Creatine, a compound often associated with gym-goers and athletes, has long been touted as a performance-enhancing supplement. But beyond the hype, what does science actually reveal about its effects on the body and mind?
From its role in energy metabolism to its potential therapeutic applications, creatine is a molecule that continues to intrigue researchers.
Dr Mehdi Boroujerdi, pharmaceutical researcher and former professor, has carried out a thorough and extensive analysis of the compound in the Handbook of Creatine and Creatinine In Vivo Kinetics. Here's a closer look at the science behind creatine supplementation.
The science of creatine
Your body naturally makes creatine, produced in the liver, kidneys and pancreas from amino acids like glycine, arginine and methionine.
It travels through the bloodstream to different tissues, like muscles, where it's used for energy. Approximately 95% of the body's creatine is stored in skeletal muscle, with the remainder distributed across the brain, heart and other tissues.
Once inside cells, creatine is converted into phosphocreatine (PCR), a high-energy molecule that plays a critical role in regenerating adenosine triphosphate (ATP), the body's primary energy converter.
The ability to quickly regenerate ATP is crucial for maintaining energy supply, especially in tissues with high energy demands, such as skeletal muscle, cardiac muscle and the brain. This ensures that cells can sustain their functions during periods of intense activity or stress, which is why it has come to the attention of athletes.
After creatine has done its job, it gets broken down into a waste product called creatinine, which is then removed from the body by the kidneys and excreted in urine.
But there are several factors that impact how creatine is stored and used in the body, for example tissue can only hold a certain amount of creatine and everyone's individual levels are different.
Crucially, despite concerns oft levied on social media, it is not a steroid. "Creatine's role in muscle development is solely to provide energy for contraction and respiration, it is certainly not a substitute for steroids," Dr Boroujerdi explains.
Creatine as a dietary supplement: what we know
Creatine monohydrate is the most widely studied and used form of creatine supplement.
As evidenced in the book, it has been shown to increase muscle creatine and phosphocreatine levels, enhancing ATP regeneration during high-intensity, short-duration activities. This translates to improved power output, sprint performance and training volume.
Beyond physical performance, creatine has demonstrated some potential benefits for cognitive function, including memory, mood and processing speed, particularly in populations with lower baseline creatine levels, such as in older adults.
Emerging evidence also explored in the book positions creatine as more than a sports supplement. It has sparked interest in its potential applications for conditions like Parkinson's disease, depression and even menopause-related muscle and bone loss – but more research is needed before any claims can be made.
"Creatine's anti-inflammatory and antioxidant properties further underscore its promise in clinical settings, though more robust trials are needed to confirm these benefits," he explains.
"With sufficient justification, appropriate dosage form, and dosing regimen, creatine may eventually be recognised as an over-the-counter therapeutic agent rather than merely a dietary supplement."
Dosing regimens and bioavailability
The standard dosing protocol for creatine involves a loading phase of 20 grams per day (split into four doses) for 5-7 days, followed by a maintenance dose of 3-5 grams per day.
"This approach rapidly saturates muscle creatine stores, but a lower daily dose of 3-5 grams can achieve similar saturation over a longer period (approximately 28 days)," Dr Boroujerdi says.
Bioavailability, however, is not absolute. Contrary to popular belief, not all orally ingested creatine is absorbed. Factors such as gastrointestinal stability and individual muscle capacity influence how much creatine is retained. Co-ingestion with carbohydrates has been shown to enhance creatine uptake by stimulating insulin-mediated transport.
Factors influencing creatine's effects
Research suggests that men and women may respond differently to creatine supplementation due to variations in muscle mass and baseline creatine levels. There are limits to our current understanding, however, and Dr Borouherdi would like to see these areas explored further.
For example, women, who typically have lower muscle creatine stores, may experience greater relative benefits. Similarly, older adults may benefit from creatine's ability to counteract age-related declines in muscle mass, bone density and cognitive function.
Vegetarians and vegans, who may obtain little to no creatine from their diets, often exhibit lower baseline creatine levels and may experience more pronounced effects from supplementation compared to omnivores – although not all vegetarian and vegan diets are the same, so impacts would differ in different individuals.
"There is a pressing need for well-designed research projects in humans, utilising labelled creatine to generate relevant data and illuminate the grey areas of our knowledge about these compounds," Dr Boroujerdi explains.
Creatine is often combined with other compounds to enhance its effects, like the amino acid beta-alanine. However, Dr Boroujerdi warns the efficacy of such combinations varies, and more research is needed to establish optimal protocols.
The verdict
Creatine remains one of the most researched and effective dietary supplements available, with a strong safety profile and a growing list of potential applications. But it does have limitations.
"Despite its many benefits, creatine is not a magic bullet. It does not directly build muscle or replace the need for proper training and nutrition. Additionally, the belief that larger doses yield greater benefits is unfounded, as muscle creatine stores have a saturation limit. Excess creatine is simply excreted as creatinine, offering no additional advantage," Dr Boroujerdi says.
Concerns about side effects, such as kidney damage, have largely been debunked in healthy individuals. However, those with pre-existing renal conditions should consult a healthcare provider before supplementation.
However, its benefits are not universal and depend on factors like baseline creatine levels, dosing strategies, and individual physiology.
"For now, creatine is best viewed as a supplement with significant potential, but not a panacea" Dr Boroujerdi says. "Whether you're an athlete, a student, or simply someone looking to support your health, understanding the science behind creatine is key to making informed decisions."
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