Creatine: A Potential Therapeutic Agent for Restoring Brain Energy

The human brain depends on a constant energy supply, which is needed for proper functioning. Energy supply impairments can jeopardize brain function and even lead to the pathogenesis or progression of neurodegenerative diseases. Chronic disruption of energy causes degradation of cellular structures and creates conditions that favor the development of Parkinson’s, Alzheimer’s, or Huntington’s disease. In addition, impaired brain energy metabolism is one of the important contributors to the pathogenesis of psychiatric disorders. Thus, interventions that can increase or regulate local energy stores in the brain might be neuroprotective and represent a good therapeutic tool for managing various neurological and neurodegenerative conditions.

One of the potential therapeutic agents for restoring brain energy is creatine. Creatine is particularly important since it replenishes ATP (a cellular unit of energy) without relying on oxygen.

Creatine is better known as one of the most popular supplements for bodybuilding. Being a completely natural compound, it has no negative effects and is commonly used by gym goers. Creatine is mostly stored in muscles where it serves as an easily available source of energy. But according to scientific findings, creatine also concentrates in the brain. It is an important component of the creatine kinase/phosphocreatine system that plays an important role in the metabolic networks of the brain and central nervous system and is involved in many of the brain’s functions. Experimental studies have indicated that creatine can protect from ischemic cell damage (which is caused by a lack of oxygen) by preventing ATP (energy) depletion and reducing structural damage to the affected brain cells.

In spite of promising laboratory findings, investigation of creatine’s effects in the human brain has produced controversial results. So far, the studies on oral supplementation with creatine have demonstrated some benefits. For instance, one study in healthy young volunteers has shown that oral supplementation with creatine monohydrate for 4 weeks leads to a significant increase in the total creatine concentration in the participants’ brain, with the most pronounced rise seen in the thalamus. The fact that creatine concentrates in the brain after consumption clearly indicates that creatine can pass the blood-brain barrier, where the benefits of creatine supplementation for the brain can be expected.

Another study has investigated the impact of creatine consumption on brain chemistry, including the brain’s high energy phosphate metabolism. After two weeks of creatine supplementation, the brain’s creatine level significantly increased, as well as the concentrations of phosphocreatine and inorganic phosphate. This study clearly demonstrates the possibility of using creatine supplementation to modify high-energy phosphate metabolism in the brain. This is especially important for people with certain brain disorders as alterations in brain phosphate metabolism have been reported in depression, schizophrenia, and in cases of cocaine and opiate abuse.

The effects of creatine supplementation in another human study demonstrated that creatine can improve cognitive performance during oxygen deprivation. The participants in this study received creatine or placebo for seven days and were then exposed to a hypoxic gas mixture. In comparison to the placebo group, supplementation with creatine helped to restore cognitive performance, especially attention capacity that was affected by hypoxia. Also, creatine helped to maintain an appropriate neuronal membrane potential in brain cells. This research has demonstrated that creatine can be a valuable supplement when energy provision by cells is jeopardized. In addition, it supports the idea that creatine is beneficial not only for recovering muscle strength but for restoring the brain function too.

Approximately half of the daily requirement (around 3–4 grams) for creatine comes from alimentary sources, while the other half is endogenously produced in the body. Creatine is a carninutrient, meaning that it is available only from animal foods (mostly meat). Since creatine is not present in plant-based foods, plasma and muscle levels of creatine are commonly lower in vegetarians and vegans compared to omnivores. Thus, individuals whose diet is based on plant foods may benefit from creatine supplementation in terms of improvements in brain function. One study in young adult females investigated the impact of creatine supplementation on cognitive functions in both vegetarians and omnivores. Compared to the placebo group, 5 days of supplementation with creatine led to significant improvements in memory. This improvement in brain function was more pronounced in vegetarians. Another study investigated the effects of 6-week-long creatine supplementation in young vegetarians. In comparison with placebo, creatine-induced significant improvements in intelligence and working memory, with both functions depend on the speed of information processing. This study showed that brain performance is dependent on the level of energy available in the brain, which can be beneficially influenced by creatine supplementation.

Creatine supplementation seems to be beneficial not only for healthy people but also for individuals with psychiatric disorders. For instance, decreased creatine levels have been reported in the brains of patients with anxiety disorders. Post-traumatic stress disorder (PTSD) is a type of anxiety condition that develops in subjects that have experienced traumatic situations. Creatine supplementation was shown to be beneficial in treatment-resistant PTSD patients in relief from symptoms and improved sleep quality.

Furthermore, studies of creatine functions in the central nervous system underline creatine’s therapeutic potential in neurodegenerative diseases, since creatine supplementation can reduce the loss of neuronal cells. Also, animal model studies have demonstrated that the size of creatine stores in the brain play an important role in Alzheimer’s disease, and creatine supplementation was found to be beneficial in animal models of Parkinson’s disease as well, a rationale for using creatine in these conditions.

To sum up, it seems that creatine can be used as a supplement for replenishing the brain’s energy stores. This can further improve cognitive functions and brain performance, with the effects more pronounced in vegans and vegetarians. In addition, creatine has therapeutic potential in psychiatric disorders and neurodegenerative conditions.

References

Turner, C.E., Byblow, W.D., Gant, N. (2015) Creatine supplementation enhances corticomotor excitability and cognitive performance during oxygen deprivation. Journal of Neuroscience. 35(4): 1773-1780. doi:10.1523/JNEUROSCI.3113-14.2015

Dechent, P., Pouwels, P.J., Wilken, B., Hanefeld, F., Frahm, J. (1999) Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. American Journal of Physiology. 277(3 Pt 2): R698-R704. PMID:10484486

Lyoo, I.K., Kong, S.W., Sung, S.M., Hirashima, F., Parow, A., Hennen, J., Cohen, B.M., Renshaw, P.F. (2003) Multinuclear magnetic resonance spectroscopy of high-energy phosphate metabolites in human brain following oral supplementation of creatine-monohydrate. Psychiatry Res. 123(2): 87-100. PMID:12850248

Brosnan, M.E., Brosnan, J.T. (2016) The role of dietary creatine. Amino Acids. 48(8): 1785-1791. doi:10.1007/s00726-016-2188-1

Benton, D., Donohoe, R. (2011) The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores. British Journal of Nutrition. 105(7):1100-1105. doi:10.1017/S0007114510004733

Rae, C., Digney, A.L., McEwan, S.R., Bates, T.C. (2003) Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proceedings. Biological Sciences. 270(1529): 2147-2150. doi:10.1098/rspb.2003.2492

Andres, R.H., Ducray, A.D., Schlattner, U., Wallimann, T., Widmer, H.R. (2008) Functions and effects of creatine in the central nervous system. Brain Research Bulletin. 76(4): 329-343. doi:10.1016/j.brainresbull.2008.02.035

This guest article originally appeared on the award-winning health and science blog and brain-themed community, BrainBlogger: Creatine and the Brain.

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