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Creatine

What is creatine?

Creatine is an amino acid derivative produced in your body from the amino acids L-arginine, glycine or L-methionine [1].

Creatine is a nonessential nutrient, which means you do not need to get it from foods in order to be healthy.

Creatine Functions in the Human Body

Creatine is produced in your liver and kidneys and transported via blood to the muscles. In the muscles, creatine appears as phosphocreatine, which is not incorporated into proteins, but it is involved in the synthesis of the energy-storing molecules adenosine triphosphate (ATP) and thus for providing energy to muscles [1].

Mechanism of action. According to one hypothesis, creatine stimulates oxygen uptake by muscles and can thus enhance muscle fiber contraction [3]. In one study, creatine supplementation was associated with increased levels of dihydrotestosterone, which stimulates muscle growth [9].

1-2 grams of creatine per day can be produced in your body [3]. The amount of creatine in the muscles does not seem to decrease with age [3].

Creatine is excreted in the urine as creatinine.

Foods High in Creatine

ANIMAL FOODS: meat (beef, pork, poultry) and fish (herring, salmon, tuna) contain about 0.5 g of creatine per serving (3 oz or 85 g) [3].  For comparison, 1-2 g of creatine per day is produced in your body [3].

Vegetarians have lower levels of creatine in the muscles [11,12]. It is not certain if mixed diet that contains creatine results in greater exercise performance than a vegetarian diet.

Creatine Supplements

Nonprescription (over-the-counter) forms [3]:

  • Creatine monohydrate (in tablets, capsules, powder, bars, gels, gums, liquids, candies)
  • Creatine anhydrous
  • Creatine citrate
  • Creatine ethyl ester, creatine ethyl ester hydrochloride
  • Creatine gluconate
  • Creatine hydrochloride
  • Creatine, dicretine and tricretine malate
  • Creatine magnesium chelate
  • Creatine nitrate
  • Creatine phosphate
  • Creatine pyroglutamate
  • Creatine pyruvate
  • Cyclocreatine
  • Phosphocreatine

Creatine supplements are usually artificially synthesized from an amino acid-like substance sarcosine (N-methylglycine) [15]. It is not known if there are any significant differences among different forms of creatine supplements [3].

Creatine Benefits

Exercise Performance

Creatine is POSSIBLY EFFECTIVE in:

  • Improving the anaerobic performance and fatigue resistance during brief, high-intensity exercise lasting for less than 30 seconds (jumping, sprinting, weight lifting) [2,3,5]
  • Increase in muscle mass [5,10,12]
  • Mild increase in muscle strength in muscular dystrophies [6,7,13]

Creatine is POSSIBLY INEFFECTIVE in improving aerobic (endurance) performance [2,5] or performance in women [5], cyclists [5], rowers [5], swimmers [5] or other highly trained [2] or older people [2,5] or in improving spinal muscular atrophy or muscle strength recovery after surgery [5].

20-30% are considered creatine nonresponders–their muscle creatine increases only slightly after supplementation by 20 g creatine/day [3].

Muscle creatine levels increase more if creatine is taken together with sugars [2]. Supplementing 5 grams of creatine with 93 grams of simple carbohydrates 4 times daily for 5 days can increase muscle creatine levels as much as 60% more than creatine alone [2,3]. Carbohydrates trigger insulin release, which stimulates creatine uptake into the muscles. Fasting stimulates creatine loss from muscles [3].

Creatine muscle stores usually get saturated within a week of taking creatine supplements, so further creatine intake only maintains the achieved creatine stores but does not increase them further [3].

Dosage for Improving Athletic Performance

  • Option 1: 20 grams per day in 4 divided doses (4 x 5 g) for 5-7 days (loading), then 2-5 g/day (maintenance) [2,3]
  • Option 2: 3 grams per day for 28 days

Other Benefits

Creatine supplements are POSSIBLY EFFECTIVE in:

  • Treatment of symptoms in genetic creatine deficiency sydromes: guanidinoacetate methyltransferase (GAMT) deficiency and arginine:glycine amidinotransferase deficiency
  • Chronic congestive heart failure [5]
  • Guanidinoacetate methyltransferase deficiency [16]

Creatine is POSSIBLY INEFFECTIVE in the treatment of amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease) [2].

There is INSUFFICIENT EVIDENCE [2,3,5] abut the effectiveness of creatine in the prevention or treatment of age related muscle loss, bipolar disorder, breathing problems during sleeping (apnea) in infants, chronic obstructive pulmonary disease (COPD), coronary artery disease, dehydration, depression, dermatomyositis, diabetes mellitus type 2, fibromyalgia, heart attack, hereditary motor sensory neuropathy, high cholesterol, HIV/AIDS-related muscle wasting, Huntington’s disease, McArdle disease, mitochondrial myopathies, multiple sclerosis, muscle cramps, orthostatic hypotension, osteoarthritis, Parkinson’s disease [8], Rett syndrome, polymyositis, rheumatoid arthritis, schizophrenia, skin aging, traumatic brain injury or vision loss due to gyrate atrophy of the retina or in improving bone density, memory or cognitive function.

Creatine Safety: Side Effects, Toxicity

Creatine is LIKELY SAFE when taken by mouth in appropriate doses for uo to 5 years [2]. Creatine taken in high doses is POSSIBLY UNSAFE –it might affect kidney, liver and heart function [2,3].

Allergy to creatine is possible [6].

Side effects may include weight gain (due to water retention), stomach upset, nausea, diarrhea, dehydration, thirst, high blood pressure, reduced blood volume, electrolyte imbalances, muscle cramping or pain, drop of blood glucose levels and asthma-like symptoms [2,3,6].

Other side effects may include aggression, altered serum creatinine levels, anorexia, anxiety, burping, confusion, constipation, depression, drowsiness, elevated liver enzymes, fainting, fever, headaches, heat intolerance, increased cortisol or insulin levels, increased symptoms of deep vein thrombosis, jaundice, lightheadedness, liver injury, mania, metabolic acidosis, myopathy (muscle disease), rhabdomyolysis (muscle breakdown), seizures, skin rashes, vomiting, worsening sleep problems, yellowing of the skin irregular heart rhythm (arrhythmia) and pigmented purpuric dermatosis [3,6].

During Pregnancy

Not enough is known about the safety of creatine supplements during pregnancy and breastfeeding, so women in these periods should avoid them [2].

Who else should avoid creatine supplements?

Individuals with the following conditions should avoid creatine supplements [3,6,14]:

  • Age lower than 18
  • Kidney disease
  • Diabetes mellitus
  • Dehydration
  • Bipolar disease
  • Allergy to creatine

People who use of gentamicin, gallium nitrate, tacrolimus, valacyclovir or other drugs that are potentially toxic for kidneys should also avoid creatine supplements [6].

Creatine Interactions With Drugs and Herbs

  • When taken together with caffeine and the herb ephedra, creatine may increase the risk of stroke [2].
  • When taken together with the antibiotics cyclosporine, amikacin, gentamicin or tobramycin, or nonsteroidal anti-inflammatory drugs or NSAIDs (ibuprofen, indomethacin, naproxen, piroxicam), creatine may increase the risk of kidney damage [2].

Frequently Asked Questions

1. Is creatine a steroid?

Creatine is not a steroid but an amino acid. It is not prohibited by the World Anti-Doping Agency [4].

2. Is creatine bad for you?

Currently, no toxic effects of creatine are known.

  1. Creatine  PubChem
  2. Creatine  MedlinePlus
  3. Creatine  Drugs.com
  4. The 2015 prohibited list  US Anti-Doping Agency
  5. Creatine, evidence  Mayo Clinic
  6. Creatine, safety  Mayo Clinic
  7. Kley RA et al, 2013, Creatine for treating muscle disorders  Cochrane
  8. Xiao Y et al, 2014, Creatine for Parkinson’s disease  Cochrane
  9. van der Merve J et al, 2009, Three weeks of creatine monohydrate supplementation affects dihydrotestosterone to testosterone ratio in college-aged rugby players  PubMed
  10. Kreider RB, 1999, EFFECTS OF PROTEIN AND AMINO-ACID SUPPLEMENTATION ON ATHLETIC PERFORMANCE Sportscience
  11. Venderley AM et al, 2006, Vegetarian diets : nutritional considerations for athletes  PubMed
  12. Burke DG et al, 2003, Effect of creatine and weight training on muscle creatine and performance in vegetarians  PubMed
  13. Matsumura T et al, A clinical trial of creatine monohydrate in muscular dystrophy patients, 2004 PubMed
  14. Lukaski HC, 2006, Creatine revisited  US Departemnt of Agriculture
  15. Creatine laboratory synthesis  Quinnipiac University
  16. Stöckler S et al, 1997, Guanidino compounds in guanidinoacetate methyltransferase deficiency, a new inborn error of creatine synthesis  PubMed

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