Introduction

Creatine is a chemical found naturally in the body, and also in red meat and seafood. It is often used to improve exercise performance and muscle mass.

Creatine is involved in making energy for muscles, with approximately 95% of it being found in skeletal muscle. The majority of sports supplements in the US contain creatine. Individuals who have lower creatine levels when they start taking creatine seem to get more benefit than individuals who start with higher levels.

People commonly use creatine for improving exercise performance and increasing muscle mass, but it is also used for muscle cramps, fatigue, multiple sclerosis (MS), depression, and many other conditions – although there is no good scientific evidence to support most of these uses.

Creatine use is allowed by the International Olympic Committee (IOC) and the US National Collegiate Athletic Association (NCAA).

What is Creatine?

It is a combination of three different amino acids:

• Glycine;
• Arginine; and
• Methionine.

Creatine is involved in a vast number of processes in the body. For example, it is a fundamental component in how your body creates its primary form of energy in muscle cells, the compound adenosine triphosphate (ATP). When muscles contract explosively, or for brief, intense work lasting no longer than 8-12 seconds, creatine (bonded with phosphoric acid as creatine phosphate) is how the muscle creates the energy necessary to do it.

• It exists in a steady state with a similar compound named creatinine that can be measured in lab tests as a marker of kidney function.
• It is passed out of your body in your urine.
• This means your body must release stored creatine each day to keep normal levels, the amount depending on your muscle mass.
• Although creatine is created naturally in your body, you must keep up your levels and do so through your daily diet.

What is the Role of Creatine?

• Creatine is a fuel source.
• Simply put, creatine helps to maintain a continuous supply of energy to working muscles by keep production up in working muscles.
• Small amounts are also found in your heart, brain and other tissues.
• The phosphate-bonded form of creatine is your body’s energy of first choice when performing anaerobic activity, for example lifting weights.
• When your body is trying to create the compound that powers quick muscle contractions, ATP, it does so by ‘borrowing’ a phosphate molecule from phosphocreatine and combining it with another compound, adenosine diphosphate (ADP).
• Only after a muscle has largely used up its store of phosphocreatine does it start to produce ATP from other sources, like glucose or fats.
• A secondary function of creatine is to draw water into muscle cells, making them more hydrated.

What are our Sources of Creatine?

• Most of the creatine in your body is created in the liver and kidneys, but the majority of it is stored in muscle tissue (approximately 95%).
• As a healthy human body is capable of creating its own creatine – and it can also be easily obtained through a diet that contains animal products – it is not considered an ‘essential’ nutrient.
• In a normal omnivorous /carnivorous diet, you consume one to two grams/day of creatine.
• However, as dietary creatine generally comes from animal products, vegan and vegetarian fitness enthusiasts and professional athletes may not get as much creatine in their diet as those who eat dairy products, eggs, and/or meat.
• This is one reason why creatine is often recommended as an important supplement for vegans and vegetarians.

What is it Used For?

• Possibly Effective for:
  • Athletic Performance: Taking creatine by mouth seems to somewhat improve rowing, jumping, and soccer performance. It is not clear if it helps with sprinting, cycling, swimming, or tennis.
  • Disorders of Creatine Metabolism or Transport: Taking creatine by mouth daily can increase creatine levels in the brain in children and young adults with conditions called GAMT deficiency or AGAT deficiency. But taking creatine does not seem to improve brain creatine levels in children who have a disorder in which creatine is not transported properly.
    • Guanidinoacetate Methyltransferase (GMAT) deficiency is an inherited disorder that primarily affects the brain and muscles.
    • Arginine: Glycine Amidinotransferase (AGAT) deficiency is an inherited disorder that primarily affects the brain.
  • Muscle Strength: Taking creatine by mouth seems to somewhat improve muscle strength in both younger and older adults. It is not clear if applying creatine to the skin helps.
  • Sarcopenia (Age-Related Muscle Loss): Taking creatine by mouth for up to 12 weeks seems to improve muscle strength in older adults. It seems to work best when used along with exercise to build muscles.

• Possibly Ineffective for:
  • Lou Gehrig Disease (Amyotrophic Lateral Sclerosis or ALS): Taking creatine by mouth does not seem to slow disease progression or improve survival in people with ALS.
  • An inherited brain disorder that affects movements, emotions, and thinking (Huntington Disease): Taking creatine by mouth does not improve symptoms in people with Huntington disease.
  • Osteopenia (Low Bone Mass): Taking creatine by mouth does not seem to slow or reduce bone loss in people with osteopenia.

There is interest in using creatine for a number of other purposes, but there is not enough reliable information to say whether it might be helpful.

What are the Side Effects?

• When taken by mouth:
  • Creatine is likely safe for most people.
  • Doses up to 25 grams daily for up to 14 days have been safely used.
  • Lower doses up to 4-5 grams daily for up to 18 months have also been safely used.
  • Creatine is possibly safe when taken long-term.
  • Doses up to 10 grams daily for up to 5 years have been safely used.
  • Side effects might include dehydration, upset stomach, and muscle cramps.
• When applied to the skin:
  • There is not enough reliable information to know if creatine is safe.
  • It might cause side effects such as redness and itching.

The majority of reported side effects (mild to moderate) are of weight gain, gastrointestinal distress, altered insulin production, inhibition of endogenous creatine synthesis, renal dysfunction, or dehydration in study participants.

Experts generally agree that there is sufficient evidence to be confident that 5 g/day of creatine is generally harmless to healthy adults, but there is not enough evidence to make an informed recommendation in favour or against doses higher than 5 g/day (Shao et al., 2006).

Are There Any Special Precautions or Warnings to Consider?

• Pregnancy and breast-feeding:
  • Creatine is used as a dietary supplement to increase muscle mass and improve exercise performance.
  • Creatine is a normal component of human milk, supplying about 9% of the infant’s daily requirements.
  • Milk levels of creatine have not been measured after exogenous administration in humans.
  • Creatine is converted into creatinine in the mother’s and infant’s bodies.
  • It may increase the infant’s serum creatinine, which may alter estimations of the infant’s kidney function.
  • Some authors speculate that creatine supplementation of nursing mothers might help avoid creatine deficiency syndromes, but no studies are available that test this hypothesis.
  • Until more data are available, it is probably best to avoid creatine supplementation unless it is prescribed by a healthcare professional.
• Children:
  • Creatine is possibly safe when taken by mouth, short-term.
  • Creatine 3-5 grams daily for 2-6 months has been taken safely in children 5-18 years of age.
  • Creatine 2 grams daily for 6 months has been taken safely in children 2-5 years of age.
  • Creatine 0.1-0.4 grams/kg daily for up to 6 months has been taken safely in both infants and children.
• Bipolar disorder:
  • Creatine might make mania worse in people with bipolar disorder (Allen, 2012) (discussed below).
• Kidney disease:
  • Creatine might make kidney disease worse in people who already have kidney disease.
  • If you have kidney disease, speak with a healthcare professional before using creatine.
• Parkinson disease:
  • Caffeine and creatine taken together may make symptoms of Parkinson disease worse.
  • If you have Parkinson disease and take creatine, use caffeine with caution.

What about Dosage?

• Creatine is found in foods such as meat and seafood. Creatine is also found in many different types of sports supplements.
• In supplements (discussed below), creatine has most often been used by adults in a one-time loading dose of up to 20 grams by mouth daily for up to 7 days, followed by a maintenance dose of 2.25-10 grams daily for up to 16 weeks.
• Speak with a healthcare provider to find out what type of product and dose might be best for a specific condition.

Interactions

A total of five (5) drugs are known to interact with creatine:

• Minor:
  • Cimetidine.
  • Probenecid.
  • Trimethoprim.
  • These are all known to interfere with the kidney’s secretion of creatinine.
• Moderate:
  • Entecavir: Using entecavir together with creatine may increase the blood levels of one or both medications.
  • Pemetrexed: Creatine may increase the blood levels of Pemetrexed. You may be more likely to develop serious side effects such as anaemia, bleeding problems, infections, and nerve damage when these medications are used together.

What about Creatine Monohydrate?

• Creatine monohydrate, the most popular form of creatine supplements, is simply creatine with one molecule of water attached to it – hence the name monohydrate.
• It is usually around 88-90% creatine by weight.
• It is not a steroid, it is totally different and works in a different manner.
• Its not a stimulant, although it is sometimes combined with stimulant ingredients (such as caffeine) in pre-workout formulas.

Supplementation and Fitness

• More Work:
  • Supplementation with creatine serves to increase creatine stores and phosphocreatine availability in the body, resulting in faster ATP formation.
  • The understanding being that the more phosphocreatine you have, the more work you can accomplish before fatigue sets it.
• Cell Hydration:
  • A secondary function of creatine is to draw water into muscle cells, making them more hydrated.
  • When muscle cells are hydrated a few things happen, the most notable being an increase in protein synthesis. Muscle protein synthesis (MPS) is the driving force behind adaptive responses to exercise and represents a widely adopted proxy for gauging chronic efficacy of acute interventions (i.e. exercise/nutrition).
  • This action of drawing water into the cell can make muscles look bigger or fuller (think weightlifters/bodybuilders).

Supplementation and Bipolar Disorder

• Negative changes in mood or anxiety following supplementation with creatine have been documented in two human trials (Roitman et al., 2007; Volek et al., 2000) and one animal experiment (Allen et al., 2010).
• Specifically, in an open-label clinical trial of creatine, Roitman et al. (2007) reported that two patients diagnosed with bipolar disorder exhibited hypomania or mania following daily supplementation with 3-5 g creatine.
• In a clinical trial examining the effectiveness of creatine to enhance heavy resistance training, Volek et al. (2000) noted that two subjects reported feeling more aggressive and nervous after 1 week of creatine supplementation (25 g/day).
• In rodents, Allen et al. (2010) observed increased depression-like behaviour in male rats supplemented with 4% creatine for five weeks, although this effect was not replicated in male rats in a follow-up study (Allen et al., in press).
• Taken together, there remains the possibility that creatine can increase risk of mania or depression in susceptible individuals.
• It is also possible that long-term high dosing of creatine alters creatine transporter function or creatine kinase activity in a manner that adversely affects emotional regulation.
• Further research is required before definitive conclusions are drawn, but caution is warranted in at-risk individuals.

For a good outline of creatine metabolism and psychiatric disorders read Patricia Allen’s article here.