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Supplement Series: Creatine

Posted by Issac Ishak on

Creatine is one of the most popular ergogenic aids for athletes.

Studies have consistently shown that creatine supplementation increases intramuscular creatine concentrations, hence the observed improvements in high-intensity exercise performance leading to greater training adaptations (0).

đŸ”čIn a 2017 review, the ISSN concluded that not only is creatine effective when it comes to improving performance, but creatine supplementation may enhance post-exercise recovery, injury prevention, thermoregulation, and has an application for those who suffer from Traumatic Brain Injuries. A number of clinical applications of creatine supplementation have been studied involving neurodegenerative diseases (e.g., muscular dystrophy, Parkinson’s, Huntington’s disease), diabetes, osteoarthritis, and brain/heart ischemia (1).

đŸ”čIn a 2017 meta-analysis.. A total of 321 abstracts were retrieved. After the review of abstracts, 26 full-length manuscripts were retrieved. Three manuscripts were excluded because they involved interventions of creatine supplementation without resistance training,18–20 and one studies presented lean tissue mass and strength results from the same participants across two manuscripts, therefore, 22 unique studies were included. Of these studies, five combined creatine supplementation with other nutritional supplements (ie, protein or conjugated linoleic acid). Table 1 shows the description of the included studies (0).

Twelve studies reported that creatine supplementation increased either lean tissue mass or muscle function, whereas ten studies showed no effect from creatine. Most studies reported no adverse effects related to creatine, but four studies reported gastrointestinal adverse events, and two studies reported muscle cramping. These adverse events did not cause participants to withdraw from these studies. Importantly, five studies with duration ranging from 3 to 52 weeks that evaluated liver or kidney function through blood or urine testing found no adverse effects. 

Creatine-supplemented groups had significantly greater increases in lean tissue mass, chest press strength, and leg press strength.

How Does Creatine Work?

I thought you'd never ask!

The most basic unit of cellular energy is a molecule called adenosine triphosphate (ATP). For a cell to use ATP, it must first break it down into several smaller molecules, and this process produces byproducts that are then “recycled” back into ATP to be used again, including one of particular interest here: adenosine diphosphate (ADP). Creatine is an essential ingredient in the process of regenerating ATP, which is why supplementing with it increases the amount of ‘work’ that your muscles can do (2).

Creatine acts by helping the body produce an important molecule in the liver called phosphocreatine (PCr). When muscles contract, they utilize energy stored in the phosphate bonds in ATP molecules. When this occurs ATP (3 phosphate groups) is no longer ATP, rather it becomes ADP (2 phosphate groups). Phosphate groups hold high energy bonds that release a ton of energy when the bonds are broken (ex. muscle contraction). Coming back to PCr, once synthesized by the liver, it’s shuttled into the bloodstream to be transported to the muscle. When PCr arrives in the muscle it ‘releases’ a phosphate group (removed by Creatine kinase) and attaches the same phosphate groups to ADP, to make ATP. Essentially, Creatine acts as a phosphate shuttle.

The downside to this system of energy generation, though, is the body’s natural creatine stores are very limited. Hence the importance of supplementation, but it can also be obtained through food!!


When you take a creatine supplement, however, your total body creatine stores rise significantly, with an average increase of in your muscles (3). This provides your muscle cells with much higher levels of readily available energy, which, unsurprisingly, improves anaerobic capacity, overall strength, and endurance/fatigue (4). It has also been theorized that It plays a role in increasing the water content of muscle cells, which positively influences muscle growth via a mechanism of cell swelling (5). This makes the muscles bigger, of course, but also positively impacts nitrogen balance and expression of specific genes related to hypertrophy (7). Other research suggests that creatine also has anti-catabolic effects, which further helps with long-term muscle gain (7). So, the bottom line here is even when you account for the increased water retention, people supplementing with creatine will generally gain muscle faster than those who don’t.

Achieving Saturation

Creatine is only effective when its levels in the muscle build-up, commonly referred to as ‘saturation’

đŸ”čYou can ensure skeletal muscle is fully saturated by a ‘Loading Phase’ of 20 grams of creatine/day (ex. 5 grams x4 times/day) for about a week. You can maintain saturation with a ‘maintenance phase’ of ~2-3 grams/day thereafter.

đŸ”čYou can also achieve saturation by taking 3-5 grams of creatine every day depending on gender/LBM.

Creatine monohydrate is the “standard” form of creatine. It was the first to hit the literature, it’s the most affordable, and it’s the most widely studied type of creatine to date. Literally hundreds of studies have shown that creatine monohydrate is effective in increasing skeletal muscle creatine concentration and enhance physical performance. Creatine variations, this includes: creatine citrate, creatine ethyl ester, creatine nitrate, and buffered forms of creatine. Main take away on the variations is, don’t focus on mechanisms over outcomes, and don’t search for solutions until you find a problem. Every time a new form of creatine comes around, it comes with technical explanations of why it could or should outperform creatine monohydrate. So far, none of them have been shown to consistently and substantially increase creatine retention, performance, or anything other than price, in comparison to creatine monohydrate (0), (1), (9).

Creatine is the most studied, proven, and time-tested supplement in all of sports nutrition. If you’re into weightlifting or athletics of any kind and haven’t tried it, then you’re missing out.

Hundreds of studies have shown that creatine

  • Increases strength and muscle gain
  • Improves power output
  • Improves rate of recovery

And there’s also evidence that it can reduce fatigue during exercise, joint pain, stiffness, and discomfort, and even symptoms of type 2 diabetes.

Plus, it’s safe, cheap, and readily available.

Take Home Points:

  • Creatine improves high-intensity exercise performance, primarily by saturating muscle storage of free creatine and phosphocreatine, which enables rapid ATP recycling during exercise.
  • Loading and cycling of creatine are fine, but not necessary.
  • Creatine may confer modest benefits for bone and brain health.
  • Creatine is largely free of side effects in healthy people, aside from occasional stomach discomfort. This discomfort can probably be attenuated by completely dissolving the creatine dose in liquid, avoiding doses above 5 grams at a time, and avoiding co-ingesting high doses (≄3-5 mg/kg) of caffeine at the same time.
  • No form of creatine has been shown to meaningfully and consistently outperform creatine monohydrate. However, creatine monohydrate degrades pretty rapidly in liquid, so it should be mixed pretty close to the time of ingestion.

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