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Creatine supplementation, sleep deprivation, cortisol, melatonin and behavior
Abstract
The effect of creatine supplementation and sleep deprivation, with intermittent moderate-intensity exercise, on cognitive and psychomotor performance, mood state, effort and salivary concentrations of cortisol and melatonin were examined. Subjects were divided into a creatine supplementation group and a placebo group. They took 5 g of creatine monohydrate or a placebo, dependent on their group, four times a day for 7 days immediately prior to the experiment. They undertook tests examining central executive functioning, short-term memory, choice reaction time, balance, mood state and effort at baseline and following 18-, 24- and 36-h sleep deprivation, with moderate intermittent exercise. Saliva samples were taken prior to each set of tests. A group x time analysis of covariance, with baseline performance the covariate, showed that the creatine group performed significantly (p < 0.05) better than the placebo group on the central executive task but only at 36 h. The creatine group demonstrated a significant (p < 0.01) linear improvement in performance of the central executive task throughout the experiment, while the placebo group showed no significant effects. There were no significant differences between the groups for any of the other variables. A significant (p < 0.001) main effect of time was found for the balance test with a linear improvement being registered. Cortisol concentrations on Day 1 were significantly (p < 0.01) higher than on Day 2. Mood significantly (p < 0.001) deteriorated up to 24 h with no change from 24 to 36 h. Effort at baseline was significantly (p < 0.01) lower than in the other conditions. It was concluded that, during sleep deprivation with moderate-intensity exercise, creatine supplementation only affects performance of complex central executive tasks.
... From the previous sub-section, we can see that creatine plays a significant role in the provision of energy to the brain. This led researchers to hypothesize that creatine supplementation might affect cognition especially among vegans, vegetarians, the elderly and, mentally fatigued and physiologically stressed individuals, who may be lacking in brain concentrations of creatine [87,88,92,111,139,144]. This depletion may be permanent, in the case of the vegans, vegetarians and the elderly; or transient, in the case of the physiologically stressed and mentally fatigued. ...
... Some previous reviewers [11,89] have suggested that task type (executive function versus attention, perception and memory tasks combined) may be a moderator. However, when we compare the results for executive functions (n = 10: [3]; Benton and Donohoe, 2013; [20,77,87,92,94,104,111,137] with those for the attention, perception and [20,77,87,88,92,94,104,116]), there is no convincing evidence for any difference between outcomes for the different task types. In fact, results show that in many of the studies, there is inconsistency even within task types (e.g., [87,92,137]|). ...
... This is consistent with previous reviews [11,117,121]. A similar pattern emerged with the stressed group (n = 7: [3,87,88,92,111,137,139,144]). However, previous reviewers (Avgerinos, 2018; [117,121]) have argued for something of an interaction effect, with a tendency for the stressed groups to show more positive effects during executive functions than during non-executive tasks. ...
... As an example of the importance of creatine in humans, creatine-deficient syndromes that deplete brain creatine stores are characterized by mental and developmental disorders such as learning delays and seizures 17,18 ; importantly, these symptoms can be partially reversed by creatine supplementation. [19][20][21] In healthy humans, there are mixed results: some studies reported benefits on cognitive functioning, [22][23][24][25][26][27][28][29][30][31][32][33] while others found no effect. [34][35][36] Likewise, the results of research regarding the effectiveness of creatine supplementation on improving measures of memory are mixed. ...
... Nevertheless, this might be attributable to the intake of lower-creatine vegetarian diets. 38,39 Other researchers, however, have failed to find beneficial effects of creatine supplementation on measures of memory in children, 36 adults 27,28,30,34 and older adults. 25,35 While multifactorial, these inconsistent findings across individual studies may be related to methodological differences (dosage and duration of creatine supplementation), population characteristics (age, sex, geographical origin), or low sample size. ...
... After exclusion of 2492 duplicates, 7277 unique publications were 30 and 1 in the United States. 34 Eight were conducted in young adults 22,24,27,28,30,33,34,36 and 2 in older adults. 25,35 Five studies were conducted in cohorts of both males and females, 27,28,30,34,36 3 in females only, 24,33,35 and 2 in males only. ...
Context
From an energy perspective, the brain is very metabolically demanding. It is well documented that creatine plays a key role in brain bioenergetics. There is some evidence that creatine supplementation can augment brain creatine stores, which could increase memory.
Objective
A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to determine the effects of creatine supplementation on memory performance in healthy humans.
Data Sources
The literature was searched through the PubMed, Web of Science, Cochrane Library, and Scopus databases from inception until September 2021.
Data Extraction
Twenty-three eligible RCTs were initially identified. Ten RCTs examining the effect of creatine supplementation compared with placebo on measures of memory in healthy individuals met the inclusion criteria for systematic review, 8 of which were included in the meta-analysis.
Data Analysis
Overall, creatine supplementation improved measures of memory compared with placebo (standard mean difference [SMD] = 0.29, 95%CI, 0.04–0.53; I2 = 66%; P = 0.02). Subgroup analyses revealed a significant improvement in memory in older adults (66–76 years) (SMD = 0.88; 95%CI, 0.22–1.55; I2 = 83%; P = 0.009) compared with their younger counterparts (11–31 years) (SMD = 0.03; 95%CI, −0.14 to 0.20; I2 = 0%; P = 0.72). Creatine dose (≈ 2.2–20 g/d), duration of intervention (5 days to 24 weeks), sex, or geographical origin did not influence the findings.
Conclusion
Creatine supplementation enhanced measures of memory performance in healthy individuals, especially in older adults (66–76 years).
Systematic Review Registration
PROSPERO registration no. 42021281027.
... In a second study by McMorris., et al. found that 20 g/day of creatine monohydrate improved executive functioning [18]. These studies demonstrate support the use of creatine monohydrate supplementation to aid in cognitive performance. ...
... Over the 28-day period of the study, there were no significant within group or between group changes in sAA or cortisol. The lack of an impact on the stress hormones tested is in line with earlier published research examining similar parameters [18,32]. One study did find that providing 20 grams of creatine monohydrate daily along with exercise may have an impact on cortisol levels, however, the current study used a dose that was 25% that of the tested dose [33]. ...
... This improvement in executive function with the CreaBev ® was not observed in the creatine monohydrate or control groups. In general, some research has found a cognitive supporting role and impact of creatine monohydrate supplementation (five grams per day, when sleep deprived); however, the effect was observed in a sleep-deprivation study [18] which utilized a daily dosage of 20 grams per day (four-times as much as the current study). The current study found cognitive support for CreaBev ® for executive function in college aged adults who were classified as healthy subjects. ...
Creatine monohydrate is a popular ergogenic aid used by athletes, adolescents and older individuals. There are various forms of creatine supplements that are on the market, however, creatine monohydrate is the most popular. Creatine itself is considered as less stable in solution when left in solution over time. Advances in product development and science may allow for a more stable aqueous solution of creatine. One major concern of ready-to-drink creatine supplements is the potential adverse gastrointestinal effects. In this randomized, double-blind, placebo-controlled design, the potential gastrointestinal effects of stabilized creatine (CreaBev®) as compared to standard creatine monohydrate versus control was tested. Subjects were randomly assigned to receive the CreaBev® supplement, creatine monohydrate supplement or no supplement (control). Subjects were instructed to consume one serving of the supplement (delivering 5 gm creatine) on a daily basis for 28 days. Subjects underwent baseline testing and end of study testing. The Severity of Dyspepsia Analysis (SODA) questionnaire and National Institutes of Health (NIH) Cognitive Test Toolbox were used to evaluate GI effects and cognition. Additional testing included body composition analysis (including fluid balance), and exploratory measurement of the stress biomarkers, salivary alpha amylase and cortisol. Following the consumption of CreaBev, no adverse gas-trointestinal side effects were reported. Cognition via the Dimension Change Test significantly improved (pre: 104 ± 14 to post: 116 ± 14; p = 0.0017) in the CreaBev group. There was no observed differences in total body fluid status over the 28 days between the groups (p > 0.05) No significant differences in levels of salivary alpha amylase, cortisol and anthropometrics were observed. The use of CreaBev did not cause any adverse GI effects and improved cognitive performance on the Dimension Change Test.
... Despite the number of positive studies available on the subject (Summarized in Table 1), differences between investigations including study populations, cognitive function testing, and supplementation dosing and duration precludes direct comparison; however, some conclusions can be made. Although controversial [28,33,34], creatine supplementation may positively influence some aspects of cognition in different experimental paradigms [10,[35][36][37][38][39][40]. Importantly, its effects seem more pronounced in stressful conditions such as hypoxia [8] and sleep deprivation combined with exercise [10,37,38]. ...
... Although controversial [28,33,34], creatine supplementation may positively influence some aspects of cognition in different experimental paradigms [10,[35][36][37][38][39][40]. Importantly, its effects seem more pronounced in stressful conditions such as hypoxia [8] and sleep deprivation combined with exercise [10,37,38]. Despite the suggestion that more complex or demanding cognitive processes are more prone to respond to supplementation (as they are more energy demanding), inconsistencies regarding cognitive test response to supplementation hampers further conclusions [37,38]), which may be attributed to differences in experimental design such as the sleep deprivation period and exercise intensity employed between studies. ...
... Importantly, its effects seem more pronounced in stressful conditions such as hypoxia [8] and sleep deprivation combined with exercise [10,37,38]. Despite the suggestion that more complex or demanding cognitive processes are more prone to respond to supplementation (as they are more energy demanding), inconsistencies regarding cognitive test response to supplementation hampers further conclusions [37,38]), which may be attributed to differences in experimental design such as the sleep deprivation period and exercise intensity employed between studies. [40] In elderly individuals, specifically, literature is conflicting on the effects of creatine supplementation on cognitive performance. ...
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 (e.g., 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 (e.g., exercise, sleep deprivation) or chronic, pathologic conditions (e.g., 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.
... As performance-related studies assessed health and safety markers, evidence began to accumulate that creatine supplementation may also offer some health and/or therapeutic benefits as we age [4,12,14,67,[69][70][71]131]. In this regard, creatine supplementation has been reported to help lower cholesterol, triglycerides and/or manage blood lipid levels [77,132,133]; reduce the accumulation of fat on the liver [133,134]; decrease homocysteine thereby reducing risk of heart disease [30,135]; serve as an antioxidant [30, [136][137][138][139]; enhance glycemic control [1,11,[140][141][142][143]; reduce the progress of some forms of cancer [8,17,18,135,[144][145][146][147]; increase strength and muscle mass [2,9,13,67,70,71,93,99,101,[148][149][150][151][152][153][154]; minimize bone loss in some studies [2,4,14,16,99,150,[155][156][157][158][159][160]; improve functional capacity in osteoarthritic and fibromyalgia patients [22,161,162]; enhance cognitive function particularly in older populations [3,27,28,69,94,127,131,159,[163][164][165][166][167][168]; and, in some instances, improve the efficacy of some anti-depressant medications [5,29,[169][170][171][172]. These findings support contentions that it is prudent for individuals to consume at least 3 g/day of creatine to support general health as one ages [1,50]. ...
... Creatine supplementation has been reported to increase brain PCr content by 5-15% and thereby enhance brain bioenergetics [21,53,69,131,171]. Consequently, research has examined whether creatine supplementation affects cognition, memory, and/or executive function in older individuals as well as patients with mild cognitive impairment [94,168,174,177,178]. Several studies have found that creatine supplementation attenuates mental fatigue [27,28,127] and/or can improve cognition, executive function, and/or memory [28, 94,127,168,177,179]. ...
... Creatine supplementation has been reported to increase brain PCr content by 5-15% and thereby enhance brain bioenergetics [21,53,69,131,171]. Consequently, research has examined whether creatine supplementation affects cognition, memory, and/or executive function in older individuals as well as patients with mild cognitive impairment [94,168,174,177,178]. Several studies have found that creatine supplementation attenuates mental fatigue [27,28,127] and/or can improve cognition, executive function, and/or memory [28, 94,127,168,177,179]. For example, Watanabe and associates [180] found that creatine supplementation (8 g/day for 5 days) increased oxygen utilization in the brain and reduced mental fatigue in participants performing repetitive mathematical calculations. ...
Although creatine has been mostly studied as an ergogenic aid for exercise, training, and sport, several health and potential therapeutic benefits have been reported. This is because creatine plays a critical role in cellular metabolism, particularly during metabolically stressed states, and limitations in the ability to transport and/or store creatine can impair metabolism. Moreover, increasing availability of creatine in tissue may enhance cellular metabolism and thereby lessen the severity of injury and/or disease conditions, particularly when oxygen availability is compromised. This systematic review assesses the peer-reviewed scientific and medical evidence related to creatine’s role in promoting general health as we age and how creatine supplementation has been used as a nutritional strategy to help individuals recover from injury and/or manage chronic disease. Additionally, it provides reasonable conclusions about the role of creatine on health and disease based on current scientific evidence. Based on this analysis, it can be concluded that creatine supplementation has several health and therapeutic benefits throughout the lifespan.
... Watanabe et al. (12) also measured cerebral hemoglobin oxygenation and observed indications for increased oxygen utilization in the brain after creatine supplementation. In addition, two studies of McMorris et al. (15,16) on creatine supplementation and sleep deprivation also pointed toward a positive effect of creatine on MF. ...
... Despite these first studies on the interaction between creatine and MF (12,15,16), the role of a possible drop in PCr in the occurrence of MF is still unclear. Therefore, the aim of this study was to determine the effect of PCr supplementation on MF and its negative effects on sport-specific psychomotor skills. ...
... Therefore, the aim of this study was to determine the effect of PCr supplementation on MF and its negative effects on sport-specific psychomotor skills. On the basis of the results of Watanabe et al. (12) and McMorris et al. (15,16), we hypothesized that a 7-d creatine supplementation protocol would postpone the occurrence of MF and improve sport-specific psychomotor skills in a mentally fatigued state. ...
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 combatting MF, we evaluated whether creatine supplementation counteracts the MF-associated impairment in sport-specific psychomotor skills.
Methods:
In 23°C, 14 healthy participants (4F 10M; mean ± SD; age:24 ± 3 y; mass:74 ± 13 kg; height:179 ± 9 cm) performed -counterbalanced, crossover and double blinded- a 90-min mentally fatiguing task (i.e. Stroop task) in two different conditions: after a 7-day creatine supplementation (CR; 20 g/day) and after a 7-day calcium lactate supplementation (PLAC; placebo), separated by a 5-week 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 to 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 to PLAC (+4.9%; p=0.026). Within the perceptual and physiological parameters, only motivation and vigor (p≤0.027) were lower in CR compared to PLAC.
Conclusion:
Creatine supplementation improved physical (strength endurance) and prolonged cognitive (Stroop accuracy) performance, yet it did not combat mental fatigue-induced impairments in short sport-specific psychomotor or cognitive (Flanker) performance. These results warrant further investigation in the potential role of creatine in combatting the MF-associated decrements in prolonged (e.g. 90-min soccer game) sport performance, and suggest a role of brain-phosphocreatine in MF.
... In the same vein, those who may not get adequate dietary creatine (e.g., vegetarians, elderly populations, etc.) have been shown to see increases in cognitive functioning through creatine monohydrate supplementation (6). As a general cognitive aid, creatine monohydrate supplementation has been shown to be effective in boosting a wide variety of parameters associated with cognition, including memory, focus, attention, etc. (6,38,(41)(42)(43). ...
... Participants engaging in moderate-intensity exercise (#65% maximal heart rate) and supplementing with 5 g of creatine monohydrate (43/d for 7 days) found a significant linear improvement in performance in random number generation tests as a measure of verbal short-term memory versus controls without creatine supplementation. However, there was no significant effect of creatine supplementation on choice reaction time tests (41). By contrast, a separate study by McMorris et al. (42) found that mean choice reaction times were significantly better than placebo under identical supplementation protocols in subjects exercising at #40% maximum heart rate. ...
... Creatine is effective in improving athletic performance in the presence of fatigue secondary to conditions such Strength and Conditioning Journal | www.nsca-scj.com as dehydration and sleep deprivation (14,30,36,41,42,65). Contrary to previous findings, Cook et al. (14) found that a combination of creatine and caffeine was effective at improving performance in sleep-deprived rugby athletes compared with placebo. ...
ABSTRACT CREATINE MONOHYDRATE SUPPLEMENTATION CAN INCREASE TOTAL CREATINE AND PHOSPHOCREATINE STORES FOR RESYNTHESIS OF ADENOSINE TRIPHOSPHATE. ALTHOUGH MOST EXISTING LITERATURE HAS INVESTIGATED CREATINE TO IMPROVE STRENGTH AND BODY COMPOSITION, IT HAS ALSO BEEN SHOWN TO PROMOTE BRAIN ENERGY HOMEOSTASIS AND IMPROVE COGNITIVE PARAMETERS. THIS MAY BE ANOTHER MECHANISM FOR PERFORMANCE ENHANCEMENT BECAUSE EXERCISE IS BOTH PHYSICALLY AND MENTALLY DEPLETING. THIS ARTICLE AIMS TO (A) REINFORCE THE EFFICACY OF CREATINE SUPPLEMENTATION IN ATHLETES, (B) SHOWCASE CREATINE'S ROLE AS A COGNITIVE ENHANCER, AND (C) ESTABLISH THE NEED FOR FUTURE INTERVENTIONS IN CREATINE'S EFFECT AS A COMPREHENSIVE ERGOGENIC AID (COMBINING PHYSICAL AND COGNITIVE BENEFITS).
... Anti-inflammatory nutrition, caloric restriction, as well as the use of supplements have been discussed to be improve mitochondrial functioning and cognition [230][231][232][233]. Various studies have also shown that creatine supplementation has a positive effect on cognition and brain function [234,235]. The effect was greater the more the participant was exposed to external stressors (e.g., hypoxia, sleep deprivation, etc.) [45,205] or the more complex the tasks were performed [236]. In this context, intake led to a lower need for sleep, earlier wake-up times, and improved sleep behavior [237]. ...
... Therefore, it is reasonable to assume that an improvement in mitochondrial health could enable a positive influence on the course of the disease. Table 6 provides a summary of the level of evidence related to the role of creatine supplementation for neurodegenerative disorders [45, 234,236]. Initial studies suggest that creatine supplementation may be neuroprotective. ...
Creatine monohydrate (CrM) is one of the most widely used nutritional supplements among active individuals and athletes to improve high-intensity exercise performance and training adaptations. However, research suggests that CrM supplementation may also serve as a therapeutic tool in the management of some chronic and traumatic diseases. Creatine supplementation has been reported to improve high-energy phosphate availability as well as have antioxidative, neuroprotective, anti-lactatic, and calcium-homoeostatic effects. These characteristics may have a direct impact on mitochondrion’s survival and health particularly during stressful conditions such as ischemia and injury. This narrative review discusses current scientific evidence for use or supplemental CrM as a therapeutic agent during conditions associated with mitochondrial dysfunction. Based on this analysis, it appears that CrM supplementation may have a role in improving cellular bioenergetics in several mitochondrial dysfunction-related diseases, ischemic conditions, and injury pathology and thereby could provide therapeutic benefit in the management of these conditions. However, larger clinical trials are needed to explore these potential therapeutic applications before definitive conclusions can be drawn.
... It may enhance cognitive function during hypoxia and combined stressors. However, results are inconsistent due to variations in study designs, including differences in stress conditions, dosages, and experimental protocols [21]. In older adults, the results are inconsistent; some studies show positive effects, while others find little to no improvement, which may be due to inadequate increases in brain creatine levels or the presence of neurodegenerative conditions [22]. ...
Depression, affecting millions of people worldwide, is a leading cause of disability globally. It affects not only daily functioning but also interpersonal relationships and overall health by increasing the risks of chronic physical and mental illnesses. Creatine, traditionally recognized for boosting physical performance through its role in producing adenosine triphosphate, has recently shown potential as an adjunctive therapy for treating depression. Creatine’s ability to enhance brain energy metabolisms and provide neuroprotection suggests that it can alleviate mood disorders by improving mitochondrial function, increasing cellular resilience, and modulating neurotransmitter systems that regulate mood.
This narrative review aims to critically evaluate the research on creatine supplementation for depression, focusing on its efficacy, mechanism of action, risks, and benefits as a treatment for mood disorders. It analyzes preclinical and clinical studies to understand creatine’s potential as an adjunctive or alternative therapy for major depressive disorder and bipolar depression and underscores any gaps in current research. Both animal models and human trials indicate creatine’s efficacy for the treatment of depression. Creatine supplementation reduces depressive symptoms, particularly when combined with selective serotonin reuptake inhibitors, and may improve brain energy metabolism and neuroplasticity. It is generally well tolerated, though caution is warranted due to potential side effects such as manic episodes in bipolar disorder and renal function impairment in patients with kidney dysfunction. Overall, creatine presents a promising addition to current depression treatments, though further research is needed to establish optimal dosing, long-term efficacy, and safety across diverse patient populations.
... CR supplementation has the ability (albeit in limited capacity) to cross the blood-brain barrier and increase brain creatine levels [3]. Using magnetic resonance spectroscopy, there is accumulating research showing that CR supplementation has favorable effects on indices of brain health and function [3][4][5][6]. Specifically, CR supplementation may affect cognitive processes related to sleep deprivation, which could have important implications on sleep quality, continuity, and quantity [3,7,8]. ...
Females historically experience sleep disturbances and overall poor sleep compared to males. Creatine has been proposed to impact sleep; however, the effects are not well known. The purpose of this study was to examine the effects of creatine supplementation on sleep among naturally menstruating females. Twenty-one participants completed a double-blind, randomized controlled trial in which they consumed 5 g creatine + 5 g maltodextrin or placebo, 10 g maltodextrin, daily for 6 weeks. Participants completed resistance training 2x/week using the TONAL® (Tonal Systems Inc., San Francisco, CA, USA) at-home gym. Pre- and post-testing assessed body composition, Pittsburgh Sleep Quality Index (PSQI), dietary intake, and muscular strength. Sleep was assessed nightly using an ŌURA® (Oulu, Finland) ring. Compared to the placebo group, those consuming creatine experienced significant increases in total sleep on training days (p = 0.013). No significant changes in chronic sleep and PSQI (pre–post) were observed. There was a significant increase in TONAL® strength score over time (p < 0.001), with no between-group differences. Participants reduced their total calorie (kcal) (p = 0.039), protein (g/kg) (p = 0.009), carbohydrate (g/kg) (p = 0.023), and fat (g) (p = 0.036) intake over time. Creatine supplementation increases sleep duration on resistance training days in naturally menstruating females.
... Creatine supplementation may have a favorable impact on several elements of cognition in many experimental scenarios, although it is disputed [19, 33,34]. However, its effects appear to be more severe in stressful circumstances like hypoxia [7, 27] and sleep loss coupled with exercise [19,35]. Athletes are also interested in improvements in cognitive processing capacity. ...
Given the importance of cognition in everyday life, medicines that improve cognition safely and affordably are highly wanted. Creatine is an amino acid-derived substance that aids in the restoration of adenosine triphosphate (ATP), which provides energy to muscle and brain tissue. Although the relationship between creatine and cognitive performance is still debatable, here is a brief description of creatine's influence on cognition with probable implications for future research on this intriguing topic.
... In a follow-up study from the same researchers, healthy young male individuals (n = 20; age: 21 ± 2 years) were randomized to supplement with creatine (20 g/day) or placebo for 7 days [53]. Participants then completed tests of executive function, short-term memory, choice reaction time, balance, and assessments of mood at baseline and after 18, 24, and 36 h of sleep deprivation. ...
There is emerging interest regarding the potential beneficial effects of creatine supplementation on indices of brain health and function. Creatine supplementation can increase brain creatine stores, which may help explain some of the positive effects on measures of cognition and memory, especially in aging adults or during times of metabolic stress (i.e., sleep deprivation). Furthermore, creatine has shown promise for improving health outcome measures associated with muscular dystrophy, traumatic brain injury (including concussions in children), depression, and anxiety. However, whether any sex- or age-related differences exist in regard to creatine and indices of brain health and function is relatively unknown. The purpose of this narrative review is to: (1) provide an up-to-date summary and discussion of the current body of research focusing on creatine and indices of brain health and function and (2) discuss possible sex- and age-related differences in response to creatine supplementation on brain bioenergetics, measures of brain health and function, and neurological diseases.
... Finally, a series of studies showed how creatine supplementation could improve beyond the more intuitive physical fatigue [33,56], the cognitive one in humans and be beneficial for brain performance [56][57][58][59]. ...
Creatine supplementation has been one of the most studied and useful ergogenic nutritional support for athletes to improve performance, strength, and muscular mass. Over time creatine has shown beneficial effects in several human disease conditions. This review aims to summarise the current evidence for creatine supplementation in advanced chronic liver disease and its complications, primarily in sarcopenic cirrhotic patients, because this condition is known to be associated with poor prognosis and outcomes. Although creatine supplementation in chronic liver disease seems to be barely investigated and not studied in human patients, its potential efficacy on chronic liver disease is indirectly highlighted in animal models of non-alcoholic fatty liver disease, bringing beneficial effects in the fatty liver. Similarly, encephalopathy and fatigue seem to have beneficial effects. Creatine supplementation has demonstrated effects in sarcopenia in the elderly with and without resistance training suggesting a potential role in improving this condition in patients with advanced chronic liver disease. Creatine supplementation could address several critical points of chronic liver disease and its complications. Further studies are needed to support the clinical burden of this hypothesis.
... Cr is known to have effects other than an energy source, and Cr supplement has been thought to be beneficial for children, pregnant and lactating women, and old people 79,249 . Cr has been reported to improve human mental performance [250][251][252][253][254][255] . Cr has been used as potential treatment in animal models of neurodegenerative diseases 256,257 . ...
It has never been easy to discover a new neurotransmitter, especially one in the central nervous system (CNS). We have been searching for new neurotransmitters for 12 years. We detected creatine (Cr) in synaptic vesicles (SVs), at a level lower than glutamate (Glu) and gamma-aminobutyric acid (GABA) but higher than acetylcholine (ACh) and 5-hydroxytryptamine (5-HT). SV Cr was reduced in mice lacking either arginine:glycine amidinotransferase (AGAT, a Cr synthetase) or SLC6A8, a Cr transporter with mutations among the most common causes of intellectual disability (ID) in men. Calcium-dependent release of Cr was detected after stimulation in brain slices. Cr release was reduced in SLC6A8 and AGAT mutants. Cr inhibited neocortical pyramidal neurons. SLC6A8 was necessary for Cr uptake into synaptosomes. Cr was found by us to be taken up into SVs in an ATP dependent manner. Thus, our biochemical, chemical, genetic and electrophysiological results suggest Cr as a neurotransmitter, illustrate a novel approach to discover neurotransmitters and provide a new basis for ID pathogenesis.
... It is of interest that dietary supplementation with Cr improves cognitive performance in both young [132] and elderly people [133]. In addition, as shown by the same authors, Cr supplementation reduces mental fatigue induced by such stress factors as mathematical calculations [132] and sleep deprivation, which reduces the content of Cr in the brain [134]. As for the latter work, its results also indicate that Cr as a dietary supplement limits the negative effects of 24-hour sleep deprivation on cognitive and psychomotor functions and mood state, whereas with shorter periods of sleep deprivation, a positive effect of Cr on these functions was not found. ...
... Creatine deficiency syndrome is characterized by mental and development disorders such as learning delays and seizures [59,60], and importantly these symptoms are reversed, at least in part, by creatine supplementation [32,34,61]. In humans, there are mixed results, with some studies finding some benefits on cognitive functioning [23,[62][63][64][65][66][67][68][69][70][71][72], while others found no effect [28, 73,74], as recently reviewed by Roschel and colleagues [5]. Similar to cognitive function, research is mixed regarding the effectiveness of creatine supplementation on improving measures of memory. ...
While the vast majority of research involving creatine supplementation has focused on skeletal muscle, there is a small body of accumulating research that has focused on creatine and the brain. Preliminary studies indicate that creatine supplementation (and guanidinoacetic acid; GAA) has the ability to increase brain creatine content in humans. Furthermore, creatine has shown some promise for attenuating symptoms of concussion, mild traumatic brain injury and depression but its effect on neurodegenerative diseases appears to be lacking. The purpose of this narrative review is to summarize the current body of research pertaining to creatine supplementation on total creatine and phophorylcreatine (PCr) content, explore GAA as an alternative or adjunct to creatine supplementation on brain creatine uptake, assess the impact of creatine on cognition with a focus on sleep deprivation, discuss the effects of creatine supplementation on a variety of neurological and mental health conditions, and outline recent advances on creatine supplementation as a neuroprotective supplement following traumatic brain injury or concussion.
... Other studies have assessed the cognitive-enhancing properties of Cr under stressed conditions. For example, in 24 h and 36 h sleep-deprived individuals, Cr supplementation significantly augmented cognitive performance compared with placebo-control [11,12]. In addition, 7 days of Cr supplementation has been shown to restore the acute hypoxia-induced decrements in cognitive performance in healthy young adults [13]. ...
Mild cognitive impairment (MCI) designates the boundary area between cognitive function in natural aging and dementia, and this is viewed as a therapeutic window to prevent the occurrence of dementia. The current study investigated the neurocognitive effects of oral creatine (Cr) supplementation in young female Wistar rats that received intracerebroventricular injections of lipopolysaccharide (LPS) to mimic MCI. Neuromolecular changes within the dentate gyrus were analyzed following behavioral testing. We also investigated both neurocognitive and neuromolecular changes following Cr supplementation in the absence of LPS in young female Wistar rats to further investigate mechanisms. Interestingly, based on trial 2 of Barnes maze test, Cr supplementation ameliorated spatial learning and memory deficit induced by LPS, shown by decreased latency time and errors to reach the escape box (p < 0.0001, n = 12). Cr supplementation also attenuated recognition memory deficit induced by LPS, shown by increased amount of time taken to explore the new object (p = 0.002, n = 12) during novel object recognition testing. Within the dentate gyrus, Cr supplementation in LPS injected rats upregulated mTORC1 signaling (p = 0.026 for mTOR phosphorylation, p = 0.002 for p70S6K phosphorylation, n = 8) as well as the synapsin (p = 0.008) and PSD-95 synaptic proteins (p = 0.015), in comparisons to LPS injected rats. However, Cr supplementation failed to further enhance spatial memory and recognition memory in the absence of LPS. In conclusion, Cr ameliorates LPS-induced cognitive impairment in a rodent MCI model. Mechanistically, these phenotypic effects may, in part, be mitigated via an upregulation of mTORC1 signaling, and an enhancement in synaptogenesis in the dentate gyrus. While preliminary, these findings may inform future research investigating neurocognitive effects of Cr for MCI patients.
... The impact of creatine on cortisol is also of interest given the protective effects of creatine during psychological and physiological stressors. Short term creatine supplementation appears to reduce exercise induced increases in cortisol following a high intensity swimming workout (Dobgenski, Santos, Campbell, & Krieder (2014) but does not alter cortisol levels following a 36-hour sleep deprivation period relative to a placebo group (McMorris, Harris, Howard, Langridge, Hall, Corbett, Dicks, & Hodgson, 2007). Further, creatine supplementation does not appear to alter resting cortisol levels in male strength power athletes (Hoffman, Ratamess, Kang, Mangine, Faigenbaum, & Stout, 2006). ...
Creatine monohydrate is a popular nutritional aid for athletes, due to the
beneficial effects on high intensity exercise performance (Cornish, Chilibeck, &
Burke, 2006; Dawson, Vladich, & Blanksby, 2002), post-exercise recovery
(Cooke et al., 2009), and increased tolerance to exercise in the heat (Kilduff et al.,
2004). Although a good deal is known about the physiological effects of creatine
supplementation, the impact on cognitive functioning is less certain. Because of
its role in converting ADP to ATP (Schlattner et al., 2016), creatine provides an
energy source to tissue with increased energy demands, including muscles and the
brain (Persky & Brazeou, 2001), supplying creatine exogenously increases the
energy supplied to neurons in health adults (Persky & Brazeou, 2001). Due to the
role in supplying a reserve energy source, creatine may be most helpful in the
brain or muscle during periods of greatest energy need. For example, mental
training appears to increase naturally occurring creatine levels in the brain,
presumably due to increases in cognitive demands during the training period
(Valenzuela et al., 2003). Thus, it is possible that creatine supplementation
should provide some benefit on more difficult cognitive tasks.
... Carbohydrates maintain blood glucose levels and may accelerate recovery after high intensity exercise [13]. Creatine may improve mood and the performance of tasks that place a heavy stress on the prefrontal cortex in sleep restricted individuals [14,15]. Some probiotic strains reduce the incidence of respiratory and gastrointestinal infections in athletes and therefore may improve exercise performance [16]. ...
Athletes are exposed to a tremendous amount of stress, both physically and mentally, when performing high intensity sports with frequent practices, pushing numerous athletes into choose to use ergogenic aids such as caffeine or β-alanine to significantly improve their performance and ease the stress and pressure that is put onto the body. The beneficial or even detrimental effects of these so-called ergogenic aids can be appreciated through the use of numerous diagnostic tools that can analyze various body fluids. In the recent years, saliva samples are gaining more ground in the field of diagnostic as it is a non-invasive procedure, contains a tremendous amount of analytes that are subject to pathophysiological changes caused by diseases, exercises, fatigue as well as nutrition and hydration. Thus, we describe here the current progress regarding potential novel biomarkers for stress and physical activity, salivary α-amylase and salivary cortisol, as well as their use and measurement in combination with different already-known or new ergogenic aids.
... Creatine supplementation in humans has consistently demonstrated improved cognitive performance and brain function and reduces mental fatigue during stressful mental tasks in healthy adults [94]. Greater cognitive improvements as a result of creatine supplementation have also been reported in individuals with cognitive impairments [95,96]. ...
Despite extensive research on creatine, evidence for use among females is understudied. Creatine characteristics vary between males and females, with females exhibiting 70–80% lower endogenous creatine stores compared to males. Understanding creatine metabolism pre- and post-menopause yields important implications for creatine supplementation for performance and health among females. Due to the hormone-related changes to creatine kinetics and phosphocreatine resynthesis, supplementation may be particularly important during menses, pregnancy, post-partum, during and post-menopause. Creatine supplementation among pre-menopausal females appears to be effective for improving strength and exercise performance. Post-menopausal females may also experience benefits in skeletal muscle size and function when consuming high doses of creatine (0.3 g·kg−1·d−1); and favorable effects on bone when combined with resistance training. Pre-clinical and clinical evidence indicates positive effects from creatine supplementation on mood and cognition, possibly by restoring brain energy levels and homeostasis. Creatine supplementation may be even more effective for females by supporting a pro-energetic environment in the brain. The purpose of this review was to highlight the use of creatine in females across the lifespan with particular emphasis on performance, body composition, mood, and dosing strategies.
... Oxidative stress is known to have a negative influence on the performance of mitochondria and, hence, on the energy homeostasis [15]. Use of exogenous Cr improves cognitive functionality of the brain, making it potentially possible to apply the compound as a pharmacological agent to treat a number of mental disorders [17]. However, it has also been claimed that 46 Some Biochemical Changes of Rat Hippocampal Slices under the Long-term Creatine Intraperitoneal Supplementation supplementing Cr over an extended period of time raises the level of aggressiveness in an individual and gives rise to aggressive behavior. ...
... Interestingly, creatine supplementation may also acutely help protect against the deleterious consequences of sleep loss. After sleep loss, creatine supplementation seems to offset deterioration in executive function, mood, reaction time, balance, and other motor skills (102)(103)(104). Although we expect creatine supplementation to be a useful strategy to help but this people cope with shift work, we are not aware of any research on this topic. ...
Shift work is commonplace in modern societies, and shift workers are predisposed to the development of numerous chronic diseases. Disruptions to the circadian systems of shift workers are considered important contributors to the biological dysfunction these people frequently experience. Because of this, understanding how to alter shift work and zeitgeber (time cue) schedules to enhance circadian system function is likely to be key to improving the health of shift workers. While light exposure is the most important zeitgeber for the central clock in the circadian system, diet and exercise are plausible zeitgebers for circadian clocks in many tissues. We know little about how different zeitgebers interact and how to tailor zeitgeber schedules to the needs of individuals; however, in this review we share some guidelines to help shift workers adapt to their work schedules based on our current understanding of circadian biology. We focus in particular on the importance of diet timing and composition. Going forward, developments in phenotyping and “envirotyping” methods may be important to understanding how to optimise shift work. Non-invasive, multimodal, comprehensive phenotyping using multiple sources of time-stamped data may yield insights that are critical to the care of shift workers. Finally, the impact of these advances will be reduced without modifications to work environments to make it easier for shift workers to engage in behaviours conducive to their health. Integrating findings from behavioural science and ergonomics may help shift workers make healthier choices, thereby amplifying the beneficial effects of improved lifestyle prescriptions for these people.
... In addition, creatine is known to decrease blood fatigue factors, such as lactic acid by promoting the resynthesis of Pcr, and as a result, affects the decrease in tremor. Another recent study also showed that creatine intake has a positive effect on restoring physical and mental performance after sleep deprivation, and in particular, has a neuroprotective effect when cellular energy supply is impaired, as in the case of severe oxygen starvation [45][46][47] . ...
Purpose:
The purpose of this study was to investigate the effects of short-term creatine intake on muscle fatigue induced by resistance exercise in healthy adolescent men, i.e., lactic acid concentration and wrist and head tremor measured by an accelerometer.
Methods:
Twelve healthy adolescent men who had no experience with creatine intake were included. The subjects were randomly assigned to the creatine group and the placebo group, followed by 5 days of creatine and placebo intake, and 5 times of 5 sets of leg press, leg extension, bench press, and arm curl exercises at 70% repetition maximum (RM). The lactic acid concentration before and after exercising, rate of perceived exertion (RPE), and accelerometer-based wrist tremor and head tremor during exercise were measured. Subsequently, after 7 days to allow for creatine washout, the same exercise treatment and measurement were performed in each group after switching drug and placebo between the groups.
Results:
The level of lactic acid before and after the acute resistance exercise trial was significantly lower in the creatine group than in the placebo group (P <0.05). The mean RPE during the resistance exercise was significantly lower in the creatine group than in the placebo group (P <0.05). There was no difference between the two groups in the mean wrist tremor during resistance exercise, but the mean head tremor values were significantly lower in the creatine group than in the placebo group in the arm curl, the last event of the exercise trials (P <0.05).
Conclusion:
Short-term creatine intake reduces the blood fatigue factor increased by resistance exercise, and is thought to suppress fatigue, especially in the latter half of resistance exercise. Therefore, these findings indicate that short-term creatine intake can have an improved effect on anaerobic exercise performance.
... During an MMA match, brain energetics (ATP turnover) would increase and PCr may be important to facilitate energy matched ATP regeneration, supporting cognitive function and enhancing neural activity 48 . From a cognitive performance perspective, there are six studies that have examined creatine supplementation on cognition in younger adults at rest [48][49][50][51][52][53] and four studies that have examined creatine under cognitive "stress" 47,[54][55][56] . The results are mixed with some showing a positive effect on a least one cognitive outcome variable 48,50,51,53 while others showed no effect 49,52 . ...
Mixed martial arts (MMA) is an intermittent sport that is physically and cognitively demanding. Nutritional strategies to support training, competition, and weight-cutting are important to optimize performance. One purported ergogenic aid that may have beneficial effects for MMA is creatine monohydrate. The purpose of this narrative review is to (1) discuss how creatine supplementation impacts MMA performance; (2) outline the effect of creatine supplementation on body composition and highlight specific strategies while cutting weight; (3) discuss how creatine can be used after weigh-ins to enhance re-hydration and glycogen re-synthesis; (4) evaluate the potential cognitive benefits of creatine supplementation; and (5) discuss practical real life strategies and considerations when considering creatine supplementation.
... Creatine has also been shown to improve cognitive performance in persons subjected to sleep deprivation. Subjects who received 20 g of creatine per day exhibited significantly less decline in cognitive performance, motor performance and mood state than subjects who had received placebo after 24 h of sleep deprivation [177]; in a subsequent study, creatine supplementation improved performance on central executive tasks after 36h of sleep deprivation, though it did not affect mood [178]. Another small study of healthy young adults who were not sleep-deprived found no effect of creatine on cognitive performance compared to placebo over 6 weeks [179]. ...
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.
... Although creatine is one of the most popular dietary supplements used to increase performance during exercise [36,37,81], studies have been documented the positive effect of creatine to improve cognitive performance in young [86], and elderly people [55]. Moreover, the neuroprotective role of creatine is widely recognized in experimental animals as model systems for neurodegenerative diseases [7,11,19,37]. ...
Phenylketonuria (PKU) is a metabolic disorder accumulating phenylalanine (Phe) and its metabolites in plasma and tissues of the patients. Regardless of the mechanisms, which Phe causes brain impairment, are poorly understood, energy deficit may have linked to the neurotoxicity in PKU. It is widely recognized that creatine is involved in maintaining of cerebral energy homeostasis. Because of this, in a previous work, we incorporated it into liposomes and this increased the concentration of creatine in the cerebral cortex. Here, we examined the effect of creatine nanoliposomes on parameters of oxidative stress, enzymes of phosphoryl transfer network, and activities of the mitochondrial respiratory chain complexes (RCC) in the cerebral cortex of young rats chemically induced hyperphenylalaninemia (HPA). HPA was induced with l-phenylalanine (5.2 µmol/g body weight; twice a day; s.c.), and phenylalanine hydroxylase inhibitor, α-methylphenylalanine (2.4 µmol/g body weight; once a day; i.p.), from the 7th to the 19th day of life. HPA reduced the activities of pyruvate kinase, creatine kinase, and complex II + III of RCC in the cerebral cortex. Creatine nanoliposomes prevented the inhibition of the activities of the complexes II + III, caused by HPA, and changes oxidative profile in the cerebral cortex. Considering the importance of the mitochondrial respiratory chain for brain energy production, our results suggesting that these nanoparticles protect against neurotoxicity caused by HPA, and can be viable candidates for treating patients HPA.
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... Plasma adrenaline has also been shown to be a predictor of prefrontal cognition, but this is probably due to the relationship between secretion of adrenaline by the adrenal medulla and the release of noradrenaline in the central nervous system by the hypothalamus via the HPA axis ). Previous research has already examined the influence of alterations in catecholamines on cognitive performance during other forms of stress including sleep deprivation ( McMorris et al., 2007), exercise (McMorris, Collard, Corbett, Dicks, & Swain, 2008) and heat ); however, to date, there is no empirical evidence directly examining this relationship during hypoxia. ...
New findings:
What is the central question of this study? What are the mechanisms responsible for the decline in cognitive performance following exposure to acute normobaric hypoxia? What are the main findings and their importance? We found that 1) performance of a complex central executive task (n-back) was reduced FiO2 0.12; 2) there was a strong correlation between performance of the n-back task and reductions in SpO2 and cerebral oxygenation; and 3) plasma adrenaline, noradrenaline, cortisol, and copeptin were not correlated with cognitive performance.
Abstract:
It is well established that hypoxia impairs cognitive function; however, the physiological mechanisms responsible for these effects have received relatively little attention. This study examined the effects of graded reductions in fraction of inspired oxygen (FiO2 ) on oxygen saturation (SpO2 ), cerebral oxygenation, cardiorespiratory variables, activity of the sympathoadrenal system (adrenaline, noradrenaline) and hypothalamic-pituitary-adrenal axis (cortisol, copeptin), and cognitive performance. Twelve healthy males (mean [SD], age: 22 [4] yrs, height: 178 [5] cm, mass: 75 [9] kg, FEV1 /FVC ratio: 85 [5] %) completed a 4-task battery of cognitive tests to examine inhibition, selective attention (Eriksen Flanker), executive function (n-back) and simple and choice reaction time (Deary-Liewald). Tests were completed before and following 60 minutes of exposure to FiO2 0.2093, 0.17, 0.145, and 0.12. Following 60 minutes of exposure response accuracy in the n-back task was significantly reduced in FiO2 0.12 compared to baseline (82 [9] vs. 93 [5] %; p < 0.001) and compared to all other conditions at the same time point (FiO2 0.2093: 92 [3] %, FiO2 0.17: 91 [6] %, FiO2 0.145: 85 [10] %, FiO2 12: 82 [9] %; all p < 0.05). The performance of the other tasks was maintained. Δ accuracy and Δ reaction time of the n-back task was correlated with both Δ SpO2 (r (9) = 0.66; p < 0.001 and r (9) = - 0.36; p = 0.037 respectively) and Δ cerebral oxygenation (r (7) = 0.55; p < 0.001 and r (7) = - 0.38; p = 0.045 respectively). Plasma adrenaline, noradrenaline, cortisol and copeptin were not significantly elevated in any condition or correlated with any of the tests of cognitive performance. These findings suggest that reductions in peripheral oxygen saturation and cerebral oxygenation, and not increased activity of the sympathoadrenal system and hypothalamic-pituitary-adrenal axis, as previously speculated, are responsible for a decrease in cognitive performance during normobaric hypoxia. This article is protected by copyright. All rights reserved.
... The authors concluded that dogs efficiently utilise and metabolize GAA to Cr. In addition, an elevated Cr intake has also been reported to accelerate skeletal muscle recovery after prolonged immobilization, slow down muscle wasting in certain myopathies and improve cognitive performance (Hespel et al., 2001;Louis et al., 2003;McMorris et al., 2007;Tarnopolsky et al., 2004). The value of Cr in the diet of geriatric dogs and possibly cats suffering from cognitive dysfunction, cachexia and sarcopenia is largely unknown. ...
The stability of creatine monohydrate (CrMH), crystallised guanidinoacetic acid (GAA‐C) and granulated GAA (GAA‐G) in a moist retorted and a dry extruded dog food formulation during production and storage was investigated. Commercial food mixtures were supplemented with CrMH, GAA‐C or GAA‐G. Uniformity after mixing and retorting or extrusion was determined based on replicate samples (moist n = 8, dry n = 10). Storage stability was evaluated at 25°C/60% relative humidity for 15 months and 40°C/75% for 6 months. Foods with CrMH were analysed for creatine (Cr) and creatinine (Crn), whereas GAA‐C and GAA‐G foods were analysed for GAA concentrations. Coefficients of variation (CV) for uniformity of the additives after mixing of moist and dry pet food formulations were below 15%, and the CV was lower in processed mixtures. Recoveries after retorting and extrusion were higher for GAA‐G (79 and 99%) and GAA‐C (89 and 86%) compared to CrMH (36 and 85%) foods. In moist CrMH food, Cr concentrations re‐increased by 54% whilst Crn concentrations decreased by 39% after storage at 25°C for 15 months. With total molar Cr + Crn remaining stable throughout storage, Crn and Cr appeared to effectively interconvert. Storage of the extruded CrMH food at 25°C for 15 months resulted in a 63% decrease in Cr and a 39% increase in Crn concentration. The decrease in Cr concentration was larger at 6 months storage at 40°C compared to 15 months storage at 25°C. Both GAA‐C and GAA‐G moist and dry foods were stable during storage (<10% decrease). This study showed that GAA is highly stable during production and storage of moist and dry canine foods whilst CrMH is relatively unstable, particularly during storage. The latter makes it difficult to establish a guaranteed Cr content in finished moist retorted and dry extruded foods with CrMH.
... Hot spots of expression of CK isoenzymes have been reported in hippocampal pyramidal cells, which are involved in learning and memory (Kaldis et al. 1996), suggesting that the CK/PCr-system plays an essential role for this group of cells. Such theory is supported by studies that showed that creatine supplementation improves the performance of complex central executive tasks during stress caused by sleep deprivation in humans (McMorris et al. 2007), and intelligence/working memory performance tests even in healthy volunteers (Watanabe et al. 2002;Rae et al. 2003). However, these studies are not unequivocal evidence supporting a particular neurotransmitter function since the highly energy-dependent release and recycling of neurotransmitters at the synapse and the bioenergetic function of creatine may explain these neurological findings. ...
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 neuromodulator. 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.
... The same group repeated the study a year later, pushing sleep deprivation up to 36 hours and showing again a better performance of the subjects treated with creatine (same dose and duration). 148 Again, in line with this hypothesis, Cook et al 149 studied, in sleep-deprived subjects, the effects of a single dose of creatine (50 or 100 mg/kg, corresponding to 3.5-7 g in a person of 70 kg) shortly before an athletic precision task which consisted of performing a number of passing with a rugby ball. They found that sleep deprivation increased the number of mistakes committed by the athletes in performing this drill and that creatine administration (as well as caffeine, which was administered in another trial of the same experiment) significantly improved the performance in sleep-deprived athletes. ...
Creatine is pivotal in energy metabolism of muscle and brain cells, both in physiological and in pathological conditions. Additionally, creatine facilitates the differentiation of muscle and neuronal cells. Evidence of effectiveness of creatine supplementation in improving several clinical conditions is now substantial, and we review it in this paper. In hereditary diseases where its synthesis is impaired, creatine has a disease‐modifying capacity, especially when started soon after birth. Strong evidence, including a Cochrane meta‐analysis, shows that it improves muscular strength and general well‐being in muscular dystrophies. Significant evidence exists also of its effectiveness in secondary prevention of statin myopathy and of treatment‐resistant depression in women. Vegetarians and vegans do not consume any dietary creatine and must synthesize all they need, spending most of their methylation capacity. Nevertheless, they have a lower muscular concentration of creatine. Creatine supplementation has proved effective in increasing muscular and neuropsychological performance in vegetarians or vegans and should, therefore, be recommended especially in those of them who are athletes, heavy‐duty laborers or who undergo intense mental effort. Convincing evidence also exists of creatine effectiveness in muscular atrophy and sarcopenia in the elderly, and in brain energy shortage (mental fatigue, sleep deprivation, environmental hypoxia as in mountain climbing, and advanced age). Furthermore, we review more randomized, placebo‐controlled trials showing that creatine supplementation is safe up to 20 g/d, with a possible caveat only in people with kidney disease. We trust that the evidence we review will be translated into clinical practice and will spur more research on these subjects.
... Moreover, a double-blind study investigating Cr supplementation for six weeks on healthy vegetarians, who have a reduced nutritional Cr supply, revealed significantly better results in intelligence test and working memory performance in the Cr-treated subjects compared with control individuals [314]. In a recent test, Cr supplementation (4 Â 5 g Cr per day for 7 days), prior to 18-36 hours of sleep deprivation, was shown to significantly improve the performance of complex central executive tasks [315,316]. Thus, it can be concluded that Cr supplementation enhances brain function under normal and stress conditions. This may be relevant for promoting Cr supplementation as a brain performance-enhancing nutritional supplement for humans. ...
... There is a tendency for increasing creatine levels with aging, but this change does not counteract the cognitive decline due to aging (Pfefferbaum et al., 1999). It is possible that creatine administration improves cognition of diseased, aged or stressed individuals whereas for younger, unstressed individuals there is no such a benefit (Mcmorris et al., 2007b;Fernandez-Espejo, 2004;Turner et al., 2015;Bender et al., 2005). ...
Creatine monohydrate supplementation (CrM) is a safe and effective intervention for improving certain aspects of sport, exercise performance, and health across the lifespan. Despite its evidence-based pedigree, several questions and misconceptions about CrM remain. To initially address some of these concerns, our group published a narrative review in 2021 discussing the scientific evidence as to whether CrM leads to water retention and fat accumulation, is a steroid, causes hair loss, dehydration or muscle cramping, adversely affects renal and liver function, and if CrM is safe and/or effective for children, adolescents, biological females, and older adults. As a follow-up, the purpose of this paper is to evaluate additional questions and misconceptions about CrM. These include but are not limited to: 1. Can CrM provide muscle benefits without exercise? 2. Does the timing of CrM really matter? 3. Does the addition of other compounds with CrM enhance its effectiveness? 4. Does CrM and caffeine oppose each other? 5. Does CrM increase the rates of muscle protein synthesis or breakdown? 6. Is CrM an anti-inflammatory intervention? 7. Can CrM increase recovery following injury, surgery, and/or immobilization? 8. Does CrM cause cancer? 9. Will CrM increase urine production? 10. Does CrM influence blood pressure? 11. Is CrM safe to consume during pregnancy? 12. Does CrM enhance performance in adolescents? 13. Does CrM adversely affect male fertility? 14. Does the brain require a higher dose of CrM than skeletal muscle? 15. Can CrM attenuate symptoms of sleep deprivation? 16. Will CrM reduce the severity of and/or improve recovery from traumatic brain injury? Similar to our 2021 paper, an international team of creatine research experts was formed to perform a narrative review of the literature regarding CrM to formulate evidence-based responses to the aforementioned misconceptions involving CrM.
Background: Preclinical studies have suggested that dietary creatine may affect sleep quality yet no studies have explored the potential association between creatine consumption and sleep patterns or disorders in the general population. Aim: This cross-sectional study aims to examine the association between creatine consumption and sleep habits and disorders among individuals aged 16 years and older, using data from the 2007–2008 National Health and Nutrition Examination Survey (NHANES). Methods: The analysis included 5988 individuals (50.5% females) with a mean age of 47.4 ± 19.5 years. Daily creatine intake was assessed through individual in-person 24-h food recall interviews, categorizing respondents into two groups: those with suboptimal creatine intake (<1.00 g per day) and those meeting recommended intake (dietary creatine ≥ 1.00 g per day). Sleep was evaluated during household interviews using questions on sleep habits and disorders from the NHANES Sleep Disorders component. Results: The average daily creatine intake among participants was 0.88 ± 0.85 g (95% CI, 0.86 to 0.90), while the mean nightly sleep duration was 6.8 ± 1.5 h (95% CI, 6.8 to 6.9). Additionally, 1331 respondents (22.2%) reported consulting a doctor or health professional for sleep-related issues. Participants with suboptimal creatine intake had a significantly higher prevalence of trouble sleeping compared to those consuming recommended amounts (23.7% vs 19.3%; P < 0.01), with an odds ratio of 1.30 (95% CI: 1.13 to 1.48) for experiencing sleep disturbances. However, the prevalence of more severe sleep disorders did not differ significantly between the two creatine sub-populations ( P > 0.05). Conclusion: Our findings suggest that participants meeting recommended creatine intake levels had a reduced risk of experiencing mild sleeping difficulties. These findings may serve as a basis for future interventional studies aimed at validating and confirming the potential benefits of dietary creatine in the field of sleep medicine.
Following an application from Alzchem Trostberg GmbH, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Austria, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to creatine and improvement in cognitive function. The Panel considers that the food constituent, creatine, is sufficiently characterised. An improvement in cognitive function in one or more of its domains is a beneficial physiological effect. The applicant identified 21 human intervention studies on creatine supplementation and measures of cognitive function through a literature search. Two additional studies published after the search was conducted were identified through the reference list of a meta‐analysis. In weighing the evidence, the Panel took into account that the acute effect of creatine on working memory, observed in two studies at 20 g/day for 5–7 days, was not seen at lower doses (2.2–14 g/day), or with continuous consumption (5 g/day for 6 weeks following a 5‐day loading phase). Furthermore, the effect on response inhibition at 20 g/day for 7 days was an isolated finding among 10 intervention studies in healthy individuals, with no effects observed on other cognitive domains. The Panel also considered that the three intervention studies conducted in diseased individuals do not support an effect of creatine supplementation on cognition, and that the available evidence for a mechanism by which creatine could exert the claimed effect is weak. The Panel concludes that a cause‐and‐effect relationship has not been established between creatine supplementation and an improvement in cognitive function in one or more of its domains.
In this alphabetically arranged chapter, supplements from acarbose through creatine are discussed in detail. For each supplement, this chapter defines what it is and how it works in the body. Further, this chapter discusses the supplement’s recommended dosage as well as the evidence for or against its different usages. Safety concerns, side effects, and precautions are next discussed as well as any potential interactions with other medications. References are provided for the data provided. The goal is for the healthcare provider to be able to reference each supplement and come away with a full, balanced, evidence-based understanding of these topics.
La creatina es el suplemento deportivo más popular por su contribución al rendimiento deportivo y al mejoramiento de la composición corporal. Debido a que cumple funciones no solo a nivel muscular, sino en todos los tejidos del cuerpo, especialmente en el sistema nervioso, su interés como ayuda en diversas condiciones de salud y enfermedad ha crecido en las últimas décadas. Sin embargo, muchas de las investigaciones han sido realizadas en animales, en modelos que no representan tan adecuadamente las realidades del ser humano, en quienes la creatina mejoraría características de la función cognitiva principalmente. En la presente revisión narrativa se detallan los hallazgos más importantes de investigaciones recientes efectuadas en seres humanos en la última década, tendientes a analizar el beneficio de la creatina en funciones cognitivas, depresión, daño al sistema nervioso central, enfermedades neurodegenerativas, salud cardiovascular y otras condiciones relevantes. Además, se discute el concepto de seguridad en su dosificación, incluyendo los resultados de estudios individuales, revisiones y metaanálisis recientes.
The discovery of a new neurotransmitter, especially one in the central nervous system, is both important and difficult. We have been searching for new neurotransmitters for 12 y. We detected creatine (Cr) in synaptic vesicles (SVs) at a level lower than glutamate and gamma-aminobutyric acid but higher than acetylcholine and 5-hydroxytryptamine. SV Cr was reduced in mice lacking either arginine:glycine amidinotransferase (a Cr synthetase) or SLC6A8, a Cr transporter with mutations among the most common causes of intellectual disability in men. Calcium-dependent release of Cr was detected after stimulation in brain slices. Cr release was reduced in Slc6a8 and Agat mutants. Cr inhibited neocortical pyramidal neurons. SLC6A8 was necessary for Cr uptake into synaptosomes. Cr was found by us to be taken up into SVs in an ATP-dependent manner. Our biochemical, chemical, genetic, and electrophysiological results are consistent with the possibility of Cr as a neurotransmitter, though not yet reaching the level of proof for the now classic transmitters. Our novel approach to discover neurotransmitters is to begin with analysis of contents in SVs before defining their function and physiology.
The discovery of a new neurotransmitter, especially one in the central nervous system (CNS), is both important and difficult. We have been searching for new neurotransmitters for 12 years. We detected creatine (Cr) in synaptic vesicles (SVs), at a level lower than glutamate (Glu) and gamma-aminobutyric acid (GABA) but higher than acetylcholine (ACh) and 5-hydroxytryptamine (5-HT). SV Cr was reduced in mice lacking either arginine:glycine amidinotransferase (AGAT, a Cr synthetase) or SLC6A8, a Cr transporter with mutations among the most common causes of intellectual disability (ID) in men. Calcium-dependent release of Cr was detected after stimulation in brain slices. Cr release was reduced in SLC6A8 and AGAT mutants. Cr inhibited neocortical pyramidal neurons. SLC6A8 was necessary for Cr uptake into synaptosomes. Cr was found by us to be taken up into SVs in an ATP dependent manner. Our biochemical, chemical, genetic and electrophysiological results are consistent with the possibility of Cr as a neurotransmitter, though not yet reaching the level of proof for the now classic transmitters. Our novel approach to discover neurotransmitters is to begin with analysis of contents in SVs before defining their function and physiology.
The discovery of a new neurotransmitter, especially one in the central nervous system (CNS), is both important and difficult. We have been searching for new neurotransmitters for 12 years. We detected creatine (Cr) in synaptic vesicles (SVs), at a level lower than glutamate (Glu) and gamma-aminobutyric acid (GABA) but higher than acetylcholine (ACh) and 5-hydroxytryptamine (5-HT). SV Cr was reduced in mice lacking either arginine:glycine amidinotransferase (AGAT, a Cr synthetase) or SLC6A8, a Cr transporter with mutations among the most common causes of intellectual disability (ID) in men. Calcium-dependent release of Cr was detected after stimulation in brain slices. Cr release was reduced in SLC6A8 and AGAT mutants. Cr inhibited neocortical pyramidal neurons. SLC6A8 was necessary for Cr uptake into synaptosomes. Cr was found by us to be taken up into SVs in an ATP dependent manner. Our biochemical, chemical, genetic and electrophysiological results are consistent with the possibility of Cr as a neurotransmitter.Our novel approach to discover neurotransmitters is to begin with analysis of contents in SVs before defining their function and physiology.
Nootropics, also known as cognitive enhancers or "smart drugs," have garnered increasing attention in the sports world as potential aids for enhancing mental performance. This thematic paper explores the intersection of nootropics and sports, delving into their potential benets and ethical considerations. While the use of these substances in sports raises intriguing possibilities for optimizing cognitive function during training and competition, it also presents signicant challenges in terms of safety, fairness, and the potential for abuse. This paper aims to provide an indepth analysis of the implications of incorporating nootropics in sports and encourages a balanced approach to this complex and evolving subject.
It has never been easy to discover a new neurotransmitter, especially one in the central nervous system (CNS). We have been searching for new neurotransmitters for 12 years. We detected creatine (Cr) in synaptic vesicles (SVs), at a level lower than glutamate (Glu) and gamma-aminobutyric acid (GABA) but higher than acetylcholine (ACh) and 5-hydroxytryptamine (5-HT). SV Cr was reduced in mice lacking either arginine:glycine amidinotransferase (AGAT, a Cr synthetase) or SLC6A8, a Cr transporter with mutations among the most common causes of intellectual disability (ID) in men. Calcium-dependent release of Cr was detected after stimulation in brain slices. Cr release was reduced in SLC6A8 and AGAT mutants. Cr inhibited neocortical pyramidal neurons. SLC6A8 was necessary for Cr uptake into synaptosomes. Cr was found by us to be taken up into SVs in an ATP dependent manner. Thus, our biochemical, chemical, genetic and electrophysiological results suggest Cr as a neurotransmitter, illustrate a novel approach to discover neurotransmitters and provide a new basis for ID pathogenesis.
It has never been easy to discover a new neurotransmitter, especially one in the central nervous system (CNS). We have been searching for new neurotransmitters for 12 years. We detected creatine (Cr) in synaptic vesicles (SVs), at a level lower than glutamate (Glu) and gamma-aminobutyric acid (GABA) but higher than acetylcholine (ACh) and 5-hydroxytryptamine (5-HT). SV Cr was reduced in mice lacking either arginine:glycine amidinotransferase (AGAT, a Cr synthetase) or SLC6A8, a Cr transporter with mutations among the most common causes of intellectual disability (ID) in men. Calcium-dependent release of Cr was detected after stimulation in brain slices. Cr release was reduced in SLC6A8 and AGAT mutants. Cr inhibited neocortical pyramidal neurons. SLC6A8 was necessary for Cr uptake into synaptosomes. Cr was found by us to be taken up into SVs in an ATP dependent manner. Thus, our biochemical, chemical, genetic and electrophysiological results suggest Cr as a neurotransmitter, illustrate a novel approach to discover neurotransmitters and provide a new basis for ID pathogenesis.
Collegiate dance is unique because it requires athletic and academic performance; therefore, optimizing physical and mental function is crucial. Research among athletic populations demonstrate improvements in body composition, performance, and cognition following creatine monohydrate (CR) supplementation, yet dancers have not been investigated. The purpose of this study was to determine the effects of CR supplementation on body composition, performance, and cognitive function in female collegiate dancers. Participants were randomized to CR (CR; n = 7; 0.1 g·kg −1·day −1 CM +0.1 g·kg −1·day −1 corn-starch maltodextrin) or placebo (PL; n = 6; 0.2 g·kg −1·day −1 corn-starch maltodextrin) for 42 days. Pre- and post-testing included body composition, total body water (TBW), Depression, Anxiety and Stress Scale, Diet History Questionnaire, the National Institute of Health Toolbox fluid cognition battery and isokinetic strength, vertical jump, medicine ball throw, and Wingate anaerobic power test. CR demonstrated a significant increase in TBW (pre, 32.2 ± 3.5 kg; post, 32.7 ± 3.6 kg; p = 0.024) and lean mass (LM; pre, 39.8 ± 3.6 kg; post, 41.5 ± 4.5 kg; p = 0.020). CR supplementation may be an effective strategy to increase TBW and estimates of LM in female collegiate dancers. Although this may optimize aesthetics, larger samples sizes with resistance training are needed to determine if CR supplementation increases muscle mass and translates to improved performance.
El monohidrato de creatina es uno de los suplementos más estudiados en el mundo de la nutrición deportiva por su rol energético e hipertrófico en el músculo esquelético. En la actualidad, se puede estar subestimando el amplio espectro de beneficios terapéuticos que aporta a la salud en otra población que pueda requerir de sus ventajas, como el sector clínico, más allá de solo relacionarlo con la mejora en las adaptaciones al ejercicio físico. En esta revisión narrativa se tiene como objetivo abordar la interacción de la suplementación con creatina y la salud del cerebro humano, conforme a la investigación disponible que hasta la fecha se ha publicado en humanos; principalmente, los efectos de la ingesta regular en la función cognitiva, las enfermedades neurodegenerativas y los trastornos psiquiátricos. La evidencia científica apoya firmemente los beneficios de la suplementación con creatina en personas que presentan los llamados errores innatos del metabolismo, como el síndrome de deficiencia de creatina causado por alteraciones genéticas en GAMT y AGAT. Además, en la función cognitiva, la suplementación con creatina podría ofrecer mayores beneficios en sujetos estresados o adultos mayores. También brindaría un efecto adicional ante los trastornos relacionados con la depresión y los síntomas de depresión unipolar y bipolar, si se combina con la medicación antidepresiva. En estas cuestiones anteriormente mencionadas, la literatura se encuentra en cierta forma mejor dilucidada en comparación con los presuntos beneficios en enfermedades neurodegenerativas, como las enfermedades de Parkinson y Huntington, y por el momento menos respaldada en el caso de la enfermedad de Alzheimer. Se requiere una mayor cantidad de investigaciones realizadas a mayor escala y con mejores diseños de estudio en humanos, con el fin de elaborar mejores protocolos de suplementación en poblaciones que presentan distintas condiciones de salud. Palabras clave: creatina, cerebro, depresión, trastornos
Aging is associated with reductions in muscle and bone mass and brain function, which may be counteracted by several lifestyle factors, of which exercise appears to be most beneficial. However, less than 20% of older adults (> 55 years of age) adhere to performing the recommended amount of resistance training (≥ 2 days/week) and less than 12% regularly meet the aerobic exercise guidelines (≥ 150 min/week of moderate to vigorous intensity aerobic exercise) required to achieve significant health benefits. Therefore, from a healthy aging and clinical perspective, it is important to determine whether other lifestyle interventions (independent of exercise) can have beneficial effects on aging muscle quality and quantity, bone strength, and brain function. Creatine, a nitrogen containing organic compound found in all cells of the body, has the potential to have favorable effects on muscle, bone, and brain health (independent of exercise) in older adults. The purpose of this narrative review is to examine and summarize the small body of research investigating the effects of creatine supplementation alone on measures of muscle mass and performance, bone mineral and strength, and indices of brain health in older adults.
زمینه و هدف: محرومیت از خواب میتواند بر افزایش اشتباهات و تصادفات، تأخیر در عملکرد و شک و شبهه در اجرای امور و اختلالات هورمونی منجر شود. در برخی شغلها محرومیت از خوابهای اجباری وجود دارد، بعنوان مثال نظامیها در زمانهای مختلفی از خواب محروم میشوند. بنابراین، هدف از پژوهش حاضر بررسی اثر زمان محرومیت از خواب دو ساعته در شب بر عملکرد جسمانی و سطوح خونی ملاتونین، کورتیزول و تستوسترون در نظامیان بود. روش پژوهش: 40 فرد نظامی بطور تصادفی به 4 گروه (گروه 1: محرومیت از ساعت 2-12، گروه 2: محرومیت از ساعت 4-2، گروه 3: محرومیت از ساعت 6-4 و گروه 4: گروه کنترل) تقسیم شدند. پروتکل شامل دو بخش بود: اندازه گیری در سطح پایه (قبل محرومیت از خواب) که همان پیش آزمون بود و اندازه گیری بعد از محرومیت خواب. اولین بخش این تحقیق در یک هفته قبل محرومیت از خواب ثبت گردید. یافتهها: در پیش و پس آزمون محرومیت خواب از ساعت 4 تا 6 قدرت بالاتنه و پایین تنه، قدرت پرش، سطوح پلاسمایی ملاتونین، کوتیزول، تستوسترون و نسبت تستوسترون به کورتیزول تفاوت معنیدار بود، همچنین در محرومیت خواب از ساعت 2 تا 4 حداقل توان، کورتیزول، تستوسترون و نسبت تستوسترون به کورتیزول بطور معنیداری نسبت به پیش آزمون تغییر کرد (05/0P≤). نتیجهگیری: حداکثر اختلال عملکرد جسمانی و هورمونی در محرومیت خواب از ساعت 2 تا 4 و 4 تا 6 مشاهده شد و بکارگیری در امور حساس و نظامی برای افرادی که در این بازههای زمانی از خواب محروم شدهاند مناسب نخواهد بود.
The ergogenic and therapeutic effects of increasing muscle creatine by supplementation are well-recognized. It appears that similar benefits to brain function and cognitive processing may also be achieved with creatine supplementation, however research in this area is more limited, and important knowledge gaps remain. The purpose of this review is to provide a comprehensive overview of the current state of knowledge about the influence of creatine supplementation on brain function in healthy individuals. It appears that brain creatine is responsive to supplementation, however higher, or more prolonged dosing strategies than those typically used to increase muscle creatine, may be required to elicit an increase in brain creatine. The optimal dosing strategy to induce this response, is currently unknown, and there is an urgent need for studies investigating this. When considering the influence of supplementation strategies on cognitive processes, it appears that creatine is most likely to exert an influence in situations whereby cognitive processes are stressed, e.g. during sleep deprivation, experimental hypoxia, or during the performance of more complex, and thus more cognitively demanding tasks. Evidence exists indicating that increased brain creatine may be effective at reducing the severity of, or enhancing recovery from mild traumatic brain injury, however, only limited data in humans are available to verify this hypothesis, thus representing an exciting area for further research.
To explicate the mechanisms which support attempts at random number production, two experiments explore the role of memory systems in random sequencing. In the first, subjects produced written random number sequences with two response vocabularies, and subjects were also required to estimate how often they had chosen particular values in their response set. Memory for responses was found to correlate with the quality of random generation, and sequences were less random with a larger response repertoire. However, memory performance did not account for the effect of response set size, suggesting different aetiologies for these effects. In a second experiment, subjects were given a concurrent memory load during random generation, and a concurrent task requiring avoidance of certain response values. Performance declined under dual-task conditions, and the avoidance requirement particularly impaired subjects' ability to inhibit prepotent responses. Findings are integrated into a view of random generation as a complex task with multiple performance constraints.
Over the past 30 years, fatigue has contributed to a number of Air Force mishaps. Resource cutbacks combined with increased operational tempos, sustained operations, and night fighting could exacerbate the problem. Extended wakefulness and circadian factors can be especially problematic in military aviation where mission demands sometimes necessitate flights as long as 17-44 hours. To effectively counter fatigue in such operations, the effects of this threat must be objectively measured and understood. This study assessed F-117A pilots during a 37-hour period of continuous wakefulness. Although none of the pilots crashed, substantial decrements were found in flight-skills, reaction times, mood, and brain activation as early as after the 26% hour of continuous wakefulness. The greatest flight degradations occurred after 27-33 hours awake, even though many pilots believed their worst performance was earlier. The decrements found in this relatively-benign test environment may be more serious under operational conditions unless personnel anticipate the most dangerous times and administer valid fatigue countermeasures.
The literature contains inconsistent data on the effects of acute sleep deprivation on the superior cognitive functions. The primary purpose of this study is to determine the effectiveness of inhibition, one of the functions of the working memory executive centre (EC), over an extended, 36-hour waking period. Inhibition is a cognitive mechanism whereby individuals ignore non-relevant information recorded in their working memory. We also tested the effects of a 36- hour period of acute sleep deprivation on simple reaction time. Twelve young, healthy volunteers (M=21.5 years, ς=2.3) performed a random generation task involving letters and a simple reaction time psychomotor test over four sessions held at 10-hour intervals. Each participant was assigned a "constant routine." Participants were kept awake in a prone position within a room whose environment was held strictly constant (light, noise, temperature, meals, etc.). This control procedure provided assurance that any variation in participant performance was solely caused by sleep deprivation. The random generation task, nearly two minutes in length, consisted in verbally producing a sequence of 100 letters in a random fashion (i.e. by inhibiting, for example, alphabetical order) and by keeping to a set rhythm... (PsycINFO Database Record (c) 2012 APA, all rights reserved)
This study examined the effects of an acute physical stressor on salivary testosterone (Tsal) and cortisol (Csal) and their relationship with the autonomic responsiveness to a mental task in fit young men (n = 30). Salivary testosterone (Tsal) and cortisol (Csal) levels were determined before and after a maximal bicycle exercise. Heart rate (HR) and skin conductance levels (SCL) were continuously recorded before, during, and after a Stroop task. Tsal and Csal levels diminished while HR and SCL increased in response to stressors in all the sample. When subjects were distributed in function of their endocrine response to the physical stressor, high Tsal responders showed higher HR reactivity than low responders, and high Csal responders showed higher SCL reactivity and lower reaction time in the Stroop task. These results show that the influence of an acute physical stressor on hormones is associated with the autonomic responses to a mental task.
In this paper, we consider the different methods that have been developed to quantify random generation behavior and incorporate
these measurement scales into a Windows95 computer program called RgCalc. RgCalc analyzes the quality of human attempts at
random generation and can provide computer-generated, pseudorandom sequences for comparison. The program is designed to be
appropriate for the analysis of various types of random generation situations employed in the psychological literature. The
different algorithms for the evaluation of a dataset are detailed and an outline of the program is described. Performance
measures are available for assessing various aspects of the response distribution, the sequencing of pairs, the ordinal relationships
between sets of items, and the tendency to repeat alternatives over different lengths. A factor analysis is used to illustrate
the multiple dimensions underlying human randomization processes.
We used positron emission tomography to contrast changes in cerebral blood flow associated with willed and routine acts. In the six tasks used, volunteers had to make a series of responses to a sequence of stimuli. For the routine acts, each response was completely specified by the stimulus. For the willed acts, the response was open-ended and therefore volunteers had to make a deliberate choice. Willed acts in the two response modalities studied (speaking a word, or lifting a finger) were associated with increased blood flow in the dorsolateral prefrontal cortex (Brodmann area 46). Willed acts were also associated with decreases in blood flow, but the location of these decreases was modality dependent.
Nine paid volunteers were sleep deprived over a period of 40 hours. Every 2 hours during total sleep deprivation (TSD) and after recovery sleep, oral temperature (OT), reaction time (RT) in a vigilance task and electroencephalogram (EEG) with eyes open and closed (C3, C4, T3 and T4) were recorded. Ten artifact-free samples from each condition were Fourier transformed. Absolute power was calculated for six bands. Analyses of variance with deprivation and time of day as factors showed the following significant results: 1) TSD induced an increase in RT, of theta power in all derivations, of beta power in both centrals and a decrease of alpha power with eyes closed; OT was not affected. 2) All bands showed a peak of power at 1800 hours, 2 hours in advance of the OT acrophase at 2000 hours. All variables recovered baseline values after 1 night of sleep. Significant linear correlations of hours of wakefulness with EEG and RT, and of EEG power with OT and RT, were observed. The present findings show a linear increase in EEG power and RT with TSD, and a diurnal oscillation of EEG power, which is independent of TSD.
The effect of oral creatine supplementation on brain metabolite concentrations was investigated in gray matter, white matter, cerebellum, and thalamus of healthy young volunteers by means of quantitative localized proton magnetic resonance spectroscopy in vivo (2.0 T, stimulated echo acquisition mode sequence; repetition time = 6,000 ms, echo time = 20 ms, middle interval = 10 ms, automated spectral evaluation). Oral consumption of 4 x 5 g creatine-monohydrate/day for 4 wk yielded a statistically significant increase (8.7% corresponding to 0.6 mM, P < 0.001) of the mean concentration of total creatine (tCr) when averaged across brain regions and subjects (n = 6). The data revealed considerable intersubject variability (3.5-13.3%), with the smallest increases observed for the two male volunteers with the largest body weights. A regional analysis resulted in significant increases of tCr in gray matter (4.7%), white matter (11.5%), and cerebellum (5.4%) and was most pronounced in thalamus (14.6% corresponding to 1.0 mM). Other findings were significant decreases of N-acetyl-containing compounds in cerebellum and thalamus as well as of choline-containing compounds in thalamus. All cerebral metabolic alterations caused by oral Cr were reversible, as evidenced by control measurements at least 3 mo after the diet. This work demonstrates that excess consumption of Cr yields regionally dependent increases of the tCr concentration in human brain over periods of several weeks.
The prefrontal cortex has long been suspected to play an important role in cognitive control, in the ability to orchestrate thought and action in accordance with internal goals. Its neural basis, however, has remained a mystery. Here, we propose that cognitive control stems from the active maintenance of patterns of activity in the prefrontal cortex that represent goals and the means to achieve them. They provide bias signals to other brain structures whose net effect is to guide the flow of activity along neural pathways that establish the proper mappings between inputs, internal states, and outputs needed to perform a given task. We review neurophysiological, neurobiological, neuroimaging, and computational studies that support this theory and discuss its implications as well as further issues to be addressed
This study examined the effects of one night of sleep deprivation on melatonin and cortisol profiles, as well as performance efficiency of military service members. Sleep intervention consisted of total lack of sleep (N = 7) or 8 hours of sleep (control group; N = 7) during the night. All parameters were measured at selected time intervals before (day 1), during (only in sleep-deprived individuals), and after (day 2) sleep intervention. Rotary pursuit scores and handgrip strength data were used as indices of psychomotor and physical performance, respectively. In sleep-deprived individuals, more salivary melatonin, but not cortisol, was secreted than in subjects who slept adequately. Significant increases in melatonin and cortisol were noted, especially at 1:30 p.m. on the day after nighttime sleep deprivation. In contrast, the tracking scores for rotary pursuit and grip strength among sleep-deprived and rested individuals were comparable. Across a normal working day (day 1), all parameters studied revealed time-specific fluctuations in both control and sleep-deprived groups. Irrespective of nighttime sleep schedule, the patterns of performance on day 2 differed from those on day 1. The tracking performance improved on day 2, whereas grip strength worsened, which may reflect inherent learning and muscle fatigue, respectively. During the night of sleep deprivation, performance declined. In conclusion, the present study showed that one night of sleep deprivation (8 hours) resulted in significant hormonal changes on the next afternoon but did not modify tracking and muscular strength performance.
A review was conducted of studies that assessed the effects of acute bouts of physical activity on adults' cognitive performance. Three groups of studies were constituted on the basis of the type of exercise protocol employed. Each group was then evaluated in terms of information-processing theory. It was concluded that submaximal aerobic exercise performed for periods up to 60 min facilitate specific aspects of information processing; however, extended exercise that leads to dehydration compromises both information processing and memory functions. The selective effects of exercise on cognitive performance are explained in terms of Sanders' [Acta Psychol. 53 (1983) 61] cognitive-energetic model.
Human anterior cingulate function has been explained primarily within a cognitive framework. We used functional MRI experiments with simultaneous electrocardiography to examine regional brain activity associated with autonomic cardiovascular control during performance of cognitive and motor tasks. Using indices of heart rate variability, and high- and low-frequency power in the cardiac rhythm, we observed activity in the dorsal anterior cingulate cortex (ACC) related to sympathetic modulation of heart rate that was dissociable from cognitive and motor-related activity. The findings predict that during effortful cognitive and motor behaviour the dorsal ACC supports the generation of associated autonomic states of cardiovascular arousal. We subsequently tested this prediction by studying three patients with focal damage involving the ACC while they performed effortful cognitive and motor tests. Each showed abnormalities in autonomic cardiovascular responses with blunted autonomic arousal to mental stress when compared with 147 normal subjects tested in identical fashion. Thus, converging neuroimaging and clinical findings suggest that ACC function mediates context-driven modulation of bodily arousal states.
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 working memory (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.
Participants in the sport of adventure racing often choose to go without sleep for a period of greater than 24 h while partaking in prolonged submaximal exercise. This study examined the effect of 30 h of sleep deprivation and intermittent physical exercise, on the cardiorespiratory markers of submaximal exercise in six subjects. Six subjects with the following physical characteristics participated in the study (mean +/- SD): age 22 +/- 0.3 years, height 180 +/- 5 cm, body mass: 77 +/- 5 kg, VO2peak 44 +/- 5 ml. kg (-1). min (-1). Three subjects engaged in normal sedentary activities while three others cycled on a cycle ergometer at 50 % VO2peak for 20 min out of every two hours during thirty hours of sleep deprivation. One week later sleep deprivation was repeated with a cross over of subjects. Every four hours, subjects completed assessments of cardiorespiratory function during 50 % VO2peak cycling. A 3 x 8 repeated measures ANOVA revealed a significantly lower heart rate with sleep deprivation (p < 0.05), but no other significant effects (p > 0.05) on respiratory gas exchange variables. Neither sleep deprivation, nor a combination of sleep deprivation and five hours of moderate intensity cycling, appear to be limiting factors to the physiological capacity to perform submaximal exercise.
To examine how exercise at moderate and maximal intensities affects performance on a choice response time, whole body psychomotor task.
Subjects (n = 12) were tested on a three-choice response time task, after rest and after exercise at 70% and 100% maximum power output (W*max). The dependent variables were time to begin forward momentum (initiation time) and time to complete the movement (movement time). Stride time for the first and second strides and number of strides to cover first 1.1 m were also measured. Blood lactate concentrations and heart rate were recorded before and after completion of each psychomotor test. The subjects subjectively assessed the amount of effort that they used to complete the task.
Repeated measures analysis of variance showed a significant effect for initiation (F2,22 = 11.47, p < 0.001) and movement times (F2,22 = 14.61, p < 0.001). Post hoc least significant difference (LSD) tests showed that initiation time after exercise at 70% W*max was significantly faster than that in the other two conditions. Speed of initiation after rest was significantly quicker than that after exercise at W*max. For movement time, LSD tests showed that time after maximal exercise was significantly slower than that in the other two conditions. Stride time for the second stride showed a significant effect (F2,22 = 6.20, p < 0.01). LSD tests found that time after exercise at W*max was significantly slower in the other two conditions. Stepwise multiple regression analyses found that the increment of change, from rest, of lactate concentrations could significantly predict the increment of change in initiation (R2 = 0.40) and movement (R2 = 0.50) times.
Exercise affects a whole body task differently from purely cognitive tasks. Central factors are probably more important than peripheral factors.
Sleep deprivation has a negative effect on cognitive and psychomotor performance and mood state, partially due to decreases in creatine levels in the brain. Therefore, creatine supplementation should lessen the negative effects of sleep deprivation.
The objective of this study was to examine the effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol.
Subjects were divided into a creatine group (n=10) and a placebo group (n=9). They took 5 g of creatine monohydrate or a placebo, dependent on their group, four times a time a day for 7 days, immediately prior to the experiment. The study was double blind. Subjects undertook tests of random movement generation (RMG), verbal and spatial recall, choice reaction time, static balance and mood state pre-test (0 h), after 6, 12 and 24 h of sleep deprivation, with intermittent exercise. They were tested for plasma concentrations of catecholamines and cortisol at 0 and 24 h.
At 24 h, the creatine group demonstrated significantly less change in performance from 0 h (delta) in RMG, choice reaction time, balance and mood state. There were no significant differences between groups in plasma concentrations of catecholamines and cortisol. Norepinephrine and dopamine concentrations were significantly higher at 24 h than 0 h, but cortisol were lower.
Following 24-h sleep deprivation, creatine supplementation had a positive effect on mood state and tasks that place a heavy stress on the prefrontal cortex.
A series of experiments explores the capacity for generating sequences of random responses, relating it to the central executive component of working memory. Experiment 1 shows a broadly similar pattern of redundancy increasing with speed of generation for both the verbal generation of digits and the manual pressing of keys. In both cases deviations from randomness are shown to reflect the increasing use of a limited number of stereotyped response sets. The remaining experiments use keyboard generation. Experiment 2 demonstrates that concurrent immediate serial recall decreases randomness, and that longer recall sequences produce less random output. Experiments 3 and 4 show that whereas simple counting has no effect on randomness, serial recall, semantic category generation, and concurrent digit generation have substantial effects, and a concurrent fluid intelligence test has the greatest influence on the randomness of key pressing. It is suggested that the task of random generation resembles that of category fluency because it requires the subject to switch retrieval plans and inhibit repetition. On this basis it is predicted that a task involving repeated switching of categories will interfere with generation, despite being predictable and having a low memory load. Experiments 5 and 6 confirm this prediction. Strengths and limitations of the switching hypothesis are discussed, as are the implications of our results for the analysis of executive processes.
We look at the effect of intracluster correlation on standard procedures in linear regression. The ordinary least squares estimator, , of the coefficient vector performs well in most cases but the usual estimator of cov() and procedures based on this such as confidence intervals and hypothesis tests can be seriously misleading. The size of the effect, however, tends to be smaller than the corresponding effect on the variance of an estimated mean in two-stage sampling provided that the cluster sample sizes are approximately equal.
Anxiety often impairs performance of “difficult” tasks (especially under test conditions), but there are numerous exceptions. Theories of anxiety and performance need to address at least two major issues: (1) the complexity and apparent inconsistency of the findings; and (2) the conceptual definition of task difficulty. Some theorists (e.g. Humphreys & Revelle, 1984; Sarason, 1988) argue that anxiety causes worry, and worry always impairs performance on tasks with high attentional or short-term memory demands. According to the processing efficiency theory, worry has two main effects: (1) a reduction in the storage and processing capacity of the working memory system available for a concurrent task; and (2) an increment in on-task effort and activities designed to improve performance. There is a crucial distinction within the theory between performance effectiveness (= quality of performance) and processing efficiency (= performance effectiveness divided by effort). Anxiety characteristically impairs efficiency more than effectiveness.
The generation of random number sequences as a measure of attention deployment has been limited due to the lack of a satisfactory index of pseudorandomness for relatively short response sequences. A new index of subjective randomization (random number generation—RNG) is presented that provides a sensitive measure of departures from randomness (reflecting the disproportion with which any number follows any other number) in a series as short as 100 responses, typically verbalized at a rate of 1/sec. The RNG index of sequential response bias is a minor modification of E. Tulving's (see record
1964-02036-001) subjective organization index that measures clustering in the repeated free recall of randomly presented word lists. Calculation of the practice-free RNG index and comparisons with another common measure are illustrated with individual data and with data obtained from random number tables. The use of RNG as a probe or simultaneous task to measure the deployment of attention or attentive effort is discussed. (10 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
The results of a multi-year research program to identify the factors associated with variations in subjective workload within and between different types of tasks are reviewed. Subjective evaluations of 10 workload-related factors were obtained from 16 different experiments. The experimental tasks included simple cognitive and manual control tasks, complex laboratory and supervisory control tasks, and aircraft simulation. Task-, behavior-, and subject-related correlates of subjective workload experiences varied as a function of difficulty manipulations within experiments, different sources of workload between experiments, and individual differences in workload definition. A multi-dimensional rating scale is proposed in which information about the magnitude and sources of six workload-related factors are combined to derive a sensitive and reliable estimate of workload.
1. The present study was undertaken to test whether creatine given as a supplement to normal subjects was absorbed, and if continued resulted in an increase in the total creatine pool in muscle. An additional effect of exercise upon uptake into muscle was also investigated.
2. Low doses (1 g of creatine monohydrate or less in water) produced only a modest rise in the plasma creatine concentration, whereas 5 g resulted in a mean peak after 1 h of 795 (sd 104) μmol/l in three subjects weighing 76–87 kg. Repeated dosing with 5 g every 2 h sustained the plasma concentration at around 1000 μmol/l. A single 5 g dose corresponds to the creatine content of 1.1 kg of fresh, uncooked steak.
3. Supplementation with 5 g of creatine monohydrate, four or six times a day for 2 or more days resulted in a significant increase in the total creatine content of the quadriceps femoris muscle measured in 17 subjects. This was greatest in subjects with a low initial total creatine content and the effect was to raise the content in these subjects closer to the upper limit of the normal range. In some the increase was as much as 50%.
4. Uptake into muscle was greatest during the first 2 days of supplementation accounting for 32% of the dose administered in three subjects receiving 6 × 5 g of creatine monohydrate/day. In these subjects renal excretion was 40, 61 and 68% of the creatine dose over the first 3 days. Approximately 20% or more of the creatine taken up was measured as phosphocreatine. No changes were apparent in the muscle ATP content.
5. No side effects of creatine supplementation were noted.
6. One hour of hard exercise per day using one leg augmented the increase in the total creatine content of the exercised leg, but had no effect in the collateral. In these subjects the mean total creatine content increased from 118.1 (sd 3.0) mmol/kg dry muscle before supplementation to 148.5 (sd 5.2) in the control leg, and to 162.2 (sd 12.5) in the exercised leg. Supplementation and exercise resulted in a total creatine content in one subject of 182.8 mmol/kg dry muscle, of which 112.0 mmol/kg dry muscle was in the form of phosphocreatine.
Plasma levels of catecholamines and pituitary adrenal hormones were measured in 20 min samples from eight subjects, in one control session and two experimental sessions, while they performed a short-term memory task under quiet of noise conditions. Performing the task led to significant increase in the plasma levels of cortisol, adrenaline and noradrenaline, whereas no variations in growth hormone and dopamine were observed. Similarly, significant changes occurred in urinary catecholamine excretion. A significant correlation was found between individual plasma cortisol increments and error-rates assessed from an accuracy of recall variable. For adrenaline and noradrenaline, an early response apparently linked with an anticipatory process preceded the task. Exposure to noise did slightly amplify cortisol response to the task, but during the first experimental session, with or without noise, the task elicited greater cortisol increases in all subjects than during the second session. These results provide evidence for a relationship between sympathoadrenocortical activity and attentional demand, whereas cortisol increments seem to be more specifically related to better coping with the task. Frequent hormone level measurements during a prolonged mental task might clarify the complex relationship between time-related bodily hormonal changes, performance and subjective feelings.
Twenty-two male soccer players (mean age 21.3 yrs) performed an incremental, multistage bicycle ergometer exercise test with work load increasing by 50 W, until volitional exhaustion. The exercise stages lasted 3 min and were separated by 1 min resting periods. Before exercise and during each load an audio-visual five-choice reaction task was administered to assess subjects' psychomotor performance. During resting intervals venous blood samples were taken for lactate (LA), adrenaline (A) and noradrenaline (NA) determinations. It was found that reaction time (RT) decreased gradually during exercise reaching its minimum (approx. 87% of pre-exercise value) at load 236 W (approx. 75% VO2max, HR 164 beats/min). Then, it increased rapidly, exceeding the resting level by 18%. The work load and heart rate (HR) associated with the minimal RT were higher (p < 0.001) than work load and HR associated with the LA threshold (by 46 W and 17 beats/min, respectively). Plasma A and NA showed an exponential increase during exercise with thresholds at 204 and 208 W, respectively (HR 149 and 154 beats/min). Work load at which plasma NA threshold occurred was significantly higher than the LA threshold but it did not differ from the work load associated with the minimal RT. Conversely, plasma A threshold was lower than the load of the minimal RT but did not differ significantly from LA threshold. It is concluded that young athletes continue to improve their psychomotor performance during exercise even at heavy work loads exceeding anaerobic, and plasma adrenaline thresholds. A relationship between reaction time and plasma catecholamines fits the U-shape curve.
