What is Creatine? A Summary of Methylguanidine Acetic Acid

We take a look at this popular sports supplement.

Meat is rich in creatine, an important energy buffer in muscle cells, and the main constituent of a popular sports supplement used by athletes. However, we’re now finding out that there’s more to it than ‘meats’ the eye.

What is creatine?

Creatine (α-methyl guanidine-acetic acid) is a substance that is present in our muscle cells. Functionally, it helps our muscles to produce energy for lifting weights, high-intensity exercise, and other strenuous activities. It has enjoyed great popularity as a supplement with athletes and bodybuilders in order to gain muscle, boost strength and increase exercise performance.

It was first identified by French chemist Michel Eugène Chevreul in 1832, who isolated it from skeletal muscle. Due to its presence in living tissue, Chevreul named it after the Greek word κρέας (kreas), meaning meat.

In 1912, Otto Folin and Wiley Glover Denis of Harvard University found that ingesting creatine led to a significant increase in intramuscular stores [1], sparking an interest in its potential as an oral supplement.

By the 1930s, German scientists began to study the relationship between creatine levels and muscle contraction, concluding that the more creatine present in muscle cells, the longer they could contract before producing lactic acid [2-3], allowing for extended training times.

During the 1960s, an interest surged in the possible uses of creatine to treat muscle diseases. In 1964, Fitch et al. were able to show that the skeletal muscles of muscular dystrophy patients have lower concentrations than their normal counterparts, which they attributed to a defect in creatine binding in muscle cells [4-5].

The potential of creatine as a performance-enhancing supplement came into public scrutiny after the 1992 Barcelona Olympics, in which several gold medallists admitted to taking it during training. Today, supplements exist in a wide variety of forms and are one of the most widely used nutritional supplements worldwide [6].

What foods contain creatine?

It is produced inside the body from the amino acids glycine and arginine, and it is widely distributed to tissues with high energy demands, such as the brain and muscles. About 95% of the body’s creatine is stored in skeletal muscle, but it is also found in small amounts in the liver, kidneys, and testes.

On average, the body produces approximately 1 gram of creatine per day in young adults [7-8], while the rest is obtained through diet. 

Creatine is naturally occurring in many foods, particularly animal protein, such as meat and fish. One pound of raw beef contains approximately 2.3g of creatine, while one pound of raw salmon contains up to 2g.

Cooking denatures creatine, so unless you like your steak extra bloody or are a big fan of sashimi, it will be difficult to get enough of it in your diet to benefit from its health properties. Red meat is also high in saturated fat and may increase your risk of all-cause mortality [9-10], so consuming that much meat to begin with might not be the wisest choice.

Luckily, it is widely available as a health supplement, and is extremely affordable. This is particularly relevant for vegans and vegetarians, whose intake is greatly diminished or absent altogether. These supplements have been found to have increased potency in vegetarians and confer other beneficial effects, such as increased cognitive capacity and performance, compared to omnivores [11-12]. Recently, some studies have suggested that this might be due to an underlying creatine deficiency [13-14].

Creatine benefits

It is an important molecule in the maintenance of cellular adenosine triphosphate (ATP) homeostasis, the cell’s balancing act. ATP is essential for the upkeep of physiological processes and is the main transporter of energy for use in metabolism. During exercise, ATP levels in muscle cells deplete very quickly, leading to the accumulation of lactic acid and the onset of cramps.

In order to be able to replenish ATP quickly, muscle cells contain stores of phosphocreatine (PCr), a high-energy phosphate compound which can donate a phosphate group to ADP to quickly form ATP. This reaction is reversible, and during periods of low energy demands, ATP can be used to convert creatine back to phosphocreatine for later use [15-16]. This important “energy reservoir” is what allows it to improve exercise performance.

The use of creatine supplements in combination with strength training has been found to increase muscle fiber size [17-18] and improve performance in high-intensity repetitive exercise in several studies [19-21]. Other studies have found no beneficial effects on performance, however [22-25]. This inconsistency has recently been attributed to conflicting experimental designs, making the literature on the effects of creatine in humans difficult to interpret.

Creatine is an energy buffer

Due to its ability to act as an energy buffer, creatine has also been shown to be neuroprotective against low oxygen levels, preventing neuronal death by regulating NMDA receptor function – a critical channel for the development of the central nervous system – and reducing oxidative stress [26-27].

There is evidence that impairments in energy production may play a role in the development of neurodegenerative diseases such as Huntington’s [28-29], and a study exploring the effect of oral administration of creatine on brain lesions found that feeding animals a mixture containing 1% creatine lead to an 83% reduction in lesion volume after two weeks [30]. Other studies have found that it might protect the brain from damage after stroke [31-33], and increase overall cognitive performance in the elderly [34] but not in young adults [35].

Phosphocreatine has also been found to be cardioprotective in several studies, particularly during heart failure, where it becomes the primary source of energy for cardiac tissue [36-37]. During periods of low oxygen, the creatine kinase system plays an important role in cardiac recovery by providing high-energy phosphate to the heart muscles [38].

Last but not least, creatine may restore skin elasticity and reduce wrinkles by replenishing collagen stores [39-40] and protecting against UV-induced DNA damage [41-42]. One study using creatine as a topical skin cream (compounded with glycerol and guarana) found a significant skin-tightening effect and reduction of wrinkles over 6 weeks [43], while another study, which used topical creatine and folic acid, also found notable improvements in skin regeneration and elasticity [44].

Disclaimer

This article is only a very brief summary, is not intended as an exhaustive guide, and is based on the interpretation of research data, which is speculative by nature. This article is not a substitute for consulting your physician about which supplements may or may not be right for you. We do not endorse supplement use or any product or supplement vendor, and all discussion here is for scientific interest.

Source: Lifespan.io is a nonprofit advocacy organization and news outlet covering aging and rejuvenation research.

Author: Kali Carrigan

References

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[3] Lundsgaard, E. (1930). Weitere Untersuchungen iiber Muskelkontraktionen ohne Milchsiiurebildung. Biochem. Z. 227, 5,1.

[4] Fitch, C. D., & Sinton, D. W. (1964). A Study of Creatine Metabolism in Diseases Causing Muscle Wasting. Journal of Clinical Investigation, 43(3): 444–452.

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[39] Blatt T., et al. (2005). Stimulation of skin’s energy metabolism provides multiple benefits for mature human skin. Biofactors 25(1-4):179-85.

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[43] Peirano R.I., et al. (2011). Dermal penetration of creatine from a face-care formulation containing creatine, guarana and glycerol is linked to effective antiwrinkle and antisagging efficacy in male subjects. Journal of Cosmetic Dermatology 10(4):273-81

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