Creatine

from Wikipedia, the free encyclopedia
Structural formula
Structural formula of creatine
General
Surname Creatine
other names
  • Creatine
  • Creatine (English)
  • N- amidinosarcosine
  • N - (Aminoiminomethyl) - N -methyl-glycine
  • α-methylguanidinoacetic acid
Molecular formula C 4 H 9 N 3 O 2
Brief description

white solid

External identifiers / databases
CAS number
  • 57-00-1 (anhydrous)
  • 6020-87-7 (mono hydrate )
EC number 200-306-6
ECHA InfoCard 100,000,278
PubChem 586
ChemSpider 566
DrugBank DB00148
Wikidata Q223600
properties
Molar mass 131.13 g mol −1
Physical state

firmly

density

1.33 g cm −3 (anhydrous)

Melting point

303 ° C (monohydrate, decomp.)

solubility
  • poorly soluble in water (17 g l −1 , monohydrate)
  • almost insoluble in ethanol and diethyl ether (monohydrate)
safety instructions
GHS labeling of hazardous substances
no GHS pictograms
H and P phrases H: no H-phrases
P: no P-phrases
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Creatine or creatine (English) (from Greek κρέας kreas , German 'meat' ) is a substance that is found in vertebrates and the like. a. contributes to the supply of the muscles with energy. Creatine is synthesized in the kidneys , the liver and the pancreas , is formally derived from the amino acids glycine , arginine and methionine and is about 90% present in skeletal muscles . Creatine was discovered in 1832 by Eugène Chevreul as an ingredient in meat broth. The German chemist Justus von Liebig identified creatine as a component in the meat of various mammal species in 1847.

In food and intake

Creatine is mainly found in meat and fish in amounts of around 2 to 7 g per kg of food, breast milk and cow's milk contain moderate amounts of creatine, while fruits and vegetables only contain traces of it. In animals, creatine occurs primarily in the skeletal muscles , the heart muscles and the brain , but in smaller quantities in practically all cells of the body. In general, white, glycolytic muscle fibers (sprint muscles) contain more creatine than red, oxidative muscle fibers (endurance muscles). Sausage products have a lower creatine content compared to fresh meat. During the preparation and storage of sausages can be a significant proportion of creatine by the action of heat and storage in a moist environment in the degradation product of creatine in to be converted. The non-enzymatic, spontaneous conversion rate of creatine to creatinine (chemical equilibrium reaction), which takes place particularly in solution, is strongly dependent on the pH value, the temperature and the time. Under favorable circumstances, creatine in an aqueous solution can remain stable for hours to days - but not for months. Therefore, there are no beverages with dissolved creatine on the market.

Since creatine is temperature-sensitive, a certain amount of creatine is also lost when meat is roasted at high temperatures through the conversion into creatinine described above. The highest concentrations of creatine per gram in foods include fresh fish or dried stockfish and fresh or dried meat . (see table below) In humans, too, creatine is mainly stored in the skeletal muscles. The body of a 75 kg adult contains between 120 and 150 g total creatine, i.e. H. of phospho-creatine (PCr, energetically charged form of creatine) plus creatine itself. In the resting body, phospho-creatine and creatine (Cr) are found in a ratio of around ⅔ PCr to ⅓ Cr, mainly in the skeletal muscles, in the heart muscle and in the Brain, but also in smaller quantities in other organs and cells. In the fast, white and predominantly glycolytic muscle fibers z. B. one finds a total creatine concentration of up to 50 mmol / l wet muscle weight or around 125-145 mmol / kg dry muscle mass Synthetic creatine is - just like naturally contained in food - via the intestine into the blood of the hepatic portal vein absorbed and then reaches the consuming organs and tissues via the bloodstream .

Creatine content of various foods (raw state)
Food Creatine content g / kg
herring 6.5-10.0
salmon 4.5
tuna 4.0 and 2.7-6.5, respectively
cod 3.0
plaice 2.0
pork meat 5.0
beef 4.5
milk 0.1
cranberry 0.02

biosynthesis

Synthesis of creatine from guanidinoacetate , catalyzed by guanidinoacetate-N-methyltransferase (GAMT)

Creatine is also produced in the human body in amounts of 1 to 2 g per day by the liver , kidneys and pancreas . About half of the daily required amount of creatine of approx. 1.5 to 2 g for adults is mainly produced in the liver from guanidinoacetate. Guanidinoacetate, for its part, is synthesized from the amino acids arginine and glycine by the L- arginine: glycine amidinotransferase (AGAT, EC  2.1.4.1 ) mainly in the kidneys and pancreas. For the methylation of guanidinoacetate, the enzyme guanidinoacetate N -methyl transferase ( GAMT , EC  2.1.1.2 ) and an activated form of the amino acid methionine , S- adenosyl methionine ( SAM ), are required. The latter reaction (see reaction scheme opposite) takes place mainly in the liver. Although the amino acids arginine, glycine and methionine are needed for the synthesis of creatine, creatine itself is not an amino acid, but a so-called guanidinium compound with a central carbon to which three nitrogen atoms are bound. The creatine produced in the body passes from the liver into the blood and from there to the target organs, e.g. B. skeletal muscles, heart muscle, brain, nerves, retina of the eye etc.

Chemical stability

Creatine can be stored for several years at room temperature and in a dry place. Instabilities show up when creatine is dissolved in water. The degree of creatine disintegration in aqueous solutions does not depend on the concentration, but on the pH value . In general, the lower the pH and the higher the temperature, the faster the breakdown. Creatine is relatively stable in solutions with neutral pH (6.5 to 7.5). A decrease in pH results in an increased rate of disintegration. When stored at temperatures of 25 degrees, creatine breaks down significantly after three days: 4% at a pH value of 5.5, 12% at a pH value of 4.5 and 21% at a pH value of 3.5 . In aqueous solutions, creatine breaks down to creatinine during storage at room temperature within several days , while the breakdown is reduced when refrigerated. So if creatine is not consumed directly after it has been dissolved in water or other drinkable solutions, it should be stored at low temperatures to counteract its breakdown. The breakdown of creatine can also be reduced or even stopped if the pH value is either reduced below 2.5 or if the pH value is increased. A very high pH value results in the deprotonation of the carboxylic acid group to the carboxylate , the reactivity of which towards nucleophiles is reduced compared to the carboxylic acid group . As a result, the decay process is slowed down by making the intramolecular cyclization more difficult. A very low pH value (below 2.5) leads to protonation of the guanidine functionality of the creatine molecule and thus to a decrease in its nucleophilicity . The consequence of this is that the intramolecular cyclization to creatinine is avoided. This effect also takes place under the acidic conditions in the stomach, which is why the breakdown into creatinine is halted. The conversion of creatine to creatinine in the gastrointestinal tract is therefore minimal, regardless of the intake time.

Physiological importance

Functions and effects in the human body

Structural formula of creatine phosphate

Creatine in the form of creatine phosphate (also phosphocreatine , PCr ) is required primarily for muscle contraction , but also for brain and nerve function . Creatine phosphate provides the phosphoryl group that is used to convert the adenosine diphosphate ( ADP ) formed during contraction back into adenosine triphosphate ( ATP ). In resting cells, around 60% of creatine occurs as phosphocreatine (energy source) and 40% as free creatine (energy precursor). The amount of creatine stored in the human body is 120 to 150 g in an adult, around 1.5–2% of total creatine is excreted as creatinine per day via the kidneys with the urine. This does not apply to sausages where the majority of the creatine has been broken down to creatinine through processing and storage; z. For example, when curing and drying a ham, around 75% of its creatine is lost during the first ten months (raw ham).

Creatine is necessary for the normal development of the human body and an optimal function of the body organs (muscles, brain, nerves, visual and hearing processes as well as reproduction). A supplementation with creatine can in terms of modified food (stress, high performance) and nutritional conditions make sense and displayed.

Creatine is necessary for the normal development of the organism, especially the brain during embryonic development and the early childhood phase, as well as for the normal physiological function of muscles and other body organs. Experimental animals in which the creatine content in muscles and brain was reduced by feeding a creatine analogue (β-guanidinyl propionic acid, GPA ) show clear pathological disorders in muscle and brain functions. In addition, transgenic test animals that no longer express creatine kinase (CK) show serious pathophysiological phenotypes, depending on which of the four creatine kinase isoforms is missing in the muscles and / or the brain.

People with creatine deficiency syndrome , with genetic defects either in the two enzymes involved in endogenous creatine synthesis ( AGAT and GAMT ) or in the creatine transporter , the protein that transports creatine to target cells, show severe neurological and neuromuscular problems pathological disorders, e.g. B. poorly developed muscles, developmental disorders, inability to learn to speak, epilepsy , autism , intellectual disabilities. This proves that a sufficient supply of creatine to the organism, together with the presence of creatine kinase, is essential for the normal development and function of the body organs.

Creatine requirement with a low-meat and meat-free diet

Vegetarians and elderly people who eat little or no meat can ingest small amounts of creatine (a maximum of 20% of the creatine ingested from mixed diets) with dairy products. Babies laying on soy are fed-based milk substitute, take just as vegans to no creatine in the diet. These groups of people have a significantly lower creatine content in the blood plasma than omnivores and synthesize their creatine requirements themselves. Older people can often have a low intake of essential amino acids and vitamin B 12 , which are required for creatine synthesis.

Therapeutic use

In medicine , creatine is used as an auxiliary therapy in the treatment of various muscle diseases such as B. used in muscular dystrophy to improve muscle growth and muscle strength. A number of animal and clinical studies with patients with various neuro-muscular and neuro-degenerative diseases such as: B. Parkinson's or Huntington's disease and amyotrophic lateral sclerosis (ALS) have shown the potential of creatine as a valuable additional therapy. Further clinical trials with larger patient numbers are being conducted primarily in the United States.

Creatine in Sports

Opportunities to increase performance through creatine supplementation

A healthy body produces many of the substances necessary for the maintenance of the body's functionality itself or takes in sufficient amounts with a balanced diet. Nevertheless, the additional intake of creatine has proven to be useful or at least not disadvantageous in a few sports. However, the amounts of additional intake, which are often given very high, should be questioned. After all, the intake of 5 g of creatine corresponds to the intake of 1.1 kg of raw beef.

Creatine supplementation has been shown to be effective both for increasing short-term performance and increasing maximum muscle strength, for example in weightlifting or sprinting, and for reducing cell damage in endurance sports such as marathons. This can also increase the training volume. In contrast to carnitine , for example , creatine is absorbed by the muscles, and phosphorylation of the creatine absorbed in this way increases the phospho-creatine (PCr) concentration and thus also the ratio of PCr / ATP, which improves the cellular energy status of the muscles. A 2006 study showed that creatine supplementation combined with strength training can increase exercise-induced increases in the number of satellite cells and myonuclei in human skeletal muscles, resulting in increased muscle fiber growth. This growth of the glycolytic, fast type II fibers and the oxidative, slow type I fibers is accompanied by an increase in muscle strength, which affects both the sprint and endurance fibers .

The European Food Safety Authority (EFSA) has officially recognized so-called health claims in a declaration for creatine, in contrast to most other dietary supplements . Put simply, these accepted health claims for creatine state that creatine supplementation leads to an increase in muscle mass and muscle strength as well as muscle performance, especially during very intense and repetitive activities. A daily intake of 3 g creatine is specified as a condition for use to increase performance.

In an official position paper of the International Society for Sports Nutrition by an international panel of experts, these and other advantages of creatine supplementation are listed based on a large number of scientific publications.

In order to renew the reserves of the energy carrier ATP, the muscles mainly use phospho-creatine (synonym creatine phosphate), especially in the first minute of activity. The nutritionist Andreas Hahn from the University of Hanover judges in his book Dietary Supplements:

“The possible meaning of creatine gifts relates exclusively to people with vigorous sporting activities that are pursued with great zeal. Due to conflicting study results, however, supplementation with creatine cannot be recommended. A short-term supplementation of creatine (up to 8 weeks) in amounts of about 20 g / day in the first week and 3 g / day in the maintenance phase is considered harmless. "

Continuous supplementation (taking creatine over a longer period of time) is also considered harmless today. After a period of four weeks after the end of creatine supplementation, the muscular content falls back to the initial value.

Great leaps in performance, as they are often advertised in exaggerated proportions by the supplement industry for food supplements , are not to be expected from supplementation with creatine. Particularly in strength training, the main focus should be on the greatest possible training intensity as well as the higher training cadence observed and published by many athletes and better recovery and nutrition.

Side effects of creatine supplementation

In individual cases and practically only during the normally unnecessary high dose phase (4 × 5 g creatine, i.e. a total of 20 g creatine per day for 7 to 10 days), creatine can lead to flatulence or mild diarrhea . Occasionally, users react with muscle cramps . However, scientific studies with a large number of athletes show that these side effects are largely based on unverified individual observations and that creatine does not cause significant gas, muscle cramps or injury. During the high dose phase, there may also be a weight gain of 1 to 3 kg. This is mainly due to water retention, because sodium and chloride ions simultaneously enter the cell with the creatine via the creatine transporter, which then leads to water retention . Gradually, the increased water uptake in the muscles due to osmotic effects normalizes , and there is an effective increase in muscle mass in the course of creatine supplementation, which is accompanied by a 10 to 20 percent increase in muscle strength.

The European Food Safety Authority (EFSA) published an opinion in 2004, according to which a daily intake of 3 g creatine is risk-free, provided the creatine ingested - especially with regard to contamination with dicyandiamide and dihydro-1,3,5-triazine derivatives and heavy metals - of sufficient purity (at least 99.95%). The alleged harmfulness of creatine to the kidneys, which has been mentioned again and again in the press, began in 1998 and is based on data from a case study in which creatine supplementation negatively affected the glomerular filtration rate of the kidney in a 25-year-old man who had previously suffered a disease kidney function suffered. A few days later, the French sports magazine L'Équipe spread the information that creatine supplementation was generally harmful to the kidneys. Various European media picked up the news and reported the same thing. The influence of creatine supplementation on clinical parameters, in particular those relating to liver and kidney function, has since been investigated in large-scale studies, with no negative effects being found. A comparative study published in 2008 by the University of Munich examined the blood and urine of 60 elderly Parkinson's patients over a period of two years. 40 patients received a creatine supplement with a daily dose of 4 g, the other 20 a placebo . Although there was an increase in serum creatine in the creatine group, all other markers of tubular or glomerular kidney function remained normal, suggesting unchanged kidney function. Gastrointestinal complaints were the main undesirable effects. The 2011 review by Kim et al. recommends that daily doses> 3–5 g should not be consumed by people with already impaired kidney function or at risk of it (given for example in diabetes mellitus, high blood pressure and reduced glomerular filtration rate ).

At this point it should be pointed out that the kidneys themselves need phospho-creatine and creatine for their normal function and accordingly also express the enzyme creatine kinase. In addition, the first of the two endogenous synthesis steps for the production of the body's own creatine takes place in the kidneys. Thus, the repeatedly wrongly cited danger of creatine for the kidneys can be clearly denied. On the contrary, since kidney patients and dialysis patients have less total body creatine, because 1) the diseased kidney can contribute less to the endogenous creatine synthesis, 2) because chronically dialyzed patients lose their own creatine through leaching and 3) dialysis patients consume little fish and meat and thus have a nutritional deficiency of creatine, it has recently been suggested to supplement these creatine-depleted patients with creatine so that the body's own pools of creatine in muscles, heart and brain would normalize again and the patients feel stronger and less tired and depressed , d. that is, their quality of life would be significantly improved.

An article by the Mayo Clinic from 2013 pointed out possible side effects and adverse interactions (e.g. with caffeine ) and also referred to the advice of the American health authority FDA to consult a doctor before use.

literature

Web links

Wikibooks: Creatine Phosphate Biosynthesis  - Learning and Teaching Materials

Individual evidence

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