Creatine

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Creatine ( or ) is a nitrogenous organic acid that occurs naturally in vertebrates. Its main role is to facilitate recycling of adenosine triphosphate (ATP), the energy currency of the cell, primarily in muscle and brain tissue. This is achieved by recycling adenosine diphosphate (ADP) to ATP via donation of phosphate groups. Creatine also acts as a pH buffer in tissues.

Creatine synthesis primarily occurs in the liver and kidneys. On average, it is produced endogenously at an estimated rate of about 8.3 mmol or 1 gram per day in young adults. Creatine is also obtained through the diet at a rate of about 1 gram per day from an omnivorous diet. Most of the human body's total creatine and phosphocreatine stores are found in skeletal muscle, while the remainder is distributed in the blood, brain, and other tissues.

Creatine was identified in 1832 when Michel Eugène Chevreul isolated it from the basified water-extract of skeletal muscle. He later named the crystallized precipitate after the Greek word for meat, ????? (kreas). In solution, creatine is in equilibrium with creatinine. Creatine is a derivative of the guanidinium cation.

Video Creatine

Biosynthesis

Creatine is not an essential nutrient as it is naturally produced in the human body from the amino acids glycine and arginine. In the first step of the biosynthesis these two amino acids are combined by the enzyme arginine:glycine amidinotransferase (AGAT, EC:2.1.4.1) to form guanidinoacetate, which 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, which is used as an energy buffer in skeletal muscles and the brain.

Synthesis primarily takes place in the kidney and liver, with creatine then being transported to the muscles via the blood. The majority of the human body's total creatine and phosphocreatine stores is located in skeletal muscle, while the remainder is distributed in the blood, brain, and other tissues. Typically, creatine is produced endogenously at an estimated rate of about 8.3 mmol or 1 gram per day in young adults. Creatine is also obtained through the diet at a rate of about 1 gram per day from an omnivorous diet. Some small studies suggest that total muscle creatine is significantly lower in vegetarians than non-vegetarians, as expected since vegetables are not a primary source of creatine. However, subjects happened to show the same levels after using supplements.

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 and guanidinoacetate methyltransferase deficiency. Both biosynthetic defects are inherited in an autosomal recessive manner. A third defect, creatine transporter defect, is caused by mutations in SLC6A8 and inherited in a X-linked manner. This condition is related to the transport of creatine into the brain.

Maps Creatine

Phosphocreatine system

Creatine, which is synthesized in the liver and kidneys, 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 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 with the use of phosphocreatine (PCr) through a reversible reaction with the enzyme creatine kinase (CK). 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. 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.

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Food safety

When creatine is mixed with protein and sugar at high temperatures (above 148 °C), the resulting reaction produces heterocyclic amines (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.

A meta-analysis from 2011 evaluating the evidence with regard to this effect of cooking meat concluded, "search for the excretion of heterocyclic amines remains a future task to definitively exclude the unproved allegation made by some national agencies".

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Supplement health effects

Use

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 improve performance. Non-athletes report taking creatine supplements to improve appearance.

Adverse effects

Side effects include:

• Weight gain due to extra water retention to the muscle
• Potential muscle cramps / strains / pulls
• Upset stomach
• Diarrhea
• Dizziness
• High blood pressure due to extra water consumption

Use of creatine by healthy adults in normal dosages does not harm kidneys; its effects on the kidney in elderly people and adolescents were not well understood as of 2012. Both the American Academy of Pediatrics and the American College of Sports Medicine recommend that individuals younger than 18 years old not use creatine.

People with kidney disease, high blood pressure, or liver disease should not take creatine as a dietary supplement.

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.

A 2009 systematic review discredited concerns that creatine supplementation could affect hydration status and heat tolerance and lead to muscle cramping and diarrhea.

Interactions

Creatine taken with medications that can harm the kidney can increase the risk of kidney damage:

• Nonsteroidal anti-inflammatory drugs (NSAIDs) - some examples are ibuprofen (Motrin, Advil) and naproxen (Aleve)
• Diuretics (water pills) - an example is furosemide (Lasix)
• Cimetidine (Tagamet)
• Probenicid

Pharmacokinetics

Endogenous serum or plasma creatine concentrations in healthy adults are normally in a range of 2-12 mg/L. A single 5 g (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. After the "loading dose" period (1-2 weeks, 12-24 g a day), it is no longer necessary to maintain a consistently high serum level of creatine. As with most supplements, each person has their own genetic "preset" amount of creatine they can hold. The rest is eliminated as waste. A typical post-loading dose is 2-5 g daily.

Creatine supplementation appears to increase the number of myonuclei 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.

Chemistry

Creatine supplements are marketed in ethyl ester, gluconate, monohydrate, and nitrate forms.

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 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.

History

In 1912, Harvard University researchers Otto Folin and Willey Glover Denis 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 creatine phosphate, and determined that creatine is a key player in the metabolism of skeletal muscle. The substance creatine is naturally formed in vertebrates.

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 in Barcelona. An August 7, 1992 article in The Times reported that Linford Christie, 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.

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. Research performed thereafter demonstrated that the consumption of high glycemic carbohydrates in conjunction with creatine increases creatine muscle stores.

Research

ALS

It is ineffective as a treatment for amyotrophic lateral sclerosis.

Muscle disorders

A meta-analysis found that creatine treatment increased muscle strength in muscular dystrophies, 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.

Parkinson's disease

Creatine's impact on mitochondrial function has led to research on its efficacy and safety for slowing Parkinson's disease. 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.

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See also

• Beta-Alanine
• Creatine methyl ester

References

External links

• Creatine bound to proteins in the PDB

Source of article : Wikipedia