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 the 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 Boljerdi, a pharmaceutical researcher and former professor, conducted a thorough and extensive analysis of this compound. Handbook of creatine and creatinine biokinetics. Let’s take a closer look at the science behind creatine supplementation.
The science of creatine
Your body naturally produces creatine. Creatine is produced in the liver, kidneys, and pancreas from amino acids such as glycine, arginine, and methionine.
It travels through the bloodstream to various tissues, such as muscles, where it is used for energy. Approximately 95% of the body’s creatine is stored in skeletal muscle, with the remainder distributed in the brain, heart, and other tissues.
Once inside cells, creatine is converted to phosphocreatine (PCR), a high-energy molecule that plays a key role in the regeneration of adenosine triphosphate (ATP), the body’s main energy converter.
The ability to rapidly regenerate ATP is critical for maintaining energy supply, especially in tissues with high energy demands such as skeletal muscle, cardiac muscle, and brain. This has attracted the attention of athletes as it allows them to maintain cellular function during periods of intense activity and stress.
After creatine has completed its role, it is broken down into a waste product called creatinine, which is removed from the body by the kidneys and excreted in the urine.
However, there are several factors that affect how creatine is stored and used in the body. For example, tissues can only hold a certain amount of creatine, and creatine levels vary from person to person.
Importantly, despite what is often feared on social media, it is not steroids. “Creatine’s role in muscle development is only to provide energy for contraction and respiration; it is not a steroid replacement,” 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 demonstrated in this book, it has been shown to increase muscle creatine and phosphocreatine levels and promote ATP regeneration during high-intensity, short-duration activities. This translates into increased power output, sprint performance, and training volume.
Beyond physical performance, creatine has been demonstrated to have potential benefits for cognitive functions such as memory, mood, and processing speed, especially in populations with low baseline creatine levels, such as the elderly.
New evidence examined in this book also positions creatine as more than just a sports supplement. There is growing interest in its potential applications for conditions such as Parkinson’s disease, depression, and even muscle and bone loss associated with menopause, but more research is needed before claims can be made.
“Creatine’s anti-inflammatory and antioxidant properties further emphasize its potential in clinical practice, but more robust trials are needed to confirm these benefits,” he explains.
“With sufficient justification, appropriate dosage forms, and dosing regimens, creatine may eventually be accepted as an over-the-counter therapeutic agent rather than just a dietary supplement.”
Dosing regimen and bioavailability
The standard dosing protocol for creatine includes 20 grams per day (divided into four doses) for 5 to 7 days, followed by a maintenance dose of 3 to 5 grams per day.
“Although this approach rapidly saturates muscle creatine stores, similar saturations can be achieved over longer periods of time (about 28 days) at lower daily doses of 3 to 5 grams,” Dr. Boroujerdi says.
However, bioavailability is not absolute. Contrary to popular belief, not all creatine taken orally is absorbed. Factors such as gastrointestinal stability and an individual’s muscular capacity influence how much creatine is retained. Co-ingestion with carbohydrates has been shown to increase creatine uptake by stimulating insulin-mediated transport.
Factors influencing the effectiveness of creatine
Research shows that men and women may respond differently to creatine supplementation due to differences in muscle mass and baseline creatine levels. However, there are limits to our current understanding, and Dr. Borowheldi would like to see these areas explored further.
For example, women who typically have lower creatine stores in their muscles may experience greater relative benefits. Similarly, older adults may benefit from creatine’s ability to counter age-related declines in muscle mass, bone density, and cognitive function.
Vegetarians and vegans who consume little or no creatine in their diets often have lower baseline creatine levels and may experience more pronounced benefits from supplements than omnivores. However, not all vegetarian and vegan diets are the same, so the effects will vary from person to person.
“There is an urgent need for well-designed research projects in humans that utilize labeled creatine to generate relevant data and clarify the gray areas of knowledge about these compounds,” explains Dr. Boroujerdi.
Creatine is often combined with other compounds to enhance its effects, such as the amino acid beta-alanine. However, Dr. Boljerdi cautions that the effectiveness of such combinations is variable and that further research is needed to establish optimal protocols.
judgment
Creatine remains one of the most studied and effective dietary supplements, with a strong safety profile and a growing list of potential uses. But it has its limits.
“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, muscle creatine stores have a saturation limit, so the idea that higher doses will provide greater benefits is unfounded. Excess creatine will simply be excreted as creatinine without any additional benefit,” says Dr. Boroujerdi.
Concerns about side effects such as kidney damage have been largely proven false in healthy people. However, people with pre-existing kidney disease should consult their healthcare provider before taking supplements.
However, its benefits are not universal and vary depending on factors such as baseline creatine levels, dosing strategy, and individual physiology.
“Currently, creatine is considered a supplement with great potential, but it is not a panacea,” Dr. Boroujerdi says. “Whether you’re an athlete, student, or just someone looking to support your health, understanding the science behind creatine is key to making informed decisions.”

