Creatine: Benefits, Side Effects, and Research
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 , 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 .
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].
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 . Other studies have found that it might protect the brain from damage after stroke [31-33], and increase overall cognitive performance in the elderly  but not in young adults .
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 .
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 , while another study, which used topical creatine and folic acid, also found notable improvements in skin regeneration and elasticity .
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.
 Folin, Otto; Denis, W. (1912). Protein metabolism from the standpoint of blood and tissue analysis. Journal of Biological Chemistry, 12 (1): 141–61.
 Lohmann, K. (1934). Ober die enzymatische Aufspaltung der Kreatinphosphore; zugleich ein Beitrag zum Chemismus der Muskelkontratraktion. Biochem. Z. 271, 264.
 Lundsgaard, E. (1930). Weitere Untersuchungen iiber Muskelkontraktionen ohne Milchsiiurebildung. Biochem. Z. 227, 5,1.
 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.
 Vignos, P.J.JR & Warner, J.L. (1963). Glycogen, creatine, and high energy phosphate in human muscle disease. Journal of Laboratory and Clinical Medicine 62: 579.
 Williams M.H., Kreider R.B., Branch J.D. (1999). Creatine: The Power Supplement. Human Kinetics, Champaign, IL.
 Brosnan J.T., da Silva R.P., Brosnan M.E. (2011). The metabolic burden of creatine synthesis. Amino Acids 40 (5): 1325–31.
 Cooper R., Naclerio F., Allgrove J., Jimenez A. (2012). Creatine supplementation with specific view to exercise/sports performance: an update. Journal of the International Society of Sports Nutrition 9 (1): 33.
 Sinha R., Cross A.J., Graubard B.I., et al. (2009). Meat intake and mortality: a prospective study of over half a million people. Archive of Internal Medicine 169(6):562–71.
 Larsson S.C. & Orsini N. (2014). Red meat and processed meat consumption and all-cause mortality: a meta-analysis. American Journal of Epidemiology 179: 282–289.
 Lukaszuk J.M., et al. (2005). Effect of a defined lacto-ovo-vegetarian diet and oral creatine monohydrate supplementation on plasma creatine concentration. Journal of Strength and Conditioning Research 19(4):735-40.
 Maccormick V.M., et al. (2004). Elevation of creatine in red blood cells in vegetarians and nonvegetarians after creatine supplementation. Canadian Journal of Applied Physiology 29(6):704-13.
 Benton D., Donohoe R. (2011). The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores. British Journal of Nutrition 105(7):1100-5.
 Rae C., et al. (2003). Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proceedings. Biological Sciences 270(1529): 2147-50.
 Meyer RA, et al. (1984). A simple analysis of the “phosphocreatine shuttle”. American Journal of Physiology 246:C365–C377
 Bessman S.P., Carpenter C.L. (1985). “The creatine-creatine phosphate energy shuttle.” Annual Review of Biochemistry 54:831–862
 Volek et al. (2004). The effects of creatine supplementation on muscular performance and body composition responses to short-term resistance training overreaching. European Journal of Applied Physiology 91(5-6):628-37.
 Olsen et al. (2006). Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training. Journal of Physiology 573(Pt 2): 525-34.
 Dawson B., Cutler M., Moody A., Lawerence S., Goodman C., Randall N. (1995). Effects of oral creatine loading on single and repeated maximal short sprints. Australian Journal of Science and Medicine in Sports 27, 56-61
 Meir R. (1995) Practical application of oral creatine supplementation in professional rugby league: A case study. Australian Strength and Conditioning Coach 3, 6-10.
 Jacobs I., Bleue S., Goodman J. (1997) Creatine ingestion increases anaerobic capacity and maximum accumulated oxygen deficit. Canadian Journal of Applied Physiology 22, 231-243
 Barnett C., Hinds M., Jenkins D.G. (1995) Effects of oral creatine loading on multiple sprint cycle performance. Australian Journal of Science and Medicine in Sports 28, 35-39
 Snow R.J., McKenna M.J., Selig S.E., Kemp J., Stathis C.G., Zhao S. (1998) Effect of creatine supplementation on sprint exercise performance and muscle metabolism. Journal of Applied Physiology 84, 1667-1673
 Deutekom M.J., Beltman G.M., De Ruiter C.J., De Koning J.J., De Haan A. (2000) No acute effects of short-term creatine supplementation on muscle properties and sprint performance. European Journal of Applied Physiology 82, 23-229
 Biwer C.J., Jensen R.L., Schmidt W.D., Watts P.B. (2003) The effect of creatine on treadmill running with high-intensity intervals. Journal of Strength and Conditioning Research 17, 439-445
 Bird, S. P. (2003). Creatine Supplementation and Exercise Performance: A Brief Review. Journal of Sports Science & Medicine, 2(4), 123–132.
 Genius J., et al. (2012). Creatine protects against excitoxicity in an in vitro model of neurodegeneration . PLoS One 7(2).
 Matthews R.T., et al. (1999). Creatine and cyclocreatine attenuate MPTP neurotoxicity. Exp Neurol.
 Tabrizi S.J., et al. (2005). High-dose creatine therapy for Huntington disease: a 2-year clinical and MRS study. Neurology 64(9):1655–1656
 Matthews et al. (1998). Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington’s disease. Journal of Neuroscience 18:156–163.
 Balestrino et al. (1999). Exogenous creatine delays anoxic depolarization and protects from hypoxic damage: dose-effect relationship. Brain Research, 816, 124–130.
 Dechent et al., (1999). Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. American Journal of Physiology 277(3 Pt 2):R698-704.
 Balestrino et al. (2002). Role of Creatine and Phosphocreatine in Neuronal Protection From Anoxic and Ischemic Damage. Amino Acids 23 (1-3), 221-229.
 McMorris T., et al. (2007). Creatine supplementation and cognitive performance in elderly individuals. Neuropsychology, Development, and Cognition, Section B: Aging Neuropsychology and Cognition 14(5):517-28.
 Rawson E.S., et al. (2008). Creatine supplementation does not improve cognitive function in young adults. Physiological Behaviour 95(1-2):130-4
 Akki A., et al. (2012). Creatine kinase overexpression improves ATP kinetics and contractile function in postischemic myocardium. American Journal of Physiology: Heart and Circulatory Physiology 303(7).
 Rodriguez P., et al. (2003). Importance of creatine kinase activity for functional recovery of myocardium after ischemia-reperfusion challenge. Journal of Cardiovascular Pharmacology 41(1):97-104.
 Bittl J.A., Balschi J.A., Ingwall J.S. (1987). Contractile failure and high-energy phosphate turnover during hypoxia: 31P-NMR surface coil studies in living rat. Circulation Research 60(6):871-8.
 Neubauer S, et al. (1988). Velocity of the creatine kinase reaction decreases in postischemic myocardium: a 31P-NMR magnetization transfer study of the isolated ferret heart. Circulatory Research 63(1):1-15.
 Blatt T., et al. (2005). Stimulation of skin’s energy metabolism provides multiple benefits for mature human skin. Biofactors 25(1-4):179-85.
 El-Domyati M., et al. (2002). Intrinsic aging vs. photoaging: a comparative histopathological, immunohistochemical, and ultrastructural study of skin. Experimental Dermatology 11(5):398-405.
 Scharffetter-Kochanek K., et al. (1997). UV-induced reactive oxygen species in photocarcinogenesis and photoaging. Biological Chemistry 378(11):1247-57.
 Lenz H., et al. (2005). The creatine kinase system in human skin: protective effects of creatine against oxidative and UV damage in vitro and in vivo. Journal of Investigative Dermatology 124(2):443-52.
 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
 Knott A., et al. (2008). A novel treatment option for photoaged skin. Journal of Cosmetic Dermatology 7(1):15-22