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November 11, 2021 4 min read
Creatine is used by athletes to increase athletic performance by improving energy supply to muscle tissues.
Its main function is to immediately supply energy to tissues with increased energy demands, such as muscle and brain. This can be achieved by phosphocreatine’s high energy phosphate bonds that are available for immediate adenosine triphosphate (ATP) replenishment in energy demanding circumstances.
It has been widely used to improve performance during anaerobic exercise. Creatine is also an essential brain compound and some hypothesize that it aids cognition by improving energy supply and neuroprotection.
In this article, I’ll give you the latest evidence on the effects of oral creatine administration on cognitive function in healthy individuals.
Creatine supplementation and cognition of healthy individuals
Evidence shows that creatine supplementation may improve short term memory and intelligence/reasoning. (1)
The effect isn’t clear on long term memory, spatial memory, executive function and attention. The effect is primarily in the elderly population as young adults didn’t’ show changes in any task, after creatine supplementation. (1)
This is in agreement with research showing that the elderly require additional energy in comparison with young individuals for completing cognitive tasks. (2)
It is possible that creatine supplementation improves cognition of diseased, aged or stressed individuals whereas for younger, unstressed individuals there is no such a benefit. (3)
There seems to be a difference in improvement on some cognitive tasks as compared to others.
It’s possible that as the task becomes more demanding, creatine could be of up to a threshold. When the difficulty level exceeds this threshold, creatine supplementation may no longer have a beneficial impact. Another factor that may account for different responses in each task is creatine dosing (daily dose x duration of treatment). Oral creatine intake is known to increase brain’s creatine concentration. (4)
However, accumulation in tissues does not depend only on daily dosing and supplementation duration. (5)
One of the greatest determinants of creatine accumulation in the brain post supplementation is the basal level of creatine. The potential for enhancing creatine levels in the brain after supplementation is inversely related to its baseline brain levels. (5)
Creatine uptake in the brain may also be affected by insulin levels or a recent meal, similar to what is seen with creatine uptake in skeletal muscle. Also, general diet habits may affect the response to exogenous creatine since this nutrient is mostly found in meat and fish.
In summary, the evidence suggests that creatine accumulation and performance in various cognitive tasks is not only a matter of dosing but is also affected by factors such as basal creatine levels, insulin levels, previous meals and general diet habits.
Creatine’s link to cognitive function
The importance of creatine in brain function is suggested by the presence of creatine kinase isoforms in multiple brain areas including the cerebellum, hippocampus, pontine reticular formation, red nucleus, cerebral cortex and choroid plexus. (6)
In addition, inborn errors of metabolism that result in deficiency of creatine transporter or creatine itself are characterized by cognitive and neurodevelopment defects (7), which may be reversed by supplementing with creatine. (8)
In support, experimental deletion of the enzyme creatine kinase in rodents results in learning problems. (9)
All of these facts underline the importance of creatine in cognitive function. There is also evidence that creatine contributes to neuroprotection by reversing mitochondrial dysfunction in neurodegenerative diseases. In a study of Huntington’s disease patients, creatine decreased glutamate availability (the primary mediator of excitotoxicity). (10)
Excitotoxicity is where nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamate become pathologically high resulting in excessive stimulation of receptors.
Creatine supplementation has been proven safe and is usually used by athletes to increase their performance, especially strength athletes/bodybuilders.
The evidence is clear on the benefits of creatine for anaerobic performance (i.e. weightlifting, sprinting, football, etc) that involve short burst of intense activity followed by a short periods of recovery before the next bout of activity.
In addition, creatine is an important compound for the brain and may support various brain regions in terms of energy supply and neuroprotection. The research to date indicates that oral creatine intake may improve performance on memory and intelligence tasks.
For other aspects of cognition, such as attention, executive function, response inhibition, word fluency, reaction time and mental fatigue, the results were inconclusive.
Creatine supplementation may have a selective positive effect on individuals subjected to various kinds of stress and aging, and I highly recommend ATP Fusion as a staple in your supplementation regimen.
1 Avgerinos, K. I., Spyrou, N., Bougioukas, K. I. & Kapogiannis, D. Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials. Exp Gerontol 108, 166-173, doi:10.1016/j.exger.2018.04.013 (2018).
2 Toescu, E. C. Normal brain ageing: models and mechanisms. Philos Trans R Soc Lond B Biol Sci 360, 2347-2354, doi:10.1098/rstb.2005.1771 (2005).
3 Turner, C. E., Byblow, W. D. & Gant, N. Creatine supplementation enhances corticomotor excitability and cognitive performance during oxygen deprivation. J Neurosci 35, 1773-1780, doi:10.1523/JNEUROSCI.3113-14.2015 (2015).
4 Dechent, P., Pouwels, P. J., Wilken, B., Hanefeld, F. & Frahm, J. Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. Am J Physiol 277, R698-704, doi:10.1152/ajpregu.1999.277.3.R698 (1999).
5 Pan, J. W. & Takahashi, K. Cerebral energetic effects of creatine supplementation in humans. Am J Physiol Regul Integr Comp Physiol 292, R1745-1750, doi:10.1152/ajpregu.00717.2006 (2007).
6 Kaldis, P., Hemmer, W., Zanolla, E., Holtzman, D. & Wallimann, T. 'Hot spots' of creatine kinase localization in brain: cerebellum, hippocampus and choroid plexus. Dev Neurosci 18, 542-554, doi:10.1159/000111452 (1996).
7 Salomons, G. S. et al. X-linked creatine transporter defect: an overview. J Inherit Metab Dis 26, 309-318, doi:10.1023/a:1024405821638 (2003).
8 Stockler, S., Hanefeld, F. & Frahm, J. Creatine replacement therapy in guanidinoacetate methyltransferase deficiency, a novel inborn error of metabolism. Lancet 348, 789-790, doi:10.1016/s0140-6736(96)04116-5 (1996).
9 Jost, C. R. et al. Creatine kinase B-driven energy transfer in the brain is important for habituation and spatial learning behaviour, mossy fibre field size and determination of seizure susceptibility. Eur J Neurosci 15, 1692-1706, doi:10.1046/j.1460-9568.2002.02001.x (2002).
10 Bender, A. et al. Creatine supplementation lowers brain glutamate levels in Huntington's disease. J Neurol 252, 36-41, doi:10.1007/s00415-005-0595-4 (2005).