Researchers have shifted their focus from the effects on exercising muscle to the health effects of creatine supplementation. In this article, we look at the brain health benefits of creatine monohydrate supplementation.
By Dr. Adam M. Gonzalez
SHIFTED’s Chief Scientific Officer
Key Points:
- Researchers have shown an emerging interest in creatine monohydrate’s benefits on brain health.
- Creatine monohydrate can increase brain creatine concentration and there are overwhelmingly positive findings related to its effects on brain health and function.
- Creatine monohydrate has shown to improve measures of cognition and memory in humans.
- Creatine supplementation can alleviate decrements in cognition, mood, and skill performance when in a sleep-deprived state.
- Increasing brain creatine concentrations may help alleviate some of the symptoms of depression and anxiety.
- Creatine supplementation prior to a head injury has shown to be neuroprotective.
- The dosage required for increasing brain creatine content may be as high as 10-20 grams per day.
Creatine Monohydrate: The holy grail of bodybuilding supplements
Supplementing daily with 5 grams of creatine monohydrate can increases skeletal muscle creatine stores by 20-40% to support the regeneration of energy [i.e., adenosine triphosphate (ATP)] via the creatine kinase/phosphocreatine energy system (9). The research clearly shows that creatine monohydrate is the most effective dietary supplement for increasing high-intensity exercise capacity and enhancing muscle gains when combined with training (9).
Given its efficacy and tremendous safety profile, creatine monohydrate is universally recommended to bodybuilders and strength athletes as there is no reason that one would want to miss out on its benefits. However, over the years, it has become more and more evident that the benefits of creatine monohydrate extend beyond muscle. It turns out that everyone – young and old, active and inactive, males and females –should consider creatine monohydrate supplementation to reap brain health benefits.
Shifting the focus of creatine monohydrate research to the brain
In the human body, approximately 95% of creatine is stored in skeletal muscle, but small quantities are also found in the brain. Like muscle, creatine is an important compound for continued homeostasis of brain bioenergetics. In other words, during energy-demanding cognitive tasks, we also use creatine to maintain ATP levels in the brain.
Over the last couple decades, researchers have shifted their focus from the effects on exercising muscle to the wider health effects of creatine supplementation – even when individuals are not engaging in exercise training. The emerging interest in the potential benefits of creatine supplementation on brain health has led to some very promising findings. Is it possible that creatine supplementation can enhance brain health and function?
First, it is well appreciated that brain creatine homeostasis plays an important role in brain health. In the rare cases of brain creatine deficiency syndromes, the faulty creatine metabolism (i.e., creatine formation and transportation) can lead to developmental delays, intellectual disability, and movement disorders. Also, several neurodegenerative disorders have been shown to be accompanied by low brain creatine concentrations (3).
For healthy individuals, creatine is supplied to the brain from both endogenous production and dietary sources such as red meat and seafood. Just as supplementing with creatine monohydrate has shown to safely increase creatine levels in skeletal muscle, there is also evidence that supplementation can increase creatine levels in the brain. The key difference seems to be that longer-term and higher-dosage creatine supplementation may be required to increase brain creatine stores. The dosage required to increase brain creatine content may be as high as 10-20 grams per day (3).
For obvious reasons, most of the brain research involving creatine supplementation has been conducted in animal models, but there has been a growing amount of human data. Collectively, creatine supplementation can increase brain creatine stores, improve cognition and memory, and reduce symptoms of depression and anxiety. Also, creatine supplementation can improve recovery from a head injury (e.g., concussion).
Creatine to improve cognitive function
Creatine monohydrate has shown to improve measures of cognition and memory in humans (4, 7). Now, creatine monohydrate will not rapidly make you an all-knowing rocket scientist. However, it shows great promise for improving cognition under stressful situations.
Stress is a hard thing to control for in research, so researchers have found unique ways to examine the effects of creatine under “stressful situation”.
One study found that creatine supplementation (20 grams per day for 7 days) improved performance on a neuropsychological test when healthy individuals were exposed to acute oxygen deprivation (10% oxygen for 90 minutes) (19). In the creatine supplemented group, corticomotor excitability increased and the hypoxia-induced decrements in cognitive performance were restored (especially attentional capacity). The creatine supplemented group also increased brain creatine concentrations by 9.2% on average (19).
Creatine monohydrate also seems to be quite beneficial during periods of mental fatigue. A study found that supplementing creatine monohydrate (20 grams per day) for 7 days enhanced a prolonged test of executive functioning (Stroop test) following a 90-minute mentally challenging task (13). Also, creatine monohydrate (8 grams per day for 5 days) has shown to reduce mental fatigue following a psychologically stressful test that requires intense concentration and effort (20). This study also showed that the cognitive benefits may be due to improved oxygenation in the brain (20).
Supplementation may also be beneficial during periods of sleep deprivation. Compared to a placebo group, young adults who supplemented creatine (20 grams per day for 7 days) displayed significant improvements in cognition tests, reaction time, balance, and mood after 24 hours of sleep deprivation (11). A follow-up study in young adults also showed benefits of creatine loading on some cognitive assessments after 36 hours of sleep deprivation (10).
Using an athletic population, another study found that a single dose of creatine monohydrate (50 or 100 mg per kg of bodyweight) consumed 1.5 hours prior to skill-based performance testing attenuated impairments in passing accuracy when athletes were only allowed to sleep for 3-5 hours the night before. Collectively, the evidence supports that creatine supplementation can alleviate decrements in cognition, mood, and skill performance when in a sleep-deprived state.
Supplementing creatine monohydrate is also particularly helpful in older populations. For example, supplementing with 20 grams per day for 7 days improved performance on memory tests in a individuals aged 68-75 years of age (12).
Creatine to reduce symptoms of depression and anxiety
The relationship between brain creatine concentrations and the development of depression/anxiety is far from being fully understood (3). However, some studies have shown that low creatine concentrations in areas of the prefrontal cortex are associated with poorer depression/anxiety scores. For example, one study reported a negative relationship between brain creatine concentrations with scores on the ‘Children’s Depression Rating Scale’ in young females (13-20 years of age) with major depressive disorder (8).
Individuals with social anxiety disorder have also been shown to have lower brain creatine concentrations than healthy control subjects (21). Even in the general population, individuals who scored lower on the ‘Depression, Anxiety, and Stress Scale’ had lower brain creatine concentrations (6).
Based upon these findings, it is possible that increasing levels of creatine in brain regions such as the prefrontal cortex via supplementation may help to alleviate some of the symptoms of depression and anxiety. The optimal dose and supplementation time course required for creatine monohydrate to potentially alleviate symptoms of depression/anxiety is not yet clear. More clinical trials examining the effects of creatine monohydrate supplementation on depression/anxiety are needed.
Creatine to recover from a head injury
Aside from the muscle benefits, one of the strongest rationales for why athletes (especially contact sports) should take creatine monohydrate is the neuroprotective effects. Supplementing with creatine monohydrate prior to suffering a traumatic brain injury (TBI) has shown to aid recovery outcomes.
There has been speculation that having higher brain creatine concentrations prior to a ‘blow to the head’ would make you more resilient to the altered energy availability and blood flow to the brain that accompany a TBI. In rat models, creatine supplementation prior to a head injury has shown to be neuroprotective (16-18). For example, compared to a placebo, supplementing creatine for 3 to 5 days prior to a controlled TBI resulted in less cortical brain damage (18). Cortical brain damage was also lessened by continuing creatine supplementation for the month following the TBI (18).
There is also evidence of neuroprotection in humans. It has been shown that initiating creatine supplementation (0.4 grams per kilogram of bodyweight daily for 6 months) following a TBI in children and adolescents (1-18 years of age) resulted in more favorable recovery outcomes including reduced amnesia, headaches, dizziness, and fatigue along with improved disability and cognitive function (14, 15). Therefore, creatine supplementation has shown great promise for alleviating symptoms associated with TBIs. The kicker here is that you should be taking creatine regularly prior to suffering a head injury.
Build your muscles – and your brain!
Creatine monohydrate can increase brain creatine concentration and there are overwhelmingly positive findings related to its effects on brain health and function. Since creatine monohydrate is not associated with any adverse side effects (1, 9) and there are only upsides for the muscle and brain health [oh yeah! – and bone health (2)], there is little argument for why you shouldn’t be supplementing with a high-quality creatine supplement.
Literally, all of the research presented in this article is from studies that provided creatine in the form of creatine monohydrate – which is the most effective and bioavailable form of creatine (5). The primary source of creatine used in research to test its safety and effectiveness has been the patented creatine monohydrate manufactured in Germany – Creapure® – which is well accepted as the gold standard of creatine.
Click here to buy SHIFTED Creatine – The most high-quality creatine on the market, 100% CreaPure® Creatine Monohydrate.
An effective and convenient way to get more creatine monohydrate in your diet is to include as part of your pre workout. See this article for more information on the effects of creatine timing.
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About the Author
Adam M. Gonzalez is an associate professor in the Department of Allied Health and Kinesiology at Hofstra University. He earned a Ph.D. in Exercise Physiology from the University of Central Florida in 2015 and holds certifications as a Certified Strength and Conditioning Specialist (CSCS), along with a Certified Sports Nutritionist Certification (CISSN).
His primary research interests include exercise and nutritional strategies to optimize body composition, maximize health, and enhance adaptations to exercise. He was also awarded the 2022 Nutritional Research Achievement Award by the National Strength and Conditioning Association.
References
- Antonio, J, Candow DG, Forbes SC, Gualano B, Jagim AR, Kreider RB, Rawson ES, Smith-Ryan AE, VanDusseldorp TA, and Willoughby DS. Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show? Journal of the International Society of Sports Nutrition 18: 13, 2021. https://pubmed.ncbi.nlm.nih.gov/33557850/
- Candow, DG, Forbes SC, Chilibeck PD, Cornish SM, Antonio J, and Kreider RB. Effectiveness of creatine supplementation on aging muscle and bone: focus on falls prevention and inflammation. Journal of clinical medicine 8: 488, 2019. https://pubmed.ncbi.nlm.nih.gov/30978926/
- 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 Medicine 1-17, 2023. https://pubmed.ncbi.nlm.nih.gov/37368234/
- Dolan, E, Gualano B, and Rawson ES. Beyond muscle: The effects of creatine supplementation on brain creatine, cognitive processing, and traumatic brain injury. European journal of sport science 19: 1-14, 2019. https://pubmed.ncbi.nlm.nih.gov/30086660/
- Escalante, G, Gonzalez AM, St Mart D, Torres M, Echols J, Islas M, and Schoenfeld BJ. Analysis of the efficacy, safety, and cost of alternative forms of creatine available for purchase on Amazon. com: are label claims supported by science? Heliyon 8: e12113, 2022. https://pubmed.ncbi.nlm.nih.gov/36544833/
- Faulkner, P, Paioni SL, Kozhuharova P, Orlov N, Lythgoe DJ, Daniju Y, Morgenroth E, Barker H, and Allen P. Relationship between depression, prefrontal creatine and grey matter volume. Journal of Psychopharmacology 35: 1464-1472, 2021. https://pubmed.ncbi.nlm.nih.gov/34697970/
- Forbes, SC, Cordingley DM, Cornish SM, Gualano B, Roschel H, Ostojic SM, Rawson ES, Roy BD, Prokopidis K, and Giannos P. Effects of creatine supplementation on brain function and health. Nutrients 14: 921, 2022. https://pubmed.ncbi.nlm.nih.gov/35267907/
- Kondo, DG, Forrest LN, Shi X, Sung Y-H, Hellem TL, Huber RS, and Renshaw PF. Creatine target engagement with brain bioenergetics: a dose-ranging phosphorus-31 magnetic resonance spectroscopy study of adolescent females with SSRI-resistant depression. Amino Acids 48: 1941-1954, 2016. https://pubmed.ncbi.nlm.nih.gov/26907087/
- Kreider, RB, Kalman DS, Antonio J, Ziegenfuss TN, Wildman R, Collins R, Candow DG, Kleiner SM, Almada AL, and Lopez HL. International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition 14: 18, 2017. https://pubmed.ncbi.nlm.nih.gov/28615996/
- McMorris, T, Harris RC, Howard AN, Langridge G, Hall B, Corbett J, Dicks M, and Hodgson C. Creatine supplementation, sleep deprivation, cortisol, melatonin and behavior. Physiology & behavior 90: 21-28, 2007. https://pubmed.ncbi.nlm.nih.gov/17046034/
- McMorris, T, Harris RC, Swain J, Corbett J, Collard K, Dyson RJ, Dye L, Hodgson C, and Draper N. Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol. Psychopharmacology 185: 93-103, 2006. https://pubmed.ncbi.nlm.nih.gov/16416332/
- McMorris, T, Mielcarz G, Harris RC, Swain JP, and Howard A. Creatine supplementation and cognitive performance in elderly individuals. Aging, Neuropsychology, and Cognition 14: 517-528, 2007. https://pubmed.ncbi.nlm.nih.gov/17828627/
- Roelands, B, Pluym B, Tassignon B, Verschueren J, and Meeusen R. Can creatine combat the mental fatigue-associated decrease in visuomotor skills? Medicine and science in sports and exercise 52: 120-130, 2020. https://pubmed.ncbi.nlm.nih.gov/31403610/
- Sakellaris, G, Kotsiou M, Tamiolaki M, Kalostos G, Tsapaki E, Spanaki M, Spilioti M, Charissis G, and Evangeliou A. Prevention of complications related to traumatic brain injury in children and adolescents with creatine administration: an open label randomized pilot study. Journal of Trauma and Acute Care Surgery 61: 322-329, 2006. https://pubmed.ncbi.nlm.nih.gov/16917445/
- Sakellaris, G, Nasis G, Kotsiou M, Tamiolaki M, Charissis G, and Evangeliou A. Prevention of traumatic headache, dizziness and fatigue with creatine administration. A pilot study. Acta paediatrica 97: 31-34, 2008. https://pubmed.ncbi.nlm.nih.gov/18053002/
- Saraiva, ALL, Ferreira APO, Silva LFA, Hoffmann MS, Dutra FD, Furian AF, Oliveira MS, Fighera MR, and Royes LFF. Creatine reduces oxidative stress markers but does not protect against seizure susceptibility after severe traumatic brain injury. Brain research bulletin 87: 180-186, 2012. https://pubmed.ncbi.nlm.nih.gov/22051612/
- Scheff, SW, and Dhillon HS. Creatine-enhanced diet alters levels of lactate and free fatty acids after experimental brain injury. Neurochemical research 29: 469-479, 2004. https://pubmed.ncbi.nlm.nih.gov/15002746/
- Sullivan, PG, Geiger JD, Mattson MP, and Scheff SW. Dietary supplement creatine protects against traumatic brain injury. Annals of neurology 48: 723-729, 2000. https://pubmed.ncbi.nlm.nih.gov/11079535/
- Turner, CE, Byblow WD, and Gant N. Creatine supplementation enhances corticomotor excitability and cognitive performance during oxygen deprivation. Journal of Neuroscience 35: 1773-1780, 2015. https://pubmed.ncbi.nlm.nih.gov/25632150/
- Watanabe, A, Kato N, and Kato T. Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation. Neuroscience research 42: 279-285, 2002. https://pubmed.ncbi.nlm.nih.gov/11985880/
- Yue, Q, Liu M, Nie X, Wu Q, Li J, Zhang W, Huang X, and Gong Q. Quantitative 3.0 T MR spectroscopy reveals decreased creatine concentration in the dorsolateral prefrontal cortex of patients with social anxiety disorder. 2012. https://pubmed.ncbi.nlm.nih.gov/23110183/