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Use of creatine in the elderly and evidence for effects on cognitive function in young and old
Abstract
The ingestion of the dietary supplement creatine (about 20 g/day for 5 days or about 2 g/day for 30 days) results in increased skeletal muscle creatine and phosphocreatine. Subsequently, the performance of high-intensity exercise tasks, which rely heavily on the creatine-phosphocreatine energy system, is enhanced. The well documented benefits of creatine supplementation in young adults, including increased lean body mass, increased strength, and enhanced fatigue resistance are particularly important to older adults. With aging and reduced physical activity, there are decreases in muscle creatine, muscle mass, bone density, and strength. However, there is evidence that creatine ingestion may reverse these changes, and subsequently improve activities of daily living. Several groups have demonstrated that in older adults, short-term high-dose creatine supplementation, independent of exercise training, increases body mass, enhances fatigue resistance, increases muscle strength, and improves the performance of activities of daily living. Similarly, in older adults, concurrent creatine supplementation and resistance training increase lean body mass, enhance fatigue resistance, increase muscle strength, and improve performance of activities of daily living to a greater extent than resistance training alone. Additionally, creatine supplementation plus resistance training results in a greater increase in bone mineral density than resistance training alone. Higher brain creatine is associated with improved neuropsychological performance, and recently, creatine supplementation has been shown to increase brain creatine and phosphocreatine. Subsequent studies have demonstrated that cognitive processing, that is either experimentally (following sleep deprivation) or naturally (due to aging) impaired, can be improved with creatine supplementation. Creatine is an inexpensive and safe dietary supplement that has both peripheral and central effects. The benefits afforded to older adults through creatine ingestion are substantial, can improve quality of life, and ultimately may reduce the disease burden associated with sarcopenia and cognitive dysfunction.
... This has led several authors to examine the possibility of creatine supplementation having an effect on cognition. While authors have put forward convincing rationales for such an effect, narrative reviews of this work have shown somewhat equivocal results [11,109,117,121]. Some argued that the equivocality of the results may be due to the heterogeneity of the nature of the participants -vegans, vegetarians, elderly and healthy young adults [117,121]. ...
... While authors have put forward convincing rationales for such an effect, narrative reviews of this work have shown somewhat equivocal results [11,109,117,121]. Some argued that the equivocality of the results may be due to the heterogeneity of the nature of the participants -vegans, vegetarians, elderly and healthy young adults [117,121]. The fact that in several studies, the participants were in some way stressed, i.e. sleep deprived or hypoxic, has also been posited as a possible factor [89,121]. ...
... This last hypothesis is based on arguments that in normal healthy individuals with balanced diets, there is no deficit in brain creatine levels [89,110], therefore supplementation has no beneficial effect. However, it has been argued that stressed individuals show decreases in brain creatine and, therefore, benefit from supplementation [89,110,117]. The stressors we examined were diet (vegans and vegetarians), ageing, hypoxia, sleep deprivation and mental fatigue, as research has been undertaken using these stressors. ...
... Creatine is a naturally occurring compound found in skeletal muscle that is essential for energy production during rest and exercise [7]. While creatine can be consumed through a diet high in meat and fish [8,9], supplementation with creatine monohydrate is typically required to fully saturate creatine stores [10]. ...
... Increasing intramuscular phosphocreatine stores contributes to an increase in ATP production and a resulting increase in exercise capacity, particularly during high-intensity exercise [14][15][16]. Creatine monohydrate is the most widely studied supplement to date, showing improvements in muscle strength, mass, and power in a variety of healthy, clinical, and older adult populations when consumed chronically [7,17,18]. Moreover, high-dose creatine supplementation has been shown to improve many cognitive domains, such as short-term memory and intelligence/reasoning, which may attenuate the exponential decline in cognitive function that many breast cancer patients experience [19]. ...
... Moreover, high-dose creatine supplementation has been shown to improve many cognitive domains, such as short-term memory and intelligence/reasoning, which may attenuate the exponential decline in cognitive function that many breast cancer patients experience [19]. Furthermore, experimental evidence has shown that short-term creatine monohydrate supplementation can also result in meaningful improvements in muscle creatine levels, muscle mass, and muscle strength [6,7,17]. ...
Breast cancer (BC) is one of the most common cancers in the United States. Advances in detection and treatment have resulted in an increased survival rate, meaning an increasing population experiencing declines in muscle mass and strength. Creatine supplementation has consistently demonstrated improvements in strength and muscle performance in older adults, though these findings have not been extended to cancer populations. PURPOSE: The purpose of this study was to investigate the effects of short-term creatine supplementation on muscular performance in BC survivors. METHODS: Using a double-blind, placebo-controlled, randomized design, 19 female BC survivors (mean ± SD age = 57.63 ± 10.77 years) were assigned to creatine (SUPP) (n = 9) or dextrose placebo (PLA) (n = 10) groups. The participants completed two familiarization sessions, then two test sessions, each separated by 7 days, where the participants supplemented with 5 g of SUPP or PLA 4 times/day between sessions. The testing sessions included sit-to-stand power, isometric/isokinetic peak torque, and upper/lower body strength via 10 repetition maximum (10RM) tests. The interaction between supplement (SUPP vs. PLA) and time (Pre vs. Post) was examined using a group × time ANOVA and effect sizes. RESULTS: No significant effects were observed for sit-to-stand power (p = 0.471; ηp² = 0.031), peak torque at 60°/second (p = 0.533; ηp² = 0.023), peak torque at 120°/second (p = 0.944; ηp² < 0.001), isometric peak torque (p = 0.905; ηp² < 0.001), 10RM chest press (p = 0.407; ηp² = 0.041), and 10RM leg extension (p = 0.932; ηp² < 0.001). However, a large effect size for time occurred for the 10RM chest press (ηp² = 0.531) and leg extension (ηp² = 0.422). CONCLUSION: Seven days of creatine supplementation does not influence muscular performance among BC survivors.
... Creatine requires a specific creatine transporter (SLC648) to cross the bloodÀbrain barrier, and SLC648 function varies with age, sex, and diet (Christie, 2007;Solis et al., 2017;Guerrero-Ontiveros and Wallimann, 1998). Despite this, in clinical trials, 4À8 weeks of oral creatine treatment at 20À40 g/ day causes a significant increase of 5%À9% in regional brain creatine as seen by in vivo magnetic resonance spectroscopic (MRS) imaging (Dechent et al., 1999;Kondo et al., 2016;Rawson and Venezia, 2011). Oral creatine showed no toxicity to subjects and had beneficial impact on brain physiology (Dechent et al., 1999;Kondo et al., 2016;Rawson and Venezia, 2011). ...
... Despite this, in clinical trials, 4À8 weeks of oral creatine treatment at 20À40 g/ day causes a significant increase of 5%À9% in regional brain creatine as seen by in vivo magnetic resonance spectroscopic (MRS) imaging (Dechent et al., 1999;Kondo et al., 2016;Rawson and Venezia, 2011). Oral creatine showed no toxicity to subjects and had beneficial impact on brain physiology (Dechent et al., 1999;Kondo et al., 2016;Rawson and Venezia, 2011). Creatine augmentation has been tested for neuroprotection in several preclinical models and in clinical trials of diseases including epilepsy, major depressive disorder (MDD), and neurodegenerative disorders such as Huntington's and Parkinson's diseases. ...
... Creatine has been clinically tested for improving cognitive function (Rawson and Venezia, 2011). Creatine treatment improved cognitive function in healthy adults after 36 hours of sleep deprivation, improving executive function, short-term memory and reaction time (Mcmorris et al., 2006). ...
... The creatine phosphate shuttle thereby serves as an important regulator of cellular metabolism. The role of creatine in energy metabolism and impact that creatine has on maintaining energy availability in diseases that depend on the CK/PCr system provides the metabolic basis on how creatine can affect health, disease, and provide therapeutic benefit [6,9,21,41,50,[64][65][66][67][68][69][70][71]. The role of creatine in energy metabolism will be discussed in greater detail in another paper in this special issue. ...
... Most creatine research initially focused on creatine's role in exercise performance, training adaptations, and safety in untrained and trained healthy individuals [1]. Creatine supplementation has been reported to increase muscle creatine and PCr levels, enhance acute exercise capacity, and improve training adaptations [44, 66,69,. The improvement in performance has generally been 10-20% on various high-intensity exercise tasks [97] that include lifetime fitness activities like fitness/weight training [77,84,91,[98][99][100][101][102][103][104][105][106][107][108], golf [109], volleyball [110], soccer [82,111,112], softball [113], ice hockey [114], running [115][116][117][118][119], and swimming [73,74,[120][121][122][123], among others. ...
... 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]. ...
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.
... The observed improvements from baseline in the Stroop Color and Word-Color interference tests following CO supplementation align with existing research demonstrating the cognitive benefits of creatine. Previous investigations have indicated that creatine supplementation can elevate brain creatine levels, potentially enhancing cognitive performance, particularly in tasks requiring memory and executive function [47,48]. The systematic review of randomized controlled trials demonstrates creatine's positive impact on healthy individuals' memory performance, which supports the observed outcomes in our study [47]. ...
... The improvements in these tasks within our study could indicate creatines' role in augmenting cognitive processing capabilities. Indeed, studies have demonstrated that creatine supplementation is associated with improved neuropsychological performance, particularly under conditions of mental stress, such as sleep deprivation or aging, akin to the demands placed on cognitive function during competitive sports [48,49]. Furthermore, the enhanced cognitive performance in the CO group could suggest a synergistic effect of creatine when combined with CAF. ...
Citation: Mabrey, G.; Koozehchian, M.S.; Newton, A.T.; Naderi, A.; Forbes, S.C.; Haddad, M. The Effect of Creatine Nitrate and Caffeine Individually or Combined on Exercise Performance and Cognitive Function: A Randomized, Crossover, Double-Blind, Placebo-Controlled Trial. Nutrients 2024, 16, 766. Abstract: This study examined the effect of creatine nitrate and caffeine alone and combined on exercise performance and cognitive function in resistance-trained athletes. In a double-blind, randomized crossover trial, twelve resistance-trained male athletes were supplemented with 7 days of creatine nitrate (5 g/day), caffeine (400 mg/day), and a combination of creatine nitrate and caffeine. The study involved twelve resistance-trained male athletes who initially provided a blood sample for comprehensive safety analysis, including tests for key enzymes and a lipid profile, and then performed standardized resistance exercises-bench and leg press at 70% 1RM-and a Wingate anaerobic power test. Cognitive function and cardiovascular responses were also examined forty-five minutes after supplementation. Creatine nitrate and caffeine that were co-ingested significantly enhanced cognitive function, as indicated by improved scores in the Stroop Word-Color Interference test (p = 0.04; effect size = 0.163). Co-ingestion was more effective than caffeine alone in enhancing cognitive performance. In contrast, no significant enhancements in exercise performance were observed. The co-ingestion of creatine nitrate and caffeine improved cognitive function, particularly in cognitive interference tasks, without altering short-term exercise performance. Furthermore, no adverse events were reported. Overall, the co-ingestion of creatine nitrate and caffeine appears to enhance cognition without any reported side effects for up to seven days.
... It is proposed as an ergogenic resource for a long time; however, its therapeutic use has gained relevance and adhesion in the last two decades. Interestingly, the role of this metabolite in the aging process has been highlighted, with many studies aiming to understand how aging affects creatine resource depletion (1)(2)(3)(4), and how creatine supplementation could mitigate this event (2,5,6). Recent studies have risen the hypothesis that creatine supplementation can help mitigate the effects of aging, supported by the fact that creatine is a natural regulator of energy homeostasis, and plays a recognized role in brain function and development (7). ...
... It is proposed as an ergogenic resource for a long time; however, its therapeutic use has gained relevance and adhesion in the last two decades. Interestingly, the role of this metabolite in the aging process has been highlighted, with many studies aiming to understand how aging affects creatine resource depletion (1)(2)(3)(4), and how creatine supplementation could mitigate this event (2,5,6). Recent studies have risen the hypothesis that creatine supplementation can help mitigate the effects of aging, supported by the fact that creatine is a natural regulator of energy homeostasis, and plays a recognized role in brain function and development (7). ...
Creatine (Cr) has been proposed as an ergogenic resource and the adhesion to its therapeutic use has gained relevance in the last 2 decades. The
role of Cr in the aging process has been highlighted, with many studies aiming to understand how aging affects the depletion of Cr resources in
muscle and brain, especially because Cr is a natural regulator of energy homeostasis and plays a recognized role in brain function and development,
justifying the rising hypothesis that Cr supplementation can help mitigate the effects of aging. Thus, we aimed to review the role of Cr (supplemented
or obtained in daily diet) and its metabolism in the aging brain, with emphasis on cognition/memory. PubMed, PsychInfo, EBSCO, Medline, BioMed
central and Science Direct, constituted the searched databases. Inclusion criteria specified peer-reviewed studies investigating creatine metabolism
and/or creatine supplementation, and assessing cognition, and memory in old adults, and published between January, 2000 to September, 2022. The
importance of creatine in the brain’s energy metabolism is well established. The relationship between the decline of cognitive function and brain
creatine storage still lacks stronger evidence. Evidence is also lacking on whether creatine supplementation is beneficial in mitigating the neural
effects of aging, remaining an open field of studies that brings optimistic perspectives.
... The observed improvements from baseline in the Stroop Color and Word-Color interference tests following CO supplementation align with existing research demonstrating the cognitive benefits of creatine. Previous investigations have indicated that creatine supplementation can elevate brain creatine levels, potentially enhancing cognitive performance, particularly in tasks requiring memory and executive function [47,48]. The systematic review of randomized controlled trials demonstrates creatine's positive impact on healthy individuals' memory performance, which supports the observed outcomes in our study [47]. ...
... The improvements in these tasks within our study could indicate creatines' role in augmenting cognitive processing capabilities. Indeed, studies have demonstrated that creatine supplementation is associated with improved neuropsychological performance, particularly under conditions of mental stress, such as sleep deprivation or aging, akin to the demands placed on cognitive function during competitive sports [48,49]. Furthermore, the enhanced cognitive performance in the CO group could suggest a synergistic effect of creatine when combined with CAF. ...
Background:
Caffeine and creatine nitrate are two purported supplements that may alter cognitive function. The primary purpose was to examine the impacts of each supplement ingested individually and co-ingested on cognitive performance. A secondary purpose was to explore the effects of caffeine and creatine nitrate alone and co-ingested on subjective feelings of readiness and sleep quality.
Methods:
In a double-blind, randomized, placebo-controlled cross over study, 12 resistance-trained participants (22±1 y; 180.0±9.5 cm; 85.9±15.1 kg) completed 4 conditions in random order: creatine nitrate (CN: 5 g/day + 0.675 g/day of maltodextrin), caffeine (CAF: 400 mg/day + 5 g/day of maltodextrin), CN+CAF (5 g/day of creatine nitrate + 400 mg/day of caffeine), and placebo (PL: 5.4 g/day of maltodextrin). Supplements were ingested for 7 days with a 7-day washout period between conditions. Before and after supplementation, participants completed a Stroop color-word test, in addition to a readiness to perform a visual analog scale and a sleep quality questionnaire (sleep latency and duration). The readiness to perform the questionnaire assessed sleep, vigor, optimism, energy, appetite, and soreness. Data were analyzed using a two-way (within-within) analysis of variance (p≤0.05) with a Tukey's post hoc when appropriate.
Results:
There was a significant interaction for the Stroop color-word interference (p=0.049), with the post hoc revealing that CN+CAF was superior to CN alone (CN+CAF: 65.9 ± 17.3; CN: 56.8 ± 10.8, p=0.007); however, no other conditions were significantly different. There was no interaction or main effects for the readiness to perform questionnaire or sleep quality (p>0.05).
Conclusion:
CAF+CN appears to be superior for cognitive performance compared to CN alone. Overall, neither supplement ingested individually or together altered subjective readiness to perform or sleep quality.
... Prior studies indicate that CrM loading (i.e., 4 × 5 g/day for 5-7 days) or low-dose longterm intake (e.g., 3-6 g/day for 4-12 weeks) increases muscle creatine retention typically by 20-40% depending on initial creatine content in the muscle [12,22,[68][69][70][71]] and brain creatine content by 5-15% [72][73][74][75][76][77]. CrM supplementation has been reported to improve acute exercise performance particularly in intermittent high-intensity exercise bouts as well as enhance training adaptations in adolescents [78][79][80][81][82], young adults [29,55,[83][84][85][86][87][88][89][90][91][92], and older individuals [8,77,[93][94][95][96][97][98][99][100][101]. ...
... Prior studies indicate that CrM loading (i.e., 4 × 5 g/day for 5-7 days) or low-dose longterm intake (e.g., 3-6 g/day for 4-12 weeks) increases muscle creatine retention typically by 20-40% depending on initial creatine content in the muscle [12,22,[68][69][70][71]] and brain creatine content by 5-15% [72][73][74][75][76][77]. CrM supplementation has been reported to improve acute exercise performance particularly in intermittent high-intensity exercise bouts as well as enhance training adaptations in adolescents [78][79][80][81][82], young adults [29,55,[83][84][85][86][87][88][89][90][91][92], and older individuals [8,77,[93][94][95][96][97][98][99][100][101]. High-intensity exercise performance is generally increased by 10-20% with greater improvements seen in individuals starting the supplementation protocol with lower muscle creatine and PCr content [102]. ...
In 2011, we published a paper providing an overview about the bioavailability, efficacy, and regulatory status of creatine monohydrate (CrM), as well as other “novel forms” of creatine that were being marketed at the time. This paper concluded that no other purported form of creatine had been shown to be a more effective source of creatine than CrM, and that CrM was recognized by international regulatory authorities as safe for use in dietary supplements. Moreover, that most purported “forms” of creatine that were being marketed at the time were either less bioavailable, less effective, more expensive, and/or not sufficiently studied in terms of safety and/or efficacy. We also provided examples of several “forms” of creatine that were being marketed that were not bioavailable sources of creatine or less effective than CrM in comparative effectiveness trials. We had hoped that this paper would encourage supplement manufacturers to use CrM in dietary supplements given the overwhelming efficacy and safety profile. Alternatively, encourage them to conduct research to show their purported “form” of creatine was a bioavailable, effective, and safe source of creatine before making unsubstantiated claims of greater efficacy and/or safety than CrM. Unfortunately, unsupported misrepresentations about the effectiveness and safety of various “forms” of creatine have continued. The purpose of this critical review is to: (1) provide an overview of the physiochemical properties, bioavailability, and safety of CrM; (2) describe the data needed to substantiate claims that a “novel form” of creatine is a bioavailable, effective, and safe source of creatine; (3) examine whether other marketed sources of creatine are more effective sources of creatine than CrM; (4) provide an update about the regulatory status of CrM and other purported sources of creatine sold as dietary supplements; and (5) provide guidance regarding the type of research needed to validate that a purported “new form” of creatine is a bioavailable, effective and safe source of creatine for dietary supplements. Based on this analysis, we categorized forms of creatine that are being sold as dietary supplements as either having strong, some, or no evidence of bioavailability and safety. As will be seen, CrM continues to be the only source of creatine that has substantial evidence to support bioavailability, efficacy, and safety. Additionally, CrM is the source of creatine recommended explicitly by professional societies and organizations and approved for use in global markets as a dietary ingredient or food additive.
... Other factors related to aging that may influence brain creatine concentrations include reduced brain and/or physical activity, depression, schizophrenia, and panic disorder. The overlap between these factors may be misleading as to what might be identified as an age-related decline (reviewed in Rawson and Venezia [25]). ...
... A large heterogeneity in respect to brain creatine assessment technique (i.e., total brain creatine as assessed by H 1 -NMR vs. brain PCr as assessed by P 31 -NMR), supplement dose and duration (range 2 to 20 g/d for 1 to 8 weeks), and population characteristics (including habitual dietary creatine intake, health status, etc.) hampers direct comparison between the few studies on the topic. Further confusion is introduced by the fact that creatine content may differ regionally within the brain [25,27]. Nevertheless, collectively, the available literature suggests possible increases in both creatine and PCr in the brain following supplementation, though smaller than that seen in muscle (~half the increase) [3]. ...
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.
... A growing collection of evidence supports that creatine supplementation may improve health status as individuals age (7,12,15). In this regard, creatine supplementation has been reported to positively influence cognitive function (12,15) and in some instances serve as an anti-depressant (17,20). ...
... A growing collection of evidence supports that creatine supplementation may improve health status as individuals age (7,12,15). In this regard, creatine supplementation has been reported to positively influence cognitive function (12,15) and in some instances serve as an anti-depressant (17,20). ...
The purpose of this study was to determine the effect of 16 wks of resistance training and creatine supplementation on strength and cognition in 26 older adults (5 male and 21 female) who were randomly assigned to the Control Group (CG, n=13) or the Intervention Group (IG, n=13). Weight and height were measured. The JAMAR™ hand dynamometer was used for the dominant and nondominant handgrip. Cognitive performance was measured with the MoCa questionnaire. Resistance training plus 5 g•d-1 of creatine supplementation were applied as the intervention protocol for 16 consecutive wks. After the 16 wks of intervention, the IG improved in both the handgrip strength (P<0.05) and cognitive performance (P<0.05). The findings indicate that 16 wks of resistance training and creatine monohydrate supplementation improved older adults' handgrip strength and cognitive performance.
... Nevertheless, supplement manufacturers have continually introduced newer forms of creatine into the marketplace. These newer forms have been purported to have better physical and chemical properties, bioavailability, efficacy, and/or safety profiles than regular CM [6]. However, there is little to no evidence that any of the newer forms of creatine are more effective and/or safer than CM whether ingested alone and/or in combination with other nutrients [7]. ...
Background
Creatine monohydrate is a widely utilized dietary supplement in sports nutrition, valued for its role in enhancing muscle energy availability, power output, and performance during high-intensity, short-duration activities. Creatine monohydrate is effective but limited by absorption inefficiencies and side effects. Enhanced forms can improve uptake, reduce gastrointestinal discomfort, and optimize muscle energy utilization, meeting athletes’ evolving performance needs.
Methods
This study involved 32 healthy male volunteers aged 18-50 years, with a BMI of 18.5-25.0 kg/m² and body weight of ≥50 kg. This study evaluated the bioavailability and safety of MuscleBlaze Creatine Monohydrate (CreAMP™) (Bright Lifecare Pvt Ltd, Gurugram, India), containing 3.0 g creatine monohydrate and 0.1 g Creabsorb™ (Indian Patent: IN202311057466), against a standard 3.0 g micronized creatine dose. In a double-blind, randomized crossover trial (CTRI/2024/08/073021), 32 healthy males (18-50 years) received both formulations under fasting conditions. The study compared two oral creatine monohydrate formulations: CreAMP™ Micronized Creatine Monohydrate (test) and Regular Micronized Creatine Monohydrate (reference) (Bright Lifecare Pvt Ltd, Gurugram, India). Blood samples were collected pre-dose and up to six hours post-dose over two periods, separated by a washout period of one week. Pharmacokinetic parameters were analyzed using Phoenix® WinNonlin® 8.5 (Certara, Radnor, PA).
Results
CreAMP™ has significantly higher bioavailability, absorption, and plasma retention compared to the reference formulation. With a 38.97% increase in bioavailability, an 18.10% higher Cmax, a 21.37% longer half-life, 34.67% lower clearance, and a 10.13% higher mean residence time, CreAMP™ demonstrates superior pharmacokinetic properties. These findings suggest that CreAMP™ offers improved creatine uptake, sustained plasma levels, and the potential for reduced dosing frequency, making it a more effective formulation for creatine supplementation.
Conclusion
The study findings establish CreAMP™ as a superior creatine formulation, offering enhanced bioavailability, faster absorption, and prolonged plasma retention. These pharmacokinetic advantages indicate that CreAMP™ offers more efficient creatine uptake, improved energy availability, and optimized performance support for athletes.
... demonstrating that brain creatine is not fully reliant on organ production or external supplementation (22). In some studies, creatine 8 supplementation reduced the brain tissue's need for oxygen (25) and improved verbal, longterm, and spatial memory (26). ...
Purpose of Research: The study evaluates the effects of creatine supplementation on physical performance, cognitive function, and safety. It examines its mechanism of action, impact on muscle mass and strength, and role in brain health. Additionally, it reviews the safety profile of creatine in diverse populations, including athletes, older adults, and individuals with chronic conditions. Research Materials and Methods: The study is based on clinical trials, meta-analyses, and systematic reviews from the past decade. Data were collected from studies on creatine supplementation at various doses, including loading and maintenance phases, and its effects on physical and cognitive outcomes, as well as kidney and liver function. Basic Results Creatine supplementation significantly improved lean body mass (mean difference = 1.32 kg; p < 0.000001) and muscle strength, with greater effects in men. It also showed potential benefits for memory, particularly in older adults, with moderate improvements in non-stress conditions. Safety evaluations indicated no adverse effects on kidney or liver function, even with long-term high-dose use. Conclusions: Creatine supplementation is a safe, effective strategy for enhancing physical performance, especially with resistance training. It also supports cognitive functions, particularly in populations with higher energy demands or age-related decline. These findings support creatine as a versatile, well-tolerated dietary supplement for sports and health applications.
... CCR offers a more accurate measurement of actual creatinine levels without the interference of renal function. Numerous studies have shown that appropriate creatine supplementation can effectively enhance muscle and cognitive function with an excellent safety profile, although the precise mechanism remains unknown.69 Our study also found that CCR was negatively associated with depression in ADSA patients. ...
INTRODUCTION
Sarcopenia, with its complex diagnostic process, is a likely independent predictor of poor prognosis in patients with Alzheimer's disease (AD). However, research on the clinical characteristics and biomarkers of AD patients with sarcopenia (ADSA) is limited.
METHODS
This study included 180 ADSA and 188 AD patients without sarcopenia (ADNSA), and evaluated demographics, cognitive function, motor capacity, emotional state, and daily living abilities.
RESULTS
ADSA patients were older, with worse motor and cognitive functions, more severe depression, poorer social functioning, and lower daily living abilities compared to ADNSA patients. Multivariate regression identified age, low Frailty Rating Scale (FRS) scores, low serum albumin level, and low creatinine/cystatin C ratio (CCR) as risk factors for sarcopenia. A nomogram model based on these indicators demonstrated high discriminative power and clinical utility.
DISCUSSION
Sarcopenia significantly affects AD patients’ various functions. The nomogram model aids in the early detection of and personalized interventions for sarcopenia in AD.
Highlights
Sarcopenia is a risk factor for Alzheimer's disease (AD), and the coexistence of sarcopenia affects various functions and quality of life in patients with AD.
Serum albumin and Frailty Rating Scale (FRS) scores are significantly associated with both sarcopenia and cognitive assessment indicators in AD patients with sarcopenia (ADSA).
The combined sarcopenia nomogram model with indexes of age at diagnosis, creatinine/cystatin C ratio (CCR), FRS score, and albumin levels can aid in effectively identifying and personalizing interventions for sarcopenia in the AD population.
... In addition, given its effects on cellular energy balance regulation and reduction of oxidative stress, clinical applications have been attributed to it, finding beneficial effects after its supplementation in neurodegenerative diseases such as muscular dystrophy (8), Huntington's disease (9), Parkinson's disease (10), diabetes (11), osteoarthritis (12), fibromyalgia (13), cerebral or cardiac ischemia (14), depression (15), and aging positively influencing cognitive function (16). Some studies have even found beneficial effects in pregnant women, improving the fetus's growth, development, and health (17). ...
Introduction: Creatine (Cr) is an effective and safe ergogenic supplement that enhances post-exercise recovery, prevents injuries, supports thermoregulation, and provides benefits in rehabilitation, as well as spinal and cerebral neuroprotection for adults and older individuals. However, the evidence regarding its benefits in the pediatric population across various contexts has not been conclusive. Objective: Analyze the impact of different doses of Cr on physical performance and muscle function in children and adolescents in general through a systematic review of the literature. Materials and methods: This review followed the PRISMA reporting guidelines in the electronic databases of PubMed/Medline and Google Scholar. It included controlled clinical trials conducted between 1997 and May 2023 that assessed the effect of Cr supplementation on muscle function and physical performance in children and adolescents. A total of 20 studies were included. Results: The subjects included young high-performance athletes from different disciplines and children or adolescents diagnosed with pathologies affecting muscle function. Significant effects were found in athletes' physical performance and muscular function at various doses and periods of supplementation, unlike those involving a pathology, which mainly did not present improvements in these variables. Conclusions: Some reports suggest a positive effect on physical performance, specifically in young athletes. However, the Cr doses, posology, and administration protocols vary between studies.
... This suggests that creatine may be a promising adjunctive treatment, especially for patients with neurodegenerative diseases and associated cognitive impairments. In age-stratified analysis, adults aged 18-60 showed significant effects from creatine supplementation, whereas the effects were not significant in individuals over 60 years old, possibly due to age-related physiological changes (42). This highlights the need for future research to further explore the effects of creatine across different age groups and to optimize supplementation strategies to meet the needs of various populations. ...
Background
This study aimed to evaluate the effects of creatine monohydrate supplementation on cognitive function in adults and explore its potential role in preventing and delaying cognitive impairment-related diseases.
Methods
Following the PRISMA 2020 guidelines, a systematic review with meta-analysis was conducted. Randomized controlled trials (RCTs) published between 1993 and 2024 were retrieved from PubMed, Scopus, and Web of Science databases. The study protocol was registered with PROSPERO (registration number: CRD42024533557). The impact of creatine supplementation on overall cognitive function, memory, executive function, attention, and information processing speed was assessed using standardized mean differences (SMD) and Hedge’s g with 95% confidence intervals (CI).
Results
Sixteen RCTs involving 492 participants aged 20.8–76.4 years, including healthy individuals and patients with specific diseases, were selected. Creatine monohydrate was the form used in all included studies. Creatine supplementation showed significant positive effects on memory (SMD = 0.31, 95% CI: 0.18–0.44, Hedges’s g = 0.3003, 95% CI: 0.1778–0.4228) and attention time (SMD = −0.31, 95% CI: −0.58 to −0.03, Hedges’s g = −0.3004, 95% CI: −0.5719 to −0.0289), as well as significantly improving processing speed time (SMD = −0.51, 95% CI: −1.01 to −0.01, Hedges’s g = −0.4916, 95% CI: −0.7852 to −0.1980). However, no significant improvements were found on overall cognitive function or executive function. Subgroup analyses revealed that creatine supplementation was more beneficial in individuals with diseases, those aged 18–60 years, and females. No significant differences were found between short- (<4 weeks) and long-term (≥4 weeks) interventions for improving cognitive function. Low-to-moderate risk of bias was found, and no significant publication bias was detected. The GRADE assessment indicates that the certainty of evidence for memory function is moderate, suggesting a reasonable level of confidence in the positive effects of creatine on memory. However, the evidence for processing speed, overall cognitive function, executive function, and attention is of low certainty, indicating that further research is needed to confirm these potential benefits.
Conclusion
Current evidence suggests that creatine monohydrate supplementation may confer beneficial effects on cognitive function in adults, particularly in the domains of memory, attention time, and information processing speed. Larger robust clinical trials are warranted to further validate these findings. Furthermore, future research should investigate the influence of different populations and intervention durations on the effects of creatine monohydrate supplementation, as well as elucidate the precise mechanisms underlying its potential cognitive-enhancing properties.
... Creatine has also been proven to have positive effects on strength. Numerous studies described an increase in overall body weight of 1-2 kg during the first week of loading as well as fat-free mass growth, even daily living performance, or neurological functionality in young or older people [43,44]. Creatine might also reduce post-exercise muscle damage via mechanisms stabilizing the sarcolemma [45]. ...
The study aimed to show the potential clinical application of supplements used among sportsmen for patients suffering from Intensive Care Unit-acquired Weakness (ICUAW) treatment. ICUAW is a common complication affecting approximately 40% of critically ill patients, often leading to long-term functional disability. ICUAW comprises critical illness polyneuropathy, critical illness myopathy, or a combination of both, such as critical illness polyneuromyopathy. Muscle degeneration begins shortly after the initiation of mechanical ventilation and persists post-ICU discharge until proteolysis and autophagy processes normalize. Several factors, including prolonged bedrest and muscle electrical silencing, contribute to muscle weakness, resulting from an imbalance between protein degradation and synthesis. ICUAW is associated with tissue hypoxia, oxidative stress, insulin resistance, reduced glucose uptake, lower adenosine triphosphate (ATP) formation, mitochondrial dysfunction, and increased free-radical production. Several well-studied dietary supplements and pharmaceuticals commonly used by athletes are proven to prevent the aforementioned mechanisms or aid in muscle building, regeneration, and maintenance. While there is no standardized treatment to prevent the occurrence of ICUAW, nutritional interventions have demonstrated the potential for its mitigation. The use of ergogenic substances, popular among muscle-building sociates, may offer potential benefits in preventing muscle loss and aiding recovery based on their work mechanisms.
... Evidence supports a correlation between decreased skeletal muscle mass and function, and impaired cognitive function, as cited in (Sui et al., 2020). Furthermore, additional evidence indicates that creatine supplementation may enhance cognitive function, as referenced in (Rawson and Venezia, 2011). Consequently, T2DM patients can potentially mitigate cognitive impairment by engaging in creatine supplementation and physical activity. ...
Objective: This study aimed to explore the risk factors, metabolic characteristics, and potential biomarkers of mild cognitive impairment in type 2 diabetes mellitus (T2DM-MCI) and to provide potential evidence for the diagnosis, prevention, and treatment of mild cognitive impairment (MCI) in patients with type 2 diabetes mellitus (T2DM).
Methods: A total of 103 patients with T2DM were recruited from the Endocrinology Department of The Second Affiliated Hospital of Dalian Medical University for inclusion in the study. The Montreal Cognitive Assessment (MoCA) was utilized to evaluate the cognitive functioning of all patients. Among them, 50 patients were categorized into the T2DM-MCI group (MoCA score < 26 points), while 53 subjects were classified into the T2DM without cognitive impairment (T2DM-NCI) group (MoCA score ≥ 26 points). Serum samples were collected from the subjects, and metabolomics profiling data were generated by Ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS). These groups were analyzed to investigate the differences in expression of small molecule metabolites, metabolic pathways, and potential specific biomarkers.
Results: Comparison between the T2DM-MCI group and T2DM-NCI group revealed significant differences in years of education, history of insulin application, insulin resistance index, insulin-like growth factor-binding protein-3 (IGFBP-3), and creatinine levels. Further binary logistic regression analysis of the variables indicated that low educational level and low serum IGFBP-3 were independent risk factor for T2DM-MCI. Metabolomics analysis revealed that differential expression of 10 metabolites between the T2DM-MCI group and T2DM-NCI group ( p < 0.05 and FDR<0.05, VIP>1.5). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis revealed that fatty acid degradation was the most significant pathway. Receiver operating characteristic (ROC) analysis shows that lysophosphatidylcholine (LPC) 18:0 exhibited greater diagnostic efficiency.
Conclusion: This study revealed that a shorter duration of education and lower serum IGFBP-3 levels are independent risk factors for T2DM-MCI. Serum metabolites were found to be altered in both T2DM-MCI and T2DM-NCI groups. T2DM patients with or without MCI can be distinguished by LPC 18:0. Abnormal lipid metabolism plays a significant role in the development of MCI in T2DM patients.
... Factors affecting brain Cr levels include aging, reduced physical activity, depression, and psychiatric abnormalities 21, 22 . Cr supplementation elicits beneficial effects under brain Cr deficit-related conditions, including physiological stress such as exercise and sleep deprivation and pathophysiological states such as creatine deficiency syndrome, mild traumatic brain injury, Alzheimer's disease, and depression 22,23 . ...
... Factors affecting brain Cr levels include aging, reduced physical activity, depression, and psychiatric abnormalities 21, 22 . Cr supplementation elicits beneficial effects under brain Cr deficit-related conditions, including physiological stress such as exercise and sleep deprivation and pathophysiological states such as creatine deficiency syndrome, mild traumatic brain injury, Alzheimer's disease, and depression 22,23 . ...
[Purpose] The maintenance of energy balance in the body, especially in energy-demanding tissues like the muscles and the central nervous system, depends on creatine (Cr). In addition to improving muscle function, Cr is necessary for the bioenergetics of the central nervous system because it replenishes adenosine triphosphate without needing oxygen. Furthermore, Cr possesses anti-oxidant, anti-apoptotic, and anti-excitotoxic properties. Clinical research on neurodegenerative illnesses has shown that Cr supplementation results in less effective outcomes. With a brief update on the possible role of Cr in human, animal, and in vitro experiments, this review seeks to offer insights into the ideal dosage regimen.[Methods] Using specified search phrases, such as “creatine and neurological disorder,” “creatine supplementation and neurodegenerative disorders,” and “creatine and brain,” we searched articles in the PubMed database and Google Scholar. We investigated the association between creatine supplementation and neurodegenerative illnesses by examining references.[Results] The neuroprotective effects of Cr were observed in in vitro and animal models of certain neurodegenerative diseases, while clinical trials failed to reproduce favorable outcomes.[Conclusion] Determining the optimal creatinine regime for increasing brain creatinine levels is essential for maintaining brain health and treating neurodegeneration.
... The production of creatine in the brain is crucial in cases of creatine-deficient disorders [9]. Numerous studies have found that taking a creatine supplement enhances learning and memory [10] and can increase muscular strength [11]. Creatine plays an important role in maintaining heart function in congestive heart failure [12] and in brain or heart ischemia-related damage [13]. ...
... Creatine supplements can increase the availability of ATP in muscles and help increase muscle strength and endurance during strenuous and short physical activity. A study in 2020 found that taking creatine supplements for 4 weeks can increase muscle strength and endurance in athletes [72]. Betaalanine supplements: Betaalanine is an amino acid that serves as a precursor to carbamic acids, which increases the concentration of acid buffer in muscles. ...
Athletes widely use nutritional supplements to increase muscle strength and endurance. This review aims to summarize the effects of commonly used dietary supplements on muscle strength and endurance in athletes. A literature search identified several dietary supplements studied for their impact on muscle performance, including protein supplements, creatine, beta-alanine, branched-chain amino acids (BCAAs), caffeine, nitrates, and vitamins and minerals. The review discussed the mechanisms by which this supplement affects muscle strength and endurance. The review methodology includes a systematic literature search, study selection, and data analysis. The review summarizes the effects of each type of supplement on muscle strength and endurance based on the available literature. The discussion includes an overview of the effectiveness and safety of using nutritional supplements to increase muscle strength and endurance in athletes, as well as limitations of studies reviewed and directions for future research. In conclusion, this review highlights the importance of choosing the right and safe nutritional supplements to improve muscle performance in athletes.
... In addition, several studies suggests that creatine supplementation increases cellular energy availability (17). Creatine has been reported to increase brain phosphocreatine content by as much as 15%, which in turn improves the metabolic processes of the brain (14,(18)(19)(20)(21). ...
Background
Mild traumatic brain injury or concussion is a global public concern, with an estimated annual incidence between 48 million and 96 million worldwide. It is a socioeconomical problem, and almost one-third of individuals with concussion suffer from severe persistent post-concussive symptoms (PPCS), with an increased risk of unemployment or terminating their studies. To date, no single treatment is available with guaranteed success. Creatine monohydrate (CrM) has shown potential as a treatment for post-concussive symptoms, having a positive impact on cognitive function, chronic fatigue, depression, and anxiety. The aim of this study is to examine the effect of CrM on PPCS assessed using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ).
Methods
The study is designed as a double-blinded randomised controlled trial. Study participants are found through neurological outpatient clinics in Denmark or through social media. They will be between 25 and 35 years of age, will have suffered from PPCS for 6–12 months prior to inclusion, and will have no comorbidities. The participants will be randomly allocated to either an intervention group (INT), placebo group (PLA), or control group (CG). Baseline data will be collected immediately after inclusion, and the study period will be 7 weeks. Follow-up data will be collected 1 week after the end of the study period. The primary outcome of the study is changes in RPQ score. Changes in weight and training status will be adjusted for as potential confounders.
Ethics and dissemination
This protocol is approved by the National Committee on Health Research (97508) and by the Danish Data Protection Agency 11.651. The investigators intend to submit their study findings for publication in peer-reviewed journals and disseminate the findings via presentation at academic meetings/conferences.
Clinical Trial registration: NCT05562232, registered September 30, 2022.
... While consistent information is available on supplementation protocols aimed at increasing muscle creatine content, much less is known regarding the optimal supplementation strategy to increase brain creatine levels, this is largely due to limited dataset that directly measures the concentration of creatine in the brain following supplementation (Roschel et al., 2021). Moreover, the large heterogenicity in respect to brain creatine assessment techniques, differences in creatine content in different regions of the brain, different creatine dosages and duration of supplementation, and variations in population characteristics, all hampers direct comparison between the few studies available on the topic (Rawson and Venezia, 2011). The available literature suggests possible increases in creatine in the brain following supplementation, though smaller than that seen in muscle (about 3%-10% vs. 20% increase in muscles from baseline) (Pan and Takahashi, 2007;Kondo et al., 2011;Turner et al., 2015). ...
Epilepsy is one of the most common neurological disorders affecting people of all ages representing a significant social and public health burden. Current therapeutic options for epilepsy are not effective in a significant proportion of patients suggesting a need for identifying novel targets for the development of more effective therapeutics. There is growing evidence from animal and human studies suggesting a role of impaired brain energy metabolism and mitochondrial dysfunction in the development of epilepsy. Candidate compounds with the potential to target brain energetics have promising future in the management of epilepsy and other related neurological disorders. Creatine is a naturally occurring organic compound that serves as an energy buffer and energy shuttle in tissues, such as brain and skeletal muscle, that exhibit dynamic energy requirements. In this review, applications of creatine supplements in neurological conditions in which mitochondrial dysfunction is a central component in its pathology will be discussed. Currently, limited evidence mainly from preclinical animal studies suggest anticonvulsant properties of creatine; however, the exact mechanism remain to be elucidated. Future work should involve larger clinical trials of creatine used as an add-on therapy, followed by large clinical trials of creatine as monotherapy.
... There is evidence to support the association of reduced skeletal muscle mass and function with reduced cognitive function [38]. Cognitive function can be improved through creatine supplementation according to other evidence [39]. Therefore, T2DM patients prevent the development of cognitive impairment via creatine supplementation and physical activity. ...
Objective: This study aimed to explore the controllable risk factors, metabolic characteristics and potential biomarkers of T2DM-MCI and to provide potential proof for the diagnosis, prevention and treatment of cognitive impairment in T2DM patients.
Methods: 103 T2DM patients who were hospitalized in the Endocrinology Department of the Second Hospital of Dalian Medical University were included. MoCA was used to evaluate the cognitive function of all subjects. 50 patients were included in T2DM-MCI group (MoCA score <26 points), and 53 subjects were in T2DM-NCI group (MoCA score ≥ 26 points). Serum samples of subjects were collected, and metabolomics data was collected by UHPLC-MS. The serum samples of 12 subjects were excluded due to poor quality, 47 subjects were in the T2DM-MCI group, 44 cases in T2DM-NCI group were used to analyze the differentially expressed small molecule metabolites, metabolics pathway and the potential specific biomarkers.
Results: Comparison between T2DM-MCI group and T2DM-NCI group, years of education, history of insulin application, and insulin resistance index, insulin-like growth factor-binding protein-3, and creatinine were significantly different between groups. Further binary logistic regression analysis of the variables showed low educational level and low serum insulin-like growth factor-binding protein-3 was an independent risk factor for T2DM-MCI. Metabolomics analysis showed that 10 metabolites were differentially expressed between T2DM-MCI group and T2DM-NCI group (P<0.05 and FDR<0.05, VIP>1.5). KEGG enrichment pathway reveals that fatty acid degradation is the most significant. ROC shows that LPC 18:0 has a greater diagnostic efficiency.
Conclusion: This study suggests that T2DM patients with low education levels, history of insulin use, high insulin resistance, low serum insulin-like growth factor binding protein-3, and low creatinine values are more susceptible to MCI. Short years of education and low serum insulin-like growth factor binding protein-3 levels are independent risk factors for MCI in combination with T2DM. There were significant differences in serum metabolites between T2DM-MCI and T2DM-NCI. Abnormal lipid metabolism plays an important role in the development of cognitive impairment in T2DM patients. LPC 18:0 can effectively differentiate T2DM-MCI and T2DM-NCI, expected to identify cognitive impairment in T2DM patients at an early stage.
... W przeprowadzonych badaniach wykazano poprawę zdolności intelektualnych, takich jak czas reakcji na bodziec oraz pamięć, szczególnie u osób w podeszłym wieku [18,19]. Suplementacja kreatyną powodowała zmniejszenie zapotrzebowania tkanki mózgowej na tlen [20]. W literaturze podkreśla się działanie antyoksydacyjne kreatyny, m.in. ...
Introduction and purpose: Creatine supplementation is playing an increasingly important role not only in sports, but is beneficial in the context of brain health (e.g., cognitive processing, brain function and recovery from injury). This is a growing field of research, and the purpose of this brief review is to provide an update on the effects of creatine supplementation on brain health in healthy people. Description of the state of knowledge: Creatine, is an organic compound produced mainly by the liver and kidneys. From the liver, kidneys and gastrointestinal tract, creatine enters through the bloodstream into skeletal muscle, where a total of about 95% of the body's total creatine is stored. It is stored in the muscles, heart and brain. Summary: There is potential for creatine supplementation to improve cognitive processing, especially in conditions characterized by creatine deficits in the brain, which can be triggered by acute stress factors (e.g., exercise, lack of sleep) or chronic, pathological conditions (e.g., creatine synthesis enzyme deficiencies, mild traumatic brain injury, aging, Alzheimer's disease). People with depression, the elderly, people with diseases associated with certain genetic defects (where creatine production and storage in the brain is impaired) are just some of the groups of people in whom creatine supplementation may be helpful. More research is needed to determine the clinical impact of long-term creatine supplementation dosing strategies on brain function and health.
... Brain creatine level in humans was reported to increase in response to mental training (Valenzuela et al., 2003). Creatine supplementation improved brain functions in young and elderly people (Rawson and Venezia, 2011), attenuated stress-induced cognitive impairment and reduced mental fatigue (Adhihetty and Beal, 2008). Indeed, it was shown to be neuroprotective in traumatic brain injury model in rats (Wyss and Schulze, 2002;Saraiva et al., 2012;Ainsley Dean et al., 2017). ...
Creatine is considered a rich dietary supplement that has beneficial antioxidant and neuroprotective role. Its use with Parkinson's disease (PD) is not well verified and needs further investigations. The current study evaluated this supplement in a mouse model of PD respecting motor effects, biochemical changes and pathophysiological modulation. Rotenone (1.5 mg/kg, s.c., day after day for two weeks) was used to induce PD in adult male Swiss mice. Creatine monohydrate was given in two doses (370 and 720 mg/kg, p.o., daily) for 21 days. L-dopa (25 mg/kg, p.o., 21 days) was administered in combination with creatine (370 mg/kg, p.o., daily) to a separate group. The study showed that creatine did not enhance the motor functions but improved the oxidative state and reduced the protein oxidation of striatum. In addition, Striatum paraoxonase and cholinergic activities were restored to normal rate after creatine administration. Creatine also proved added value to conventional L-dopa therapy. In conclusion, creatine dietary supplementation is of ameliorating role to pathophysiological changes associated to PD though motor functions may not be enhanced.
... It is reported that the Cr supplementation may increase brain PCr concentration by 5 to 15%, thus improving brain bioenergetics. [46,47] In 2002, an interesting discovery was made by Watanabe and collaborators, who have stated that Cr supplementation 8 g/day for 5 days caused increased oxygen utilization in the brain cells, what led to a reduction of mental fatigue in subjects. [48] Evidence-based medicine have found that creatine supplementation may be a powerful tool in suppressing mental fatigue and/or improving cognitive and executive functions and/or memory. ...
Creatine is one of the most often used supplements nowadays. Its popularity can be attributed to a wide variety of clinical implications. The intent of this paper was to evaluate and review the latest publications about the usage and potential clinical effects on the human body of creatine supplementation and to bring attention to new findings in this subject. Authors explored PubMed, CrossRef and Google Scholar using keywords: creatine, supplements, ergogenic aids, neuroprotection, bioenergetics. Furthermore, the references of selected articles were manually investigated for additional relevant articles. The bibliography focused mainly on systematic reviews, randomized controlled trials (RCTs) and case reports. The selection of individual articles was carried out in accordance with the determinants of general medicine readership. There is still a lot to learn about creatine supplementation and its potentially beneficial effects. Further evidence-based studies are required, as the amount of reliable data and information is still not sufficient and lots of them have yet to be examined.
... Most evidence for nutritional interventions against fatigue comes from the chronic fatigue syndrome. Several studies have demonstrated a potential benefit on fatigue from creatine supplementation, both stand-alone or in combination with exercise training (66) . Creatine is mainly stored in muscles, where it is converted into phosphocreatine through the enzyme creatine kinase. ...
Fatigue is defined as a symptom leading to the inability to continue functioning at the expected activity level. It is a highly prevalent symptom, challenging to frame into monodimensional pathophysiological mechanisms. As a result, fatigue is often underestimated in the clinical setting and is wrongly considered an unavoidable consequence of ageing. Several potential mechanisms responsible for fatigue have been proposed, including sleep patterns, autonomic nervous system abnormalities and biological complexity. Inflammation and mitochondrial dysfunction are among the most promising mechanisms through which malnutrition may cause fatigue. Not surprisingly, fatigue is highly prevalent in inflammatory conditions (e.g. COVID-19 infection). The nutritional status may also represent a critical factor in the development and presentation of fatigue, which may mimic the exhaustion of the individual's metabolic reserves. For example, the insufficient dietary intake of energy and proteins may determine the catabolism of body fat and muscles, disrupt the homeostatic balance and cause the onset of fatigue. It is necessary to conduct research on fatigue. By characterising its pathophysiological mechanisms, it will be possible to (1) support the design and development of targeted interventions, (2) improve the quality of life of many persons by acting on the symptom and (3) reduce the direct and indirect costs of a burdening condition typical of advancing age. In the present review, we provide an overview of the role that nutrition may play as a determinant of fatigue in older people, also in the context of the COVID-19 pandemic.
... Under normal conditions, Cr is synthesized in the brain and used to form PCr through creatine kinase. PCr donates its phosphate group to adenosine diphosphate (ADP) to resynthesize adenosine triphosphate (ATP) under conditions of ATP exhaustion [16,17]. Thus, PCr allows ATP synthesis even in the absence of oxygen and glucose [18]. ...
Ischemic heart disease is the main cause of death globally. Cardioprotection is the process whereby mechanisms that reduce myocardial damage, and activate protective factors, contribute to the preservation of the heart. Targeting these processes could be a new strategy in the treatment of post-ischemic heart failure (HF). Triiodothyronine (T3) and thyroxine (T4), which have multiple effects on the heart, prevent myocardial damage. This study describes the formulation, and characterization, of chemically modified polymeric nanoparticles incorporating T3, to target the thyroid hormone receptors. Modified T3 was conjugated to polylactide-co-glycolide (PLGA) to facilitate T3 delivery and restrict its nuclear translocation. Modified T3 and PLGA-T3 was characterized with 1H-NMR. The protective role of synthesized phosphocreatine (PCr) encapsulated PLGA-T3 nanoparticles (PLGA-T3/PCr NPs) and PLGA-T3 nanoparticles (PLGA-T3 NPs) in hypoxia-mediated cardiac cell insults was investigated. The results showed that PLGA-T3/PCr NPs represent a potentially new therapeutic agent for the control of tissue damage in cardiac ischemia and resuscitation.
... Based on the fact that creatine use shows development in athletic and sportive performance, the effects of creatine use in athletes, sedentary, elderly individuals and some patient population is an area researched in literature (34,56,58,59). Contradictory results have been found in studies conducted on the use of creatine (2,18,31,56). ...
Creatine, which is a popular ergogenic aid, is shown among the most effective methods used as a performance enhancer in athletes. The aim of this review is to summarize the current publications to show the uses and effects of creatine in exercise. In the present study prepared in a systematic review style, full-text articles about creatine use published in Science Citation Index (SCI), SCI-Expanded, and PubMed/MEDLINE databases' journals between 2010 and 2021 were examined. The searching was performed by "creatine", "creatine monohydrate" and "creatine supplementation" keywords. Data from 46 studies showed that creatine loading in individuals who train during high intensity and short term exercise forms affect performance positively, develop muscle mass/strength and increase muscle creatine phosphate (PCr) stores. It was also found that creatine supplement applied with strength training in elderly individuals increased muscle mass, muscle strength, and movement capacity. It is determined that there is no definitive and clear procedure regarding the usage dosage for creatine. In addition, though some studies have reported that creatine use has a positive effect on cognitive performance, a definite judgment has not been reached. Consequently, it has been demonstrated that creatine supplementation is an effective ergogenic aid for the development of muscle and strength for athletes of all levels. The increase in the number of studies on the creatine usage dosage to be examined in different athlete profiles may lead to a decrease in the contradictions about the usage procedure.
... When used in athletes, dietary supplementation of creatine has been suggested to improve cognitive performance (90,91), alleviate mental fatigue (91,92), attenuate effects of sleep deprivation (90,93), and improve memory (94). Many studies report an improvement in cognitive processing following creatine supplementation, but these studies are difficult to compare because of the differences in subject population, supplementation protocols, and cognitive outcomes measured (95)(96)(97). Also, attempts to translate "improved cognitive processing" to athletes and athletic performance are few. ...
Creatine is a popular and widely used ergogenic dietary supplement among athletes, for which studies have consistently shown increased lean muscle mass and exercise capacity when used with short-duration, high-intensity exercise. In addition to strength gains, research has shown that creatine supplementation may provide additional benefits including enhanced postexercise recovery, injury prevention, rehabilitation, as well as a number of potential neurologic benefits that may be relevant to sports. Studies show that short- and long-term supplementation is safe and well tolerated in healthy individuals and in a number of patient populations.
... The body converts creatine into phosphocreatine and stores it in the muscles where it can be used as an energy source [13]. Furthermore, creatine is also made synthetically [14] and is one of the most popular natural supplements [15][16][17][18] used for improving muscle power, strength, and gaining lean mass [17][18][19][20]. For that reason, creatine and physical exercise are often referred together. ...
Creatine supplementation of the population with type 2 diabetes mellitus (T2DM) combined with an exercise program is known to be a possible therapy adjuvant with hypoglycemic effects. However, excessive administration of creatine leads to the production of methylamine which is deaminated by the enzyme semicarbazide-sensitive amine oxidase (SSAO) and as a result, cytotoxic compounds are produced. SSAO activity and reaction products are increased in the serum of T2DM patients. Creatine supplementation by diabetics will further augment the activity of SSAO. The current review aims to find a feasible way to ameliorate T2DM for patients who exercise and desire to consume creatine. Several natural agents present in food which are involved in the regulation of SSAO activity directly or indirectly are reviewed. Particularly, zinc-α2-glycoprotein (ZAG), zinc (Zn), copper (Cu), histamine/histidine, caffeine, iron (Fe), and vitamin D are discussed. Inhibiting SSAO activity by natural agents might reduce the potential adverse effects of creatine metabolism in population of T2DM.
... Algunos estudios, han mostrado que el contenido de Cr disminuye con la edad, lo que no se conoce es, si se debe a los bajos niveles de actividad física o al propio envejecimiento 24 . Además, la cantidad y tamaño de las fibras de Tipo II disminuyen progresivamente con el envejecimiento, observando algunos estudios 25 , que aquellos individuos con mayor cantidad de fibras de tipo II y mayor área de sesión transversal, responden mejor a la suplementación con Cr, lo que puede determinar que, los adultos mayores tengan una respuesta anabólica atenuada a la suplementación con Cr 9 . ...
La creatina es un suplemento deportivo con una elevada evidencia científica sobre sus efectos en el rendimiento y con resul- tados emergentes en la salud, incluida la de deportistas vegetarianos y adultos mayores. El tipo de creatina y las dosis efectivas, han sido bien estudiadas presentando resultados consistentes. Sin embargo, no son muchos los estudios que han evaluado el momento de la ingesta en cuanto a su interacción con los efectos de la creatina. El objetivo de esta revisión, es analizar la diferente literatura científica existente sobre los protocolos de suplementación con creatina y su interacción con el momento de la ingesta, con el fin de evaluar si existe un efecto mayor de la dosis ergogénica considerada efectiva de creatina cuando esta es ingerida antes, después del entrenamiento o en otro momento del día. Los resultados de este trabajo presentaron diferentes tipos de protocolos y dosis en la suplementación con creatina, a pesar de ser diversos los protocolos mostrados en la literatura, el más efectivo constó de un consumo de 0,3 g/kg/d durante cinco días, seguido de un consumo de 0,03 g/kg/d consiguiendo de esta forma, una mayor reserva de PCr en el músculo esquelético. Los estudios mostraron mayores beneficios cuando la ingesta de creatina se realizó en los momentos cercanos al entreno debido al mayor flujo sanguíneo, apuntando los estudios a mejoras significativas en un consumo post-entreno, debido a que la creatina puede aumentar la formación de de glucógeno en el músculo y aumentar la sensibilidad a la insulina.
... Algunos estudios, han mostrado que el contenido de Cr disminuye con la edad, lo que no se conoce es, si se debe a los bajos niveles de actividad física o al propio envejecimiento 24 . Además, la cantidad y tamaño de las fibras de Tipo II disminuyen progresivamente con el envejecimiento, observando algunos estudios 25 , que aquellos individuos con mayor cantidad de fibras de tipo II y mayor área de sesión transversal, responden mejor a la suplementación con Cr, lo que puede determinar que, los adultos mayores tengan una respuesta anabólica atenuada a la suplementación con Cr 9 . ...
José Manuel Jurado-Castro, et al. 48 Arch Med Deporte 2021;38(1):48-53 Revisión Resumen La creatina es un suplemento deportivo con una elevada evidencia científica sobre sus efectos en el rendimiento y con resul-tados emergentes en la salud, incluida la de deportistas vegetarianos y adultos mayores. El tipo de creatina y las dosis efectivas, han sido bien estudiadas presentando resultados consistentes. Sin embargo, no son muchos los estudios que han evaluado el momento de la ingesta en cuanto a su interacción con los efectos de la creatina. El objetivo de esta revisión, es analizar la diferente literatura científica existente sobre los protocolos de suplementación con creatina y su interacción con el momento de la ingesta, con el fin de evaluar si existe un efecto mayor de la dosis ergogénica considerada efectiva de creatina cuando esta es ingerida antes, después del entrenamiento o en otro momento del día. Los resultados de este trabajo presentaron diferentes tipos de protocolos y dosis en la suplementación con creatina, a pesar de ser diversos los protocolos mostrados en la literatura, el más efectivo constó de un consumo de 0,3 g/kg/d durante cinco días, seguido de un consumo de 0,03 g/kg/d consiguiendo de esta forma, una mayor reserva de PCr en el músculo esquelético. Los estudios mostraron mayores beneficios cuando la ingesta de creatina se realizó en los momentos cercanos al entreno debido al mayor flujo sanguíneo, apuntando los estudios a mejoras significativas en un consumo post-entreno, debido a que la creatina puede aumentar la formación de de glucógeno en el músculo y aumentar la sensibilidad a la insulina. Palabras clave: Creatina. Deporte. Suplementos dietéticos. Rendimiento deportivo. Summary Creatine is a sports supplement with high scientific evidence on its effects on performance and with emerging health's results, including for vegetarian athletes and older adults. The creatine type and effective doses have been well studied, presenting consistent results. However, not many studies have evaluated the ingestion timing in terms of its interaction with the creatine effects. The aim of this review is to analyze the different existing scientific literature on creatine supplementation protocols and their interaction with the timing of ingestion, in order to assess whether there is a greater effect of the ergogenic dose of creatine considered effective when It is ingested before, post workout or at another time of the day. The results of this work presented different types of protocols and doses in creatine supplementation, despite being diverse the protocols shown in the literature, the most effective consisted of a consumption of 0.3 g/kg/d for five days, followed by a consumption of 0.03 g/kg/d, thus achieving a greater reserve of PCr in skeletal muscle. Studies showed greater benefits when creatine intake was carried out in the moments close to workout due to greater blood flow, the studies pointing to significant improvements in post-workout consumption, since creatine can increase the rate of glycogen uptake in muscle and increase insulin sensitivity.
... Some studies have shown that Cr content reduces with age, what is not known is if this is due to low levels of physical activity or the ageing process 24 . Furthermore, the quantity and amount of Type II fibres diminishes progressively with age, with some studies 25 observing that individuals with more type II fibres and a larger transversal session area, respond better to Cr supplementation, which can determine that older adults have an attenuated anabolic response to Cr supplementation 9 . ...
Creatine is a sports supplement with high scientific evidence on its effects on performance and with emerging health’s results, including for vegetarian athletes and older adults. The creatine type and effective doses have been well studied, presenting consistent results. However, not many studies have evaluated the ingestion timing in terms of its interaction with the creatine effects. The aim of this review is to analyze the different existing scientific literature on creatine supplementation protocols and their interaction with the timing of ingestion, in order to assess whether there is a greater effect of the ergogenic dose of creatine considered effective when It is ingested before, post workout or at another time of the day. The results of this work presented different types of protocols and doses in creatine supplementation, despite being diverse the protocols shown in the literature, the most effective consisted of a consumption of 0.3 g/kg/d for five days, followed by a consumption of 0.03 g/kg/d, thus achieving a greater reserve of PCr in skeletal muscle. Studies showed greater benefits when creatine intake was carried out in the moments close to workout due to greater blood flow, the studies pointing to significant improvements in post-workout consumption, since creatine can increase the rate of glycogen uptake in muscle and increase insulin sensitivity
... Creatine supplementation has been shown to support greater neural ATP resynthesis, which provides a cognitive advantage for tasks that rely on the frontal cortex (i.e., cognition, attention, memory) [92]. Brain creatine concentrations appear to be variable based/depending upon age, lifestyle choices, diet, and other factors [93], which is relevant when considering creatine supplementation for females across the lifespan. ...
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.
... Creatine, used originally as an ergogenic aid by elite athletes to enhance performance, has found its way into the lives of "ordinary people". Individuals of all ages and fitness levels use CR on a regular basis [120][121][122][123][124][125][126][127][128], as demonstrated by sales in 2019 that surpassed USD 360 million [129]. The question then becomes: who should use CR and what types of benefits can various subsets of individuals gain from its use? ...
The use of dietary supplements has become increasingly common over the past 20 years. Whereas supplements were formerly used mainly by elite athletes, age and fitness status no longer dictates who uses these substances. Indeed, many nutritional supplements are recommended by health care professionals to their patients. Creatine (CR) is a widely used dietary supplement that has been well-studied for its effects on performance and health. CR also aids in recovery from strenuous bouts of exercise by reducing inflammation. Although CR is considered to be very safe in recommended doses, a caveat is that a preponderance of the studies have focused upon young athletic individuals; thus there is limited knowledge regarding the effects of CR on children or the elderly. In this review, we examine the potential of CR to impact the host outside of the musculoskeletal system, specifically, the immune system, and discuss the available data demonstrating that CR can impact both innate and adaptive immune responses, together with how the effects on the immune system might be exploited to enhance human health.
... This finding may show a beneficial effect of exercise in protecting against the age-related loss of muscle mass, known as sarcopenia. Aging and sarcopenia have been linked with a decline in muscle creatine, which is exacerbated with physical inactivity [51]. ...
Life expectancy has risen in the past decades, resulting in an increase in the number of aged individuals. Exercise remains one of the most cost-effective treatments against disease and the physical consequences of aging. The purpose of this research was to investigate the effects of aging, long-term and lifelong exercise on the rat urinary metabolome. Thirty-six male Wistar rats were divided into four equal groups: exercise from 3 to 12 months of age (A), lifelong exercise from 3 to 21 months of age (B), no exercise (C), and exercise from 12 to 21 months of age (D). Exercise consisted in swimming for 20 min/day, 5 days/week. Urine samples collection was performed at 3, 12 and 21 months of life and their analysis was conducted by liquid chromatography-mass spectrometry. Multivariate analysis of the metabolite data did not show any discrimination between groups at any of the three aforementioned ages. However, multivariate analysis discriminated the three ages clearly when the groups were treated as one. Univariate analysis showed that training increased the levels of urinary amino acids and possibly protected against sarcopenia, as evidenced by the higher levels of creatine in the exercising groups. Aging was accompanied by decreased levels of urinary amino acids and signs of increased glycolysis. Concluding, both aging and, to a lesser degree, exercise affected the rat urinary metabolome, including metabolites related to energy metabolism, with exercise showing a potential to mitigate the consequences of aging.
... Creatine supplementation increases availability of creatine and phosphocreatine in muscle, and supports anabolism by promoting the expression of growth factors like insulin growth factor (IGF)-1 and the phosphorylation of signaling proteins [70]. It has been proven to improve muscle mass and enhance exercise capacity in adolescents, adults, and even vulnerable elders and in conjunction with resistance training can result in greater adaptations in skeletal muscle than training alone [71][72][73]. There is conflicting data showing that creatine supplementation may attenuate muscle atrophy following immobilization and benefit exercise-related rehabilitation. ...
Purpose of Review
Decades of research on nutrition and exercise on athletes and bodybuilders has yielded various strategies to promote anabolism and improve muscle health and growth. We reviewed these interventions in the context of muscle loss in critically ill patients.
Recent Findings
For critically ill patients, ensuring optimum protein intake is important, potentially using a whey-containing source and supplemented with vitamin D and leucine. Agents like hydroxyl β-methylbutyrate and creatine can be used to promote muscle synthesis. Polyunsaturated fatty acids stimulate muscle production as well as have anti-inflammatory properties that may be useful in critical illness. Adjuncts like oxandralone promote anabolism. Resistance training has shown mixed results in the ICU setting but needs to be explored further with specific outcomes.
Summary
Critically ill patients suffer from severe proteolysis during hospitalization as well as persistent inflammation, immunosuppression, and catabolism syndrome after discharge. High protein supplementation, ergogenic aids, anti-inflammatories, and anabolic adjuncts have shown potential in alleviating muscle loss and should be used in intensive care units to optimize patient recovery.
... Furthermore, considering genetic creatine deficiency syndromes are often characterized by cognitive impairment, developmental delay, autistic behavior, and seizures, it is clear that creatine contributes to healthy brain function [60]. Researchers have since tested this hypothesis and have shown that creatine supplementation can aid in the improvement of cognitive processes such as memory and attention in both young [61] and older individuals [62,63]. It has also been shown that creatine exhibits potential anti-depressant properties [64]. ...
Creatine is a naturally occurring compound, functioning in conjunction with creatine kinase to play a quintessential role in both cellular energy provision and intracellular energy shuttling. An extensive body of literature solidifies the plethora of ergogenic benefits gained following dietary creatine supplementation; however, recent findings have further indicated a potential therapeutic role for creatine in several pathologies such as myopathies, neurodegenerative disorders, metabolic disturbances, chronic kidney disease and inflammatory diseases. Furthermore, creatine has been found to exhibit non-energy-related properties, such as serving as a potential antioxidant and anti-inflammatory. Despite the therapeutic success of creatine supplementation in varying clinical populations, there is scarce information regarding the potential application of creatine for combatting the current leading cause of mortality, cardiovascular disease (CVD). Taking into consideration the broad ergogenic and non-energy-related actions of creatine, we hypothesize that creatine supplementation may be a potential therapeutic strategy for improving vascular health in at-risk populations such as older adults or those with CVD. With an extensive literature search, we have found only four clinical studies that have investigated the direct effect of creatine on vascular health and function. In this review, we aim to give a short background on the pleiotropic applications of creatine, and to then summarize the current literature surrounding creatine and vascular health. Furthermore, we discuss the varying mechanisms by which creatine could benefit vascular health and function, such as the impact of creatine supplementation upon inflammation and oxidative stress.
... This evidence comes from the findings that during the 1st half of life the exercising groups showed a higher increase in blood creatine than the non-exercising groups, resulting in the former ending up with an overall increase at 21 months, whereas the latter ended up with an overall decrease. A decline in the muscle creatine content with aging has been linked to sarcopenia, and physical inactivity may exacerbate this decline (Rawson and Venezia 2011). Thus, our data suggest a possible usefulness of the blood creatine concentration as an index of sarcopenia and its mitigation by regular exercise, although direct evidence for this through body composition assessment will be needed. ...
Regular exercise is an important part of a healthy lifestyle, as it helps maintain a healthy weight and reduces the risk of chronic diseases. We explored the effects of lifelong exercise and aging on rat metabolism through a metabolomics approach. Thirty-six rats were divided into four equal groups: exercise during the 1st half of life (3–12 months), lifelong exercise (3–21 months), no exercise, and exercise during the 2nd half of life (12–21 months). Exercise consisted in swimming for 20 min, five times a week. Blood samples collected at 3, 12, and 21 months of life were analysed by 1H NMR spectroscopy. The groups that exercised during the 2nd half of life weighed less than the groups that did not. Exercise had an orexigenic effect during the 1st half and an anorexigenic effect during the 2nd half. Multivariate analysis showed a clear discrimination between ages when groups were treated as one and between the exercising and non-exercising groups at 12 months. Univariate analysis showed many effects of aging and some effects of exercise on metabolites involved in carbohydrate, lipid and protein metabolism. Especially during the 1st half, exercise had anabolic effects, whereas aging had catabolic effects on amino acid metabolism. In two cases (glycine and succinate), exercise (especially during the 1st half) mitigated potentially harmful effects of aging. The higher values of succinate and the lower values of lactate during the 1st half in the exercising groups suggest increased oxidative metabolism. In conclusion, moderate-intensity exercise for life or half-life had strong and potentially healthful effects on body weight and (partly) appetite, as well as on some blood metabolites. The effects of aging on the rat blood metabolome seemed to be stronger than those of exercise.
A exploração de estratégias para prevenir ou retardar o aparecimento de doenças mentais, incluindo a identificação de fatores de risco, tornou-se uma das principais prioridades da saúde pública global. A Doença de Alzheimer (DA) é uma condição neurodegenerativa progressiva caracterizada por déficits cognitivos e deterioração funcional. A busca por intervenções terapêuticas eficazes tem levado ao estudo de várias abordagens, incluindo a suplementação com creatina, um composto conhecido por seu papel no metabolismo energético das células. A presente revisão enfoca ideias recentes sobre o papel da creatina na cognição e na saúde mental. O material utilizado compreende artigos descritivos sobre o metabolismo do suplemento e ainda estudos experimentais com modelos animais servindo de base para demostrar o benefício da creatina na Doenças de Alzheimer e outras doenças neurodegenerativas.
Introduction: Creatine is a naturally occurring compound vital for energy metabolism, particularly in high-energy-demand tissues like muscles and the brain. Traditionally, research on creatine has focused on its ergogenic effects in sports, but emerging research suggests it may also positively impact brain health. Studies are exploring creatine monohydrate's role in improving cognitive function, mitigating neurodegenerative processes, and supporting mental health. This dual functionality highlights the compound's versatility as both a performance enhancer and a potential therapeutic agent for neurological health. By expanding the scope of creatine research beyond physical performance, we can better understand and utilize its full capabilities to enhance human health. This research review examines the growing evidence suggesting that creatine supplementation could significantly benefit brain health and the management of neurological diseases. Aim of the study: This review aims to synthesize current findings on creatine's cognitive benefits and its therapeutic potential for neurological disorders, critically analyzing preclinical and clinical studies to identify gaps and suggest future research directions.Materials and Methods: A comprehensive literature search was conducted using PubMed and Google Scholar databases, covering studies published between 2000 and 2024. Keywords such as creatine supplementation, brain health and neurodegeneration were used. Exclusion criteria included non-peer-reviewed articles, studies with insufficient data, and those not in English. Conclusions: This review highlights the potential benefits of creatine supplementation for cognitive and neurodegenerative diseases, noting its positive effects on memory, alleviating depression and anxiety, and offering neuroprotection. Future research should aim to standardize dosing, extend follow-up periods, and include larger, more diverse populations.
Background: Ischemic heart disease is the main cause of death globally. Cardioprotection is the process whereby mechanisms that reduce myocardial damage, and activate protective factors, contribute to the preservation of the heart. Targeting these processes could be a new strategy in the treatment of post-ischemic heart failure (HF). Triiodothyronine (T3) and thyroxine (T4), which have multiple effects on the heart, prevent myocardial damage.
Results: This study describes the formulation, and characterization, of chemically modified polymeric nanoparticles incorporating T3, to target the thyroid hormone receptors. Modified T3 was conjugated to polylactide-co-glycolide (PLGA) to facilitate the active targeting of PLGA-T3. Modified T3 and PLGA-T3 was characterized with ¹H-NMR. Protective role of synthesized Phosphocreatine (PCr) encapsulated PLGA-T3 nanoparticles (PLGA-T3/PCr NPs) and PLGA-T3 nanoparticles (PLGA-T3 NPs) in hypoxia-mediated cardiac cell insults were investigated.
Conclusions: Data demonstrated that PLGA-T3/PCr NPs represent a potentially new therapeutic for the control of tissue damage in cardiac ischemia and resuscitation.
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
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.
Multiple studies have been conducted, many within the last 3-5 years, to develop a deeper understanding into how certain chemical substances enhance and improve certain aspects of our performance, both mental and physical. The successful synthesis, isolation and purification of such human performance enhancing substances have led to breakthroughs not only in the treatment of debilitating diseases such as Alzheimer’s and Parkinson’s disease, but also have a significant impact on endurance training. While the chief use of such performance enhancing agents is in the treatment of diseases like anaemia, depression, attention deficit and neurodegenerative disorders, such substances are also misused and sometimes abused in sport. This review highlights 6 major substances used as performance enhancers, namely, creatine, racetams, melatonin, caffeine, cholinergics and EPO. The six substances enhance different features of human performance. The chemistry of these substances, their chemical biology, methods of synthesis and latest data obtained from various clinical trials are discussed.
Type 1 diabetes (T1D) has been reported to cause cognitive decline, but brain metabolic changes during this process are still far from being fully understood. Here, we found that streptozotocin (STZ)-induced T1D mice exhibited impaired learning and memory at 11 weeks after STZ treatment but not at 3 weeks. Therefore, we studied metabolic alterations in six different brain regions of T1D mice with and without cognitive decline, and attempted to identify key metabolic pathways related to diabetic cognitive dysfunction. The results demonstrate that lactate had already increased in all brain regions of T1D mice prior to cognitive decline, but a decreased TCA cycle was only observed in hippocampus, cortex and striatum of T1D mice with cognitive impairment. Reduced N-acetylaspartate and choline were found in all brain regions of T1D mice, irrespective of cognitive decline. In addition, disrupted neurotransmitter metabolism was noted to occur in T1D mice before cognitive deficit. Of note, we found that the level of uridine was significantly reduced in cerebellum, cortex, hypothalamus and midbrain of T1D mice when cognitive decline was presented. Therefore, brain region-specific metabolic alterations may comprise possible biomarkers for the early-diagnosis and monitoring of diabetic cognitive decline. Moreover, down-regulated TCA cycle and pyrimidine metabolism could be closely related to T1D-associated cognitive impairment.
Dementia and neurodegenerative diseases such as Parkinson’s and Alzheimer’s are becoming an increasingly important cause of medical and social concern due to the growth in the ageing population. Mechanisms and Metal Involvement in Neurodegenerative Diseases delivers in one volume a streamlined source of information on each of the main neurodegenerative diseases including mild cognitive impairment, Parkinson's, Alzheimer's, Freiderich's ataxia, prion disease, multiple sclerosis and alcoholic brain damage.
Each chapter is structured to give the definition of disease, proteins involved with structure of normal protein and abnormal proteins, pathology associated with the abnormal proteins, oxidative stress and inflammation, iron homeostatic mechanisms, primary neurotransmitter involved, other metal involvement and therapeutic strategies. Structures of the adherent protein involved in the disease process are also presented with emphasis on the chemical structures used in the treatment of each neurodegenerative disease together with their biochemical mode of action.
Written by acknowledged experts in their respective areas this new book provides readers with readily accessible information on each of the neurodegenerative diseases.
Creatine supplementation is a widely used and heavily studied ergogenic aid. Athletes use creatine to increase muscle mass, strength, and muscle endurance. While the performance and muscle- building effects of creatine supplementation have been well documented, the mechanisms responsible for these muscular adaptations have been less studied. Objective: The purpose of this review is to examine studies of the mechanisms underlying muscular adaptations to creatine supplementation. Data sources: PubMed and SPORTDiscus databases were searched from 1992 to 2007 using the terms creatine, creatine supplementation, creatine monohydrate, and phosphocreatine. Study selection: Studies of creatine supplementation in healthy adults were included. Data extraction: Due to the small number of studies identified, a meta-analysis was not performed. Data synthesis: Several potential mechanisms underlying muscular adaptations to creatine supplementation were identified, including: metabolic adaptations, changes in protein turnover, hormonal alterations, stabilization of lipid membranes, molecular modifications, or as a general training aid. The mechanisms with the greatest amount of support (metabolic adaptations, molecular modifications, and general training aid) may work in concert rather than independently. Conclusions: Creatine supplementation may alter skeletal muscle directly, by increased muscle glycogen and phosphocreatine, faster phosphocreatine resynthesis, increased expression of endocrine and growth factor mRNA, or indirectly, through increased training volume. Keywords: dietary supplement, creatine monohydrate, phosphocreatine, muscle, sport nutrition
The protective effect of short-term creatine supplementation (CrS) upon markers of strenuous contractile activity-induced
damage in human and rat skeletal muscles was investigated. Eight Ironman triathletes were randomized into the placebo (Pl;
n=4) and creatine-supplemented (CrS; n=4) groups. Five days prior to the Ironman competition, the CrS group received creatine monohydrate (20gday−1) plus maltodextrin (50g) divided in two equal doses. The Pl group received maltodextrin (50gday−1) only. The effect of CrS (5gday−1/kg body weight for 5days) was also evaluated in a protocol of strenuous contractile activity induced by electrical stimulation
in rats. Blood samples were collected before and 36 and 60h after the competition and were used to determine plasma activities
of creatine kinase (CK), lactate dehydrogenase (LDH), aldolase (ALD), glutamic oxaloacetic acid transaminase (GOT), glutamic
pyruvic acid transaminase (GPT), and C-reactive protein (CRP) level. In rats, plasma activities of CK and LDH, muscle vascular
permeability (MVP) using Evans blue dye, muscle force and fatigue were evaluated. Activities of CK, ALD, LDH, GOT, GTP, and
levels of CRP were increased in the Pl group after the competition as compared to basal values. CrS decreased plasma activities
of CK, LDH, and ALD, and prevented the rise of GOT and GPT plasma activities. In rats, CrS delayed the fatigue, preserved
the force, and prevented the rise of LDH and CK plasma activities and MVP in the gastrocnemius muscle. CrS presented a protective
effect on muscle injury induced by strenuous contractile activities.
KeywordsExercise-Muscle injury-Dietary supplement-Endurance-Triathlon-Creatine
The literature on creatine supplementation supporting its efficacy has grown rapidly and has included studies in both healthy volunteers and patient populations. However, the first rule in the development of therapeutic agents is safety. Creatine is well-tolerated in most individuals in short-term studies. However, isolated reports suggest creatine may be associated with various side effects affecting several organ systems including skeletal muscle, the kidney and the gastrointestinal tract. The majority of clinical studies fail to find an increased incidence of side effects with creatine supplementation. To date, studies have not found clinically significant deviations from normal values in renal, hepatic, cardiac or muscle function. Few data are available on the long-term consequences of creatine supplementation.
This review concerns a number of substances that have been receiving much attention, particularly in the media, for their potential to protect against age-related cognitive decline, and a focus is placed upon recent findings. Omega-3 fatty acids appear to play important roles in preserving neuronal structure and function and minimizing cognitive decline, whereas the antioxidant vitamins C and E appear to be particularly beneficial for combating age-related oxidative stress when administered in combination. Fruit and vegetable polyphenols also offer great potential, although most research thus far has involved rodents. Finally, there is mixed evidence regarding the cognitive enhancing properties of Ginkgo biloba, and the B vitamins folate and cobalamin, with all of these requiring further investigation.
Creatine supplementation has been found to significantly increase muscle strength and hypertrophy in young adults (</= 35 yr) particularly when consumed in conjunction with a resistance training regime. Literature examining the efficacy of creatine supplementation in older adults (55-82 yr) suggests creatine to promote muscle strength and hypertrophy to a greater extent than resistance training alone. The following is a review of literature reporting on the effects of creatine supplementation on intramuscular high energy phosphates, skeletal muscle morphology and quality of life in older adults. Results suggest creatine supplementation to be a safe, inexpensive and effective nutritional intervention, particularly when consumed in conjunction with a resistance training regime, for slowing the rate of muscle wasting that is associated with aging. Physicians should strongly consider advising older adults to supplement with creatine and to begin a resistance training regime in an effort to enhance skeletal muscle strength and hypertrophy, resulting in enhanced quality of life.
Background
Older adults with cognitive problems have a higher risk of falls, at least twice that of cognitively normal older adults. The consequences of falls in this population are very serious: fallers with cognitive problems suffer more injuries due to falls and are approximately five times more likely to be admitted to institutional care. Although the mechanisms of increased fall risk in cognitively impaired people are not completely understood, it is known that impaired cognitive abilities can reduce attentional resource allocation while walking. Since cognitive enhancers, such as cholinesterase inhibitors, improve attention and executive function, we hypothesise that cognitive enhancers may reduce fall risk in elderly people in the early stages of cognitive decline by improving their gait and balance performance due to an enhancement in attention and executive function.
Method/Design
Double blinded randomized controlled trial with 6 months follow-up in 140 older individuals with Mild Cognitive Impairment (MCI). Participants will be randomized to the intervention group, receiving donepezil, and to the control group, receiving placebo. A block randomization by four and stratification based on fall history will be performed. Primary outcomes are improvements in gait velocity and reduction in gait variability. Secondary outcomes are changes in the balance confidence, balance sway, attention, executive function, and number of falls.
Discussion
By characterizing and understanding the effects of cognitive enhancers on fall risk in older adults with cognitive impairments, we will be able to pave the way for a new approach to fall prevention in this population. This RCT study will provide, for the first time, information regarding the effect of a medication designed to augment cognitive functioning have on the risk of falls in older adults with Mild Cognitive Impairment. We expect a significant reduction in the risk of falls in this vulnerable population as a function of the reduced gait variability achieved by treatment with cognitive enhancers. This study may contribute to a new approach to prevent and treat fall risk in seniors in early stages of dementia.
Trial Registration
The protocol for this study is registered with the Clinical Trials Registry, identifier number: NCT00934531 http://www.clinicaltrials.gov
Supplementation with creatine-based substances as a means of enhancing athletic performance has become widespread. Until recently, however, the effects of creatine supplementation on cognitive performance has been given little attention. This study used a new form of creatine--creatine ethyl ester--to investigate whether supplementation would improve performance in five cognitive tasks, using a double-blind, placebo-controlled study. Creatine dosing led to an improvement over the placebo condition on several measures. Although creatine seems to facilitate cognition on some tasks, these results require replication using objective measures of compliance. The improvement is discussed in the context of research examining the influence of brain energy capacity on cognitive performance.
Numerous creatine formulations have been developed primarily to maximize creatine absorption. Creatine ethyl ester is alleged to increase creatine bio-availability. This study examined how a seven-week supplementation regimen combined with resistance training affected body composition, muscle mass, muscle strength and power, serum and muscle creatine levels, and serum creatinine levels in 30 non-resistance-trained males. In a double-blind manner, participants were randomly assigned to a maltodextrose placebo (PLA), creatine monohydrate (CRT), or creatine ethyl ester (CEE) group. The supplements were orally ingested at a dose of 0.30 g/kg fat-free body mass (approximately 20 g/day) for five days followed by ingestion at 0.075 g/kg fat free mass (approximately 5 g/day) for 42 days. Results showed significantly higher serum creatine concentrations in PLA (p = 0.007) and CRT (p = 0.005) compared to CEE. Serum creatinine was greater in CEE compared to the PLA (p = 0.001) and CRT (p = 0.001) and increased at days 6, 27, and 48. Total muscle creatine content was significantly higher in CRT (p = 0.026) and CEE (p = 0.041) compared to PLA, with no differences between CRT and CEE. Significant changes over time were observed for body composition, body water, muscle strength and power variables, but no significant differences were observed between groups. In conclusion, when compared to creatine monohydrate, creatine ethyl ester was not as effective at increasing serum and muscle creatine levels or in improving body composition, muscle mass, strength, and power. Therefore, the improvements in these variables can most likely be attributed to the training protocol itself, rather than the supplementation regimen.
Previous animal and human studies showed that photic stimulation (PS) increased cerebral blood flow and glucose uptake much more than oxygen consumption, suggesting selective activation of anaerobic glycolysis. In the present studies, image-guided 1H and 31P magnetic resonance spectroscopy (MRS) was used to monitor the changes in lactate and high-energy phosphate concentrations produced by PS of visual cortex in six normal volunteers. PS initially produced a significant rise (to 250% of control, p less than 0.01) in visual cortex lactate during the first 6.4 min of PS, followed by a significant decline (p = 0.01) as PS continued. The PCr/Pi ratios decreased significantly from control values during the first 12.8 min of PS (p less than 0.05), and the pH was slightly increased. The positive P100 deflection of the visual evoked potential recorded between 100 and 172 ms after the strobe was significantly decreased from control at 12.8 min of PS (p less than 0.05). The finding that PS caused decreased PCr/Pi is consistent with the view that increased brain activity stimulated ATPase, causing a rise in ADP that shifted the creatine kinase reaction in the direction of ATP synthesis. The rise in lactate together with an increase in pH suggest that intracellular alkalosis, caused by the shift of creatine kinase, selectively stimulated glycolysis.
Cross-sections of whole vastus lateralis muscle from 20 men, 19 to 84 years of age, were prepared, and the cross-sectional area (microns2) of 375 type 1 and 375 Type 2 fibres was measured in five different regions throughout each muscle. In muscles from the old individuals, the mean CSA of Type 2 fibres was on average nearly 35% smaller (P less than 0.001) while the mean CSA of Type 1 fibres was on average just over 6% smaller (NS) than in muscles from the young individuals. There was a highly significant (P less than 0.001) variation in the mean CSA of both fibre types within all muscles. In the old muscles, there was no significant difference in mean fibre CSA between deep and superficial parts while in the young muscles the mean fibre CSA was significantly (P less than 0.05) larger in deep regions than superficially. The range of the fibre CSA was larger in the old muscles with an increased number of both hypotrophied and atrophied fibres as well as large, sometimes very large, fibres. The standard deviation of the fibre CSA of Type 2 fibres was significantly (P less than 0.001) larger than for Type 1 fibres in 60% of the regions of the old muscles compared to 12.5% of the regions of the young muscles, but the standard deviation for the whole muscles was more or less unaffected with increasing age. In the old age group, there were fewer muscles and regions with a correlation between the CSA of Type 1 and Type 2 fibres than in the young age group. In conclusion the age-related changes in the mean fibre CSA, and in the pattern of variation in fibre CSA throughout the muscle and in small sample regions, suggest a combination of a progressive denervation process and an altered physical activity level as the two major mechanisms underlying the effects of normal development and ageing on the human vastus lateralis muscle.
Background: Elevated homocysteine concentrations may contribute to cognitive impairment. Most elevations in homocysteine result from inadequate folate, vitamin B-12, or vitamin B-6 intake. It is not clear whether the observed associations between homocysteine and cognitive measures are causal or whether they are due to homocysteine, to independent actions of the B vitamins, or to both.
Objective: We aimed to assess the individual and independent effects of baseline plasma homocysteine, folate, vitamin B-12, and vitamin B-6 and of dietary B vitamin intakes on 3-y changes in cognitive measures in 321 aging men.
Design: Participants were from the Veterans Affairs Normative Aging Study. Cognitive function was assessed with the Mini-Mental State Examination and on the basis of measures of memory, verbal fluency, and constructional praxis, which were adapted from the revised Wechsler Adult Intelligence Scale and the Consortium to Establish a Registry for Alzheimer’s Disease batteries at 2 time points. At baseline, dietary intakes were assessed with a food-frequency questionnaire, and blood was drawn for the measurement of B vitamins and homocysteine.
Results: Over a mean 3-y follow-up, declines in constructional praxis, measured by spatial copying, were significantly associated with plasma homocysteine, folate, and vitamins B-6 and B-12 and with the dietary intake of each vitamin. Folate (plasma and dietary) remained independently protective against a decline in spatial copying score after adjustment for other vitamins and for plasma homocysteine. Dietary folate was also protective against a decline in verbal fluency. A high homocysteine concentration was associated with a decline in recall memory.
Conclusions: Low B vitamin and high homocysteine concentrations predict cognitive decline. Spatial copying measures appear to be most sensitive to these effects in a general population of aging men.
The purpose of this investigation was to examine the effects of preceding oral creatine monohydrate with a lacto-ovo-vegetarian diet on muscle creatine concentration. Thirty-two healthy men, who regularly consumed an omnivorous diet, were randomly assigned to consume a weight maintaining, lacto-ovo-vegetarian (LOV; n = 16) or omnivorous (Omni It = 16) diet for 20 days. In addition to their assigned diet, on day 22 of the study, subjects were assigned in a double-blind manner to receive either creatine monohydrate (CM; 0.3 g . kg . d(-1) + 20g Polycose) or an equivalent dose of placebo (PL) for 5 days. There were no significant differences between the LOV and Omni groups at baseline with respect to age, height, and weight. The results demonstrated that consuming a LOV diet for 21 days was an effective procedure to decrease muscle creatine concentration (p < .01) in individuals who normally consume meat and fish in their diet. However, muscle total creatine (TCr) following creatine supplementation did not differ statistically between LOV and Omni diet groups (148.6 +/- 4.5 vs. 141.7 +/- 4.5 mmol . kg(-1) d.m.).
It has been suggested that a decline in skeletal muscle oxidative capacity is a general consequence of aging in humans. However, previous studies have not always controlled for the effects of varying levels of physical activity on muscle oxidative capacity. To test the hypothesis that, when matched for comparable habitual physical activity levels, there would be no age-related decline in the oxidative capacity of a locomotor muscle, the postexercise recovery time of phosphocreatine was compared in the tibialis anterior muscle of young [n = 19; 33.8 +/- 4.8 (SD) yr] and older [n = 18; 75.5 +/- 4.5 yr] healthy women and men of similar, relatively low, activity levels. The intramuscular metabolic measurements were accomplished by using phosphorus magnetic resonance spectroscopy. The results indicate that there was no age effect on the postexercise recovery time of phosphocreatine recovery. thus supporting the stated hypothesis. These data suggest that there is no requisite decline in skeletal muscle oxidative capacity with aging in humans, at least through the seventh decade.
Subtle cognitive decrements in older people are important in terms of the associated morbidity and as a risk factor for dementia. However, their pathophysiological basis is poorly understood. Proton magnetic resonance spectroscopy (1H‐MRS) may provide the means to investigate early changes in brain metabolite concentrations. We examined the relationships between N‐acetylaspartate (NAA), choline (Cho) and creatine (Cr) metabolite ratios in a voxel in the parietal cortex and cognitive function in 88 healthy, non‐demented, unmedicated men aged 65–70 years. We also used linear regression to give a value for each metabolite adjusted for the levels of the other two metabolites. Both NAA/Cr and Cho/Cr ratios correlated positively with tests of verbal memory and a verbal memory factor (e.g. NAA/Cr and Logical Memory: r = 0.24, P < 0.05). Cho/Cr ratios also correlated positively with tests of visual memory (e.g. visual reproduction: r = 0.21, P < 0.05). Adjusted Cr levels correlated negatively and significantly with tests of verbal memory and the Verbal Memory Factor. The regression analysis suggested that Cr levels better explained the correlations between NAA/Cr and Cho/Cr ratios and cognitive variables than NAA or Cho levels. These results suggest that in healthy men aged 65–70 years, metabolite levels relate to cognitive performance. Rising Cr levels may be an early marker of cognitive decline.
Purpose:
The purpose of this study was to examine the effect of creatine supplementation in conjunction with resistance training on physiological adaptations including muscle fiber hypertrophy and muscle creatine accumulation.
Methods:
Nineteen healthy resistance-trained men were matched and then randomly assigned in a double-blind fashion to either a creatine (N = 10) or placebo (N = 9) group. Periodized heavy resistance training was performed for 12 wk. Creatine or placebo capsules were consumed (25 g x d(-1)) for 1 wk followed by a maintenance dose (5 g x d(-1)) for the remainder of the training.
Results:
After 12 wk, significant (P < or = 0.05) increases in body mass and fat-free mass were greater in creatine (6.3% and 6.3%, respectively) than placebo (3.6% and 3.1%, respectively) subjects. After 12 wk, increases in bench press and squat were greater in creatine (24% and 32%, respectively) than placebo (16% and 24%, respectively) subjects. Compared with placebo subjects, creatine subjects demonstrated significantly greater increases in Type I (35% vs 11%), IIA (36% vs 15%), and IIAB (35% vs 6%) muscle fiber cross-sectional areas. Muscle total creatine concentrations were unchanged in placebo subjects. Muscle creatine was significantly elevated after 1 wk in creatine subjects (22%), and values remained significantly greater than placebo subjects after 12 wk. Average volume lifted in the bench press during training was significantly greater in creatine subjects during weeks 5-8. No negative side effects to the supplementation were reported.
Conclusion:
Creatine supplementation enhanced fat-free mass, physical performance, and muscle morphology in response to heavy resistance training, presumably mediated via higher quality training sessions.
Purpose:
To study the effect of creatine (Cr) supplementation combined with resistance training on muscular performance and body composition in older men.
Methods:
Thirty men were randomized to receive creatine supplementation (CRE, N = 16, age = 70.4 +/- 1.6 yr) or placebo (PLA, N = 14, age = 71.1 +/- 1.8 yr), using a double blind procedure. Cr supplementation consisted of 0.3-g Cr.kg(-1) body weight for the first 5 d (loading phase) and 0.07-g Cr.kg(-1) body weight thereafter. Both groups participated in resistance training (36 sessions, 3 times per week, 3 sets of 10 repetitions, 12 exercises). Muscular strength was assessed by 1-repetition maximum (1-RM) for leg press (LP), knee extension (KE), and bench press (BP). Muscular endurance was assessed by the maximum number of repetitions over 3 sets (separated by 1-min rest intervals) at an intensity corresponding to 70% baseline 1-RM for BP and 80% baseline 1-RM for the KE and LP. Average power (AP) was assessed using a Biodex isokinetic knee extension/flexion exercise (3 sets of 10 repetitions at 60 degrees.s(-1) separated by 1-min rest). Lean tissue (LTM) and fat mass were assessed using dual energy x-ray absorptiometry.
Results:
Compared with PLA, the CRE group had significantly greater increases in LTM (CRE, +3.3 kg; PLA, +1.3 kg), LP 1-RM (CRE, +50.1 kg; PLA +31.3 kg), KE 1-RM (CRE, +14.9 kg; PLA, +10.7 kg), LP endurance (CRE, +47 reps; PLA, +32 reps), KE endurance (CRE, +21 reps; PLA +14 reps), and AP (CRE, +26.7 W; PLA, +18 W). Changes in fat mass, fat percentage, BP 1-RM, and BP endurance were similar between groups.
Conclusion:
Creatine supplementation, when combined with resistance training, increases lean tissue mass and improves leg strength, endurance, and average power in men of mean age 70 yr.
No direct information on brain energetics and energy-related compounds in the first seconds of physiological activation has been reported to date. In this study visual cortex high energy phosphate changes were monitored in 11 normal subjects during 3.5 s activation and the following 23.5 s by a simple 31P magnetic resonance spectroscopic method. An intraactivation decrease of phosphocreatine (PCr) was observed in all subjects, with changes in pH in three, one of them also presenting a change in adenosine triphosphate (ATP). In the subgroup of eight subjects without changes in pH, the mean rate of mean PCr decrease (DPCr) was 7.24 ± 0.78 %/s, and the postactivation mean rate of mean PCr recovery was
As of 1985 the population of persons aged 65 or over in the United States numbered 28.5 million. By the year 2000, persons in the 65+ age group are expected to represent 13 percent of the population, and this percentage may climb to 21.2 percent by 2030. In 1985, older men were twice as likely to be married as older women. Sixty-seven percent of older noninsiutionalized persons lived in a family setting as of 1985. About 30 percent lived alone. About 90 percent of those over the age of 65 were white, 8 percent black, 3 percent were Hispanic, and 2 percent belonged to other racial groups. About half the 65+ population lived in eight states (California, New York, Florida, Illinois, Michigan, Ohio, Pennsylvania, and Texas). The median income of older persons in 1985 was 6,313 for females, and families headed by persons over the age of 65 reported a median income of 48,800, and about 83 percent of these persons owned their homes free and clear. About 11 percent or 2.9 million older Americans were in the labor force in 1985, including 1.8 million men and 1.2 million women. The educational level of this group has been steadily increasing. Even though the older population group represented 12 percent of the U.S. population in 1984, they were projected to account for 31 percent of all personal health care expenditures. (MN)
Creatine ethyl ester was incubated at 37 °C in both water and phosphate-buffered saline and the diagnostic methylene resonances in the 1H NMR spectrum were used to identify the resultant products. It was found that mild aqueous conditions result in the cyclization of creatine ethyl ester to provide inactive creatinine as the exclusive product, and this transformation becomes nearly instantaneous as the pH approaches 7.4. This study demonstrates that mild non-enzymatic conditions are sufficient for the cyclization of creatine ethyl ester into creatinine, and together with previous results obtained under enzymatic conditions suggests that there are no physiological conditions that would result in the production of creatine. It is concluded that creatine ethyl ester is a pronutrient for creatinine rather than creatine under all physiological conditions encountered during transit through the various tissues, thus no ergogenic effect is to be expected from supplementation.
Cerebral creatine deficiency syndromes (CCDSs) are a group of inborn errors of creatine metabolism comprising two autosomal recessive disorders that affect the biosynthesis of creatine--i.e. arginine:glycine amidinotransferase deficiency (AGAT; MIM 602360) and guanidinoacetate methyltransferase deficiency (GAMT; MIM 601240)--and an X-linked defect that affects the creatine transporter, SLC6A8 deficiency (SLC6A8; MIM 300036). The biochemical hallmarks of these disorders include cerebral creatine deficiency as detected in vivo by 1H magnetic resonance spectroscopy (MRS) of the brain, and specific disturbances in metabolites of creatine metabolism in body fluids. In urine and plasma, abnormal guanidinoacetic acid (GAA) levels are found in AGAT deficiency (reduced GAA) and in GAMT deficiency (increased GAA). In urine of males with SLC6A8 deficiency, an increased creatine/creatinine ratio is detected. The common clinical presentation in CCDS includes mental retardation, expressive speech and language delay, autistic like behaviour and epilepsy. Treatment of the creatine biosynthesis defects has yielded clinical improvement, while for creatine transporter deficiency, successful treatment strategies still need to be discovered. CCDSs may be responsible for a considerable fraction of children and adults affected with mental retardation of unknown etiology. Thus, screening for this group of disorders should be included in the differential diagnosis of this population. In this review, also the importance of CCDSs for the unravelling of the (patho)physiology of cerebral creatine metabolism is discussed.
In mammals, creatine is taken up from the diet and can be synthesized endogenously by a two-step mechanism involving the enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT). Creatine (Cr) is taken up by cells through a specific transporter, CT1. While the major part of endogenous synthesis of Cr is thought to occur in kidney, pancreas and liver, the brain widely expresses AGAT, GAMT and CT1, both during development and in adulthood. The adult central nervous system (CNS) has a limited capacity to take up Cr from periphery, and seems to rely more on its endogenous Cr synthesis. In contrast, the embryonic CNS might be more dependent on Cr supply from periphery than on endogenous synthesis. This review will focus on the expression and function of AGAT, GAMT and CT1 in the mammalian CNS, both during development and in adulthood. Emphasis will also be placed on their specific roles in the different cell types of the brain, to analyze which brain cells are responsible for the CNS capacity of (i) endogenous Cr synthesis and (ii) Cr uptake from the periphery, and which brain cells are the main Cr consumers. The potential role of CT1 as guanidinoacetate transporter between "AGAT-only" and "GAMT-only" expressing cells will also be explored.
Background:
Physical activity is beneficial for healthy ageing. It may also help maintain good cognitive function in older age. Aerobic activity improves cardiovascular fitness, but it is not known whether this sort of fitness is necessary for improved cognitive function. Studies in which activity, fitness and cognition are reported in the same individuals could help to resolve this question.
Objectives:
To assess the effectiveness of physical activity, aimed at improving cardiorespiratory fitness, on cognitive function in older people without known cognitive impairment.
Search strategy:
We searched MEDLINE, EMBASE, PEDro, SPORTDiscus, PsycINFO, CINAHL, Cochrane Controlled Trials Register (CENTRAL), Dissertation abstracts international and ongoing trials registers on 15 December 2005 with no language restrictions.
Selection criteria:
All published randomised controlled trials comparing aerobic physical activity programmes with any other intervention or no intervention with participants older than 55 years of age were eligible for inclusion.
Data collection and analysis:
Eleven RCTs fulfilling the inclusion criteria are included in this review. Two reviewers independently extracted the data from these included studies.
Main results:
Eight out of 11 studies reported that aerobic exercise interventions resulted in increased cardiorespiratory fitness of the intervention group (an improvement on the maximum oxygen uptake test which is considered to be the single best indicator of the cardiorespiratory system) of approximately 14% and this improvement coincided with improvements in cognitive capacity. The largest effects on cognitive function were found on motor function and auditory attention (effect sizes of 1.17 and 0.50 respectively). Moderate effects were observed for cognitive speed (speed at which information is processed; effect size 0.26) and visual attention (effect size 0.26).
Authors' conclusions:
There is evidence that aerobic physical activities which improve cardiorespiratory fitness are beneficial for cognitive function in healthy older adults, with effects observed for motor function, cognitive speed, auditory and visual attention. However, the majority of comparisons yielded no significant results. The data are insufficient to show that the improvements in cognitive function which can be attributed to physical exercise are due to improvements in cardiovascular fitness, although the temporal association suggests that this might be the case. Larger studies are still required to confirm whether the aerobic training component is necessary, or whether the same can be achieved with any type of physical exercise. At the same time, it would be informative to understand why some cognitive functions seem to improve with (aerobic) physical exercise while other functions seem to be insensitive to physical exercise. Clinicians and scientists in the field of neuropsychology should seek mutual agreement on a smaller battery of cognitive tests to use, in order to render research on cognition clinically relevant and transparent and heighten the reproducibility of results for future research.
We examined the effects of 6 wk of low-dose creatine supplementation on body composition, muscle function, and body creatine retention.
Twenty healthy men and women (21 ± 2 y old) were randomized to receive creatine (0.03 g · kg(-1) · d(-1); n = 10, 4 women) or placebo (n = 10, 4 women) for 6 wk in a double-blind placebo-controlled fashion. Participants were tested on two occasions before supplementation to establish a reliable baseline, and then were retested after supplementation. Testing included body composition, maximal strength (three-repetition maximal concentric knee extension at 180 degrees/s), muscle fatigue (five sets of 30 concentric knee extensions at 180 degrees/s), and plasma creatine concentration.
There were no significant differences in body mass, fat-free mass, fat mass, body fat percentage, total body water, or maximal strength in either group from before to after supplementation (all P > 0.05). After supplementation, plasma creatine increased significantly in the creatine group (+182%, P = 0.03), with no difference in the placebo group. Compared with baseline values, creatine-supplemented volunteers were more resistant to fatigue during sets 2 (7%), 3 (9%), 4 (9%), and 5 (11%) (all P < 0.05). In placebo-supplemented participants, there was no improvement in fatigue resistance during sets 2 (0%), 3 (1%), 4 (0%), and 5 (-1%) (all P > 0.05).
Ingesting a low dose (≈2.3 g/d) of creatine for 6 wk significantly increased plasma creatine concentration and enhanced resistance to fatigue during repeated bouts of high-intensity contractions.
The economic burden due to the sequela of sarcopenia (muscle wasting in the elderly) are staggering and rank similarly to the costs associated with osteoporotic fractures. In this article, we discuss the societal burden and determinants of the loss of physical function with advancing age, the physiologic mechanisms underlying dynapenia (muscle weakness in the elderly), and provide perspectives on related critical issues to be addressed.
Recent epidemiological findings from longitudinal aging studies suggest that dynapenia is highly associated with both mortality and physical disability even when adjusting for sarcopenia indicating that sarcopenia may be secondary to the effects of dynapenia. These findings are consistent with the physiologic underpinnings of muscle strength, as recent evidence demonstrates that alterations in muscle quantity, contractile quality and neural activation all collectively contribute to dynapenia.
Although muscle mass is essential for regulation of whole body metabolic balance, overall neuromuscular function seems to be a critical factor for maintaining muscle strength and physical independence in the elderly. The relative contribution of physiologic factors contributing to muscle weakness are not fully understood and further research is needed to better elucidate these mechanisms between muscle groups and across populations.
Creatine and protein supplementation can enhance the training outcomes of young subjects, but it is not clear if there are benefits for older individuals. Therefore, the purpose of this study was to determine the effects of creatine and protein supplementation on strength gains following a traditional resistance training program for middle-aged and older men.
This study assessed changes in strength of men aged 48-72 years following 14 weeks of resistance training supplemented with creatine and/or protein. A double-blind, randomized, placebo-controlled design placed 42 males into one of four groups: Resistance Trained Placebo (RTP, n=10); Resistance Trained Creatine (RTCr, 5g Cr, n=10); Resistance Trained Protein (RTPr, 35g whey Pr, n=11); or Resistance Trained Creatine and Protein (RTCrPr, 5g Cr and 35g Pr, n=11).
All groups trained 3 days per week for 14 weeks. The resistance training program was based on progressive overload. Training loads corresponded to 80% 1 RM (one repetition maximum strength), 3 sets of 8 repetitions for the following exercises: knee extension/knee flexion; bicep curl/tricep extension; military press; lat pull down; seated leg press; and bench press.
1 RM for each exercise and measures of lean body mass were assessed prior to and following the 14 week program.
Each group significantly (p < 0.05) increased strength and lean body mass, however, there were no significant group effects or group X trial interactions.
Resistance training in middle-aged and older men significantly increased muscular strength and added muscle mass with no additional benefits from creatine and/or protein supplementation.
There are a number of forms of creatine available that attempt to improve the solubility and permeability, with the anticipation this will result in an improved pharmacokinetic profile and ultimately an enhanced ergogenic response. Previous research has shown that the different salt forms can improve solubility resulting in slightly altered pharmacokinetic profiles, however specific data exploring the conversion of esterified derivatives to creatine is lacking. The purpose of this study was to examine the assertion that creatine ethyl ester undergoes enzymatic conversion to creatine in human tissues. The IN VITRO response of creatine ethyl ester to incubation in human plasma was examined by H-NMR analysis. Lyophilized human plasma was reconstituted in D2O and phosphate-buffered saline and 1.5 mg of the analyte was added. Following incubation at 37 degrees C for 4 h and subsequent protein precipitation, the supernatant was analyzed by NMR, utilizing the diagnostic chemical shift of the methylene signal to determine the species present in solution, I.E. creatine ethyl ester, creatine, or creatinine. Both creatine and creatinine were run in parallel as control experiments and each assay was run in triplicate. As expected both creatine and creatinine remained unchanged. However, conversion of creatine ethyl ester to creatine by the esterases in human plasma was not observed to any detectable extent and the only species detected after the incubation period was creatinine. While not a definitive characterization of the IN VIVO behavior, these results strongly warrant a complete IN VIVO pharmacokinetic analysis of creatine ethyl ester since it appears these "pronutrients" may actually provide large exogenous sources of pharmacologically inactive creatinine rather than ergogenic creatine.
The rate of the non-enzymatic hydrolysis of creatine ethyl ester (CEE) was studied at 37 degrees C over the pH range of 1.6-7.0 using (1)H NMR. The ester can be present in solution in three forms: the unprotonated form (CEE), the monoprotonated form (HCEE(+)), and the diprotonated form (H(2)CEE(2+)). The values of pK(a1) and pK(a2) of H(2)CEE(2+) were found to be 2.30 and 5.25, respectively. The rate law is found to be Rate=-dCCEE/dt=k++[H2CEE2+][OH-]+k+[HCEE+][OH-]+k0[CEE][OH-] where the rate constants k(++), k(+), and k(0) are (3.9+/-0.2)x10(6)L mol(-1)s(-1), (3.3+/-0.5)x10(4)L mol(-1)s(-1), and (4.9+/-0.3)x10(4)L mol(-1)s(-1), respectively. Calculations performed at the density functional theory level support the hypothesis that the similarity in the values of k(+) and k(0) results from intramolecular hydrogen bonding that plays a crucial role. This study indicates that the half-life of CEE in blood is on the order of one minute, suggesting that CEE may hydrolyze too quickly to reach muscle cells in its ester form.
Total creatine (Cr) levels are widely used as an internal reference for the quantification of other metabolites in (1)H magnetic resonance spectroscopy (MRS). However, Cr plays an important role in brain energy metabolism, and its levels can be modulated by conditions of energy production and demand. Therefore, abnormal Cr levels in patient vs. control populations could confound the utility of this metabolite as an internal reference. We quantified Cr levels in 22 healthy controls, 15 acutely manic patients with bipolar disorder and 15 acutely ill patients with schizophrenia using (1)H MRS in the anterior cingulate cortex, and the parieto-occipital cortex at 4 Tesla. Patients with schizophrenia had a statistically significant reduction in Cr levels as compared with controls; bipolar disorder patients showed no difference in Cr as compared with controls. In addition, older age was associated with reductions in Cr in healthy controls, but not in patients with either disorder. These findings indicate that the use of Cr as an internal reference in schizophrenia MRS research is problematic unless Cr levels are shown to be normal in the study population. They also add to the literature on bioenergetic abnormalities in schizophrenia.
Total and free testosterone concentrations decline progressively with advancing age because of defects at all levels of the hypothalamic-pituitary-testicular axis. Low total and bioavailable testosterone levels have been associated with decreased skeletal muscle mass, muscle strength, physical function, bone mineral density, and fracture risk, although these associations are weak. The risks and health benefits of long-term testosterone remain poorly understood. Physiologic testosterone replacement of young, androgen-deficient men and older men with low testosterone levels is associated with an increase in fat-free mass, grip strength, and fractional muscle protein synthesis, but we do not know whether testosterone replacement improves quadriceps strength, power, muscle fatigability, and physical function in older men, and whether it can reduce the risk of disability and falls. Testosterone replacement increases vertebral bone mineral density in young hypogonadal men and older men with low testosterone levels, but we do not know whether testosterone reduces fracture risk. Concerns about the potential adverse effects of testosterone on the prostate have encouraged the development of selective androgen receptor modulators that increase muscle mass while sparing the prostate.
To determine whether low-dose creatine and protein supplementation during resistance training (RT; 3 d x wk(-1); 10 wk) in older men (59-77 yr) is effective for improving strength and muscle mass without producing potentially cytotoxic metabolites (formaldehyde).
Older men were randomized (double-blind) to receive 0.1 g x kg(-1) creatine + 0.3 g x kg(-1) protein (CP; n = 10), creatine (C; n = 13), or placebo (PLA; n = 12) on training days. Measurements before and after RT included lean tissue mass (air-displacement plethysmography), muscle thickness (ultrasound) of elbow, knee, and ankle flexors and extensors, leg and bench press strength, and urinary indicators of cytotoxicity (formaldehyde), myofibrillar protein degradation [3-methylhistidine (3-MH)],and bone resorption [cross-linked N-telopeptides of type I collagen (NTx)].
Subjects in C and CP groups combined experienced greater increases in body mass and total muscle thickness than PLA (P < 0.05). Subjects who received CP increased lean tissue mass (+5.6%) more than C (+2.2%) or PLA (+1.0%; P < 0.05) and increased bench press strength (+25%) to a greater extent than C and PLA combined (+12.5%; P < 0.05). CP and C did not differ from PLA for changes in formaldehyde production (+24% each). Subjects receiving creatine (C and CP) experienced a decrease in 3-MH by 40% compared with an increase of 29% for PLA (P < 0.05) and a reduction in NTx (-27%) versus PLA (+13%; P = 0.05).
Low-dose creatine combined with protein supplementation increases lean tissue mass and results in a greater relative increase in bench press but not leg press strength. Low-dose creatine reduces muscle protein degradation and bone resorption without increasing formaldehyde production.
Maximum values for isometric strength, dynamic strength, and speed of movement (MEV) in the quadriceps muscle were measured in 114 male subjects who were between 11 and 70 yr. Biopsy samples were taken from the quadriceps muscle in 51 of the subjects (22-65 yr. old). Isometric and dynamic strength increased up to the third decade, remained almost constant to the fifth decade, and then decreased with increasing age. However, no measurable external atrophy of the quadriceps muscle, explaining the decline in strength, could be seen in old age. Histochemical changes in the muscle tissue such as decreased proportion of type II fibers and a selective atrophy of type II fibers, were seen with increasing age. The strength decline in old age was also observed to correlate significantly with the type II fiber area. Multiple regression analyses indicated, however, that mechanisms other than the type II fiber atrophy might be responsible for the decline in strength performance during aging. The implications of these findings are discussed.
Nine healthy subjects were studied under control conditions and following 5 mo of heavy resistance training and 5 wk of immobilization in elbow casts. Needle biopsies were taken from triceps brachii and analyzed for adenosine triphosphate (ATP), adenosine diphosphate (ADP), creatine (C), creatine phosphate (CP, and glycogen concentrations. Training resulted in an 11% increase in arm circumference and a 28% increase in maximal elbow extension strength. Immobilization resulted in decreases in arm circumference and elbow extension strength of 5% and 35%, respectively. Training also resulted in significant increases in resting concentrations of muscle creatine (by 39%), CP (by 22%), ATP (by 18%), and glycogen (by 66%). Conversely, immobilization significantly reduced CP concentration by 25% and glycogen concentration by 40%. It was concluded that heavy-resistance training results in increases in muscle energy reserves which may be reversed by a period of immobilization-induced disuse.
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.
Brain phosphorus metabolism was measured in 22 patients with depressive disorders. Ten of them had DSM-III-R bipolar disorder, and 12 had major depression. In bipolar patients, phosphomonoester (PME) and intracellular pH were significantly increased in the depressive state than in the euthymic state, while those values in the euthymic state were significantly low as compared to age-matched normal controls. Phosphocreatine (PCr) was significantly decreased in severely depressed patients compared to mild depressives. These findings suggest that high energy phosphate metabolism, intracellular pH and membrane phospholipid metabolism are altered in depressive disorders.
Using a population-based hospital discharge registry with E codes, we examine the 1989 hospitalizations of older adults in Washington State for fall-related injuries. Fall-related trauma accounted for 5.3% of all hospitalizations of older adults, with hospital charges totaling 92 per person is reported. The importance of preventing fall-related injuries in older adults is discussed.
We used phosphorus magnetic resonance spectroscopy to study the calf muscles of elderly normal (mean +/- SD) (80.0 +/- 5.12 years), elderly impaired (80.7 +/- 0.58 years), old normal (66.8 +/- 1.92 years), and young normal people (24.6 +/- 4.72 years). Relative levels of inorganic phosphate (Pi), phosphocreatine (PCr), and adenosine triphosphate were measured with a 1.9-tesla, 30-cm bore magnet at rest and following plantra flexon exercise. No differences were found at rest or during recovery from exercise in the elderly normal subjects with respect to gender or the presence of stable medical problems treated with medication. At rest there was an age-related decrease in the ratio of PCr/Pi. After exercise, the time constant of PCr recovery increased with age. A mild 7-week exercise regimen consisting of plantar flexion had no effect on time constant of PCr recovery in the elderly subjects. Four elderly impaired subjects had lower PCr/Pi ratios at rest and slower time constant of PCr recovery after exercise than normal elderly subjects. We conclude that gender and the presence of stable medical problems had no effect on muscle metabolism in the elderly and that the elderly recovered slower than young controls. This slower recovery was not corrected with a mild exercise program.
1. A method is described enabling the determination of fat, water, electrolytes, protein, DNA, RNA and total creatine in a single sample of human muscle obtained by the percutaneous needle-biopsy technique. The amino acid content can also be analysed in the same muscle sample.
2. Fifty healthy subjects were studied: 29 between 19 and 40 years of age, 11 between 41 and 60 years of age, and 10 between 61 and 85 years of age. The two groups aged less than 60 years showed only marginal differences in muscle composition, whereas the highest age group showed increases in muscle fat content in relation to tissue weight and decreases in alkali-soluble protein content in relation to both tissue weight and tissue DNA content. Also, potassium, magnesium, total creatine and RNA contents were decreased in this age group when related to tissue DNA content. When alkali-soluble protein was used as a reference base, only magnesium content was decreased.
3. A comparison was also made between female (n = 23) and male (n = 18) subjects in the age groups below 60 years. Differences observed included a higher fat content in female muscle, and an increase in total creatine content in relation to tissue weight. The alkali-soluble protein content was lower per muscle cell in the females when calculated on the basis of DNA content.
4. The results show that in the assessment of muscle constituents, age and sex must be taken into account.
Percutaneous muscle biopsies were obtained from the vastus lateralis of physically active men (n = 12) 1) at rest, 2) immediately after an exercise bout consisting of 30 maximal voluntary knee extensions of constant angular velocity (3.14 rad/s), and 3) 60 s after termination of exercise. Creatine phosphate (CP) content was analyzed in pools of freeze-dried fast-twitch (FT) and slow-twitch (ST) muscle fiber fragments, and ATP, CP, creatine, and lactate content were assayed in mixed pools of FT and ST fibers. CP content at rest was 82.7 +/- 11.2 and 73.1 +/- 9.5 (SD) mmol/kg dry wt in FT and ST fibers (P less than 0.05). After exercise the corresponding values were 25.4 +/- 19.8 and 29.7 +/- 14.4 mmol/kg dry wt. After 60 s of recovery CP increased (P less than 0.01) to 41.3 +/- 12.6 and 49.6 +/- 11.7 mmol/kg dry wt in FT and ST fibers, respectively. CP content after recovery, relative to initial level, was higher in ST compared with FT fibers (P less than 0.05). ATP content decreased (P less than 0.05) and lactate content rose to 67.4 +/- 28.3 mmol/kg dry wt (P less than 0.001) in response to exercise. It is concluded that basal CP content is higher in FT fibers than in ST fibers. CP content also appears to be higher in ST fibers after a 60-s recovery period after maximal short-term exercise. These data are consistent with the different metabolic profiles of FT and ST fibers.
To study risk factors for falling, we conducted a one-year prospective investigation, using a sample of 336 persons at least 75 years of age who were living in the community. All subjects underwent detailed clinical evaluation, including standardized measures of mental status, strength, reflexes, balance, and gait; in addition, we inspected their homes for environmental hazards. Falls and their circumstances were identified during bimonthly telephone calls. During one year of follow-up, 108 subjects (32 percent) fell at least once; 24 percent of those who fell had serious injuries and 6 percent had fractures. Predisposing factors for falls were identified in linear-logistic models. The adjusted odds ratio for sedative use was 28.3; for cognitive impairment, 5.0; for disability of the lower extremities, 3.8; for palmomental reflex, 3.0; for abnormalities of balance and gait, 1.9; and for foot problems, 1.8; the lower bounds of the 95 percent confidence intervals were 1 or more for all variables. The risk of falling increased linearly with the number of risk factors, from 8 percent with none to 78 percent with four or more risk factors (P less than 0.0001). About 10 percent of the falls occurred during acute illness, 5 percent during hazardous activity, and 44 percent in the presence of environmental hazards. We conclude that falls among older persons living in the community are common and that a simple clinical assessment can identify the elderly persons who are at the greatest risk of falling.
Methods are described for the determination of glycogen, glycolytic intermediates, and high-energy phosphates in muscle biopsy samples. Initial freezedrying of samples and extraction of metabolites with relatively weak acid are preferred. Normal values in muscle are similar to those found by other workers. Variation in muscle content of ATP, ATP + ADP + AMP, phosphorylcreatine (PC), creatine (Cr), PC + Cr, and glycogen, between legs, between sites on the same muscle, or as a result of error introduced during analysis, was small compared with the between-individuals variance. The importance of the different sources of variance on taking a biopsy is discussed.