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Creatine and brain health: cognitive and neurological benefits

by P. Debraux | 16 January 2024

creatine, nutrition, supplementation, brain, health, cognitive, depression, anxiety, science

Creatine is a nitrogen compound produced and synthesized endogenously in the human body. Synthesis involves the non-essential amino acids arginine and glycine, as well as the essential amino acid methionine. This two-stage process takes place mainly in the liver and brain. Creatine can also be consumed exogenously through food sources such as red meat and seafood, or by ingesting commercially manufactured creatine supplements. The most common form of creatine supplementation is creatine monohydrate, known for its efficacy and bioavailability in increasing plasma creatine levels and improving creatine content in tissues such as muscle, thereby enhancing physical performance.

In fact, it helps muscles produce energy when lifting heavy loads or making high-intensity efforts. In the body, creatine is phosphorylated to form phosphocreatine, which serves as a rapid energy source in cells, particularly muscle and brain cells, by regenerating adenosine triphosphate, the body's main energy carrier.

But beyond these benefits for muscle mass, a growing body of research over the last few decades has been looking at how creatine supplementation affects our health, with or without exercise, with a particular focus on the brain. So, if creatine is a key player in energy metabolism, could it also make a significant contribution to the energy-consuming processes of our most complex organ, the brain? What possibilities might creatine supplementation offer for brain health, beyond its traditional domain in sport and resistance training?

What is creatine and what impact does it have on brain function?

Creatine is synthesized in the liver, pancreas and kidneys, mainly from the amino acids arginine, glycine and methionine. It can also be obtained from dietary sources such as red meat and fish, and via supplementation. Once produced or ingested, creatine circulates in the bloodstream to body tissues, including the brain.

Creatine crosses the blood-brain barrier via a specialized creatine transporter (CT1). Once in the brain, it is absorbed by neurons and glial cells. This transporter is essential, as creatine in the brain must be continually replenished to maintain optimal levels for neurological function.

The brain, despite its relatively small size, is an energy-hungry organ, accounting for around 20% of the body's energy expenditure. Creatine's main function in the brain is to maintain levels of adenosine triphosphate (ATP), the cell's main source of energy. It does this by donating phosphate groups to adenosine diphosphate (ADP), regenerating ATP and thus sustaining the energy demands of neuronal activity and brain function.

Given its crucial role in energy metabolism, creatine's impact on brain function is extremely important. Sufficient levels of creatine in the brain support various cognitive processes, particularly those requiring rapid energy production, such as memory, attention and problem-solving. A growing number of animal studies and human clinical trials show that creatine supplementation can improve cognitive performance, particularly in tasks requiring rapid and intense use of brain power. Conversely, low creatine levels in the brain accompany many neurodegenerative disorders, with the extent of creatine deficiency often corresponding to the severity of the disorder.

How does creatine contribute to cognitive and memory enhancement?

Research indicates that creatine supplementation can have a positive impact on various cognitive processes. This is particularly evident in tasks requiring rapid and extensive use of brain power. Studies of creatine supplementation have shown improvements in tasks requiring rapid problem solving, greater attention span and improved memory recall. Researchers believe that these benefits stem from creatine's role in maintaining ATP levels, crucial for optimal brain function.

Memory, both short- and long-term, is an energy-intensive process for the brain. Adequate creatine levels ensure a steady supply of ATP, essential for memory formation and recall. Experimental studies suggest that creatine supplementation can lead to significant improvements in memory performance, especially in senior citizens, but also in situations where the brain is subject to metabolic stress, such as sleep deprivation or mental fatigue.

Beyond the immediate cognitive enhancement, creatine has potential as a neuroprotective agent. By maintaining cellular energy levels in the brain, creatine can help prevent neuronal damage and support brain health over time. This aspect of creatine is of particular interest in research into aging and neurodegenerative diseases, where the brain's energy metabolism is often compromised.

For people looking to optimize their cognitive performance, particularly in mentally demanding or stressful situations, creatine supplementation could be a valuable addition to their routine. For students, professionals and the elderly, creatine's cognitive benefits suggest a practical, non-invasive way to support brain health and function.

Creatine in the management of traumatic brain injury

Traumatic brain injury (TBI), including concussion, represents a significant challenge in both medical and sporting contexts. As research progresses, creatine is emerging as an unexpected protagonist in the potential management of traumatic brain injury, and could influence the recovery and treatment of traumatic brain injury.

Traumatic brain injury often leads to an energy crisis in the brain, where ATP demand exceeds supply. In addition, TBI reduces creatine concentration in the brain. Creatine supplementation could then act as an energy buffer, maintaining ATP levels and potentially mitigating post-injury energy deficits.

Creatine may have neuroprotective properties when ingested in supplementation before or after cortical contusion, greatly reducing cortical damage. Animal studies have shown promising results, where creatine supplementation prior to brain injury led to a reduction in the severity of brain damage. In human studies, although the data are still emerging, there are indications that creatine could help to achieve faster recovery and better overall outcomes after brain injury. By stabilizing cellular energy levels, it could help reduce cell death and support brain tissue recovery following injury.

For athletes, particularly in high-impact sports where concussion is a risk, creatine supplementation could offer (to some extent) a protective effect. In the post-TBI rehabilitation phase, creatine could support cognitive and neurological recovery processes.

Although current research into the role of creatine in the management of TBI is promising, it is still in its infancy. Future clinical trials and studies are needed to fully understand the scope of creatine's efficacy in this area.

Assessing creatine's potential in neurodegenerative diseases

Neurodegenerative diseases, such as Alzheimer's and Parkinson's, pose significant challenges due to their progressive nature and currently limited therapeutic options. These diseases occur when neurons in the central or peripheral nervous system lose function or eventually die.

Alzheimer's disease is the most common cause of neurodegenerative dementia, resulting in progressive memory loss, difficulty expressing oneself and thinking, disorientation and ultimately death. It is characterized by changes in the brain's energy metabolism. Creatine, which plays a central role in energy production, could help mitigate these metabolic changes, but this has only been partially demonstrated in animals, and has not yet been studied in humans.

Parkinson's disease affects more than 10 million people worldwide, and is characterized by motor control affected by tremors, increased rigidity and loss of balance. Cellular oxidative damage and mitochondrial dysfunction are characteristic of Parkinson's disease. This disease involves mitochondrial dysfunction in neurons. This suggested that creatine supplementation might help. However, while animal studies have shown promising results, human clinical trials have produced mixed results. Most long-term studies failed to observe clinical improvements in patients' health.

Muscular dystrophies (such as Duchenne and Becker, for example) are neuromuscular diseases that result in a significant reduction in free creatine and phosphocreatine stores in skeletal muscle, often linked to a lower content of creatine-transporting proteins and impaired creatine absorption and release. They mainly affect men, and are characterized by progressive muscle weakness, difficulty in moving, and cardiac and/or respiratory problems.

Studies have shown significant improvements due to creatine supplementation in boys with Duchenne and Becker muscular dystrophies. Improvements include increased grip strength, fat-free mass and exercise capacity. In addition, creatine supplementation combined with exercise showed an increase in muscle mass, grip strength and mitochondrial content. In contrast, creatine supplementation showed no significant effects in patients with myotonic dystrophy type 1 or myotonic dystrophy type 2. This suggests that the benefits of creatine supplementation may be disease-specific.

Creatine supplementation appears to be safe, well tolerated and increases muscle strength in patients with muscular dystrophies, particularly in young people. The benefits of creatine supplementation in these patient populations may vary according to the type of muscular dystrophy and patient age.

Despite the promising aspects of creatine supplementation, larger and more rigorous clinical trials are needed to establish its efficacy in the management of neurodegenerative diseases and to understand how creatine interacts with the pathophysiological mechanisms of neurodegenerative diseases.

Creatine and mood disorders: a new therapeutic avenue?

Mood disorders such as depression, bipolar disorder, anxiety disorders and post-traumatic stress disorder are major contributors to disability worldwide, with recent estimates suggesting that around 5-6% of the world's population will experience symptoms of these disorders at some point in their lives. In addition, research suggests that the prevalence of mood disorders increased by 28% in 2020 due to the effects of the 2019 coronavirus pandemic.

Importantly, current therapies for mood disorders often fail to adequately support patients. For example, clinical trials indicate that verbal and behavioral therapies, such as cognitive-behavioral therapy, significantly alleviate symptoms in only 43-50% of patients with depression. Furthermore, a systematic review of 522 clinical trials revealed that antidepressant pharmacotherapies reduced symptoms in only 60% of patients. These figures are partly explained by the fact that around 28% of patients stop taking their antidepressants within the first month of prescription, while around 44% do so within the first three months and around 73% within the first six months, largely due to the high prevalence of side effects, including sexual dysfunction (71.8% of patients), weight gain (63.5%) and emotional numbness (64.5%).

Creatine plays a role in maintaining the balance of neurochemicals in the brain, which can be crucial to mental health. By supporting energy metabolism in the brain, creatine could influence the functioning of neurotransmitter systems linked to mood regulation.

Research into creatine supplementation shows promise in reducing the symptoms of major depressive disorder. These studies indicate that creatine may enhance the effects of certain antidepressants, leading to more significant improvements in mood and cognitive symptoms of depression, particularly in women. Creatine's role in energy metabolism could address aspects of the bioenergetic hypothesis of depression, which postulates that deficient energy production in the brain could contribute to depressive symptoms.

There is less research on anxiety than on depression. But some data suggest that creatine may also have anxiolytic (anti-anxiety) effects. This is based on the premise that improving the brain's energy metabolism could positively affect the brain regions involved in anxiety.

Despite encouraging results, there are still significant gaps in our understanding of creatine's impact on mood disorders. Further research is needed to establish dosing guidelines, understand the mechanisms involved and identify populations that could benefit the most from creatine supplementation. And understanding how creatine could be effectively integrated into existing therapeutic approaches for mood disorders is another area for further research.


As you will have gathered, well beyond its traditional role in sports nutrition, creatine's potential applications in cognitive enhancement, brain injury recovery, neurodegenerative disease management and mood disorders are interesting, but still require a great deal of research to better understand effective dosages in different clinical populations. But regular creatine supplementation can increase creatine concentration in the brain, which over time may help explain some of the promising effects on measures of brain health and function.

Creatine shows promise in boosting cognitive function, particularly in tasks requiring rapid, high-intensity mental activity. Emerging research suggests a neuroprotective role for creatine, indicating potential benefits in the recovery from traumatic brain injury. Although current evidence is mixed, creatine's role in energy metabolism could offer benefits in the management of diseases such as muscular dystrophy. Finally, creatine could help reinforce traditional treatments for mood disorders, offering a new therapeutic avenue.


  1. Candow DG, Forbes SC, Ostojic SM, Prokopidis K, Stock MS, Harmon KK and Faulkner P. "Heads Up" for Creatine Supplementation and its Potential Applications for Brain Health and Function. Sports Med 53 (1) : S49-S65, 2023.

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