Creatine is so much more than just an effective way of building muscles.
A simple search on PubMed for creatine and brain shows the many ways creatine can both protect and enhance brain function and help with energy levels and even depression.
Here are my top 5
1. Creatine for the Treatment of Depression.
Depressed mood, which can occur in the context of major depressive disorder, bipolar disorder, and other conditions, represents a serious threat to public health and wellness. Conventional treatments are not effective for a significant proportion of patients and interventions that are often beneficial for treatment-refractory depression are not widely available.
There is, therefore, an immense need to identify novel antidepressant strategies, particularly strategies that target physiological pathways that are distinct from those addressed by conventional treatments. There is growing evidence from human neuroimaging, genetics, epidemiology, and animal studies that disruptions in brain energy production, storage, and utilization are implicated in the development and maintenance of depression. Creatine, a widely available nutritional supplement, has the potential to improve these disruptions in some patients, and early clinical trials indicate that it may have efficacy as an antidepressant agent.
2. Creatine as a booster for human brain function.
Creatine, a naturally occurring nitrogenous organic acid found in animal tissues, has been found to play key roles in the brain including buffering energy supply, improving mitochondrial efficiency, directly acting as an anti-oxidant and acting as a neuroprotectant.
Much of the evidence for these roles has been established in vitro or in pre-clinical studies. Here, we examine the roles of creatine and explore the current status of translation of this research into use in humans and the clinic. Some further possibilities for use of creatine in humans are also discussed.
3. Creatine as a Neuroprotector: an Actor that Can Play Many Parts.
Creatine is a nitrogenous organic acid that plays a central role as an energy buffer in high energy demanding systems, including the muscular and the central nervous system. It can be acquired from diet or synthesized endogenously, and its main destination is the system creatine/phosphocreatine that strengthens cellular energetics via a temporal and spatial energy buffer that can restore cellular ATP without a reliance on oxygen. This compound has been proposed to possess secondary roles, such as direct and indirect antioxidant, immunomodulatory agent, and possible neuromodulation.
However, these effects may be associated with its bioenergetic role in the mitochondria. Given the fundamental roles that creatine plays in the CNS, several preclinical and clinical studies have tested the potential that creatine has to treat degenerative disorders. However, although in vitro and in vivo animal models are highly encouraging, most clinical trials fail to reproduce positive results suggesting that the prophylactic use for neuroprotection in at-risk populations or patients is the most promising field.
Nonetheless, the only clearly positive data of the creatine supplementation in human beings are related to the (rare) creatine deficiency syndromes. It seems critical that future studies must establish the best dosage regime to increase brain creatine in a way that can relate to animal studies, provide new ways for creatine to reach the brain, and seek larger experimental groups with biomarkers for prediction of efficacy.
4. Dietary supplement creatine protects against traumatic brain injury.
Creatine, one of the most common food supplements used by individuals at almost every level of athleticism, promote gains in performance, strength, and fat-free mass. Recent experimental findings have demonstrated that creatine affords significant neuroprotection against ischemic and oxidative insults.
The present experiments investigated the possible effect of creatine dietary supplementation on brain tissue damage after experimental traumatic brain injury. Results demonstrate that chronic administration of creatine ameliorated the extent of cortical damage by as much as 36% in mice and 50% in rats.
Protection seems to be related to creatine-induced maintenance of mitochondrial bioenergetics. Mitochondrial membrane potential was significantly increased, intramitochondrial levels of reactive oxygen species and calcium were significantly decreased, and adenosine triphosphate levels were maintained. Induction of mitochondrial permeability transition was significantly inhibited in animals fed creatine. This food supplement may provide clues to the mechanisms responsible for neuronal loss after traumatic brain injury and may find use as a neuroprotective agent against acute and delayed neurodegenerative processes.
5. Creatine protects against excitoxicity in an in vitro model of neurodegeneration.
Creatine has been shown to be neuroprotective in aging, neurodegenerative conditions and brain injury. As a common molecular background, oxidative stress and disturbed cellular energy homeostasis are key aspects in these conditions. Moreover, in a recent report we could demonstrate a life-enhancing and health-promoting potential of creatine in rodents, mainly due to its neuroprotective action. In order to investigate the underlying pharmacology mediating these mainly neuroprotective properties of creatine, cultured primary embryonal hippocampal and cortical cells were challenged with glutamate or H(2)O(2).
In good agreement with our in vivo data, creatine mediated a direct effect on the bioenergetic balance, leading to an enhanced cellular energy charge, thereby acting as a neuroprotectant. Moreover, creatine effectively antagonized the H(2)O(2)-induced ATP depletion and the excitotoxic response towards glutamate, while not directly acting as an antioxidant. Additionally, creatine mediated a direct inhibitory action on the NMDA receptor-mediated calcium response, which initiates the excitotoxic cascade. Even excessive concentrations of creatine had no neurotoxic effects, so that high-dose creatine supplementation as a health-promoting agent in specific pathological situations or as a primary prophylactic compound in risk populations seems feasible. In conclusion, we were able to demonstrate that the protective potential of creatine was primarily mediated by its impact on cellular energy metabolism and NMDA receptor function, along with reduced glutamate spillover, oxidative stress and subsequent excitotoxicity.