Creatine is a nitrogenous organic acid that naturally occurs in humans and helps to supply energy to muscle cells. Creatine was identified in 1832 when Michel Eugène Chevreul discovered it as a component of skeletal muscle which he later named creatine after the Greek word for flesh, Kreas.

Natural Creatine in the Body

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.

Sources of Creatine

In humans, typically half 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. Vegetarian creatine can be obtained via chemical synthesis using plant-derived amino acids.

Creatine and the Treatment of Muscular Diseases

Creatine supplementation has been, and continues to be, investigated as a possible therapeutic approach for the treatment of 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.).

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.

Creatine as a Diagnostic of Kidney Function

Hospitals and doctors routinely measure blood creatinine levels (a break-down product of creatine phosphate in muscle) 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.

History of use as a nutritional supplement

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. The first commercially available creatine supplement was Phosphagen, which was released by nutrition company EAS.

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 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.

At the time, low-potency creatine supplements were available in Britain, but creatine supplements designed for strength enhancement were not commercially available until 1993 when a company called Experimental and Applied Sciences (EAS) introduced the compound to the sports nutrition market under the name Phosphagen. Another advance in creatine supplementation was Phosphagen HP. Research at the University of Memphis funded and designed by EAS showed that the consumption of high glycemic carbohydrates in conjunction with creatine vastly increases creatine muscle stores and performance.

The combination of creatine and carbohydrates is the only formula that has been proven in published studies to improve muscular performance and weight gain over regular creatine. Many products from several different companies now contain this formula. In 1998, the launch of the first creatine-carbohydrate-alpha lipoic acid supplement, Cell-Tech, by another company called MuscleTech Research and Development, took place. Alpha lipoic acid enhances muscle phosphocreatine levels and total muscle creatine concentrations. This approach to creatine supplementation was validated in a study by the Department of Human Kinetics at St. Francis Xavier University. Another important event in creatine supplementation occurred in 2004 when the first creatine ethyl ester supplements were launched.

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.

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.

Creatine and Athletic Performance

Creatine is often taken by athletes to increase muscle mass. 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 marginally 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%. It must be noted creatine has no significant effect on aerobic exercise.

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.

Also, research has 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 fibre, thereby increasing myonuclei numbers necessary for fibre 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 fibres. This increase in myonuclei probably stems from creatine’s ability to increase levels of the myogenic transcription factor MRF4.

Current studies indicate that short-term creatine supplementation in healthy individuals is safe. 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. Creatine use is not considered doping and is not banned by sport-governing bodies. However in some countries, such as Germany and France, creatine is banned.