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Some people can’t imagine working out without it, while others avoid it due to many myths surrounding its use. Whether you’re among those who take creatine or (incorrectly) categorise it as a steroid, the fact remains that creatine is the most thoroughly studied dietary supplement available. It occurs naturally in the human body, and we also obtain some of it from animal-based foods. However, plant-based foods contain no creatine.
As a dietary supplement, creatine is available in various forms, but each one serves the same purpose—replenishing creatine where it’s needed in the body. Despite the availability of different forms, creatine monohydrate still proves to be the most effective choice. [1]
How Creatine Works
The human body, made up of a multitude of cell types, derives energy from molecules of adenosine triphosphate (ATP). ATP releases energy by converting to ADP (adenosine diphosphate). During this process, ATP loses one phosphate group, and the released energy powers essential processes, such as muscle contraction.
ATP is generated in the mitochondria (the cell’s “power plants”), but when there’s an immediate and high demand, it needs to be replenished right away. Muscles contain only enough ATP for a few seconds of work, so the rest must be efficiently recycled. This is where creatine phosphate comes into play—a form of creatine in the body that has a phosphate group attached. Through creatine phosphate, the phosphate group is transferred back to ADP, recycling it into ATP. Thanks to creatine, a steady supply of immediate energy is maintained.
Supplementing with creatine boosts its concentration in muscles, enabling faster and more sustained energy recycling. With regular use, you may notice improved endurance and enhanced muscle recovery. It’s true that creatine also brings water into the muscle cells. However, this isn’t a side effect in the sense of “water retention.” Creatine hydrates the muscle cells, making them fuller and enhancing the exchange of nutrients and other compounds. People with naturally higher creatine levels (due to genetics or diet) may not notice as significant an effect on performance and recovery.
The Brain as a Selfish Organ
The human brain is a high-energy, self-centred organ. Despite making up only about 2% of total body mass, it consumes as much as 20% of the body’s total energy at rest.[2] When the body is low on readily available energy, glucose is redirected to the brain, while the rest of the body operates in a state of insulin resistance. Though the brain relies on ATP produced from glucose, where ATP is used, creatine is also present to help recycle it.
Creatine, an essential source of immediate energy for the brain, can cross the blood-brain barrier. [3] Taking creatine as a supplement increases its concentration in the brain, where it supports various energy-intensive processes.
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The Effect of Creatine on the Brain
Brain cells, or neurons, are constantly active and require a massive amount of energy. Processes like neurotransmitter transmission and signal conduction consume large quantities of ATP. Consequently, when ATP levels are low, many brain functions can be compromised, potentially resulting in symptoms such as anxiety, depressive symptoms, fatigue, memory and concentration issues, or reduced cognitive performance.[4]
The impact of creatine deficiency on the brain is well-documented in individuals with congenital creatine deficiency, which stems from a lack of enzymes that naturally produce creatine in the body. Symptoms of this deficiency include delayed development, cognitive dysfunction, seizures, epilepsy, movement disorders, ADHD, autism, and aggressive behaviour.[5]
Beyond its impact on the brain, creatine also supports overall nerve health. Nerve damage can be monitored through neurofilaments released into the blood from damaged nerves. Studies have shown lower neurofilament levels in individuals taking creatine, suggesting that creatine has a neuroprotective effect.[6]
Creatine Enhances Cognitive Abilities
Creatine supplementation is extensively studied in the context of skeletal muscle and physical performance. However, recent years have seen increased focus on its effects on various brain functions. In a study on rats given creatine intranasally, the creatine-treated rats demonstrated improved problem-solving, making fewer errors when searching for a maze exit.[7]
A 2018 systematic review, which included six studies, found improved short-term memory and intelligence in healthy individuals who received creatine.[8] A newer 2023 study demonstrated enhancements in cognitive functions, such as faster information processing and better recall, after six weeks of taking 5g of creatine daily.[9]
Lack of sleep is typically accompanied by poor focus and diminished mental performance. Even a single dose of creatine can help minimise this effect. A dose of 0.35g of creatine per kilogram of body weight (equivalent to 24.5g for a person weighing 70 kg) can partially mitigate the metabolic consequences of sleep deprivation, thereby improving performance even during tired days. Nevertheless, prioritising quality sleep remains the best approach to avoid needing such measures.[10]
Given its effects on the brain, creatine is also known to reduce symptoms of “brain fog,” often triggered by sleep deprivation and stress. Creatine’s impact on memory is particularly significant in people over 66, where age-related memory decline is a factor.[11]
The Impact of Creatine on Mental Health
- Low creatine levels in certain brain areas have been linked to symptoms of depression and anxiety disorders, suggesting that creatine supplementation may offer some relief for these symptoms.[12]
- Low creatine has also been observed in people with social anxiety disorder, where reduced levels in the prefrontal cortex are associated with anxiety symptoms.[13]
- Research on mice has shown that creatine has antidepressant effects, partly due to its ability to bind to adenosine receptors, similar to ketamine.[14]
- A large study investigating the prevalence of depression among creatine users found that those who regularly take creatine have a 32% lower risk of developing depression.[15]
- Another study from South Korean researchers showed that a standard dose of creatine — 5g daily over eight weeks — enhanced the effects of antidepressants in women with depression.[16]
How Much Creatine to Take
Just as with creatine supplementation for physical activity, the ideal dose for cognitive benefits is 5g daily, with timing not being a critical factor. Like any health regimen, regular use of supplements is key, and their benefits are typically seen over time. Additional advantages of creatine supplementation are summarised in this article.
Conclusion
The safety and effectiveness of creatine for improving physical performance and brain function have been confirmed by hundreds of studies. Its supplementation can benefit athletes and fitness enthusiasts, as well as everyday individuals who aren’t typically highly active. Creatine is safe, and despite myths about its impact on kidney health, it poses no cause for concern. When taken regularly, it may not only enhance physical performance but also improve mood, sleep, and cognitive function. However, it is no substitute for a balanced diet, regular exercise, and quality sleep.
[1] Jäger R, Purpura M, Shao A, Inoue T, Kreider RB. Analysis of the efficacy, safety, and regulatory status of novel forms of creatine - doi: 10.1007/s00726-011-0874-6
[2] Deitmer, Joachim W et al. “Energy Dynamics in the Brain: Contributions of Astrocytes to Metabolism and pH Homeostasis.” - doi:10.3389/fnins.2019.01301
[3] Fernandes-Pires, Gabriella, and Olivier Braissant. “Current and potential new treatment strategies for creatine deficiency syndromes.” - doi:10.1016/j.ymgme.2021.12.005
[4] Illes P, Rubini P, Yin H, Tang Y. Impaired ATP Release from Brain Astrocytes May be a Cause of Major Depression - doi: 10.1007/s12264-020-00494-7
[5] Mercimek-Andrews S, Salomons GS. Creatine Deficiency Disorders - https://www.ncbi.nlm.nih.gov/books/NBK3794/
[6] Ostojic, Sergej M et al. “Dietary creatine is associated with lower serum neurofilament light chain levels.”- doi:10.1139/apnm-2024-0064
[7] Chen, Kaiqing, and Xiaoping Hu. “Intranasal creatine administration increases brain creatine level and improves Barnes maze performance in rats.” - doi:10.1016/j.brainresbull.2023.110703
[8] Avgerinos KI, Spyrou N, Bougioukas KI, Kapogiannis D. Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials - doi: 10.1016/j.exger.2018.04.013
[9] Sandkühler, Julia Fabienne et al. “The effects of creatine supplementation on cognitive performance-a randomised controlled study.” - doi:10.1186/s12916-023-03146-5
[10] Gordji-Nejad, A., Matusch, A., Kleedörfer, S. et al. Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation - https://doi.org/10.1038/s41598-024-54249-9
[11] Konstantinos Prokopidis, Panagiotis Giannos, Konstantinos K Triantafyllidis, Konstantinos S Kechagias, Scott C Forbes, Darren G Candow, Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials - https://doi.org/10.1093/nutrit/nuac064
[12] Faulkner, Paul et al. “Relationship between depression, prefrontal creatine and grey matter volume.” - doi:10.1177/02698811211050550
[13] Yue, Qiang et al. “Quantitative 3.0T MR spectroscopy reveals decreased creatine concentration in the dorsolateral prefrontal cortex of patients with social anxiety disorder.” - doi:10.1371/journal.pone.0048105
[14] Cunha MP, Pazini FL, Rosa JM, Ramos-Hryb AB, Oliveira Á, Kaster MP, Rodrigues AL. Creatine, similarly to ketamine, affords antidepressant-like effects in the tail suspension test via adenosine A₁ and A2A receptor activation - doi: 10.1007/s11302-015-9446-7
[15] Bakian, A.V., Huber, R.S., Scholl, L. et al. Dietary creatine intake and depression risk among U.S. adults - https://doi.org/10.1038/s41398-020-0741-x
[16] Lyoo, In Kyoon et al. “A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder.” - doi:10.1176/appi.ajp.2012.12010009
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