Creatine is an endogenous compound synthesized from arginine, glycine and methionine. This dietary supplement can be acquired from food sources such as meat and fish, along with athlete supplement powders. Since the majority of creatine is stored in skeletal muscle, dietary creatine supplementation has traditionally been important for athletes and bodybuilders to increase the power, strength, and mass of the skeletal muscle. However, new uses for creatine have emerged suggesting that it may be important in preventing or delaying the onset of neurodegenerative diseases associated with aging. On average, 30% of muscle mass is lost by age 80, while muscular weakness remains a vital cause for loss of independence in the elderly population. In light of these new roles of creatine, the dietary supplement’s usage has been studied to determine its efficacy in treating congestive heart failure, gyrate atrophy, insulin insensitivity, cancer, and high cholesterol. In relation to the brain, creatine has been shown to have antioxidant properties, reduce mental fatigue, protect the brain from neurotoxicity, and improve facets/components of neurological disorders like depression and bipolar disorder. The combination of these benefits has made creatine a leading candidate in the fight against age-related diseases, such as Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, long-term memory impairments associated with the progression of Alzheimer’s disease, and stroke. In this review, we explore the normal mechanisms by which creatine is produced and its necessary physiology, while paying special attention to the importance of creatine supplementation in improving diseases and disorders associated with brain aging and outlining the clinical trials involving creatine to treat these diseases.
2018-avgerinos.pdf: “Effects of creatine supplementation on cognitive function of healthy individuals_ A systematic review of randomized controlled trials”, Konstantinos I. Avgerinos, Nikolaos Spyrou, Konstantinos I. Bougioukas, Dimitrios Kapogiannis
To assess the effects of creatine supplementation, associated or not with strength training, upon emotional and cognitive measures in older woman.
This is a 24-week, parallel-group, double-blind, randomized, placebo-controlled trial. The individuals were randomly allocated into one of the following groups (n = 14 each): 1) placebo, 2) creatine supplementation, 3) placebo associated with strength training or 4) creatine supplementation associated with strength training. According to their allocation, the participants were given creatine (4 x 5 g/d for 5 days followed by 5 g/d) or placebo (dextrose at the same dosage) and were strength trained or not. Cognitive function, assessed by a comprehensive battery of tests involving memory, selective attention, and inhibitory control, and emotional measures, assessed by the Geriatric Depression Scale, were evaluated at baseline, after 12 and 24 weeks of the intervention. Muscle strength and food intake were evaluated at baseline and after 24 weeks.
After the 24-week intervention, both training groups (ingesting creatine supplementation and placebo) had significant reductions on the Geriatric Depression Scale scores when compared with the non-trained placebo group (p = 0.001 and p = 0.01, respectively) and the non-trained creatine group (p < 0.001 for both comparison). However, no statistically-significant differences were observed between the non-trained placebo and creatine (p = 0.60) groups, or between the trained placebo and creatine groups (p = 0.83). Both trained groups, irrespective of creatine supplementation, had better muscle strength performance than the non-trained groups. Neither strength training nor creatine supplementation altered any parameter of cognitive performance. Food intake remained unchanged.
Creatine supplementation did not promote any significant change in cognitive function and emotional parameters in apparently healthy older individuals. In addition, strength training per se improved emotional state and muscle strength, but not cognition, with no additive effects of creatine supplementation.
2016-meregefilho.pdf: “Does brain creatine content rely on exogenous creatine in healthy youth? A proof-of-principle study”, Mr. Carlos Alberto Abujabra Merege-Filho, Dr. Maria Concepción Garcia Otaduy, Dr. Ana Lúcia Sá-Pinto, Miss Maira Okada Oliveira, Miss Lívia de Souza Gonçalves, Miss Ana Paula Tanaka Hayashi, Prof.Dr. Hamilton Roschel, Dr. Rosa Maria Rodrigues Pereira, Dr. Clovis Artur Silva, Dr. Sonia Maria Dozzi Brucki, Dr. Claudia da Costa Leite, Prof. Bruno Gualano
Background: We investigated the effects of sleep deprivation with or without acute supplementation of caffeine or creatine on the execution of a repeated rugby passing skill.
Method: Ten elite rugby players completed 10 trials on a simple rugby passing skill test (20 repeats per trial), following a period of familiarisation. The players had between 7–9 h sleep on 5 of these trials and between 3–5 h sleep (deprivation) on the other 5. At a time of 1.5 h before each trial, they undertook administration of either: placebo tablets, 50 or 100 mg/kg creatine, 1 or 5 mg/kg. Saliva was collected before each trial and assayed for salivary free cortisol and testosterone.
Results: Sleep deprivation with placebo application resulted in a significant fall in skill performance accuracy on both the dominant and non-dominant passing sides (p < 0.001). No fall in skill performance was seen withdoses of 1 or 5 mg/kg, and the two doses were not significantly different in effect. Similarly, no deficit was seen with creatine administration at 50 or 100 mg/kg and the performance effects were not significantly different. Salivary testosterone was not affected by sleep deprivation, but trended higher with the 100 mg/kg creatine dose, compared to the placebo treatment (p = 0.067). Salivary cortisol was elevated (p = 0.001) with the 5 mg/kg dose of caffeine (vs. placebo).
Conclusion: Acute sleep deprivation affects performance of a simple repeat skill in elite athletes and this was ameliorated by a single dose of eitheror creatine. Acute creatine use may help to alleviate decrements in skill performance in situations of sleep deprivation, such as transmeridian travel, and caffeine at low doses appears as efficacious as higher doses, at alleviating sleep deprivation deficits in athletes with a history of low use. Both options are without the side effects of higher dose use.
2020-vancutsem.pdf: “Can Creatine Combat the Mental Fatigue-associated Decrease in Visuomotor Skills?”, (2020-01; ):
Purpose: The importance of the brain in sports was recently confirmed by the negative effect of mental fatigue (MF) on sport-specific psychomotor skills. Creatine supplementation improves strength but can also improve cognitive functioning. To explore the role of creatine in combating MF, we evaluated whether creatine supplementation counteracts the MF-associated impairment in sport-specific psychomotor skills.
Methods: In 23°C, 14 healthy participants (4 females, 10 males; mean ± SD, age = 24 ± 3 yr, mass = 74 ± 13 kg, height = 179 ± 9 cm) performed a 90-min mentally fatiguing task (counterbalanced, crossover, and double-blinded; ie., Stroop task) in two different conditions: after a 7-d creatine supplementation (CR; 20 g·d−1) and after a 7-d calcium lactate supplementation (placebo [PLAC]), separated by a 5-wk washout. In both conditions, a 7-min sport-specific visuomotor task, a dynamic handgrip strength endurance task, and a 3-min Flanker task was performed before and after the mentally fatiguing task. Physiological and perceptual responses were measured throughout the protocol.
Results: Handgrip strength endurance was higher in CR compared with PLAC (p = 0.022). MF impaired visuomotor response time (+4.4%; p = 0.022) and Flanker accuracy (−5.0%; p = 0.009) in both conditions. Accuracy on the Stroop task was higher in CR compared with PLAC (+4.9%; p = 0.026). Within the perceptual and physiological parameters, only motivation and vigor (p ≤ 0.027) were lower in CR compared with PLAC.
Conclusion: Creatine supplementation improved physical (strength endurance) and prolonged cognitive (Stroop accuracy) performance, yet it did not combat MF-induced impairments in short sport-specific psychomotor or cognitive (Flanker) performance. These results warrant further investigation in the potential role of creatine in combating the MF-associated decrements in prolonged (eg., 90-min soccer game) sport performance and suggest a role of brain phosphocreatine in MF.
[Keywords: creatine supplementation, phosphocreatine, mental exertion, cognitive fatigue, visuomotor response time, cognitive performance]
2009-katseres.pdf: “Non-enzymatic hydrolysis of creatine ethyl ester”, Nicholas S. Katseres, David W. Reading, Luay Shayya, John C. DiCesare, Gordon H. Purser
Creatine supplementation is in widespread use to enhance sports-fitness performance, and has been trialled successfully in the treatment of neurological, neuromuscular and atherosclerotic disease. Creatine plays a pivotal role in brain energy homeostasis, being a temporal and spatial buffer for cytosolic and mitochondrial pools of the cellular energy currency, adenosine triphosphate and its regulator, adenosine diphosphate. In this work, we tested the hypothesis that oral creatine supplementation (5 g d(-1) for six weeks) would enhance intelligence test scores and working memory performance in 45 young adult, vegetarian subjects in a double-blind, placebo-controlled, cross-over design. Creatine supplementation had a significant positive effect (p < 0.0001) on both (backward digit span) and intelligence (Raven’s Advanced Progressive Matrices), both tasks that require speed of processing. These findings underline a dynamic and significant role of brain energy capacity in influencing brain performance.
Supplementation with creatine-based substances as a means of enhancing athletic performance has become widespread. Until recently, however, the effects of creatine supplementation on cognitive performance has been given little attention. This study used a new form of creatine—creatine ethyl ester—to investigate whether supplementation would improve performance in 5 cognitive tasks, using a double-blind, placebo-controlled study. Creatine dosing led to an improvement over the placebo condition on several measures. Although creatine seems to facilitate cognition on some tasks, these results require replication using objective measures of compliance. The improvement is discussed in the context of research examining the influence of brain energy capacity on cognitive performance.
Background: Creatine monohydrate is a nutritional supplement often consumed by athletes in anaerobic sports. Creatine is naturally found in most meat products; therefore, vegetarians have reduced creatine stores and may benefit from supplementation.
Objective: to determine the effects of creatine supplementation on vegetarians.
Data Sources: PubMed and SPORTDiscus. Eligibility criteria: Randomized (parallel group, cross-over studies) or prospective studies.
Intervention: Creatine supplementation. Study appraisal and synthesis: A total of 64 records were identified, and eleven full-text articles (covering nine studies) were included in this systematic review.
Results: Creatine supplementation in vegetarians increased total creatine, creatine, and phosphocreatine concentrations in vastus lateralis and gastrocnemius muscle, plasma, and red blood cells, often to levels greater than omnivores. Creatine supplementation had no effect on brain levels of phosphocreatine. Creatine supplementation increased lean tissue mass, type II fiber area, insulin-like growth factor-1, muscular strength, muscular endurance, Wingate mean power output, and brain function (memory and intelligence) in vegetarian participants. Studies were mixed on whether creatine supplementation improved exercise performance in vegetarians to a greater extent compared to omnivores.
Limitations: Studies that were reviewed had moderate-high risk of bias.
Conclusions: Overall, it appears vegetarian athletes are likely to benefit from creatine supplementation.
“Creatine Supplementation and Brain Health”, (2021-01-18):
There is a robust and compelling body of evidence supporting the ergogenic and therapeutic role of creatine supplementation in muscle. Beyond these well-described effects and mechanisms, there is literature to suggest that creatine may also be beneficial to brain health (eg., cognitive processing, brain function, and recovery from trauma). This is a growing field of research, and the purpose of this short review is to provide an update on the effects of creatine supplementation on brain health in humans.
There is a potential for creatine supplementation to improve cognitive processing, especially in conditions characterized by brain creatine deficits, which could be induced by acute stressors (eg., exercise, sleep deprivation) or chronic, pathologic conditions (eg., creatine synthesis enzyme deficiencies, mild traumatic brain injury, aging, Alzheimer’s disease, depression).
Despite this, the optimal creatine protocol able to increase brain creatine levels is still to be determined. Similarly, supplementation studies concomitantly assessing brain creatine and cognitive function are needed. Collectively, data available are promising and future research in the area is warranted.
[Keywords: phosphorylcreatine, dietary supplement, cognition, brain injury, concussion]