatine in the mouse model of ALS are due either to an increased availability of energy to injured nerve cells or to a blocking of the chemical pathway that leads to cell death.

Second, a study by Canadian researchers Mark Tarnopolsky and Joan Martin of McMaster University Medical Center in Hamilton, Ontario found that creatine can cause modest increases in strength in people with a variety of neuromuscular disorders. The latter paper was published in the March 1999 issue of Neurology.

Hospitals and doctors routinely measure blood creatinine levels to determine kidney function. Creatine is broken down to creatinine, which is eliminated through the kidneys. High creatinine serum levels are thus an indication of renal failure.

In 1912, researchers found that ingesting creatine can dramatically boost the creatine content of the muscle. In the late 1920s, after finding that the intramuscular stores of creatine can be increased by ingesting creatine in larger than normal amounts, scientists discovered creatine phosphate, and determined that creatine is a key player in the metabolism of skeletal muscle.

While creatine's influence on physical performance has been well documented since the early twentieth century, it only recently came into public view following the 1992 Olympics in Barcelona. An August 7, 1992 article in The Times reported that Linford Christie, the gold medal winner at 100 meters, had utilized creatine prior to the Olympics, and an article in Bodybuilding Monthly named Britain's Sally Gunnell, gold medalist in the 400-meter hurdles, as another creatine user. Several medal-winning British rowers also used creatine during their preparations for the Barcelona games. Most of the original studies have involved Creatine Monohydrate - recent studies have shown that other forms are much more effective.


Creatine Ethyl Ester (CEE) is becoming a widely used form of creatine, with many companies now carrying both creatine monohydrate-based supplements and Creatine Ethyl Ester supplements, or combinations of both. CEE is touted to have absorption rates tens of times higher than regular creatine monohydrate by several supplement companies - however no peer-reviewed studies have emerged to conclusively prove these claims. Once ingested, however, creatine is highly bioavailable (easily measured by its plasma appearance kinetics and urinary excretion), whether it is ingested as the crystalline monohydrate form, the free form in solution, or even in meat. Creatine salts will become the free form when dissolved in aqueous solution. With studies repeatedly reporting an upper maximal range for muscular creatine concentration, it is unlikely that the form of creatine ingested results in increased or altered final gains. [citation needed]

Creatine Ethyl Ester (CEE) is not allowed to be sold in Germany and France.

Creatine is often taken by humans as a supplement for those wishing to gain muscle mass (bodybuilding). There are a number of forms but the most common are creatine monohydrate - creatine bonded with a molecule of water, and creatine ethyl ester (CEE) – which is creatine monohydrate with an ester attached. A number of methods for ingestion exist - as a powder mixed into a drink, or as a pill.

There is scientific evidence that taking creatine supplements can increase athletic performance in high-intensity anaerobic repetitive cycling sprints, but studies in swimmers and runners have been less than promising, possibly due to the weight gain. Ingesting creatine can increase the level of phosphocreatine in the muscles up to 20%.

Some studies have shown that creatine supplementation increases both total and fat-free body mass, though it is difficult to say how much of this is due to the training effect. Since body mass gains of about 1 kg (about 2.2 pounds) can occur in a week's time, several studies suggest that the gain is simply due to greater water retention inside the muscle cells. However, studies into the long-term effect of creatine supplementation suggest that body mass gains cannot be explained by increases in intracellular water alone. In the longer term, the increase in total body water is reported to be proportional to the weight gains, which means that the percentage of total body water is not significantly changed. The magnitude of the weight gains during training over a period of several weeks argue against the water-retention theory.


Research  has also shown that creatine increases the activity of myogenic cells. These cells, sometimes called satellite cells, are myogenic stem cells that make hypertrophy (increase in size of cells) of adult skeletal muscle possible. These stem cells are simply generic or non-specific cells that have the ability to form new muscle cells following damage to the muscle tissue, or to fuse with the existing muscle fibres in the case of exercise to permit growth of the muscle fibre. Following proliferation (reproduction) and subsequent differentiation (to become a specific type of cell), these satellite cells will fuse with one another or with the adjacent damaged muscle fiber, thereby increasing myonuclei numbers necessary for fiber growth and repair. The study, published in the International Journal of Sports Medicine was able to show that creatine supplementation increased the number of myonuclei donated from satellite cells. This increases the potential for growth of those fibers. This increase in myonuclei probably stems from creatine's ability to increase levels of the myogenic transcription factor MRF4 (Hespel, 2001).

Other studies indicate that short-term creatine supplementation in healthy individuals is safe (Robinson et al., 2000). Longer-term studies have occasionally been done, but have been small. One such study that is often cited involved a minimum length of 3 months, but only had 10 creatine subjects (Mayhew et al 2002).

There has been controversy over the incidence of muscle cramping with the use of creatine. A study at the University of Memphis showed no reports of muscle cramping in subjects taking creatine-containing supplements during various exercise training conditions in trained and untrained endurance athletes (Kreider R. et al, 1998). Cramping though is typically associated with Creatine Monohydrate Powder and is not a problem with either Kre-Alkalyn or Creatine Ethyl Ester.

Creatine use is not considered doping and is not banned by sport-governing bodies.

References:

Burke DG, Chilibeck PD, Parise G, Tarnopolsky MA, Candow DG. (2003). "Effect of alpha-lipoic acid combined with creatine monohydrate on human skeletal muscle creatine and phosphagen concentration.". Int J Sport Nutr Exerc Metab. Sep (13). PMID 14669930..
Dangott B, Schultz E, Mozdziak PE. (2000). "Dietary creatine monohydrate supplementation increases satellite cell mitotic activity during compensatory hypertrophy". International Journal of Sports Medicine 2000 Jan (21(1):): 13-6. PMID 10683092..
Engelhardt M, Neumann G, Berbalk A, Reuter I. (1998). "Creatine supplementation in endurance sports.". British Journal of Med Sci Sports Exerc. 30 (7): 1123-9. PMID 9662683.
Greenhaff PL et al. (1993). "Influence of oral creatine supplementation on muscle torque during repeated bouts of maximal voluntary exercise in men.". Clinical Science 84: 565-571. PMID 8504634..
Hespel P, Op't Eijnde B, Van Leemputte M, Urso B, Greenhaff PL, Labarque V, Dymarkowski S, Van Hecke P, Richter EA. (2001). "Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans". J Physiol. 2001 Oct 15 (536(Pt 2)): 625-33. PMID 11600695..
Hultman E, Soderlund K, Timmons JA, et al. (1996). "Muscle creatine loading in men.". J Appl Physiol (81): 232-237. PMID 8828669..
Juhn MS. (2003). "Popular sports supplements and ergogenic aids". Sports Med. 33 (2): 921-39. PMID 12974658.
Klivenyi P, Ferrante RJ, Matthews RT, Bogdanov MB, Klein AM, Andreassen OA, Mueller G, Wermer M, Kaddurah-Daouk R, Beal MF. (mar 1999). "Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis.". Nature Medicine. 5 (3): 347-350. PMID 10086395..
Kreider R. (1998). "Creatine: The Ergogenic/Anabolic Supplement". Mesomorphosis 1 (4). [3]
Kreider R, Rasmussen C, Ransom J, Almada AL. (1998). "Effects of creatine supplementation during training on the incidence of muscle cramping, injuries and GI distress.". J Strength Cond Res. 12 (275).
Mayhew DL, Mayhew JL, Ware JS (2002). "Effects of long-term creatine supplementation on liver and kidney functions in American college football players.". Int J Sport Nutr Exerc Metab. 12 (4): 453-60. PMID 12500988..
Phillips, Bill. "Sports Supplememt Review 3rd issue. (2000)".
Powers ME et al. (2003). "Creatine Supplementation Increases Total Body Water Without Altering Fluid Distribution". Journal of Athletic Training 38 (1): 44-50. PMID 12937471..
Rae C, Digney AL, McEwan SR, Bates TC. (2003). "Oral creatine monohydrate supplementation improves cognitive performance; a placebo-controlled, double-blind cross-over trial.". Proceedings of the Royal Society of London - Biological Sciences 270 (1529): 2147-2150. PMID 14561278..
Robinson TM et al. (2000). "Dietary creatine supplementation does not affect some haematological indices, or indices of muscle damage and hepatic and renal function". British Journa
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