Creatine ( or ) is an
organic compound
In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...
with the nominal formula (H
2N)(HN)CN(CH
3)CH
2CO
2H. It exists in various modifications (
tautomer
Tautomers () are structural isomers (constitutional isomers) of chemical compounds that readily interconvert.
The chemical reaction interconverting the two is called tautomerization. This conversion commonly results from the relocation of a hydr ...
s) in solution. Creatine is found in
vertebrate
Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...
s where it facilitates recycling of
adenosine triphosphate
Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms of ...
(ATP), primarily in
muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
and
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
tissue. Recycling is achieved by converting
adenosine diphosphate
Adenosine diphosphate (ADP), also known as adenosine pyrophosphate (APP), is an important organic compound in metabolism and is essential to the flow of energy in living cells. ADP consists of three important structural components: a sugar backbon ...
(ADP) back to ATP via donation of
phosphate groups. Creatine also acts as a
buffer
Buffer may refer to:
Science
* Buffer gas, an inert or nonflammable gas
* Buffer solution, a solution used to prevent changes in pH
* Buffering agent, the weak acid or base in a buffer solution
* Lysis buffer, in cell biology
* Metal ion buffer
* ...
.
History
Creatine was first identified in 1832 when
Michel Eugène Chevreul
Michel Eugène Chevreul (31 August 1786 – 9 April 1889) was a French chemist and centenarian whose work influenced several areas in science, medicine, and art. His early work with animal fats revolutionized soap and candle manufacturing and led ...
isolated it from the basified water-extract of
skeletal muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
. He later named the crystallized precipitate after the
Greek word for meat, κρέας (''kreas''). In 1928, creatine was shown to exist in
equilibrium with
creatinine. Studies in the 1920s showed that consumption of large amounts of creatine did not result in its excretion. This result pointed to the ability of the body to store creatine, which in turn suggested its use as a dietary supplement.
In 1912,
Harvard University
Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...
researchers
Otto Folin and
Willey Glover Denis
Willey Glover Denis (February 26, 1879 – January 9, 1929) was an American biochemist and physiologist. She was noted particularly for her collaborations with Otto Folin, including studies of protein metabolism. She was a pioneer in the field ...
found evidence 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 ''
phosphocreatine
Phosphocreatine, also known as creatine phosphate (CP) or PCr (Pcr), is a phosphorylated form of creatine that serves as a rapidly mobilizable reserve of high-energy phosphates in skeletal muscle, myocardium and the brain to recycle adenosine tr ...
'' (creatine phosphate), and determined that creatine is a key player in the metabolism of
skeletal muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
. The substance creatine is naturally formed in vertebrates.
The discovery of phosphocreatine
was reported in 1927.
[ In the 1960s, creatine kinase (CK) was shown to phosphorylate ADP using phosphocreatine (PCr) to generate ATP. It follows that ATP, not PCr is directly consumed in muscle contraction. CK uses creatine to "buffer" the ATP/ADP ratio.
While creatine's influence on physical performance has been well documented since the early twentieth century, it came into public view following the ]1992 Olympics 1992 Olympics may refer to:
*1992 Summer Olympics, which were held in Barcelona, Spain
*1992 Winter Olympics
)
, nations = 64
, athletes = 1,801 (1313 men, 488 women)
, events = 57 in 6 sports (12 disciplines)
, opening = 8 ...
in Barcelona
Barcelona ( , , ) is a city on the coast of northeastern Spain. It is the capital and largest city of the autonomous community of Catalonia, as well as the second most populous municipality of Spain. With a population of 1.6 million within ci ...
. An August 7, 1992 article in ''The Times
''The Times'' is a British daily national newspaper based in London. It began in 1785 under the title ''The Daily Universal Register'', adopting its current name on 1 January 1788. ''The Times'' and its sister paper ''The Sunday Times'' (fou ...
'' reported that Linford Christie
Linford Cicero Christie (born 2 April 1960) is a Jamaican-born British former sprinter. He is the only British man to have won gold medals in the 100 metres at all four major competitions open to British athletes: the Olympic Games, the World ...
, the gold medal winner at 100 meters, had used creatine before the Olympics. An article in ''Bodybuilding Monthly'' named Sally Gunnell, who was the gold medalist in the 400-meter hurdles, as another creatine user. In addition, ''The Times'' also noted that 100 meter hurdler Colin Jackson began taking creatine before the Olympics.
left, relays phosphate to ADP.">Phosphocreatine relays phosphate to ADP.
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 (formerly Experimental & Applied Sciences) was a distributor of creatine nutritional supplements with approximately 300 staff, annual sales exceeding $300 million, and offices/distributors in 54 countries.
History
EAS was founded in Paci ...
(EAS) introduced the compound to the sports nutrition market under the name ''Phosphagen''. Research performed thereafter demonstrated that the consumption of high glycemic
The glycemic response to a food or meal is the effect that food or meal has on blood sugar (glucose) levels after consumption.Sadler M. Food, Glycaemic Response and Health. ILSI Europe Concise Monograph Series 2011:1-30Available from ILSI Europe ...
carbohydrates in conjunction with creatine increases creatine muscle stores.
left, The cyclic derivative creatinine exists in equilibrium with its tautomer and with creatine.
Metabolic role
Creatine is a naturally occurring non-protein compound and the primary constituent of phosphocreatine, which is used to regenerate ATP
ATP may refer to:
Companies and organizations
* Association of Tennis Professionals, men's professional tennis governing body
* American Technical Publishers, employee-owned publishing company
* ', a Danish pension
* Armenia Tree Project, non ...
within the cell. 95% of the human body's total creatine and phosphocreatine stores are found in skeletal muscle, while the remainder is distributed in the blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
, brain, testes, and other tissues. The typical creatine content of skeletal muscle (as both creatine and phosphocreatine) is 120 mmol per kilogram of dry muscle mass, but can reach up to 160 mmol/kg through supplementation. Approximately 1–2% of intramuscular creatine is degraded per day and an individual would need about 1–3 grams of creatine per day to maintain average (unsupplemented) creatine storage. An omnivorous diet provides roughly half of this value, with the remainder synthesized in the liver and kidneys.
Creatine is not an essential nutrient
A nutrient is a substance used by an organism to survive, grow, and reproduce. The requirement for dietary nutrient intake applies to animals, plants, fungi, and protists. Nutrients can be incorporated into cells for metabolic purposes or excret ...
. It is an amino acid derivative
In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. F ...
, naturally produced in the human body from the amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s glycine and arginine
Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...
, with an additional requirement for S-Adenosyl methionine
''S''-Adenosyl methionine (SAM), also known under the commercial names of SAMe, SAM-e, or AdoMet, is a common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. Although these anabolic reactions occur throug ...
(a derivative of methionine
Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical ro ...
) to catalyze the transformation of guanidinoacetate to creatine. In the first step of the biosynthesis
Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...
, the enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
arginine:glycine amidinotransferase (AGAT
EC:2.1.4.1
mediates the reaction of glycine and arginine to form guanidinoacetate
Glycocyamine (or guanidinoacetate) is a metabolite of glycine in which the amino group has been converted into a guanidine by guanylation (transfer of a guanidine group from arginine). In vertebrate organism it is then transformed into creatine by ...
. This product is then methylated by guanidinoacetate ''N''-methyltransferase (GAMT
EC:2.1.1.2
, using ''S''-adenosyl methionine as the methyl donor. Creatine itself can be phosphorylated by creatine kinase to form phosphocreatine
Phosphocreatine, also known as creatine phosphate (CP) or PCr (Pcr), is a phosphorylated form of creatine that serves as a rapidly mobilizable reserve of high-energy phosphates in skeletal muscle, myocardium and the brain to recycle adenosine tr ...
, which is used as an energy buffer in skeletal muscles and the brain. A cyclic form of creatine, called creatinine, exists in equilibrium with its tautomer
Tautomers () are structural isomers (constitutional isomers) of chemical compounds that readily interconvert.
The chemical reaction interconverting the two is called tautomerization. This conversion commonly results from the relocation of a hydr ...
and with creatine.
Phosphocreatine system
Creatine is transported through the blood and taken up by tissues with high energy demands, such as the brain and skeletal muscle, through an active transport system. The concentration of ATP
ATP may refer to:
Companies and organizations
* Association of Tennis Professionals, men's professional tennis governing body
* American Technical Publishers, employee-owned publishing company
* ', a Danish pension
* Armenia Tree Project, non ...
in skeletal muscle is usually 2–5 mM, which would result in a muscle contraction of only a few seconds. During times of increased energy demands, the phosphagen (or ATP/PCr) system rapidly resynthesizes ATP from ADP
Adp or ADP may refer to:
Aviation
* Aéroports de Paris, airport authority for the Parisian region in France
* Aeropuertos del Perú, airport operator for airports in northern Peru
* SLAF Anuradhapura, an airport in Sri Lanka
* Ampara Air ...
with the use of phosphocreatine
Phosphocreatine, also known as creatine phosphate (CP) or PCr (Pcr), is a phosphorylated form of creatine that serves as a rapidly mobilizable reserve of high-energy phosphates in skeletal muscle, myocardium and the brain to recycle adenosine tr ...
(PCr) through a reversible reaction catalysed by the enzyme creatine kinase (CK). The phosphate group is attached to an NH center of the creatine. In skeletal muscle, PCr concentrations may reach 20–35 mM or more. Additionally, in most muscles, the ATP regeneration capacity of CK is very high and is therefore not a limiting factor. Although the cellular concentrations of ATP are small, changes are difficult to detect because ATP is continuously and efficiently replenished from the large pools of PCr and CK. A proposed representation has been illustrated by Krieder et al. Creatine has the ability to increase muscle stores of PCr, potentially increasing the muscle's ability to resynthesize ATP from ADP to meet increased energy demands.
Creatine supplementation appears to increase the number of myonuclei
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscle ...
that satellite cells will 'donate' to damaged muscle fibers, which 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.
Genetic deficiencies
Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects. Clinically, there are three distinct disorders of creatine metabolism. Deficiencies in the two synthesis enzymes can cause L-arginine:glycine amidinotransferase deficiency caused by variants in '' GATM'' and guanidinoacetate methyltransferase deficiency
Guanidinoacetate methyltransferase deficiency (GAMT deficiency) is an autosomal recessive cerebral creatine deficiency that primarily affects the nervous system and muscles. It is the first described disorder of creatine metabolism, and results fro ...
, caused by variants in ''GAMT
Guanidinoacetate N-methyltransferase () is an enzyme that catalyzes the chemical reaction and is encoded by gene ''GAMT'' located on chromosome 19p13.3.
:S-adenosyl-L-methionine + guanidinoacetate \rightleftharpoons S-adenosyl-L-homocysteine + ...
''. Both biosynthetic defects are inherited in an autosomal recessive manner. A third defect, creatine transporter defect
Creatine transporter deficiency (CTD) is an inborn error of creatine metabolism in which creatine is not properly transported to the brain and muscles due to defective creatine transporters. CTD is an Sex linkage, X-linked disorder caused by patho ...
, is caused by mutations in ''SLC6A8
Sodium- and chloride-dependent creatine transporter 1 is a protein that in humans is encoded by the ''SLC6A8'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity ...
'' and inherited in a X-linked manner. This condition is related to the transport of creatine into the brain.
Vegetarians
Some studies suggest that total muscle creatine is significantly lower in vegetarians than non-vegetarians. It is postulated that this finding is due to an omnivorous diet being the primary source of creatine. Research shows that supplementation is needed to raise the concentration of creatine in the muscles of lacto-ovo vegetarian
Lacto-ovo vegetarianism or ovo-lacto vegetarianism is a type of vegetarianism which forbids animal flesh but allows the consumption of animal products such as dairy and eggs. Unlike pescetarianism, it does not include fish or other seafood. A ...
s and vegan
Veganism is the practice of abstaining from the use of animal product—particularly in diet—and an associated philosophy that rejects the commodity status of animals. An individual who follows the diet or philosophy is known as a vegan. Di ...
s up to non-vegetarian levels.
Studies have shown that they have lower creatine concentrations in muscle and blood, but not brain.
Pharmacokinetics
Most of the research to-date on creatine has predominantly focused on the pharmacological properties of creatine, yet there is a lack of research into the pharmacokinetics of creatine. Studies have not established pharmacokinetic parameters for clinical usage of creatine such as volume of distribution, clearance, bioavailability, mean residence time, absorption rate, and half life. A clear pharmacokinetic profile would need to be established prior to optimal clinical dosing.
Dosing
Loading phase
An approximation of 0.3 g/kg/day divided into 4 equal spaced intervals has been suggested since creatine needs may vary based on body weight. It has also been shown that taking a lower dose of 3 grams a day for 28 days can also increase total muscle creatine storage to the same amount as the rapid loading dose of 20 g/day for 6 days. However, a 28 day loading phase does not allow for ergogenic benefits of creatine supplementation to be realized until fully saturated muscle storage.
Supplementing creatine with carbohydrates or carbohydrates and protein has been shown to augment creatine retention.
This elevation in muscle creatine storage has been correlated with ergogenic benefits discussed in the research section. However, higher doses for longer periods of time are being studied to offset creatine synthesis deficiencies and mitigating diseases.
Maintenance phase
After the 5–7 day loading phase, muscle creatine stores are fully saturated and supplementation only needs to cover the amount of creatine broken down per day. This maintenance dose was originally reported to be around 2–3 g/day (or 0.03 g/kg/day), however, some studies have suggested 3–5 g/day maintenance dose to maintain saturated muscle creatine.
Absorption
Endogenous serum or plasma creatine concentrations in healthy adults are normally in a range of 2–12 mg/L. A single 5 gram (5000 mg) oral dose in healthy adults results in a peak plasma creatine level of approximately 120 mg/L at 1–2 hours post-ingestion. Creatine has a fairly short elimination half life, averaging just less than 3 hours, so to maintain an elevated plasma level it would be necessary to take small oral doses every 3–6 hours throughout the day.
Clearance
It has been shown that once supplementation of creatine stops, muscle creatine stores return to baseline in 4–6 weeks.
Exercise and sport
Creatine supplements are marketed in ethyl ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides are ...
, gluconate
Gluconic acid is an organic compound with molecular formula C6H12O7 and condensed structural formula HOCH2(CHOH)4COOH. It is one of the 16 stereoisomers of 2,3,4,5,6-pentahydroxyhexanoic acid.
In aqueous solution at neutral pH, gluconic acid fo ...
, monohydrate
In chemistry, a hydrate is a substance that contains water or its constituent elements. The chemical state of the water varies widely between different classes of hydrates, some of which were so labeled before their chemical structure was underst ...
, and nitrate
Nitrate is a polyatomic ion
A polyatomic ion, also known as a molecular ion, is a covalent bonded set of two or more atoms, or of a metal complex, that can be considered to behave as a single unit and that has a net charge that is not zer ...
forms.
Creatine supplementation for sporting performance enhancement is considered safe for short-term use but there is a lack of safety data for long term use, or for use in children and adolescents.
A 2018 review article in the ''Journal of the International Society of Sports Nutrition'' said that creatine monohydrate might help with energy availability for high-intensity exercise.
Creatine use can increase maximum power and performance in high-intensity anaerobic repetitive work (periods of work and rest) by 5% to 15%. Creatine has no significant effect on aerobic endurance, though it will increase power during short sessions of high-intensity aerobic exercise.
A survey of 21,000 college athletes showed that 14% of athletes take creatine supplements to try to improve performance. Non-athletes report taking creatine supplements to improve appearance.
Research
Cognitive performance
Creatine is reported to have a beneficial effect on brain function and cognitive processing, although the evidence is difficult to interpret systematically and the appropriate dosing is unknown. The greatest effects appears to be in individuals who are stressed (due, for instance, to sleep deprivation
Sleep deprivation, also known as sleep insufficiency or sleeplessness, is the condition of not having adequate duration and/or quality of sleep to support decent alertness, performance, and health. It can be either chronic or acute and may vary ...
) or cognitively impaired.
Muscular disease
A meta-analysis found that creatine treatment increased muscle strength in muscular dystrophies
Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily affe ...
, and potentially improved functional performance. Creatine treatment does not appear to improve muscle strength in people who have metabolic myopathies. High doses of creatine lead to increased muscle pain and an impairment in activities of daily living when taken by people who have McArdle disease
Glycogen storage disease type V (GSD5, GSD-V), also known as McArdle's disease, is a metabolic disorder, one of the metabolic myopathies, more specifically a muscle glycogen storage disease, caused by a deficiency of myophosphorylase. Its inci ...
.
According to a clinical study focusing on people with various muscular dystrophies, using a pure form of creatine monohydrate can be beneficial in rehabilitation after injuries and immobilization.
Mitochondrial diseases
Parkinson's disease
Creatine's impact on mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
l function has led to research on its efficacy and safety for slowing Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
. As of 2014, the evidence did not provide a reliable foundation for treatment decisions, due to risk of bias, small sample sizes, and the short duration of trials.
Huntington's disease
Several primary studies have been completed but no systematic review on Huntington's disease
Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an unst ...
has been completed yet.
ALS
It is ineffective as a treatment for amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...
.
Adverse effects
Side effects include:
* Weight gain due to extra water retention to the muscle
* Potential muscle cramps / strains / pulls
* Upset stomach
* Diarrhea
* Dizziness
One well-documented effect of creatine supplementation is weight gain within the first week of the supplement schedule, likely attributable to greater water retention due to the increased muscle creatine concentrations by means of osmosis
Osmosis (, ) is the spontaneous net movement or diffusion of solvent molecules through a selectively-permeable membrane from a region of high water potential (region of lower solute concentration) to a region of low water potential (region of ...
.
A 2009 systematic review discredited concerns that creatine supplementation could affect hydration status and heat tolerance and lead to muscle cramping and diarrhea.
Renal function
A 2019 systematic review published by the National Kidney Foundation investigated whether creatine supplementation had adverse effects on renal function. They identified 15 studies from 1997–2013 that looked at standard creatine loading and maintenance protocols of 4–20 g/day of creatine versus placebo. They utilized serum creatinine, creatinine clearance, and serum urea levels as a measure of renal damage. While in general creatine supplementation resulted in slightly elevated creatinine levels that remained within normal limits, supplementation did not induce renal damage (P value< 0.001). Special populations included in the 2019 Systematic review included type 2 diabetic patients and post-menopausal women, bodybuilders, athletes, and resistance trained populations. The study also discussed 3 case studies where there were reports that creatine affected renal function.
In a joint statement between the American College of Sports Medicine
The American College of Sports Medicine (ACSM), headquartered in Indianapolis, Indiana, is a sports medicine and exercise science membership organization. Founded in 1954, ACSM holds conferences, publishes books and journals, and offers certific ...
, Academy of Nutrition and Dietetics, and Dietitians in Canada on performance enhancing nutrition strategies, creatine was included in their list of ergogenic aids and they do not list renal function as a concern for use.
The most recent position stand on creatine from the ''Journal of International Society of Sports Nutrition'' states that creatine is safe to take in healthy populations from infants to the elderly to performance athletes. They also state that long term (5 years) use of creatine has been considered safe.
It is important to mention that kidneys themselves, for normal physiological function, need phosphocreatine and creatine and indeed kidneys express significant amounts of creatine kinases (BB-CK and u-mtCK isoenzymes). At the same time, the first of two steps for endogenous creatine synthesis takes place in the kidneys themselves. Patients with kidney disease and those undergoing dialysis treatment generally show significantly lower levels of creatine in their organs, since the pathological kidneys are both hampered in creatine synthesis capability and are in back-resorption of creatine from the urine in the distal tubules. In addition, dialysis patients lose creatine due to wash out by the dialysis treatment itself and thus become chronically creatine depleted. This situation is exacerbated by the fact that dialysis patients generally consume less meat and fish, the alimentary sources of creatine. Therefore, to alleviate chronic creatine depletion in these patients and allow organs to replenish their stores of creatine, it was recently proposed to supplement dialysis patients with extra creatine, preferably by intra-dialytic administration. Such a supplementation with creatine in dialysis patients is expected to significantly improve the health and quality of the patients by improving muscle strength, coordination of movement, brain function and to alleviate depression and chronic fatigue that are common in these patients.
Safety
Contamination
A 2011 survey of 33 supplements commercially available in Italy found that over 50% of them exceeded the European Food Safety Authority recommendations in at least one contaminant. The most prevalent of these contaminants was creatinine, a breakdown product of creatine also produced by the body. Creatinine was present in higher concentrations than the European Food Safety Authority recommendations in 44% of the samples. About 15% of the samples had detectable levels of dihydro-1,3,5-triazine or a high dicyandiamide
2-Cyanoguanidine is a nitrile derived from guanidine. It is a dimer of cyanamide, from which it can be prepared. 2-Cyanoguanidine is a colourless solid that is soluble in water, acetone, and alcohol, but not nonpolar organic solvents.
Production ...
concentration. Heavy metals contamination was not found to be a concern, with only minor levels of mercury being detectable. Two studies reviewed in 2007 found no impurities.
Interactions
Creatine taken with medications that can harm the kidney can increase the risk of kidney damage:
*Nonsteroidal anti-inflammatory drug
Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
s (NSAIDs) – some examples are ibuprofen
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arte ...
(Motrin, Advil) and naproxen (Aleve)
*Diuretic
A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics in ...
s (water pills) – an example is furosemide
Furosemide is a loop diuretic medication used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It may also be used for the treatment of high blood pressure. It can be taken by injection into a vein or by mouth ...
(Lasix)
*Cimetidine
Cimetidine, sold under the brand name Tagamet among others, is a histamine H2 receptor antagonist that inhibits stomach acid production. It is mainly used in the treatment of heartburn and peptic ulcers.
The development of longer-acting H2 rec ...
(Tagamet)
*Probenicid
Probenecid, also sold under the brand name Probalan, is a medication that increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia.
Probenecid was developed as an alternative to caronamide to competitive ...
A National Institutes of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
study suggests that caffeine
Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class. It is mainly used recreationally as a cognitive enhancer, increasing alertness and attentional performance. Caffeine acts by blocking binding of adenosine t ...
interacts with creatine to increase the rate of progression of Parkinson's Disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
.
Food and cooking
When creatine is mixed with protein and sugar at high temperatures (above 148 ℃), the resulting reaction produces carcinogenic heterocyclic amine
Heterocyclic amines, also sometimes referred to as HCAs, are chemical compounds containing at least one heterocyclic ring, which by definition has atoms of at least two different elements, as well as at least one amine (nitrogen-containing) group. ...
s (HCAs). Such a reaction happens when grilling or pan-frying meat. Creatine content (as a percentage of crude protein) can be used as an indicator of meat quality.
Dietary considerations
Creatine-monohydrate is suitable for vegetarians and vegans, as the raw materials used for the production of the supplement have no animal origin.
See also
* Beta-Alanine
* Creatine methyl ester
Creatine methyl ester is the methyl ester derivative of the amino acid creatine. It can be prepared by the esterification of creatine with methanol.Process for preparation of creatine ester hydrochloride. Sun, Leda; Zhao, Qinhu; Liu, Ruirui. (2007 ...
References
External links
Creatine bound to proteins
in the PDB
{{Authority control
Amino acids
Bodybuilding supplements
Dietary supplements
Ergogenic aids
Guanidines
Myostatin inhibitors