Creatine

Creatine is an amino acid derivative that plays an important role in energy storage. Its phosphorylated form, phosphocreatine, is responsible for phosphorylating adenosine diphosphate (ADP) into adenosine triphosphate (ATP).1This is an important reaction because ATP acts as a phosphate donor which is responsible for catalyzing various reactions in the brain and muscle tissues that are essential for maintaining high function. While 95% of the body's creatine is found in skeletal muscle tissues, creatine also has effects in brain tissue. A number of studies have examined the effects of creatine on cognitive performance, mostly with respect to attention and working memory.

Pharmacology of Creatine

Creatine is an amino acid like compound formed from the reaction between L-arginine and glycine.2It is phosphorylated into phosphocreatine. Phosphocreatine acts as a phosphate donor to ADP, in order to generate ATP, which is the energy currency in the human body.1

creatine_conversion

Creatine (Cr) is converted into phosphocreatine (PCr), its active form. Subsequently, phosphocreatine is responsible for acting as a phosphate donor, in order to convert ADP to ATP. An increase in ATP levels is very important, as ATP acts as a phosphate donor that catalyzes many processes in the brain and muscle tissue.

For purposes of supplementation, creatine is usually consumed in the form of creatine monohydrate. Creatine is also naturally found in red meat and fish.1Therefore, vegetarian people tend to have lower levels of creatine in the body. Average levels of creatine are roughly 1.7g/kg body weight (e.g., 120g for an individual weighing 70kg).1

Creatine and Cognition

Several studies have aimed to study the effect of creatine supplementation on various aspects of cognition. It has been shown by several studies that creatine supplementation can lead to increases in brain levels of creatine.3,4,5

In elderly individuals, there is evidence that creatine may be helpful for improvement of short term working memory and attention. In one study involving 36 elderly adult participants (mean age 76), it was found that supplementation with creatine monohydrate led to significant differences in performance on the number recall and spatial recall tasks, two tests of working memory.6

One study looked at both physical and cognitive performance in response to creatine supplementation. In this double blind study of 19 participants, it was found that creatine administration resulted in significantly lower random movement generation after 24 hours. Regarding mood, creatine resulted in significantly lower self-reported fatigue and vigor after 24 hours compared with placebo. Regarding attention, it was found that the group ingesting creatine exhibited significantly lower changes in time taken on the choice reaction time test, compared to placebo at the 24 hour mark. This indicates that creatine may act as an important modulator of attention, possibly through decreased fatigue.7

creatine_attention_CRT_task

Creatine has been shown to speed up reaction times in the Choice Reaction Time task, at 24 hours after ingestion.

The effects of creating on vegetarians is of interest, because the most common sources of creatine in food are from red meat and fish.8In a study involving 128 young females, it was found that creatine consumption (5g) improved memory, improved performance in choice reaction times, and did not have an effect on verbal fluency and vigilance.8

creatine_vegetarian_improved_word_recall

Creatine was found to improved performance on the word recall task, a test for memory.

One study did report that creatine supplementation for a period of 6 weeks did not result in improvements in simple reaction time, logical symbolic reasoning, mathematical processing and memory recall.9

Editorial Opinion

Creatine supplementation may be beneficial for metabolic and cognitive gains. We recommend creatine supplementation for serious athletes who desire to achieve peak physical performance, as there is substantial evidence showing benefits of creatine on athletic performance. In the context of cognition, there is promising evidence regarding the efficacy of creatine for cognitive peformance, particularly with regards to attention and fatigue. Vegetarians may be interested in creatine supplementation, as some vegetarian diets may be mildly deficient in creatine. For other people, the potential gains from creatine may not outweigh the costs associated with careful dietary planning self-monitoring that is required in order to maintain safety. It is important to maintain adequate hydration when leveraging creatine for these purposes, as well as to plan out supplementation cycles.

  1. Owen, L., & Sunram-Lea, S. I. (2011). Metabolic agents that enhance ATP can improve cognitive functioning: a review of the evidence for glucose, oxygen, pyruvate, creatine, and L-carnitine. Nutrients, 3(8), 735-755.

  2. Guoyao, W. U., & Morris, S. M. (1998). Arginine metabolism: nitric oxide and beyond. Biochemical Journal, 336(1), 1-17.

  3. Dechent, P., Pouwels, P. J. W., Wilken, B., Hanefeld, F., & Frahm, J. (1999). Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 277(3), R698-R704.

  4. Lyoo, I. K., Kong, S. W., Sung, S. M., Hirashima, F., Parow, A., Hennen, J., ... & Renshaw, P. F. (2003). Multinuclear magnetic resonance spectroscopy of high-energy phosphate metabolites in human brain following oral supplementation of creatine-monohydrate. Psychiatry Research: Neuroimaging, 123(2), 87-100.

  5. Pan, J. W., & Takahashi, K. (2007). Cerebral energetic effects of creatine supplementation in humans. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 292(4), R1745-R1750.

  6. McMorris, T., Mielcarz, G., Harris, R. C., Swain, J. P., & Howard, A. (2007). Creatine supplementation and cognitive performance in elderly individuals. Aging, Neuropsychology, and Cognition, 14(5), 517-528.

  7. McMorris, T., Harris, R. C., Swain, J., Corbett, J., Collard, K., Dyson, R. J., ... & Draper, N. (2006). 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(1), 93-103.

  8. Benton, D., & Donohoe, R. (2011). The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores. British journal of nutrition, 1

  9. Rawson, E. S., Lieberman, H. R., Walsh, T. M., Zuber, S. M., Harhart, J. M., & Matthews, T. C. (2008). Creatine supplementation does not improve cognitive function in young adults. Physiology & behavior, 95(1), 130-134.

Emails worth reading.

Once a week, we'll send you the most compelling research, stories and updates from the world of human enhancement.

HVMN Co-founders Michael Brandt and Geoffrey Woo