Creatine

Anti-Inflammatory and Anti-Catabolic Effects of Creatine Supplementation: A Brief Review

Type of study: literature review

Number of citations: 17

Year: 2022

Authors: Dean M. Cordingley, S. Cornish, D. Candow

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Creatine supplementation, when combined with resistance training, increases muscle mass, performance, and bone health, while also reducing inflammation and potentially attenuating cancerous tumor growth.

Abstract: It is well established that creatine supplementation, primarily when combined with resistance training, significantly increases measures of muscle mass and performance (primarily strength). Emerging research also indicates that creatine supplementation may have favorable effects on measures of bone biology. These anabolic adaptations may be related to creatine influencing cellular hydration status, high-energy phosphate metabolism, growth factors, muscle protein kinetics, and the bone remodeling process. Accumulating research also suggests that creatine supplementation has anti-inflammatory and anti-catabolic properties, which may help create a favorable environment for muscle and bone accretion and recovery from exercise. Creatine supplementation has the ability to decrease markers of inflammation and possibly attenuate cancerous tumor growth progression. From a musculoskeletal perspective, there is some evidence to show that creatine supplementation reduces measures of muscle protein catabolism (primarily in males) and bone resorption when combined with resistance training. The purpose of this brief review is to summarize the current body of literature examining the potential anti-inflammatory and anti-catabolic effects of creatine supplementation across various research populations.

Creatine supplementation in the aging population: effects on skeletal muscle, bone and brain

Type of study: literature review

Number of citations: 86

Year: 2016

Authors: B. Gualano, E. Rawson, D. Candow, P. Chilibeck

Journal: Amino Acids

Journal ranking: Q2

Key takeaways: Creatine supplementation can improve lean mass and muscle function in older individuals, with potential effects on bone remodeling and cognitive processing.

Abstract: This narrative review aims to summarize the recent findings on the adjuvant application of creatine supplementation in the management of age-related deficits in skeletal muscle, bone and brain metabolism in older individuals. Most studies suggest that creatine supplementation can improve lean mass and muscle function in older populations. Importantly, creatine in conjunction with resistance training can result in greater adaptations in skeletal muscle than training alone. The beneficial effect of creatine upon lean mass and muscle function appears to be applicable to older individuals regardless of sex, fitness or health status, although studies with very old (>90 years old) and severely frail individuals remain scarce. Furthermore, there is evidence that creatine may affect the bone remodeling process; however, the effects of creatine on bone accretion are inconsistent. Additional human clinical trials are needed using larger sample sizes, longer durations of resistance training (>52 weeks), and further evaluation of bone mineral, bone geometry and microarchitecture properties. Finally, a number of studies suggest that creatine supplementation improves cognitive processing under resting and various stressed conditions. However, few data are available on older adults, and the findings are discordant. Future studies should focus on older adults and possibly frail elders or those who have already experienced an age-associated cognitive decline.

Creatine supplementation for older adults: Focus on sarcopenia, osteoporosis, frailty and Cachexia.

Type of study: literature review

Number of citations: 32

Year: 2022

Authors: D. Candow, P. Chilibeck, Scott C. Forbes, C. Fairman, B. Gualano, H. Roschel

Journal: Bone

Journal ranking: Q1

Key takeaways: Creatine supplementation combined with resistance training can improve muscle and bone health in older adults, potentially aiding in the treatment of frailty and cachexia.

Creatine supplementation and aging musculoskeletal health

Type of study: meta-analysis

Number of citations: 94

Year: 2014

Authors: D. Candow, P. Chilibeck, Scott C. Forbes

Journal: Endocrine

Journal ranking: Q2

Key takeaways: Creatine supplementation combined with resistance training improves muscle mass, upper body strength, and bone mineral density in aging musculoskeletal health.

Abstract: Sarcopenia refers to the progressive loss of muscle mass and muscle function and is a contributing factor for cachexia, bone loss, and frailty. Resistance training produces several physiological adaptations which improve aging musculoskeletal health, such as increased muscle and bone mass and strength. The combination of creatine supplementation and resistance training may further lead to greater physiological benefits. We performed meta-analyses which indicate creatine supplementation combined with resistance training has a positive effect on aging muscle mass and upper body strength compared to resistance training alone. Creatine also shows promise for improving bone mineral density and indices of bone biology. The combination of creatine supplementation and resistance training could be an effective intervention to improve aging musculoskeletal health.

Effect of creatine supplementation during resistance training on lean tissue mass and muscular strength in older adults: a meta-analysis

Type of study: meta-analysis

Number of citations: 156

Year: 2017

Authors: P. Chilibeck, M. Kaviani, D. Candow, G. Zello

Journal: Open Access Journal of Sports Medicine

Journal ranking: Q1

Key takeaways: Creatine supplementation during resistance training increases lean tissue mass and upper and lower body muscular strength in older adults, but the exact mechanisms of these positive effects remain unclear.

Abstract: The loss of muscle mass and strength with aging results in significant functional impairment. Creatine supplementation has been used in combination with resistance training as a strategy for increasing lean tissue mass and muscle strength in older adults, but results across studies are equivocal. We conducted a systematic review and meta-analysis of randomized controlled trials of creatine supplementation during resistance training in older adults with lean tissue mass, chest press strength, and leg press strength as outcomes by searching PubMed and SPORTDiscus databases. Twenty-two studies were included in our meta-analysis with 721 participants (both men and women; with a mean age of 57–70 years across studies) randomized to creatine supplementation or placebo during resistance training 2–3 days/week for 7–52 weeks. Creatine supplementation resulted in greater increases in lean tissue mass (mean difference =1.37 kg [95% CI =0.97–1.76]; p<0.00001), chest press strength (standardized mean difference [SMD] =0.35 [0.16–0.53]; p=0.0002), and leg press strength (SMD =0.24 [0.05–0.43]; p=0.01). A number of mechanisms exist by which creatine may increase lean tissue mass and muscular strength. These are included in a narrative review in the discussion section of this article. In summary, creatine supplementation increases lean tissue mass and upper and lower body muscular strength during resistance training of older adults, but potential mechanisms by which creatine exerts these positive effects have yet to be evaluated extensively.

How Does Creatine Supplementation Affect Physical Performance and Muscle Recovery? - A Literature Review of Its Effects, Mechanisms of Action, Safety and Side Effects

Type of study: systematic review

Number of citations: 0

Year: 2025

Authors: Martyna Pacanowska, Małgorzata Blecharczyk, Igor Zydlewski, Martyna Mrozek, Alicja Nowik, Marcin Sękulski, Maciej Kosiński, Paweł Jakubiec

Journal: Quality in Sport

Journal ranking: brak

Key takeaways: Creatine supplementation enhances physical performance and muscle recovery, with long-term use not causing significant adverse side effects and improving muscle strength and endurance without affecting liver and kidney function.

Abstract: Introduction: Creatine is a naturally occurring compound that plays a primary role in energy metabolism, particularly within muscle cells. Its main sites of synthesis include the liver, kidneys, and pancreas [1,2]. This compound is crucial for muscle recovery following exercise. Creatine's ability to rapidly replenish ATP stores reduces fatigue and muscle soreness, thereby accelerating the recovery process. By increasing the availability of phosphocreatine in muscle cells, creatine significantly enhances the capacity to perform both short-duration and high-intensity exercises [4,8]. This allows athletes to complete more repetitions per set and recover faster between sets. Consequently, creatine supplementation has gained increasing popularity, particularly among athletes and physically active individuals. Additionally, creatine's influence on muscle protein synthesis is also linked to its ability to improve muscle cell hydration [15]. Aim of the Study: The aim of this study is to evaluate the impact of creatine supplementation on physical performance and muscle recovery, as well as to review its efficacy, safety, and potential side effects. Material and Methods: A review and analysis of randomized clinical trials and clinical studies from 2010 to 2025 available in PubMed and Google Scholar. Conclusions: Research findings indicate that long-term creatine use does not cause significant adverse side effects. Individuals supplementing with creatine have shown an increase in lean body mass without any undesirable effects on liver and kidney function. By improving muscle strength and endurance, creatine helps stabilize joints, thereby reducing the risk of musculoskeletal injuries [13]. From a practical perspective, these findings provide valuable insights for athletes, coaches, and physically active individuals striving to enhance both short-term and long-term training outcomes through creatine supplementation.

The impact of creatine levels on musculoskeletal health in the elderly: a mendelian randomization analysis

Type of study: non-rct observational study

Number of citations: 1

Year: 2024

Authors: Minping Hong, Junyan Wang, Liqin Jin, Keng Ling

Journal: BMC Musculoskeletal Disorders

Journal ranking: Q2

Key takeaways: Higher creatine levels may help maintain hand grip strength in individuals aged 60 and older, but other bone health parameters show no significant associations.

Abstract: Musculoskeletal health among the elderly emerges as a pivotal public health concern against the backdrop of a globally aging population. Creatine, popular within fitness circles, has emerged as a subject of scientific inquiry for its potential benefits on elderly' musculoskeletal well-being. Despite extensive documentation of its effects on athletic performance, investigations into creatine's long-term contributions to the musculoskeletal health of the elderly are comparatively limited. Utilizing publicly accessible genetic datasets, this study aimed to explore the potential causal link between creatine levels and a variety of musculoskeletal health markers in the elderly population, such as osteoarthritis (OA), rheumatoid arthritis (RA), osteoporosis (OP), bone-specific alkaline phosphatase, bone mineral density(BMD), serum calcium levels, and reduced hand grip strength in individuals aged 60 and above. Our methodological approach was grounded in Mendelian Randomization (MR) analysis, with a primary emphasis on the Inverse Variance Weighted (IVW) technique, to explore potential causal links under specific assumptions and limitations inherent to MR analysis. A significant inverse relationship was observed between creatine levels and reduced hand grip strength in individuals aged 60 and above (OR = 0.64, b=-0.44, p = 0.01), suggesting higher creatine levels might be beneficial in maintaining hand grip strength. Conversely, analysis of other bone health parameters, including bone-specific alkaline phosphatase, bone mineral density, serum calcium levels, and conditions such as osteoarthritis, rheumatoid arthritis, and osteoporosis, yielded p-values exceeding 0.05, denoting no statistically significant associations. This study provides preliminary evidence indicating a link between creatine levels and decreased hand grip strength among the elderly, notably in individuals aged 60 and older. This finding is significant for understanding the potential impact of creatine supplementation on elderly Musculoskeletal health and underscores the need for evidence-based decision-making in nutritional supplementation. To robustly validate these observations, it is essential to conduct future randomized controlled trials with large sample sizes.

Creatine and strength training in older adults: an update

Type of study: meta-analysis

Number of citations: 3

Year: 2024

Authors: Scott C. Forbes, D. Candow

Journal: Translational Exercise Biomedicine

Journal ranking: brak

Key takeaways: Creatine combined with strength training enhances lean tissue mass and upper body strength, but does not enhance lower-body strength or bone mineral density in older adults.

Abstract: Abstract Aging is associated with numerous physiological, musculoskeletal, and neurological impairments including a loss of muscle, strength, function, bone mineral, and cognition. Strength training is an effective intervention to counter these age-associated declines. In addition, creatine supplementation is purported to enhance strength training gains in lean tissue mass, muscular strength, and function. There is emerging evidence that creatine combined with strength training can alter bone geometry and cognitive performance. The purpose of this review is to update previous meta-analyses examining creatine combined with strength training on lean tissue mass and bone density compared to strength training and placebo. A secondary purpose was to explore the effects of creatine and strength training on cognition. Updated meta-analyses revealed that creatine enhances lean tissue mass (mean difference [MD]: 1.18 kg, 95 % CI: 0.70–1.67; p<0.00001) and upper body muscular strength (standard mean difference [SMD]: 0.24, 95 % CI: 0.05–0.43; p=0.02) compared to strength training and placebo. Creatine combined with strength training had no greater effects compared to strength training and placebo on lower body muscular strength (SMD: 0.17, 95 % CI: −0.03–0.38; p=0.09), whole-body (MD: −0.00 g cm−2; 95 % CI: −0.01–0.00, p=0.32), femoral neck (MD: −0.00 g cm−2; 95 % CI: −0.01–0.00, p=1.00), or lumbar bone mineral density (MD: 0.00 g cm−2, 95 % CI: −0.01–0.01; p=045). There is preliminary evidence that combining strength training and creatine is an effective strategy to improve bone geometry in postmenopausal females and cognitive function in older adults. Overall, the combination of creatine and strength training has favorable effects on lean tissue mass and upper body strength. In contrast, creatine combined with strength training does not enhance lower-body strength or bone mineral.

Creatine supplementation effect on recovery following exercise-induced muscle damage: A systematic review and meta-analysis of randomized controlled trials.

Type of study: meta-analysis

Number of citations: 14

Year: 2021

Authors: Jiaming Yue, M. Rahimi

Journal: Journal of food biochemistry

Journal ranking: Q1

Key takeaways: Creatine supplementation effectively reduces muscle damage and improves muscle function after exercise-induced muscle damage, particularly within 24 to 96 hours post-exercise.

Abstract: Exercise-induced muscle damage (EIMD) causes increased soreness, impaired function of muscles, and reductions in muscle force. Accumulating evidence suggests the beneficial effects of creatine on EIMD. Nevertheless, outcomes differ substantially across various articles. The main aim of this meta-analysis was to evaluate the effect of creatine on recovery following EIMD. Medline, Embase, Cochrane Library, Scopus, and Google Scholar were systematically searched up to March 2021. The Cochrane Collaboration tool for examining the risk of bias was applied for assessing the quality of studies. Weighted mean difference (WMD), 95% confidence interval (CI), and random-effects model, were applied for estimating the overall effect. Between studies, heterogeneity was examined using the chi-squared and I2 statistics. Nine studies met the inclusion criteria. Pooled data showed that creatine significantly reduced creatine kinase (CK) concentration overall (WMD = -30.94; 95% CI: -53.19, -8.69; p = .006) and at three follow-up times (48, 72, and 96 hr) in comparison with placebo. In contrast, effects were not significant in lactate dehydrogenase (LDH) concentration overall (WMD = -5.99; 95% CI: -14.49, 2.50; p = .167), but creatine supplementation leaded to a significant reduction in LDH concentrations in trials with 48 hr measurement of LDH. The current data indicate that creatine consumption is better than rest after diverse forms of damaging and exhaustive exercise or passive recovery. The benefits relate to a decrease in muscle damage indices and improved muscle function because of muscle power loss after exercise. PRACTICAL APPLICATIONS: Creatine supplementation would be effective in reducing the immediate muscle damage that happens <24, 24, 48, 72, and 96 hr post-exercise. In the current meta-analysis, the positive effects of creatine could cause a decrease in CK concentration overall. But, due to high heterogeneity and the medium risk of bias for articles, we suggest that these results are taken into account and the facts are interpreted with caution by the readers.

The Application of Creatine Supplementation in Medical Rehabilitation

Type of study: literature review

Number of citations: 29

Year: 2021

Authors: K. K. Harmon, Jeffrey R. Stout, D. Fukuda, P. Pabian, E. Rawson, M. Stock

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Creatine supplementation shows promise in preserving muscle mass, strength, and physical function in medical rehabilitation, but more research is needed to confirm its effectiveness in various diseases.

Abstract: Numerous health conditions affecting the musculoskeletal, cardiopulmonary, and nervous systems can result in physical dysfunction, impaired performance, muscle weakness, and disuse-induced atrophy. Due to its well-documented anabolic potential, creatine monohydrate has been investigated as a supplemental agent to mitigate the loss of muscle mass and function in a variety of acute and chronic conditions. A review of the literature was conducted to assess the current state of knowledge regarding the effects of creatine supplementation on rehabilitation from immobilization and injury, neurodegenerative diseases, cardiopulmonary disease, and other muscular disorders. Several of the findings are encouraging, showcasing creatine’s potential efficacy as a supplemental agent via preservation of muscle mass, strength, and physical function; however, the results are not consistent. For multiple diseases, only a few creatine studies with small sample sizes have been published, making it difficult to draw definitive conclusions. Rationale for discordant findings is further complicated by differences in disease pathologies, intervention protocols, creatine dosing and duration, and patient population. While creatine supplementation demonstrates promise as a therapeutic aid, more research is needed to fill gaps in knowledge within medical rehabilitation.

Creatine in Health and Disease

Type of study: systematic review

Number of citations: 115

Year: 2021

Authors: R. Kreider, J. Stout

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Creatine supplementation has several health and therapeutic benefits throughout the lifespan, including promoting general health, enhancing cellular metabolism, and aiding in recovery from injury and managing chronic diseases.

Abstract: 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.

Creatine for Exercise and Sports Performance, with Recovery Considerations for Healthy Populations

Type of study: literature review

Number of citations: 89

Year: 2021

Authors: B. Wax, C. Kerksick, Andrew R. Jagim, J. Mayo, B. Lyons, R. Kreider

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Creatine supplementation improves short-duration, high-intensity exercise performance and may speed up recovery time, but its benefits during endurance exercise and tasks with increased body mass may be contradictory.

Abstract: Creatine is one of the most studied and popular ergogenic aids for athletes and recreational weightlifters seeking to improve sport and exercise performance, augment exercise training adaptations, and mitigate recovery time. Studies consistently reveal that creatine supplementation exerts positive ergogenic effects on single and multiple bouts of short-duration, high-intensity exercise activities, in addition to potentiating exercise training adaptations. In this respect, supplementation consistently demonstrates the ability to enlarge the pool of intracellular creatine, leading to an amplification of the cell’s ability to resynthesize adenosine triphosphate. This intracellular expansion is associated with several performance outcomes, including increases in maximal strength (low-speed strength), maximal work output, power production (high-speed strength), sprint performance, and fat-free mass. Additionally, creatine supplementation may speed up recovery time between bouts of intense exercise by mitigating muscle damage and promoting the faster recovery of lost force-production potential. Conversely, contradictory findings exist in the literature regarding the potential ergogenic benefits of creatine during intermittent and continuous endurance-type exercise, as well as in those athletic tasks where an increase in body mass may hinder enhanced performance. The purpose of this review was to summarize the existing literature surrounding the efficacy of creatine supplementation on exercise and sports performance, along with recovery factors in healthy populations.

Beyond muscles: The untapped potential of creatine.

Type of study:

Number of citations: 74

Year: 2016

Authors: Lisa A. Riesberg, Stephanie A Weed, T. Mcdonald, J. Eckerson, K. Drescher

Journal: International immunopharmacology

Journal ranking: Q1

Key takeaways: Creatine supplementation may benefit individuals with certain neurological conditions and may have a regulatory impact on the immune system.

Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?

Type of study:

Number of citations: 120

Year: 2021

Authors: J. Antonio, D. Candow, Scott C. Forbes, B. Gualano, Andrew R. Jagim, R. Kreider, E. Rawson, A. Smith‐Ryan, Trisha A. VanDusseldorp, D. Willoughby, T. Ziegenfuss

Journal: Journal of the International Society of Sports Nutrition

Journal ranking: Q1

Key takeaways: Creatine supplementation is safe and effective for improving muscle mass, performance, and recovery, with benefits for older adults, patients, and various other populations.

Abstract: Supplementing with creatine is very popular amongst athletes and exercising individuals for improving muscle mass, performance and recovery. Accumulating evidence also suggests that creatine supplementation produces a variety of beneficial effects in older and patient populations. Furthermore, evidence-based research shows that creatine supplementation is relatively well tolerated, especially at recommended dosages (i.e. 3-5 g/day or 0.1 g/kg of body mass/day). Although there are over 500 peer-refereed publications involving creatine supplementation, it is somewhat surprising that questions regarding the efficacy and safety of creatine still remain. These include, but are not limited to: 1. Does creatine lead to water retention? 2. Is creatine an anabolic steroid? 3. Does creatine cause kidney damage/renal dysfunction? 4. Does creatine cause hair loss / baldness? 5. Does creatine lead to dehydration and muscle cramping? 6. Is creatine harmful for children and adolescents? 7. Does creatine increase fat mass? 8. Is a creatine 'loading-phase' required? 9. Is creatine beneficial for older adults? 10. Is creatine only useful for resistance / power type activities? 11. Is creatine only effective for males? 12. Are other forms of creatine similar or superior to monohydrate and is creatine stable in solutions/beverages? To answer these questions, an internationally renowned team of research experts was formed to perform an evidence-based scientific evaluation of the literature regarding creatine supplementation.

Creatine Supplementation and Its Effect on Musculotendinous Stiffness and Performance

Type of study: rct

Number of citations: 24

Year: 2003

Authors: M. Watsford, A. Murphy, W. Spinks, A. Walshe

Journal: Journal of Strength and Conditioning Research

Journal ranking: Q1

Key takeaways: Creatine supplementation increases jump performance without causing increased musculotendinous stiffness or a higher risk of muscle strain injuries.

Abstract: Anecdotal reports suggesting that creatine (Cr) supplementation may cause side effects, such as an increased incidence of muscle strains or tears, require scientific examination. In this study, it was hypothesized that the rapid fluid retention and “dry matter growth” evident after Cr supplementation may cause an increase in musculotendinous stiffness. Intuitively, an increase in musculotendinous stiffness would increase the chance of injury during exercise. Twenty men were randomly allocated to a control or an experimental group and were examined for musculotendinous stiffness of the triceps surae and for numerous performance indices before and after Cr ingestion. The Cr group achieved a significant increase in body mass (79.7 ± 10.8 kg vs. 80.9 ± 10.7 kg), counter movement jump height (40.2 ± 4.8 cm vs. 42.7 ± 5.9 cm), and 20-cm drop jump height (32.3 ± 3.3 cm vs. 35.1 ± 4.8 cm) after supplementation. No increase was found for musculotendinous stiffness at any assessment load. There were no significant changes in any variables within the control group. These findings have both performance- and injury-related implications. Primarily, anecdotal evidence suggesting that Cr supplementation causes muscular strain injuries is not supported by this study. In addition, the increase in jump performance is indicative of performance enhancement in activities requiring maximal power output.

Creatine in T Cell Antitumor Immunity and Cancer Immunotherapy

Type of study:

Number of citations: 20

Year: 2021

Authors: Bo Li, Lili Yang

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Creatine supplementation enhances antitumor T cell immunity and synergizes with other cancer immunotherapy modalities, potentially improving antitumor efficacy.

Abstract: Creatine is a broadly used dietary supplement that has been extensively studied for its benefit on the musculoskeletal system. Yet, there is limited knowledge regarding the metabolic regulation of creatine in cells beyond the muscle. New insights concerning various regulatory functions for creatine in other physiological systems are developing. Here, we highlight the latest advances in understanding creatine regulation of T cell antitumor immunity, a topic that has previously gained little attention in the creatine research field. Creatine has been identified as an important metabolic regulator conserving bioenergy to power CD8 T cell antitumor reactivity in a tumor microenvironment; creatine supplementation has been shown to enhance antitumor T cell immunity in multiple preclinical mouse tumor models and, importantly, to synergize with other cancer immunotherapy modalities, such as the PD-1/PD-L1 blockade therapy, to improve antitumor efficacy. The potential application of creatine supplementation for cancer immunotherapy and the relevant considerations are discussed.

The Role of Creatine in the Development and Activation of Immune Responses

Type of study: literature review

Number of citations: 25

Year: 2021

Authors: E. Bredahl, J. Eckerson, S. Tracy, T. Mcdonald, K. Drescher

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Creatine supplementation can impact both innate and adaptive immune responses, potentially enhancing human health beyond the musculoskeletal system.

Abstract: 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.

Creatine Supplementation and Brain Health

Type of study: literature review

Number of citations: 103

Year: 2021

Authors: H. Roschel, B. Gualano, Sergej M Ostojic, Eric S Rawson

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Creatine supplementation shows potential in improving cognitive processing and brain health, particularly in conditions with brain creatine deficits.

Abstract: 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.

Effects of Creatine Supplementation on Brain Function and Health

Type of study: literature review

Number of citations: 69

Year: 2022

Authors: Scott C. Forbes, Dean M. Cordingley, S. Cornish, B. Gualano, H. Roschel, S. Ostojić, E. Rawson, B. Roy, K. Prokopidis, P. Giannos, D. Candow

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Creatine supplementation shows potential in increasing brain creatine content and attenuating symptoms of concussion, mild traumatic brain injury, and depression, but its effect on neurodegenerative diseases remains unclear.

Abstract: While the vast majority of research involving creatine supplementation has focused on skeletal muscle, there is a small body of accumulating research that has focused on creatine and the brain. Preliminary studies indicate that creatine supplementation (and guanidinoacetic acid; GAA) has the ability to increase brain creatine content in humans. Furthermore, creatine has shown some promise for attenuating symptoms of concussion, mild traumatic brain injury and depression but its effect on neurodegenerative diseases appears to be lacking. The purpose of this narrative review is to summarize the current body of research pertaining to creatine supplementation on total creatine and phophorylcreatine (PCr) content, explore GAA as an alternative or adjunct to creatine supplementation on brain creatine uptake, assess the impact of creatine on cognition with a focus on sleep deprivation, discuss the effects of creatine supplementation on a variety of neurological and mental health conditions, and outline recent advances on creatine supplementation as a neuroprotective supplement following traumatic brain injury or concussion.

The creatine kinase system and pleiotropic effects of creatine

Type of study:

Number of citations: 654

Year: 2011

Authors: T. Wallimann, M. Tokarska-Schlattner, U. Schlattner

Journal: Amino Acids

Journal ranking: Q2

Key takeaways: Creatine supplementation has beneficial effects on muscle and bone growth, neuroprotection, and overall health, with potential applications in senior people, dialysis patients, and premature infants.

Abstract: The pleiotropic effects of creatine (Cr) are based mostly on the functions of the enzyme creatine kinase (CK) and its high-energy product phosphocreatine (PCr). Multidisciplinary studies have established molecular, cellular, organ and somatic functions of the CK/PCr system, in particular for cells and tissues with high and intermittent energy fluctuations. These studies include tissue-specific expression and subcellular localization of CK isoforms, high-resolution molecular structures and structure–function relationships, transgenic CK abrogation and reverse genetic approaches. Three energy-related physiological principles emerge, namely that the CK/PCr systems functions as (a) an immediately available temporal energy buffer, (b) a spatial energy buffer or intracellular energy transport system (the CK/PCr energy shuttle or circuit) and (c) a metabolic regulator. The CK/PCr energy shuttle connects sites of ATP production (glycolysis and mitochondrial oxidative phosphorylation) with subcellular sites of ATP utilization (ATPases). Thus, diffusion limitations of ADP and ATP are overcome by PCr/Cr shuttling, as most clearly seen in polar cells such as spermatozoa, retina photoreceptor cells and sensory hair bundles of the inner ear. The CK/PCr system relies on the close exchange of substrates and products between CK isoforms and ATP-generating or -consuming processes. Mitochondrial CK in the mitochondrial outer compartment, for example, is tightly coupled to ATP export via adenine nucleotide transporter or carrier (ANT) and thus ATP-synthesis and respiratory chain activity, releasing PCr into the cytosol. This coupling also reduces formation of reactive oxygen species (ROS) and inhibits mitochondrial permeability transition, an early event in apoptosis. Cr itself may also act as a direct and/or indirect anti-oxidant, while PCr can interact with and protect cellular membranes. Collectively, these factors may well explain the beneficial effects of Cr supplementation. The stimulating effects of Cr for muscle and bone growth and maintenance, and especially in neuroprotection, are now recognized and the first clinical studies are underway. Novel socio-economically relevant applications of Cr supplementation are emerging, e.g. for senior people, intensive care units and dialysis patients, who are notoriously Cr-depleted. Also, Cr will likely be beneficial for the healthy development of premature infants, who after separation from the placenta depend on external Cr. Cr supplementation of pregnant and lactating women, as well as of babies and infants are likely to be of benefit for child development. Last but not least, Cr harbours a global ecological potential as an additive for animal feed, replacing meat- and fish meal for animal (poultry and swine) and fish aqua farming. This may help to alleviate human starvation and at the same time prevent over-fishing of oceans.

Creatine promotes cancer metastasis through activation of Smad2/3.

Type of study: non-rct experimental

Number of citations: 91

Year: 2021

Authors: Liwen Zhang, Zijing Zhu, Huiwen Yan, Wen Wang, Zhenzhen Wu, Fei Zhang, Qixiang Zhang, Guizhi Shi, Jun-Feng Du, Huiyun Cai, Xuanxuan Zhang, D. Hsu, P. Gao, Hai-long Piao, Gang Chen, Pengcheng Bu

Journal: Cell metabolism

Journal ranking: Q1

Key takeaways: Creatine supplements can promote colorectal and breast cancer metastasis and shorten mouse survival, suggesting caution when considering their use for muscle mass or disease treatment.

Effects of Creatine Supplementation on Properties of Muscle, Bone, and Brain Function in Older Adults: A Narrative Review

Type of study: literature review

Number of citations: 28

Year: 2021

Authors: Scott C. Forbes, D. Candow, L. H. Ferreira, Tácito P. Souza-Junior

Journal: Journal of Dietary Supplements

Journal ranking: Q2

Key takeaways: Creatine supplementation may have beneficial effects on muscle mass, bone strength, and brain function in older adults, independent of exercise.

Abstract: Abstract Aging is associated with reductions in muscle and bone mass and brain function, which may be counteracted by several lifestyle factors, of which exercise appears to be most beneficial. However, less than 20% of older adults (> 55 years of age) adhere to performing the recommended amount of resistance training (≥ 2 days/week) and less than 12% regularly meet the aerobic exercise guidelines (≥ 150 min/week of moderate to vigorous intensity aerobic exercise) required to achieve significant health benefits. Therefore, from a healthy aging and clinical perspective, it is important to determine whether other lifestyle interventions (independent of exercise) can have beneficial effects on aging muscle quality and quantity, bone strength, and brain function. Creatine, a nitrogen containing organic compound found in all cells of the body, has the potential to have favorable effects on muscle, bone, and brain health (independent of exercise) in older adults. The purpose of this narrative review is to examine and summarize the small body of research investigating the effects of creatine supplementation alone on measures of muscle mass and performance, bone mineral and strength, and indices of brain health in older adults.

Beyond sports: Efficacy and safety of creatine supplementation in pathological or paraphysiological conditions of brain and muscle

Type of study: systematic review

Number of citations: 63

Year: 2019

Authors: M. Balestrino, E. Adriano

Journal: Medicinal Research Reviews

Journal ranking: Q1

Key takeaways: Creatine supplementation improves muscular strength and well-being in muscular dystrophies, prevents statin myopathy, and treats treatment-resistant depression in women, with safety up to 20 g/d.

Abstract: Creatine is pivotal in energy metabolism of muscle and brain cells, both in physiological and in pathological conditions. Additionally, creatine facilitates the differentiation of muscle and neuronal cells. Evidence of effectiveness of creatine supplementation in improving several clinical conditions is now substantial, and we review it in this paper. In hereditary diseases where its synthesis is impaired, creatine has a disease‐modifying capacity, especially when started soon after birth. Strong evidence, including a Cochrane meta‐analysis, shows that it improves muscular strength and general well‐being in muscular dystrophies. Significant evidence exists also of its effectiveness in secondary prevention of statin myopathy and of treatment‐resistant depression in women. Vegetarians and vegans do not consume any dietary creatine and must synthesize all they need, spending most of their methylation capacity. Nevertheless, they have a lower muscular concentration of creatine. Creatine supplementation has proved effective in increasing muscular and neuropsychological performance in vegetarians or vegans and should, therefore, be recommended especially in those of them who are athletes, heavy‐duty laborers or who undergo intense mental effort. Convincing evidence also exists of creatine effectiveness in muscular atrophy and sarcopenia in the elderly, and in brain energy shortage (mental fatigue, sleep deprivation, environmental hypoxia as in mountain climbing, and advanced age). Furthermore, we review more randomized, placebo‐controlled trials showing that creatine supplementation is safe up to 20 g/d, with a possible caveat only in people with kidney disease. We trust that the evidence we review will be translated into clinical practice and will spur more research on these subjects.

Creatine supplementation and endurance performance: surges and sprints to win the race

Type of study: literature review

Number of citations: 34

Year: 2023

Authors: Scott C. Forbes, D. Candow, João Henrique Falk Neto, M. Kennedy, Jennifer L Forbes, M. Machado, Erik Bustillo, José Gómez-López, Andres Zapata, J. Antonio

Journal: Journal of the International Society of Sports Nutrition

Journal ranking: Q1

Key takeaways: Creatine supplementation may improve endurance performance by increasing anaerobic work capacity and supporting high-intensity aerobic exercise, particularly in sports with multiple intensity surges.

Abstract: ABSTRACT Creatine supplementation is an effective ergogenic aid to augment resistance training and improve intense, short duration, intermittent performance. The effects on endurance performance are less known. The purpose of this brief narrative review is to discuss the potential mechanisms of how creatine can affect endurance performance, defined as large muscle mass activities that are cyclical in nature and are >~3 min in duration, and to highlight specific nuances within the literature. Mechanistically, creatine supplementation elevates skeletal muscle phosphocreatine (PCr) stores facilitating a greater capacity to rapidly resynthesize ATP and buffer hydrogen ion accumulation. When co-ingested with carbohydrates, creatine enhances glycogen resynthesis and content, an important fuel to support high-intensity aerobic exercise. In addition, creatine lowers inflammation and oxidative stress and has the potential to increase mitochondrial biogenesis. In contrast, creatine supplementation increases body mass, which may offset the potential positive effects, particularly in weight-bearing activities. Overall, creatine supplementation increases time to exhaustion during high-intensity endurance activities, likely due to increasing anaerobic work capacity. In terms of time trial performances, results are mixed; however, creatine supplementation appears to be more effective at improving performances that require multiple surges in intensity and/or during end spurts, which are often key race-defining moments. Given creatines ability to enhance anaerobic work capacity and performance through repeated surges in intensity, creatine supplementation may be beneficial for sports, such as cross-country skiing, mountain biking, cycling, triathlon, and for short-duration events where end-spurts are critical for performance, such as rowing, kayaking, and track cycling.

Creatine supplementation protocols with or without training interventions on body composition: a GRADE-assessed systematic review and dose-response meta-analysis

Type of study: meta-analysis

Number of citations: 9

Year: 2024

Authors: Fereshteh Pashayee-Khamene, Zeinab Heidari, Omid Asbaghi, D. Ashtary-Larky, K. Goudarzi, Scott C. Forbes, D. Candow, R. Bagheri, M. Ghanavati, F. Dutheil

Journal: Journal of the International Society of Sports Nutrition

Journal ranking: Q1

Key takeaways: Creatine supplementation has a small effect on body mass, fat-free mass, and body fat percentage, with greater effects when combined with resistance training.

Abstract: ABSTRACT Background Despite the robust evidence demonstrating positive effects from creatine supplementation (primarily when associated with resistance training) on measures of body composition, there is a lack of a comprehensive evaluation regarding the influence of creatine protocol parameters (including dose and form) on body mass and estimates of fat-free and fat mass. Methods Randomized controlled trials (RCTs) evaluating the effect of creatine supplementation on body composition were included. Electronic databases, including PubMed, Web of Science, and Scopus were searched up to July 2023. Heterogeneity tests were performed. Random effect models were assessed based on the heterogeneity tests, and pooled data were examined to determine the weighted mean difference (WMD) with a 95% confidence interval (CI). Results From 4831 initial records, a total of 143 studies met the inclusion criteria. Creatine supplementation increased body mass (WMD: 0.86 kg; 95% CI: 0.76 to 0.96, I2 = 0%) and fat-free mass (WMD: 0.82 kg; 95% CI: 0.57 to 1.06, I2 = 0%) while reducing body fat percentage (WMD: −0.28 %; 95% CI: −0.47 to −0.09; I2 = 0%). Studies that incorporated a maintenance dose of creatine or performed resistance training in conjunction with supplementation had greater effects on body composition. Conclusion Creatine supplementation has a small effect on body mass and estimates of fat-free mass and body fat percentage. These findings were more robust when combined with resistance training.

International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine

Type of study: literature review

Number of citations: 538

Year: 2017

Authors: R. Kreider, D. Kalman, J. Antonio, T. Ziegenfuss, R. Wildman, Rick Collins, D. Candow, S. Kleiner, A. Almada, H. Lopez

Journal: Journal of the International Society of Sports Nutrition

Journal ranking: Q1

Key takeaways: Creatine supplementation improves exercise performance, enhances recovery, and is safe and well-tolerated for use in healthy individuals and various patient populations.

Abstract: Creatine is one of the most popular nutritional ergogenic aids for athletes. Studies have consistently shown that creatine supplementation increases intramuscular creatine concentrations which may help explain the observed improvements in high intensity exercise performance leading to greater training adaptations. In addition to athletic and exercise improvement, research has shown that creatine supplementation may enhance post-exercise recovery, injury prevention, thermoregulation, rehabilitation, and concussion and/or spinal cord neuroprotection. Additionally, a number of clinical applications of creatine supplementation have been studied involving neurodegenerative diseases (e.g., muscular dystrophy, Parkinson’s, Huntington’s disease), diabetes, osteoarthritis, fibromyalgia, aging, brain and heart ischemia, adolescent depression, and pregnancy. These studies provide a large body of evidence that creatine can not only improve exercise performance, but can play a role in preventing and/or reducing the severity of injury, enhancing rehabilitation from injuries, and helping athletes tolerate heavy training loads. Additionally, researchers have identified a number of potentially beneficial clinical uses of creatine supplementation. These studies show that short and long-term supplementation (up to 30 g/day for 5 years) is safe and well-tolerated in healthy individuals and in a number of patient populations ranging from infants to the elderly. Moreover, significant health benefits may be provided by ensuring habitual low dietary creatine ingestion (e.g., 3 g/day) throughout the lifespan. The purpose of this review is to provide an update to the current literature regarding the role and safety of creatine supplementation in exercise, sport, and medicine and to update the position stand of International Society of Sports Nutrition (ISSN).

The Additive Effects of Creatine Supplementation and Exercise Training in an Aging Population: A Systematic Review of Randomized Controlled Trials

Type of study: systematic review

Number of citations: 26

Year: 2020

Authors: Aaron Stares, M. Bains

Journal: Journal of Geriatric Physical Therapy

Journal ranking: Q2

Key takeaways: Creatine supplementation combined with moderate- to high-intensity exercise may improve muscle health in older adults, but its effects on bone and cognition remain unclear.

Abstract: Supplemental Digital Content is Available in the Text. Background and Purpose: The role of creatine supplementation in young athletes and bodybuilders is well established including ergogenic properties of muscular hypertrophy, strength, power, and endurance. Whether the benefits of creatine supplementation translate to an aging population with moderate training stimulus remains unclear especially in regard to gender, creatine dose, and duration. This systematic review assessed whether creatine supplementation combined with exercise results in additive improvements in indices of skeletal muscle, bone, and mental health over exercise alone in healthy older adults. Methods: PubMed, CINAHL, and Web of Science databases were utilized to identify randomized controlled trials of creatine supplementation combined with exercise in an aging population with additional predetermined inclusion and exclusion criteria. Two reviewers independently screened the titles and abstracts, reviewed full-text articles, and performed quality assessments using the Physiotherapy Evidence Database scale. Results and Discussion: Seventeen studies were comprehensively reviewed according to categories of strength, endurance, functional capacity, body composition, cognition, and safety. These studies suggest that any additive ergogenic creatine effects on upper and/or lower body strength, functional capacity, and lean mass in an older population would require a continuous and daily low-dose creatine supplementation combined with at least 12 weeks of resistance training. Potential creatine specific increases in regional bone mineral density of the femur are possible but may require at least 1 year of creatine supplementation combined with moderate resistance training, and additional long-term clinical trials are warranted. The limited data suggested no additive effects of creatine over exercise alone on indices of mental health. The beneficial effects of creatine supplementation are more consistent in older women than in men. Conclusions: Creatine monohydrate is safe to use in older adults. While creatine in conjunction with moderate- to high-intensity exercise in an aging population may improve skeletal muscle health, additional studies are needed to determine the effective dosing and duration paradigm for potential combined creatine and exercise effects on bone and cognition in older adults.

Creatine Supplementation in Women’s Health: A Lifespan Perspective

Type of study: literature review

Number of citations: 50

Year: 2021

Authors: A. Smith‐Ryan, Hannah E. Cabre, J. Eckerson, D. Candow

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Creatine supplementation may improve strength, exercise performance, skeletal muscle size, function, and mood in women, particularly during menses, pregnancy, post-partum, and menopause.

Abstract: 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.

Role of Creatine in the Heart: Health and Disease

Type of study:

Number of citations: 55

Year: 2021

Authors: M. Balestrino

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Creatine supplementation may be useful in heart failure, ischemia, and preventing cardiac toxicity from chemotherapy compounds like anthracyclines.

Abstract: Creatine is a key player in heart contraction and energy metabolism. Creatine supplementation (throughout the paper, only supplementation with creatine monohydrate will be reviewed, as this is by far the most used and best-known way of supplementing creatine) increases creatine content even in the normal heart, and it is generally safe. In heart failure, creatine and phosphocreatine decrease because of decreased expression of the creatine transporter, and because phosphocreatine degrades to prevent adenosine triphosphate (ATP) exhaustion. This causes decreased contractility reserve of the myocardium and correlates with left ventricular ejection fraction, and it is a predictor of mortality. Thus, there is a strong rationale to supplement with creatine the failing heart. Pending additional trials, creatine supplementation in heart failure may be useful given data showing its effectiveness (1) against specific parameters of heart failure, and (2) against the decrease in muscle strength and endurance of heart failure patients. In heart ischemia, the majority of trials used phosphocreatine, whose mechanism of action is mostly unrelated to changes in the ergogenic creatine-phosphocreatine system. Nevertheless, preliminary data with creatine supplementation are encouraging, and warrant additional studies. Prevention of cardiac toxicity of the chemotherapy compounds anthracyclines is a novel field where creatine supplementation may also be useful. Creatine effectiveness in this case may be because anthracyclines reduce expression of the creatine transporter, and because of the pleiotropic antioxidant properties of creatine. Moreover, creatine may also reduce concomitant muscle damage by anthracyclines.

Creatine Supplementation and Skeletal Muscle Metabolism for Building Muscle Mass- Review of the Potential Mechanisms of Action.

Type of study: literature review

Number of citations: 74

Year: 2017

Authors: F. Farshidfar, Mark A Pinder, S. Myrie

Journal: Current protein & peptide science

Journal ranking: Q2

Key takeaways: Creatine supplementation enhances muscle mass through multiple pathways, including protein synthesis and myogenesis, but the exact mechanisms of action remain unclear.

Abstract: Creatine, a very popular supplement among athletic populations, is of growing interest for clinical applications. Since over 90% of creatine is stored in skeletal muscle, the effect of creatine supplementation on muscle metabolism is a widely studied area. While numerous studies over the past few decades have shown that creatine supplementation has many favorable effects on skeletal muscle physiology and metabolism, including enhancing muscle mass (growth/hypertrophy); the underlying mechanisms are poorly understood. This report reviews studies addressing the mechanisms of action of creatine supplementation on skeletal muscle growth/hypertrophy. Early research proposed that the osmotic effect of creatine supplementation serves as a cellular stressor (osmosensing) that acts as an anabolic stimulus for protein synthesis signal pathways. Other reports indicated that creatine directly affects muscle protein synthesis via modulations of components in the mammalian target of rapamycin (mTOR) pathway. Creatine may also directly affect the myogenic process (formation of muscle tissue), by altering secretions of myokines, such as myostatin and insulin-like growth factor-1, and expressions of myogenic regulatory factors, resulting in enhanced satellite cells mitotic activities and differentiation into myofiber. Overall, there is still no clear understanding of the mechanisms of action regarding how creatine affects muscle mass/growth, but current evidence suggests it may exert its effects through multiple approaches, with converging impacts on protein synthesis and myogenesis.

Effect of the Combination of Creatine Monohydrate Plus HMB Supplementation on Sports Performance, Body Composition, Markers of Muscle Damage and Hormone Status: A Systematic Review

Type of study: systematic review

Number of citations: 26

Year: 2019

Authors: Julen Fernández-Landa, J. Calleja-González, Patxi León-Guereño, Alberto Caballero-García, A. Córdova, J. Mielgo-Ayuso

Journal: Nutrients

Journal ranking: Q1

Key takeaways: The combination of 3-10g/day of creatine monohydrate and 3g/day of HMB for 1-6 weeks may improve sports performance and body composition, but does not show positive effects on exercise-induced muscle damage or anabolic-catabolic hormones.

Abstract: Although there are many studies showing the isolated effect of creatine monohydrate (CrM) and β-hydroxy β-methylbutyrate (HMB), it is not clear what effect they have when they are combined. The main purpose of this systematic review was to determine the efficacy of mixing CrM plus HMB in comparison with their isolated effects on sports performance, body composition, exercise induced markers of muscle damage, and anabolic-catabolic hormones. This systematic review was carried out in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement guidelines and the PICOS model, for the definition of the inclusion criteria. Studies were found by searching PubMed/MEDLINE, Web of Science (WOS), and Scopus electronic databases from inception to July 3rd 2019. Methodological quality and risk of bias were assessed by two authors independently, and disagreements were resolved by third-party evaluation, in accordance with the Cochrane Collaboration Guidelines samples. The literature was examined regarding the effects of the combination of CrM plus HMB on sport performance using several outcome variables (athletic performance, body composition, markers of muscle damage, and hormone status). This systematic review included six articles that investigated the effects of CrM plus HMB on sport performance (two on strength performance, showing improvements in one of them; three on anaerobic performance, presenting enhancements in two of them; and one on aerobic performance, not presenting improvements), body composition (three on body mass, showing improvements in one of them; two on fat free mass, presenting increases in one of them; and two on fat mass, showing decreases in one of them) and markers of muscle damage and hormone status (four on markers of muscle damage and one on anabolic-catabolic hormones, not showing benefits in any of them). In summary, the combination of 3–10 g/day of CrM plus 3 g/day of HMB for 1–6 weeks could produce potential positive effects on sport performance (strength and anaerobic performance) and for 4 weeks on body composition (increasing fat free mass and decreasing fat mass). However, this combination seems to not show positive effects relating to markers of exercise-induced muscle damage and anabolic-catabolic hormones.

OS EFEITOS DA SUPLEMENTAÇÃO DE CREATINA NO DESEMPENHO DOS ATLETAS: UMA REVISÃO DE LITERATURA

Type of study: systematic review

Number of citations: 0

Year: 2024

Authors: Albertino Neto Lopes Borges, Daniel de Aquino Iedo de Melo, Líllian Tavares de Lima, Ronildo Oliveira Figueiredo

Journal: Revista ft

Journal ranking: brak

Key takeaways: Creatine supplementation significantly improves muscle performance and body composition during high-intensity training, reducing cramps and injuries in various sports.

Abstract: Creatine is a highly popular dietary supplement among athletes due to its ergogenic potential. In view of this, this study aims to verify in the specialized literature the main effects of creatine supplementation on athlete performance. The methodology used comprised a narrative literature review, with 12 scientific articles selected from the period 2017 to 2024 in the following databases: PubMed, Medline, Scielo and Lilacs. The results demonstrate that creatine supplementation produces ergogenic effects, positively impacting athletes' muscle strength, endurance and power, reducing the incidence of cramps and injuries, especially in American football, soccer, basketball, tennis and handball. Thus, it is concluded that this supplementation promotes significant improvements in muscle performance and body composition during athletes' periodized training, involving the repetition of high-intensity exercises in short, medium and prolonged periods.

Creatine as a Compound and Supplement Metabolism, Mechanism of Action, Effects, and Adverse Effects - A Review

Type of study:

Number of citations: 0

Year: 2025

Authors: Szymon Szypulski, Aleksandra Zielińska, Sebastian Iwaniuk, Ignacy Maciejewski, Kinga Tylczyńska, Jakub Skiba, Maria Michalska, Kinga Kowalik, Zuzanna Skiba, Natalia Tylczyńska

Journal: Quality in Sport

Journal ranking: brak

Key takeaways: Creatine supplementation positively impacts athletic performance, muscle gains, and has shown beneficial effects in various medical conditions, making it a popular and safe supplement for various age groups.

Abstract: In a world of evolving athletic competition and scientific advancement, the pursuit of optimal supplement applications to achieve peak performance should come as no surprise. One of the most popular and extensively researched supplements is creatine, for which numerous studies over many years have supported its positive impact on athletic and strength performance, as well as muscle and strength gains. Over time, attention has also shifted toward exploring creatine’s potential applications in other areas of medicine, as well as its use across various populations and age groups. Currently, the significance and importance of creatine are being highlighted not only in the context of its use across various sports disciplines, but also for its demonstrated beneficial effects in a range of medical conditions. These include improved prognosis in osteoporosis, osteopenia, and age-related sarcopenia, as well as its neuroprotective effects- for example, in brain injuries, ischemic diseases, diabetes, and other related conditions. Creatine, a compound naturally present in the human body- both endogenously synthesized and obtained through dietary intake- can also be consumed as a supplement, exhibiting excellent bioavailability that results in tissue saturation, primarily within muscle tissue. Due to its well-documented positive effects, and being recognized as a safe supplement with virtually no significant adverse or health-compromising effects, creatine continues to grow in popularity. Given its approval for use by organizations such as the International Olympic Committee and the endorsement of the International Society of Sports Nutrition, it is well on its way to becoming a leading supplement on the market. It is increasingly used by professional and amateur athletes, but also by a wide range of other populations across various age groups. Additionally, the concept of lifelong creatine supplementation is being increasingly discussed as a potentially beneficial strategy.

The effects of creatine supplementation on cognitive performance—a randomised controlled study

Type of study: rct

Number of citations: 11

Year: 2023

Authors: J. F. Sandkühler, Xenia Kersting, Annika Faust, Eva Kathrin Königs, George Altman, Ulrich Ettinger, S. Lux, A. Philipsen, Helge Müller, Jan Brauner

Journal: BMC Medicine

Journal ranking: Q1

Key takeaways: Creatine supplementation may have a small beneficial effect on cognitive performance, but larger studies are needed to confirm or rule out this effect.

Abstract: Abstract Background Creatine is an organic compound that facilitates the recycling of energy-providing adenosine triphosphate (ATP) in muscle and brain tissue. It is a safe, well-studied supplement for strength training. Previous studies have shown that supplementation increases brain creatine levels, which might increase cognitive performance. The results of studies that have tested cognitive performance differ greatly, possibly due to different populations, supplementation regimens, and cognitive tasks. This is the largest study on the effect of creatine supplementation on cognitive performance to date. Methods Our trial was preregistered, cross-over, double-blind, placebo-controlled, and randomised, with daily supplementation of 5 g for 6 weeks each. We tested participants on Raven’s Advanced Progressive Matrices (RAPM) and on the Backward Digit Span (BDS). In addition, we included eight exploratory cognitive tests. About half of our 123 participants were vegetarians and half were omnivores. Results Bayesian evidence supported a small beneficial effect of creatine. The creatine effect bordered significance for BDS ( p = 0.064, η 2 P = 0.029) but not RAPM ( p = 0.327, η 2 P = 0.008). There was no indication that creatine improved the performance of our exploratory cognitive tasks. Side effects were reported significantly more often for creatine than for placebo supplementation ( p = 0.002, RR = 4.25). Vegetarians did not benefit more from creatine than omnivores. Conclusions Our study, in combination with the literature, implies that creatine might have a small beneficial effect. Larger studies are needed to confirm or rule out this effect. Given the safety and broad availability of creatine, this is well worth investigating; a small effect could have large benefits when scaled over time and over many people. Trial registration The trial was prospectively registered (drks.de identifier: DRKS00017250, https://osf.io/xpwkc/ ).

Creatine supplementation with specific view to exercise/sports performance: an update

Type of study:

Number of citations: 271

Year: 2012

Authors: R. Cooper, F. Naclerio, J. Allgrove, A. Jiménez

Journal: Journal of the International Society of Sports Nutrition

Journal ranking: Q1

Key takeaways: Creatine supplementation increases strength, fat-free mass, and muscle morphology when combined with heavy resistance training, but its effects diminish as exercise duration increases.

Abstract: Creatine is one of the most popular and widely researched natural supplements. The majority of studies have focused on the effects of creatine monohydrate on performance and health; however, many other forms of creatine exist and are commercially available in the sports nutrition/supplement market. Regardless of the form, supplementation with creatine has regularly shown to increase strength, fat free mass, and muscle morphology with concurrent heavy resistance training more than resistance training alone. Creatine may be of benefit in other modes of exercise such as high-intensity sprints or endurance training. However, it appears that the effects of creatine diminish as the length of time spent exercising increases. Even though not all individuals respond similarly to creatine supplementation, it is generally accepted that its supplementation increases creatine storage and promotes a faster regeneration of adenosine triphosphate between high intensity exercises. These improved outcomes will increase performance and promote greater training adaptations. More recent research suggests that creatine supplementation in amounts of 0.1 g/kg of body weight combined with resistance training improves training adaptations at a cellular and sub-cellular level. Finally, although presently ingesting creatine as an oral supplement is considered safe and ethical, the perception of safety cannot be guaranteed, especially when administered for long period of time to different populations (athletes, sedentary, patient, active, young or elderly).

The Potential Role of Creatine in Vascular Health

Type of study: literature review

Number of citations: 29

Year: 2021

Authors: H. Clarke, R. Hickner, M. Ormsbee

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Creatine supplementation may serve as an adjuvant therapy for managing vascular health in at-risk populations by exhibiting antioxidant and anti-inflammatory effects.

Abstract: Creatine is an organic compound, consumed exogenously in the diet and synthesized endogenously via an intricate inter-organ process. Functioning in conjunction with creatine kinase, creatine has long been known for its pivotal role in cellular energy provision and energy shuttling. In addition to the abundance of evidence supporting the ergogenic benefits of creatine supplementation, recent evidence suggests a far broader application for creatine within various myopathies, neurodegenerative diseases, and other pathologies. Furthermore, creatine has been found to exhibit non-energy related properties, contributing as a possible direct and in-direct antioxidant and eliciting anti-inflammatory effects. In spite of the new clinical success of supplemental creatine, there is little scientific insight into the potential effects of creatine on cardiovascular disease (CVD), the leading cause of mortality. Taking into consideration the non-energy related actions of creatine, highlighted in this review, it can be speculated that creatine supplementation may serve as an adjuvant therapy for the management of vascular health in at-risk populations. This review, therefore, not only aims to summarize the current literature surrounding creatine and vascular health, but to also shed light onto the potential mechanisms in which creatine may be able to serve as a beneficial supplement capable of imparting vascular-protective properties and promoting vascular health.

The potential therapeutic effects of creatine supplementation on body composition and muscle function in cancer.

Type of study:

Number of citations: 34

Year: 2019

Authors: C. Fairman, K. Kendall, N. Hart, D. Taaffe, D. Galvão, Robert U. Newton

Journal: Critical reviews in oncology/hematology

Journal ranking: Q1

Key takeaways: Creatine supplementation shows potential therapeutic effects on lean body mass, strength, and physical function in individuals with cancer at heightened risk for muscle loss.

Benefits of Creatine Supplementation for Vegetarians Compared to Omnivorous Athletes: A Systematic Review

Type of study: systematic review

Number of citations: 60

Year: 2020

Authors: M. Kaviani, Keely A. Shaw, P. Chilibeck

Journal: International Journal of Environmental Research and Public Health

Journal ranking: Q2

Key takeaways: Creatine supplementation benefits vegetarian athletes by increasing muscle strength, endurance, and brain function, but its impact on exercise performance remains mixed.

Abstract: Background: Creatine monohydrate is a nutritional supplement often consumed by athletes in anaerobic sports. Creatine is naturally found in most meat products; therefore, vegetarians have reduced creatine stores and may benefit from supplementation. Objective: to determine the effects of creatine supplementation on vegetarians. Data sources: PubMed and SPORTDiscus. Eligibility criteria: Randomized controlled trials (parallel group, cross-over studies) or prospective studies. Participants: Vegetarians. Intervention: Creatine supplementation. Study appraisal and synthesis: A total of 64 records were identified, and eleven full-text articles (covering nine studies) were included in this systematic review. Results: Creatine supplementation in vegetarians increased total creatine, creatine, and phosphocreatine concentrations in vastus lateralis and gastrocnemius muscle, plasma, and red blood cells, often to levels greater than omnivores. Creatine supplementation had no effect on brain levels of phosphocreatine. Creatine supplementation increased lean tissue mass, type II fiber area, insulin-like growth factor-1, muscular strength, muscular endurance, Wingate mean power output, and brain function (memory and intelligence) in vegetarian participants. Studies were mixed on whether creatine supplementation improved exercise performance in vegetarians to a greater extent compared to omnivores. Limitations: Studies that were reviewed had moderate–high risk of bias. Conclusions: Overall, it appears vegetarian athletes are likely to benefit from creatine supplementation.

Can Creatine Supplementation Interfere with Muscle Strength and Fatigue in Brazilian National Level Paralympic Powerlifting?

Type of study: rct

Number of citations: 29

Year: 2020

Authors: Carlos Rodrigo Soares Freitas Sampaio, F. Aidar, A. P. Ferreira, J. L. Santos, A. C. Marçal, D. Matos, R. F. Souza, O. C. Moreira, Ialuska Guerra, J. Fernandes Filho, L. Marcucci-Barbosa, Albená Nunes-Silva, P. Almeida-Neto, Breno G. Cabral, V. Reis

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Creatine supplementation reduces fatigue index in Paralympic powerlifting athletes without affecting muscle force and peak torque levels.

Abstract: The aim of the present study was to analyze the effect of creatine (Cr) supplementation on peak torque (PT) and fatigue rate in Paralympic weightlifting athletes. Eight Paralympic powerlifting athletes participated in the study, with 25.40 ± 3.30 years and 70.30 ± 12.15 kg. The measurements of muscle strength, fatigue index (FI), peak torque (PT), force (kgf), force (N), rate of force development (RFD), and time to maximum isometric force (time) were determined by a Musclelab load cell. The study was performed in a single-blind manner, with subjects conducting the experiments first with placebo supplementation and then, following a 7-day washout period, beginning the same protocol with creatine supplementation for 7 days. This sequence was chosen because of the lengthy washout of creatine. Regarding the comparison between conditions, Cr supplementation did not show effects on the variables of muscle force, peak torque, RFD, and time to maximum isometric force (p > 0.05). However, when comparing the results of the moments with the use of Cr and placebo, a difference was observed for the FI after seven days (U3: 1.12; 95% CI: (0.03, 2.27); p = 0.02); therefore, the FI was higher for placebo. Creatine supplementation has a positive effect on the performance of Paralympic powerlifting athletes, reducing fatigue index, and keeping the force levels as well as PT.

“Heads Up” for Creatine Supplementation and its Potential Applications for Brain Health and Function

Type of study: literature review

Number of citations: 28

Year: 2023

Authors: D. Candow, Scott C. Forbes, S. Ostojić, K. Prokopidis, M. Stock, K. K. Harmon, P. Faulkner

Journal: Sports Medicine (Auckland, N.z.)

Journal ranking: Q1

Key takeaways: Creatine supplementation shows potential benefits for brain health and function, particularly in aging adults and during metabolic stress, but sex and age-related differences remain unclear.

Abstract: There is emerging interest regarding the potential beneficial effects of creatine supplementation on indices of brain health and function. Creatine supplementation can increase brain creatine stores, which may help explain some of the positive effects on measures of cognition and memory, especially in aging adults or during times of metabolic stress (i.e., sleep deprivation). Furthermore, creatine has shown promise for improving health outcome measures associated with muscular dystrophy, traumatic brain injury (including concussions in children), depression, and anxiety. However, whether any sex- or age-related differences exist in regard to creatine and indices of brain health and function is relatively unknown. The purpose of this narrative review is to: (1) provide an up-to-date summary and discussion of the current body of research focusing on creatine and indices of brain health and function and (2) discuss possible sex- and age-related differences in response to creatine supplementation on brain bioenergetics, measures of brain health and function, and neurological diseases.

The Effect of Creatine Supplementation on Resistance Training–Based Changes to Body Composition: A Systematic Review and Meta-analysis

Type of study: meta-analysis

Number of citations: 3

Year: 2024

Authors: Imtiaz Desai, M. Wewege, Matthew D. Jones, Briana K. Clifford, Anurag Pandit, N. Kaakoush, David Simar, Amanda D. Hagstrom

Journal: Journal of Strength and Conditioning Research

Journal ranking: Q1

Key takeaways: Creatine supplementation increases lean body mass by 1.14 kg and reduces body fat percentage by 0.88% and 0.73 kg more than resistance training alone, with no significant differences between training status or carbohydrate subgroups.

Abstract: Supplemental Digital Content is Available in the Text. Abstract Desai, I, Wewege, MA, Jones, MD, Clifford, BK, Pandit, A, Kaakoush, NO, Simar, D, and Hagstrom, AD. The effect of creatine supplementation on resistance training-based changes to body composition: A systematic review and meta-analysis. J Strength Cond Res 38(10): 1813–1821, 2024—The purpose of this review was to determine the added effect of creatine supplementation on changes in body composition with resistance training in adults younger than 50 years. The review protocol was preregistered on the Open Science Framework (osf.io/x48a6/). Our primary outcome was lean body mass (LBM); secondary outcomes were body fat percentage (%) and body fat mass (kg). We performed a random-effects meta-analysis in R using the metafor package. Subgroup analyses were conducted to examine the effects of training status and use of a carbohydrate drink with creatine. We conducted a meta-regression to examine the moderating effect of total training volume. Statistical significance was set at p < 0.05. One thousand six hundred ninety-four records were screened, and 67 full-text articles were assessed for eligibility. Twelve studies were included in the meta-analysis. Fifty-two percentages of the studies had low risk, 41% some concerns, and 7% high risk of bias. Compared with resistance training (RT) alone, creatine supplementation increased LBM by 1.14 kg (95% CI 0.69 to 1.59), and reduced body fat percentage by −0.88% (95% CI −1.66 to −0.11) and body fat mass by −0.73 kg (95% CI −1.34 to −0.11). There were no differences between training status or carbohydrate subgroups. Training volume was not associated with effect size in all outcomes; 7 g or 0.3 g/kg of body mass of creatine per day is likely to increase LBM by 1 kg and reduce fat mass by 0.7 kg more than RT alone. Concurrent carbohydrate ingestion did not enhance the hypertrophy benefits of creatine.

The Effect of Creatine Supplementation on Lean Body Mass with and Without Resistance Training

Type of study: rct

Number of citations: 0

Year: 2025

Authors: Imtiaz Desai, Anurag Pandit, A. Smith‐Ryan, David Simar, D. Candow, N. Kaakoush, Amanda D. Hagstrom

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Creatine supplementation alone increased lean body mass after a 7-day wash-in, but did not enhance lean body mass growth when combined with resistance training.

Abstract: Background/Objectives: Creatine monohydrate (CrM) is considered to be one of the most effective supplements for enhancing lean body mass during resistance training. However, CrM may influence body water content, potentially confounding lean body mass measurements. Therefore, this randomised controlled trial assessed the effect of CrM alone on lean body mass following a supplement wash-in, and when combined with a resistance training program. Methods: Sixty-three (34 females, 29 males, 31 ± 8 years) participants were randomised to supplement with CrM (5 g/day for 13 weeks: wash-in + 12-week resistance training) or serve as a control (received no creatine or placebo). Lean body mass was measured using dual X-ray absorptiometry at baseline, post 7-day wash-in, and post 12 weeks of resistance training. Both groups began the same training program post CrM wash-in. Results: After the 7-day wash-in, the supplement group gained 0.51 ± 1.79 kg more lean body mass than the control group (p = 0.03). Following the wash-in, both groups gained 2 kg after resistance training (p < 0.0001), with no between-group difference in lean body mass growth (p = 0.71). Sex-disaggregated analysis showed that the supplement group, only in females, gained 0.59 ± 1.61 kg more lean body mass than the controls (p = 0.04). There were no group differences in lean body mass growth following resistance training in females (p = 0.10) or males (p = 0.35). Conclusions: A 7-day CrM wash-in increased lean body mass, particularly in females. Thereafter, CrM did not enhance lean body mass growth when combined with resistance training, likely due to its short-term effects on lean body mass measurements. A maintenance dose of higher than 5 g/day may be necessary to augment lean body mass growth.

Effect of Creatine Supplementation on Body Composition and Malnutrition-Inflammation Score in Hemodialysis Patients: An Exploratory 1-Year, Balanced, Double-Blind Design

Type of study: rct

Number of citations: 4

Year: 2024

Authors: Ana C B Marini, R. Schincaglia, D. Candow, Gustavo D. Pimentel

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Creatine supplementation in hemodialysis patients does not reduce malnutrition-inflammation scores but enhances fat-free mass and skeletal muscle mass index, likely due to increased intracellular water.

Abstract: Hemodialysis has a detrimental effect on fat-free mass (FFM) and muscle strength over time. Thus, we aimed to evaluate the effect of creatine supplementation on the body composition and Malnutrition-Inflammation Score (MIS) in patients with chronic kidney disease (CKD) undergoing hemodialysis. An exploratory 1-year balanced, placebo-controlled, and double-blind design was conducted with hemodialysis patients (≥18 years). The creatine group (CG) received 5 g of creatine monohydrate and 5 g of maltodextrin per day and the placebo group (PG) received 10 g of maltodextrin per day. MIS and body composition were analyzed at three time points: pre, intermediate (after 6 months), and post (after 12 months). After 6 months, 60% of patients on creatine experienced an increase in FFM compared to a 36.8% increase for those on placebo. Moreover, 65% of patients on creatine increased their skeletal muscle mass index (SMMI) compared to only 15.8% for those on placebo. Creatine increased intracellular water (ICW) in 60% of patients. MIS did not change after the intervention. In the CG, there was an increase in body weight (p = 0.018), FFM (p = 0.010), SMMI (p = 0.022). CG also increased total body water (pre 35.4 L, post 36.1 L; p = 0.008), mainly due to ICW (pre 20.2 L, intermediate 20.7 L, post 21.0 L; p = 0.016). Long-term creatine supplementation in hemodialysis patients did not attenuate the MIS, but enhanced FFM and SMMI, which was likely triggered by an increase in ICW.

Effects of creatine supplementation on body composition, strength, and sprint performance.

Type of study: rct

Number of citations: 456

Year: 1998

Authors: R. Kreider, Maria Pontes Ferreira, M. Wilson, P. Grindstaff, S. Plisk, J. Reinardy, E. Cantler, A. Almada

Journal: Medicine and science in sports and exercise

Journal ranking: Q1

Key takeaways: Creatine supplementation during intense resistance/agility training promotes greater gains in fat/bone-free mass, isotonic lifting volume, and sprint performance.

Abstract: PURPOSE To determine the effects of 28 d of creatine supplementation during training on body composition, strength, sprint performance, and hematological profiles. METHODS In a double-blind and randomized manner, 25 NCAA division IA football players were matched-paired and assigned to supplement their diet for 28 d during resistance/agility training (8 h x wk[-1]) with a Phosphagen HP (Experimental and Applied Sciences, Golden, CO) placebo (P) containing 99 g x d(-1) of glucose, 3 g x d(-1) of taurine, 1.1 g x d(-1) of disodium phosphate, and 1.2 g x d(-1) of potassium phosphate (P) or Phosphagen HP containing the P with 15.75 g x d(-1) of HPCE pure creatine monohydrate (HP). Before and after supplementation, fasting blood samples were obtained; total body weight, total body water, and body composition were determined; subjects performed a maximal repetition test on the isotonic bench press, squat, and power clean; and subjects performed a cycle ergometer sprint test (12 x 6-s sprints with 30-s rest recovery). RESULTS Hematological parameters remained within normal clinical limits for active individuals with no side effects reported. Total body weight significantly increased (P < 0.05) in the HP group (P 0.85 +/- 2.2; HP 2.42 +/- 1.4 kg) while no differences were observed in the percentage of total body water. DEXA scanned body mass (P 0.77 +/- 1.8; HP 2.22 +/- 1.5 kg) and fat/bone-free mass (P 1.33 +/- 1.1; HP 2.43 +/- 1.4 kg) were significantly increased in the HP group. Gains in bench press lifting volume (P -5 +/- 134; HP 225 +/- 246 kg), the sum of bench press, squat, and power clean lifting volume (P 1,105 +/- 429; HP 1,558 +/- 645 kg), and total work performed during the first five 6-s sprints was significantly greater in the HP group. CONCLUSION The addition of creatine to the glucose/taurine/electrolyte supplement promoted greater gains in fat/bone-free mass, isotonic lifting volume, and sprint performance during intense resistance/agility training.

Effects of oral creatine supplementation on muscular strength and body composition.

Type of study: rct

Number of citations: 171

Year: 2000

Authors: M. D. Becque, J. Lochmann, D. Melrose

Journal: Medicine and science in sports and exercise

Journal ranking: Q1

Key takeaways: Oral creatine supplementation during arm flexor strength training leads to greater increases in muscular strength, upper arm muscle area, and fat-free mass compared to strength training alone.

Abstract: PURPOSE The purpose of this investigation was to examine the effects of 6 wk of oral creatine supplementation during a periodized program of arm flexor strength training on arm flexor IRM, upper arm muscle area, and body composition. METHODS Twenty-three male volunteers with at least 1 yr of weight training experience were assigned in a double blind fashion to two groups (Cr, N = 10; Placebo, N = 13) with no significant mean pretest one repetition maximum (IRM) differences in arm flexor strength. Cr ingested 5 g of creatine monohydrate in a flavored, sucrose drink four times per day for 5 d. After 5 d, supplementation was reduced to 2 g x d(-1). Placebo ingested a flavored, sucrose drink. Both drinks were 500 mL and made with 32 g of sucrose. IRM strength of the arm flexors, body composition, and anthropometric upper arm muscle area (UAMA) were measured before and after a 6-wk resistance training program. Subjects trained twice per week with training loads that began at 6RM and progressed to 2RM. RESULTS IRM for Cr increased (P < 0.01) from (mean +/- SD) 42.8 +/- 17.7 kg to 54.7 +/- 14.1 kg, while IRM for Placebo increased (P < 0.01) from 42.5 +/- 15.9 kg to 49.3 +/- 15.7 kg. At post-test IRM was significantly (P < 0.01) greater for Cr than for Placebo. Body mass for Cr increased (P < 0.01) from 86.7 +/- 14.7 kg to 88.7 +/- 13.8 kg. Fat-free mass for Cr increased (P < 0.01) from 71.2 +/- 10.0 kg to 72.8 +/- 10.1 kg. No changes in body mass or fat-free mass were found for Placebo. There were no changes in fat mass and percent body fat for either group. UAMA increased (P < 0.01) 7.9 cm2 for Cr and did not change for Placebo. CONCLUSION Creatine supplementation during arm flexor strength training lead to greater increases in arm flexor muscular strength, upper arm muscle area, and fat-free mass than strength training alone.

Creatine Enhances the Effects of Cluster-Set Resistance Training on Lower-Limb Body Composition and Strength in Resistance-Trained Men: A Pilot Study

Type of study: rct

Number of citations: 18

Year: 2021

Authors: D. Bonilla, R. Kreider, J. Petro, R. Romance, Manuel García-Sillero, J. Benítez-Porres, S. Vargas-Molina

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Creatine supplementation combined with cluster-set resistance training and a high-protein diet significantly improves lower-limb body composition and strength in resistance-trained men.

Abstract: Creatine monohydrate (CrM) supplementation has been shown to improve body composition and muscle strength when combined with resistance training (RT); however, no study has evaluated the combination of this nutritional strategy with cluster-set resistance training (CS-RT). The purpose of this pilot study was to evaluate the effects of CrM supplementation during a high-protein diet and a CS-RT program on lower-limb fat-free mass (LL-FFM) and muscular strength. Twenty-three resistance-trained men (>2 years of training experience, 26.6 ± 8.1 years, 176.3 ± 6.8 cm, 75.6 ± 8.9 kg) participated in this study. Subjects were randomly allocated to a CS-RT+CrM (n = 8), a CS-RT (n = 8), or a control group (n = 7). The CS-RT+CrM group followed a CrM supplementation protocol with 0.1 g·kg−1·day−1 over eight weeks. Two sessions per week of lower-limb CS-RT were performed. LL-FFM corrected for fat-free adipose tissue (dual-energy X-ray absorptiometry) and muscle strength (back squat 1 repetition maximum (SQ-1RM) and countermovement jump (CMJ)) were measured pre- and post-intervention. Significant improvements were found in whole-body fat mass, fat percentage, LL-fat mass, LL-FFM, and SQ-1RM in the CS-RT+CrM and CS-RT groups; however, larger effect sizes were obtained in the CS-RT+CrM group regarding whole body FFM (0.64 versus 0.16), lower-limb FFM (0.62 versus 0.18), and SQ-1RM (1.23 versus 0.75) when compared to the CS-RT group. CMJ showed a significant improvement in the CS-RT+CrM group with no significant changes in CS-RT or control groups. No significant differences were found between groups. Eight weeks of CrM supplementation plus a high-protein diet during a CS-RT program has a higher clinical meaningfulness on lower-limb body composition and strength-related variables in trained males than CS-RT alone. Further research might study the potential health and therapeutic effects of this nutrition and exercise strategy.

Effect of creatine supplementation on body composition and performance: a meta-analysis.

Type of study: meta-analysis

Number of citations: 298

Year: 2003

Authors: J. David Branch

Journal: International journal of sport nutrition and exercise metabolism

Journal ranking: Q2

Key takeaways: Creatine supplementation effectively increases lean body mass and performance in short-term, repetitive-bout, laboratory-based exercises, but not in running or swimming.

Abstract: BACKGROUND Creatine supplementation (CS) has been reported to increase body mass and improve performance in high-intensity, short-duration exercise tasks. Research on CS, most of which has come into existence since 1994, has been the focus of several qualitative reviews, but only one meta-analysis, which was conducted with a limited number of studies. PURPOSE This study compared the effects of CS on effect size (ES) for body composition (BC) variables (mass and lean body mass), duration and intensity (< or = 30 s, [ATP-PCr = A]; 30-150 s [glycolysis = G]; >150 s, [oxidative phosphorylation = O]) of the exercise task, type of exercise task (single, repetitive, laboratory, field, upper-body, lower-body), CS duration (loading, maintenance), and subject characteristics (gender, training status). METHODS A search of MEDLINE and SPORTDiscus using the phrase "creatine supplementation" revealed 96 English-language, peer-reviewed papers (100 studies), which included randomized group formation, a placebo control, and human subjects who were blinded to treatments. ES was calculated for each body composition and performance variable. RESULTS Small, but significant (ES > 0, p < or = .05) ES were reported for BC (n=163, mean +/- SE=0.17 +/- 0.03), ATP-PCr (n=17, 0.24 +/- 0.02), G (n=135, 0.19 +/- 0.05), and O (n=69, 0.20 +/- 0.07). ES was greater for change in BC following a loading-only CS regimen (0.26 +/- 0.03, p=.0003) compared to a maintenance regimen (0.04 +/- 0.05), for repetitive-bout (0.25 +/- 0.03,p=.028) compared to single-bout (0.18 +/- 0.02) exercise, and for upper-body exercise (0.42 +/- 0.07, p<.0001) compared to lower (0.21 +/- 0.02) and total body (0.13 +/- 0.04) exercise. ES for laboratory-based tasks (e.g., isometric/isotonic/isokinetic exercise, 0.25 +/- 0.02) were greater (p=.014) than those observed for field-based tasks (e.g., running, swimming, 0.14 +/- 0.04). There were no differences in BC or performance ES between males and females or between trained and untrained subjects. CONCLUSION ES was greater for changes in lean body mass following short-term CS, repetitive-bout laboratory-based exercise tasks < or = 30 s (e.g., isometric, isokinetic, and isotonic resistance exercise), and upper-body exercise. CS does not appear to be effective in improving running and swimming performance. There is no evidence in the literature of an effect of gender or training status on ES following CS.

Creatine supplementation enhances isometric strength and body composition improvements following strength exercise training in older adults.

Type of study: rct

Number of citations: 264

Year: 2003

Authors: A. Brose, G. Parise, M. Tarnopolsky

Journal: The journals of gerontology. Series A, Biological sciences and medical sciences

Journal ranking: Q1

Key takeaways: Creatine supplementation during resistance exercise training in older adults enhances increases in strength, fat-free mass, and muscle strength without significant side effects.

Abstract: We sought to determine whether creatine monohydrate (CrM) supplementation would enhance the increases in strength and fat-free mass that develop during resistance exercise training in older adults. Twenty-eight healthy men and women over the age of 65 years participated in a whole-body resistance exercise program 3 days per week for 14 weeks. The study participants were randomly allocated, in a double-blind fashion, to receive either CrM (5 g/d + 2 g of dextrose; n = 14) or placebo (7 g of dextrose; n = 14). The primary outcome measurements included the following: total body mass, fat-free mass, one-repetition maximum strength for each body part, isometric knee extension, handgrip, and dorsiflexion strength, chair stand performance, 30-m walk test, 14-stair climb performance, muscle fiber type and area, and intramuscular total creatine. Fourteen weeks of resistance exercise training resulted in significant increases in all measurements of strength and functional tasks and muscle fiber area for both groups (p <.05). CrM supplementation resulted in significantly greater increases in fat-free mass and total body mass, as compared with placebo (p <.05). The CrM group also showed a greater increase in isometric knee extension strength in men and women, as compared with placebo (p <.05), and also greater gains in isometric dorsiflexion strength (p <.05), but in men only. There was a significant increase in intramuscular total creatine in the CrM group (p <.05). Finally, there were no significant side effects of treatment or exercise training. This study confirms that supervised heavy resistance exercise training can safely increase muscle strength and functional capacity in older adults. The addition of CrM supplementation to the exercise stimulus enhanced the increase in total and fat-free mass, and gains in several indices of isometric muscle strength.

Body composition measured by multi-frequency bioelectrical impedance following creatine supplementation.

Type of study:

Number of citations: 3

Year: 2023

Authors: Emily A Buck, Michael J Saunders, Elizabeth S Edwards, Christopher J Womack

Journal: The Journal of sports medicine and physical fitness

Journal ranking: Q2

Key takeaways: Creatine supplementation increases total body water and fat-free mass, as detected by multi-frequency bioelectrical impedance, but does not affect fat-free mass.

Abstract: BACKGROUND Acute fluid ingestion increases estimated body fat percentage (BF%) measurements by single frequency (SF-BIA) and multi-frequency bioelectrical impedance (MF-BIA). It is unknown if MF-BIA accurately measures total BF% and total body water (TBW) after creatine supplementation, which causes fluid retention, and resultant increases in fat-free mass and TBW. The purpose of this study was to analyze the effect of creatine supplementation on body composition and TBW measured through a popular MF-BIA device (InBody 770). METHODS Thirteen male and 14 female subjects (18-22 years) completed one week of creatine monohydrate (0.3 g/kg body weight) or maltodextrin. Pre- and post-supplementation body composition measurements included dual-energy X-ray absorptiometry (DEXA), SF-BIA measured by an Omron HBF-306C device, and MF-BIA measured by an InBody 770 device to measure BF%, fat free mass (FFM), and fat mass (FM). Additionally, intracellular water (ICW), extracellular water (ECW), and TBW were estimated by MF- BIA. RESULTS FFM increased more in the creatine group than the placebo group measured by all body composition modes (1.2 kg, 1.9 kg, and 1.1 kg increase for SF-BIA, MF-BIA, and DEXA respectively, P<0.05). Creatine supplementation resulted in a 2% increase (P<0.05) in TBW measured by MF-BIA (40.4±9.5 to 41.2±9.6 kg). CONCLUSIONS One week of creatine supplementation increased TBW as detected by the InBody 770 device. Changes in body composition that occurred due to the increase in TBW were detected as an increase in FFM measured by SF-BIA, MF-BIA, and DEXA.

Effects of creatine monohydrate timing on resistance training adaptations and body composition after 8 weeks in male and female collegiate athletes

Type of study: rct

Number of citations: 2

Year: 2022

Authors: Nicholas E. Dinan, A. Hagele, Andrew R. Jagim, Michael G. Miller, C. Kerksick

Journal: Frontiers in Sports and Active Living

Journal ranking: Q1

Key takeaways: Creatine monohydrate supplementation before or after training does not significantly impact resistance training adaptations and body composition in male and female athletes.

Abstract: Background Limited research is available on the potential impact of creatine monohydrate administration before or after workouts among athletes. This study aimed to investigate the effects of pre- vs. post-exercise creatine monohydrate supplementation on resistance training adaptations and body composition. Methods In a randomized, double-blind, placebo-controlled, parallel design, 34 healthy resistance-trained male and female athletes were randomly assigned and matched according to fat free mass to consume a placebo, or 5-g dose of creatine monohydrate within 1 h before training, or within 1 h after training for 8 weeks, while completing a weekly resistance training program. Participants co-ingested 25-gram doses of both whey protein isolate and maltodextrin along with each assigned supplement dose. Body composition, muscular strength, and endurance, along with isometric mid-thigh pull were assessed before and after the 8-week supplementation period. A 3 × 2 mixed factorial (group x time) ANOVA with repeated measures on time were used to evaluate differences. Results All groups experienced similar and statistically significant increases in fat free mass (+1.34 ± 3.48 kg, p = 0.04), upper (+2.21 ± 5.69 kg, p = 0.04) and lower body strength (+7.32 ± 10.01 kg, p < 0.001), and decreases in body mass (−1.09 ± 2.71 kg, p = 0.03), fat mass (−2.64 ± 4.16 kg, p = 0.001), and percent body fat (−2.85 ± 4.39 kg, p < 0.001). Conclusions The timing of creatine monohydrate did not exert any additional influence over the measured outcomes.

Creatine Supplementation: Its Effect on Human Muscular Performance and Body Composition

Type of study:

Number of citations: 124

Year: 1996

Authors: J. Volek, W. Kraemer

Journal: Journal of Strength and Conditioning Research

Journal ranking: Q1

Key takeaways: Creatine monohydrate supplementation improves muscle performance and endurance during high-intensity exercise, potentially leading to increased body mass.

Abstract: The use of creatine (Cr) in its supplemental form, Cr monohydrate, has become rather widespread. The discovery that the Cr and phosphocreatine (PCr) content in human muscle can be increased by oral ingestion of supplemental Cr has led to numerous studies examining its benefits on exercise performance. Cr monohydrate supplementation appears to result in an increased ability to maintain power output during high-intensity exercise and increase the rate of PCr resynthesis during the recovery phase of intermittent high-intensity exercise. Subjects supplemented with Cr monohydrate demonstrate a reduction in the accumulation of plasma lactate, ammonia, and hypoxanthine, indicating an alteration in energy metabolism and an attenuation of ATP degradation. Thus, higher concentrations of Cr seem to enhance the muscle's ability to sustain the high ATP turnover rates encountered during strenuous exercise. Another potential benefit is an increase in body mass which results from the ingestion of Cr monohydrate; however, the composition of the weight gain remains undetermined. This article discusses the theoretical basis for Cr supplementation and reviews what is known about its effects on performance.

The Impact of Short-Term Supplementation With Guanidinoacetic Acid and Creatine Versus Creatine Alone on Body Composition Indices in Healthy Men and Women: Creatine-Guanidinoacetic Acid Affects Body Composition

Type of study: rct

Number of citations: 0

Year: 2024

Authors: Sonja Baltic, David Nedeljkovic, N. Todorović, L. Rátgéber, J. Betlehem, P. Ács, V. Štajer, Sergej M. Ostojic

Journal: Journal of Nutrition and Metabolism

Journal ranking: Q2

Key takeaways: Short-term supplementation with creatine and guanidinoacetic acid (GAA) improves extracellular mass in healthy men and women, but not in women.

Abstract: The main objective of this pilot study was to compare the effects of short-term supplementation with a mixture containing creatine and guanidinoacetic acid (GAA) versus creatine alone on body composition indices in men and women. Twenty-three apparently healthy young adults (mean age: 21.4 ± 0.6 years; 10 females) were randomly assigned to receive either a mixture (consisting of 2 g of creatine monohydrate and 2 g of GAA) or an equimolar amount of creatine monohydrate in a pretest–posttest control group experimental crossover design. After the intervention period, participants entered a 2-week washout phase to minimize any residual effects of the treatment. Body composition was assessed using a multifrequency bioelectrical impedance analysis at baseline (preadministration) and at the 7-day follow-up (postadministration). A significant interaction effect was found for extracellular mass (p=0.009), with creatine–GAA outperforming creatine in augmenting extracellular mass across the whole sample. In the male subsample, creatine was superior to the mixture in increasing intracellular water (p=0.049), whereas the mixture increased extracellular mass, contrasting with the reduction observed with creatine alone (p=0.008). No significant differences between interventions were reported in the female subsample (p > 0.05), indicating that adding GAA to creatine may produce unique, sex-specific effects on body composition. Further studies are needed to validate our findings across different demographic cohorts and various interventional regimens.

Influence of age, sex, and type of exercise on the efficacy of creatine supplementation on lean body mass: A systematic review and meta-analysis of randomized clinical trials.

Type of study: meta-analysis

Number of citations: 24

Year: 2022

Authors: F. M. Delpino, L. M. Figueiredo, Scott C. Forbes, D. Candow, Heitor O. Santos

Journal: Nutrition

Journal ranking: Q2

Key takeaways: Creatine supplementation combined with resistance training increases lean body mass, with males showing greater gains than females during the same program.

Beyond muscle: the effects of creatine supplementation on brain creatine, cognitive processing, and traumatic brain injury

Type of study: literature review

Number of citations: 110

Year: 2018

Authors: E. Dolan, B. Gualano, E. Rawson

Journal: European Journal of Sport Science

Journal ranking: Q1

Key takeaways: Creatine supplementation may increase brain creatine, potentially benefiting cognitive processes and reducing the severity of mild traumatic brain injury.

Abstract: Abstract The ergogenic and therapeutic effects of increasing muscle creatine by supplementation are well-recognized. It appears that similar benefits to brain function and cognitive processing may also be achieved with creatine supplementation, however research in this area is more limited, and important knowledge gaps remain. The purpose of this review is to provide a comprehensive overview of the current state of knowledge about the influence of creatine supplementation on brain function in healthy individuals. It appears that brain creatine is responsive to supplementation, however higher, or more prolonged dosing strategies than those typically used to increase muscle creatine, may be required to elicit an increase in brain creatine. The optimal dosing strategy to induce this response, is currently unknown, and there is an urgent need for studies investigating this. When considering the influence of supplementation strategies on cognitive processes, it appears that creatine is most likely to exert an influence in situations whereby cognitive processes are stressed, e.g. during sleep deprivation, experimental hypoxia, or during the performance of more complex, and thus more cognitively demanding tasks. Evidence exists indicating that increased brain creatine may be effective at reducing the severity of, or enhancing recovery from mild traumatic brain injury, however, only limited data in humans are available to verify this hypothesis, thus representing an exciting area for further research.

The effects of creatine supplementation on cognitive function in adults: a systematic review and meta-analysis

Type of study: meta-analysis

Number of citations: 8

Year: 2024

Authors: Chen Xu, Siyuan Bi, Wenxin Zhang, Lin Luo

Journal: Frontiers in Nutrition

Journal ranking: Q1

Key takeaways: Creatine monohydrate supplementation may improve memory, attention time, and information processing speed in adults, but its effects on overall cognitive function and executive function remain unclear.

Abstract: 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.

Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials

Type of study: systematic review

Number of citations: 89

Year: 2018

Authors: K. Avgerinos, N. Spyrou, K. Bougioukas, D. Kapogiannis

Journal: Experimental Gerontology

Journal ranking: Q1

Key takeaways: Oral creatine supplementation may improve short-term memory and intelligence in healthy individuals, but its effect on other cognitive domains remains unclear.

Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials

Type of study: meta-analysis

Number of citations: 29

Year: 2022

Authors: K. Prokopidis, P. Giannos, K. Triantafyllidis, K. Kechagias, Scott C. Forbes, D. Candow

Journal: Nutrition Reviews

Journal ranking: Q1

Key takeaways: Creatine supplementation improves memory performance in healthy individuals, particularly in older adults aged 66-76 years.

Abstract: Abstract Context From an energy perspective, the brain is very metabolically demanding. It is well documented that creatine plays a key role in brain bioenergetics. There is some evidence that creatine supplementation can augment brain creatine stores, which could increase memory. Objective A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to determine the effects of creatine supplementation on memory performance in healthy humans. Data Sources The literature was searched through the PubMed, Web of Science, Cochrane Library, and Scopus databases from inception until September 2021. Data Extraction Twenty-three eligible RCTs were initially identified. Ten RCTs examining the effect of creatine supplementation compared with placebo on measures of memory in healthy individuals met the inclusion criteria for systematic review, 8 of which were included in the meta-analysis. Data Analysis Overall, creatine supplementation improved measures of memory compared with placebo (standard mean difference [SMD] = 0.29, 95%CI, 0.04–0.53; I2 = 66%; P = 0.02). Subgroup analyses revealed a significant improvement in memory in older adults (66–76 years) (SMD = 0.88; 95%CI, 0.22–1.55; I2 = 83%; P = 0.009) compared with their younger counterparts (11–31 years) (SMD = 0.03; 95%CI, −0.14 to 0.20; I2 = 0%; P = 0.72). Creatine dose (≈ 2.2–20 g/d), duration of intervention (5 days to 24 weeks), sex, or geographical origin did not influence the findings. Conclusion Creatine supplementation enhanced measures of memory performance in healthy individuals, especially in older adults (66–76 years). Systematic Review Registration PROSPERO registration no. 42021281027.

The effects and benefits of creatine supplementation on brain health

Type of study: systematic review

Number of citations: 0

Year: 2024

Authors: Elena Sztemberg, Dominik Łepecki, Bartłomiej Grodziński, Robert Tomaszewski, Marcin Mikusek-Pham Van, Karolina Krawiel, Marta Kras, Marek Król, Aleksandra Cieślik, Hanna Gruszczyńska

Journal: Quality in Sport

Journal ranking: brak

Key takeaways: Creatine supplementation may improve brain health and manage neurological diseases, offering benefits such as memory enhancement, depression relief, and neuroprotection.

Abstract: 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.

Creatine Activity as a Neuromodulator in the Central Nervous System.

Type of study: systematic review

Number of citations: 7

Year: 2023

Authors: G. Meftahi, B. Hatef, G. Pirzad Jahromi

Journal: Archives of Razi Institute

Journal ranking: Q2

Key takeaways: Creatine supplementation may improve cognitive health and performance by acting as a neuromodulator in the central nervous system, potentially reducing neuronal cell loss in neurological diseases.

Abstract: Creatine is a nutritional compound that potentially influences cognitive processing and neuroprotection. Recent evidence has demonstrated that similar to neurotransmitters, creatine is released in an excitotoxic and action potential-dependent manner and acts as a neuromodulator. Creatine deficiency syndromes are characterized by severe mental and developmental disorders. Studies have reported that brain creatine content could be enhanced with creatine supplementation. Nevertheless, there is still limited knowledge about the effects of creatine on the central nervous system. However, ample evidence has proved the neuroprotective effects of creatine on various mental aspects, such as cognition, memory skills, and spatial memory. The present review aimed to review available experimental data and clinical observations confirming creatine roles in the central transmission process. A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, and Google Scholar database using all available MeSH terms for Creatine, Phosphocreatine, Bioenergetics, Nervous system, Brain, Cognition, and Neuroprotection. Electronic database searches were combined and duplicates were removed. Here, first, creatine and its potential influence on cognitive health and performance were briefly reviewed. Next, the existing experimental and clinical evidence was specifically explored to understand how creatine could interact as a neurotransmitter in the nervous system. Studies have revealed that exogenous creatine supplementation decreases neuronal cell loss in experimental paradigms of neurological diseases. It was observed that creatine could interact with the N-methyl-D-aspartate receptor, Na+-K+-ATPase enzyme, GABAA receptor, serotonin 1A receptors, and presumably α1-adrenoceptor and play critical roles in the central transmission process which implies that creatine can be considered a neuromodulator.

Creatine as a booster for human brain function. How might it work?

Type of study:

Number of citations: 85

Year: 2015

Authors: C. Rae, S. Bröer

Journal: Neurochemistry International

Journal ranking: Q2

Key takeaways: Creatine plays key roles in the brain by buffering energy supply, improving mitochondrial efficiency, acting as an anti-oxidant, and acting as a neuroprotectant, but its clinical use remains in early stages.

Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation

Type of study: non-rct experimental

Number of citations: 18

Year: 2024

Authors: A. Gordji-Nejad, A. Matusch, Sophie Kleedörfer, Harshal Jayeshkumar Patel, Alexander Drzezga, D. Elmenhorst, Ferdinand Binkofski, Andreas Bauer

Journal: Scientific Reports

Journal ranking: Q1

Key takeaways: Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation, suggesting its potential as a long-term sleep aid.

Creatine supplementation research fails to support the theoretical basis for an effect on cognition: Evidence from a systematic review

Type of study: systematic review

Number of citations: 1

Year: 2024

Authors: T. McMorris, Beverley J Hale, Beatrice S. Pine, Thomas B. Williams

Journal: Behavioural Brain Research

Journal ranking: Q2

Key takeaways: Creatine supplementation can increase brain creatine content, but its effects on cognition remain equivocal.

Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation

Type of study: rct

Number of citations: 170

Year: 2002

Authors: Airi Watanabe, N. Kato, Tadafumi Kato

Journal: Neuroscience Research

Journal ranking: Q2

Key takeaways: Creatine supplementation reduces mental fatigue and increases oxygen utilization in the brain, potentially improving performance in high-intensity tasks.

The Potential and Challenges of Creatine Supplementation for Cognition/Memory in Older Adults

Type of study: systematic review

Number of citations: 3

Year: 2023

Authors: M. Machado, R. Pereira

Journal: European Journal of Geriatrics and Gerontology

Journal ranking: Q4

Key takeaways: Creatine supplementation may help mitigate the neural effects of aging, but stronger evidence is needed to confirm its relationship with cognitive decline in older adults.

Abstract: 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.

Effect of age, diet, and tissue type on PCr response to creatine supplementation.

Type of study: rct

Number of citations: 45

Year: 2017

Authors: M. Solis, G. Artioli, M. Otaduy, C. Leite, W. Arruda, Raquel Ramos Veiga, B. Gualano

Journal: Journal of applied physiology

Journal ranking: Q1

Key takeaways: Creatine supplementation increases muscle phosphorylcreatine in all age groups and vegetarians, but not in omnivores, and does not affect brain phosphorylcreatine levels.

Abstract: Creatine/phosphorylcreatine (PCr) responses to creatine supplementation may be modulated by age, diet, and tissue, but studies assessing this possibility are lacking. Therefore we aimed to determine whether PCr responses vary as a function of age, diet, and tissue. Fifteen children, 17 omnivorous and 14 vegetarian adults, and 18 elderly individuals ("elderly") participated in this study. Participants were given placebo and subsequently creatine (0.3 g·kg-1·day-1) for 7 days in a single-blind fashion. PCr was measured through phosphorus magnetic resonance spectroscopy (31P-MRS) in muscle and brain. Creatine supplementation increased muscle PCr in children (P < 0.0003) and elderly (P < 0.001), whereas the increase in omnivores did not reach statistically significant difference (P = 0.3348). Elderly had greater PCr increases than children and omnivores (P < 0.0001 for both), whereas children experienced greater PCr increases than omnivores (P = 0.0022). In relation to diet, vegetarians (P < 0.0001), but not omnivores, had significant increases in muscle PCr content. Brain PCr content was not affected by creatine supplementation in any group, and delta changes in brain PCr (-0.7 to +3.9%) were inferior to those in muscle PCr content (+10.3 to +27.6%; P < 0.0001 for all comparisons). PCr responses to a standardized creatine protocol (0.3 g·kg-1·day-1 for 7 days) may be affected by age, diet, and tissue. Whereas creatine supplementation was able to increase muscle PCr in all groups, although to different extents, brain PCr was shown to be unresponsive overall. These findings demonstrate the need to tailor creatine protocols to optimize creatine/PCr accumulation both in muscle and in brain, enabling a better appreciation of the pleiotropic properties of creatine.NEW & NOTEWORTHY A standardized creatine supplementation protocol (0.3 g·kg-1·day-1 for 7 days) effectively increased muscle, but not brain, phosphorylcreatine. Older participants responded better than younger participants whereas vegetarians responded better than omnivores. Responses to supplementation are thus dependent on age, tissue, and diet. This suggests that a single "universal" protocol, originally designed for increasing muscle creatine in young individuals, may lead to heterogeneous muscle responses in different populations or even no responses in tissues other than skeletal muscle.

Can Creatine Combat the Mental Fatigue-associated Decrease in Visuomotor Skills?

Type of study: rct

Number of citations: 55

Year: 2019

Authors: J. Van Cutsem, B. Roelands, Bert Pluym, Bruno Tassigno, J. Verschueren, K. De Pauw, R. Meeusen

Journal: Medicine & Science in Sports & Exercise

Journal ranking: Q1

Key takeaways: Creatine supplementation improved physical strength endurance and cognitive performance, but did not counteract mental fatigue-induced impairments in short sport-specific psychomotor or cognitive tasks.

Abstract: PURPOSE The importance of the brain in sports was recently confirmed by the negative effect of mental fatigue (MF) on sport-specific psychomotor skills. Creatine supplementation improves strength, but can also improve cognitive functioning. To explore the role of creatine in combatting MF, we evaluated whether creatine supplementation counteracts the MF-associated impairment in sport-specific psychomotor skills. METHODS In 23°C, 14 healthy participants (4F 10M; mean ± SD; age:24 ± 3 y; mass:74 ± 13 kg; height:179 ± 9 cm) performed -counterbalanced, crossover and double blinded- a 90-min mentally fatiguing task (i.e. Stroop task) in two different conditions: after a 7-day creatine supplementation (CR; 20 g/day) and after a 7-day calcium lactate supplementation (PLAC; placebo), separated by a 5-week washout. In both conditions, a 7-min sport-specific visuomotor task, a dynamic handgrip strength endurance task and a 3-min Flanker task was performed before and after the mentally fatiguing task. Physiological and perceptual responses were measured throughout the protocol. RESULTS Handgrip strength endurance was higher in CR compared to PLAC (p=0.022). MF impaired visuomotor response time (+4.4%; p=0.022) and Flanker accuracy (-5.0%; p=0.009) in both conditions. Accuracy on the Stroop task was higher in CR compared to PLAC (+4.9%; p=0.026). Within the perceptual and physiological parameters, only motivation and vigor (p≤0.027) were lower in CR compared to PLAC. CONCLUSION Creatine supplementation improved physical (strength endurance) and prolonged cognitive (Stroop accuracy) performance, yet it did not combat mental fatigue-induced impairments in short sport-specific psychomotor or cognitive (Flanker) performance. These results warrant further investigation in the potential role of creatine in combatting the MF-associated decrements in prolonged (e.g. 90-min soccer game) sport performance, and suggest a role of brain-phosphocreatine in MF.