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Creatine

Creatine is an organic compound with the nominal formula (H2N).

It exists in various tautomers in solutions,

Creatine facilitates recycling of adenosine triphosphate (ATP), primarily in muscle and brain tissue. 

Recycling is achieved by converting adenosine diphosphate (ADP) back to ATP via donation of phosphate groups.

Biological half-life 3 hours

It has influence on physical performance.

The consumption of high glycemic carbohydrates in conjunction with creatine increases creatine muscle stores.

Creatine is a naturally occurring non-protein compound.

It is a the primary constituent of phosphocreatine, which is used to regenerate ATP within the cell. 

Creatine is a naturally occurring amino acid derivative that is found in the muscles and brain of vertebrates. 

It is commonly used as a dietary supplement by athletes and bodybuilders to help improve athletic performance.

Creatine works by increasing the amount of phosphocreatine in the muscles, which provides energy during high-intensity exercise like weight lifting and sprinting. 

It may also help to reduce muscle damage and inflammation, improve muscle recovery, and increase muscle mass in response to resistance training.

Creatine is found in foods like meat and fish, and the body can synthesize it from amino acids like glycine, arginine, and methionine. However, supplementing with creatine in powder, capsule, or liquid form can increase the body’s stores of phosphocreatine and provide a more significant performance-enhancing effect.

95% of the human body’s total creatine and phosphocreatine stores are found in skeletal muscle, while the remainder is distributed in the blood, brain, testes, and other tissues.

The 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.

About 1–3 grams of creatine per day to maintain average creatine storage.

An omnivorous diet provides roughly half of this value, with the remainder synthesized in the liver and kidneys.

It is not an essential nutrient.

Creatine is an amino acid derivative, naturally produced in the human body from the amino acids glycine and arginine.

The additional requirement for S-Adenosyl methionine to catalyze the transformation of guanidinoacetate to creatine. 

Creatine can be phosphorylated by creatine kinase to form phosphocreatine, 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 and with creatine.

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 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) catalyzed by the enzyme creatine kinase (CK). 

In skeletal muscle, PCr concentrations may reach 20–35 mM or more. 

In most muscles, the ATP regeneration capacity of CK is very high and is therefore not a limiting factor. 

ATP is continuously and efficiently replenished from the large pools of PCr and CK.

Creatine has the ability to increase muscle stores of PCr.

It can potentially increase the muscle’s ability to resynthesize ATP from ADP to meet increased energy demands.

Creatine supplementation increases the number of myonuclei that satellite cells add to damaged muscle fibers, increasing the potential for growth of those muscle fibers. 

Creatine increases levels of the myogenic transcription factor MRF4.

Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects, with three distinct disorders of creatine metabolism. 

Deficiencies in the two synthesis enzymes can cause L-arginine:glycine amidinotransferase deficiency.

A third defect, is a creatine transporter defect.

Some studies suggest that total muscle creatine is significantly lower in vegetarians than non-vegetarians, possibly due to an omnivorous diet being the primary source of creatine. 

Creatine supplementation is needed to raise the concentration of creatine in the muscles of lacto-ovo vegetarians and vegans up to non-vegetarian levels.

An approximation of 0.3 g/kg/day divided into 4 equal spaced intervals has been suggested for creatine supplementation.

Supplementing creatine with carbohydrates  and protein has been augments creatine retention.

The 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; 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.

Once supplementation of creatine stops, muscle creatine stores return to baseline in 4–6 weeks.

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.

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 by 5% to 15%.

Creatine is reported to have a beneficial effect on brain function and cognitive processing, with the greatest effect in individuals who are stressed due to sleep deprivation or cognitively impairment.

Creatine treatment increases muscle strength in muscular dystrophies, and potentially improved functional performance, but 

does not 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.

In people with various muscular dystrophies, creatine monohydrate can be beneficial in their rehabilitation after injuries and immobilization.

Creatine supplementation increases total testosterone, free testosterone, DHT or causes hair loss/baldness.

Side effects include:

Weight gain due to extra water retention to the muscle

Potential muscle cramps / strains / pulls

Upset stomach

Diarrhea

Dizziness

Weight gain within the first week of the supplement schedule, is likely attributable to greater water retention due to the increased muscle creatine concentrations by means of osmosis.

Creatine supplementation results in slightly elevated creatinine levels that remained within normal limits.

Supplementation does not induce renal damage.

Renal function is not a concern for use of creatine supplements.

Creatine is safe to take in healthy populations from infants to the elderly to performance athletes. 

Long term (5 years) use of creatine is considered safe.

Kidneys, for normal physiological function, need phosphocreatine and creatine and kidneys express significant amounts of creatine kinases.

The first of two steps for endogenous creatine synthesis takes place in the kidneys.

Patients with kidney disease and those on dialysis generally show significantly lower levels of creatine in their organs.

Impaired kidneys have deceased creatine synthesis capability and abnormal resorption of creatine from the urine in the distal tubules. 

Dialysis patients lose creatine due to the wash out process 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 is suggested  to supplement dialysis patients with extra creatine, preferably by intra-dialytic administration. 

Such a supplementation 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.

A National Institutes of Health study suggests that caffeine interacts with creatine to increase the rate of progression of Parkinson’s Disease.

When creatine is mixed with protein and sugar at high temperatures, the resulting reaction produces carcinogenic heterocyclic amines.

 This occurs when grilling or pan-frying meat.

Creatine can be used as an indicator of meat quality.

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