Effects Of Creatine Supplementation Research Articles

Creatine supplementation: facts and myths

Introduction: Creatine (N-methylguanidinoacetic acid) is a peptide built of three amino acids: glycine, arginine and methionine. Its function is to store energy. It is common practice to intake creatine as a dietary supplement. Because of that, we decided to try to answer the question if there are scientifically documented advantages of creatine supplementation. Review method: We analyzed the newest research conducted from 2017 to 2024. The studies were searched in online databases like PubMed and Google Scholar. We focused on the impact of creatine supplementation on the ageing population, professional athletes, the course of some diseases, cognitive functions and body composition Results: Creatine supplementation is beneficial in professional sports. There are some signals that creatine may worsen lung conditions in sportsmen. In the ageing population, creatine supplementation boosts the results of resistance training on ageing muscle performance. There are suggestions that in this population bone geometry changes due to a combination of training and creatine supplementation may be protective against hip fracture. Creatine can also enhance cognitive functions as well as lead to positive changes in body composition. Supplementation of creatine seems to reduce symptoms of long COVID-19. It may be also beneficial among children with dermatomyositis and patients with ischemic heart disease. Conclusions: Creatine supplementation may be beneficial in some populations. It can also enhance cognitive functions as well as lead to changes in body composition. Some effects of creatine supplementation are still controversial and further investigation is needed to determine its usefulness. Keywords: creatine, body composition, long COVID-19, ageing population, professional sport, cognitive functions, dermatomyositis, ischemic heart disease

Reduced guanidinoacetate in plasma of patients with autosomal dominant Fanconi syndrome due to heterozygous P341L GATM variant and study of organoids towards treatment.

Autosomal dominant Fanconi syndrome due to a GATM variant (GATM-FS), causes accumulation of misfolded arginine-glycine amidinotransferase (AGAT) in proximal renal tubules leading to cellular injury. GATM-FS presents during childhood and progresses to end-stage kidney disease (ESKD) in adults. We study creatine metabolism in two individuals of unrelated families with a known GATM variant and the effect of creatine supplementation in kidney organoids. Plasma and urine metabolites were measured by mass spectrometry. Brain creatine was assessed by magnetic resonance spectroscopy (MRS). Guanidinoacetate (GAA) synthesis by the AGAT mutant was measured in patient-derived immortalized lymphocytes using stable isotopes of arginine and glycine. The effect of creatine on GATM expression was assessed in human kidney cells and organoids. Several family members from two unrelated families were diagnosed with Fanconi syndrome and had the c.1022C>T (p. P341L) variant in GATM. Two affected individuals in both families had moderately reduced plasma GAA levels. In comparison to wild-type cells, GAA synthesis by patient-derived GATM P341L+/- lymphoblastoid cell lines (LCL) was reduced, but not absent as in GATM cells from a patient with creatine deficiency syndrome. In vitro studies on human kidney organoids revealed reduced AGAT expression after treatment with creatine. Finally, we showed in one patient that creatine supplementation (5 g daily) substantially increased plasma creatine levels. We report low plasma and urine GAA in patients with autosomal dominant GATM-FS and show that creatine downregulates AGAT in human kidney cells.

Effect of creatine supplementation on cognitive function and mood

Background: Creatine, a naturally occurring compound plays a crucial role in cellular energy metabolism, particularly in tissues with high energy demands like muscles and the brain. Beyond its well-established role in physical performance enhancement, recent research has revealed its potential benefits for cognitive functions and mood regulation. This review paper aims to comprehensively analyze the existing literature on creatine supplementation's effects on cognitive functions and mood. State of Knowledge: Findings suggest that creatine supplementation enhances memory, attention, and executive functions, especially under conditions of stress or sleep deprivation. Moreover, it exhibits mood-stabilizing effects, potentially offering relief for symptoms of depression and fatigue. Creatine's ability to augment brain energy metabolism, alongside its neuroprotective properties, underlies its cognitive and mood-enhancing effects. While generally safe, caution is advised, particularly in populations with kidney diseases or those using medications affecting kidney function. Summary: Creatine emerges as a promising adjunct therapy for enhancing cognitive functions and promoting emotional well-being beyond its traditional role in physical performance.The review underscores the need for further research to elucidate the precise mechanisms of creatine's effects and explore its synergistic potential with other cognitive-enhancing supplements.

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

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. 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). 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. 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.

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

BackgroundCreatine 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.MethodsOur 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.ResultsBayesian evidence supported a small beneficial effect of creatine. The creatine effect bordered significance for BDS (p = 0.064, η2P = 0.029) but not RAPM (p = 0.327, η2P = 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.ConclusionsOur 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 registrationThe trial was prospectively registered (drks.de identifier: DRKS00017250, https://osf.io/xpwkc/).

Effects of creatine supplementation on strength exercise and its optimization through carbohydrates: A review

Nutritional supplements integrated with any physical or sports activity are substances aimed at increasing physical performance, improving physical effort efficiency, enhancing physical recovery processes after intense exertion, enhancing training quality, and facilitating physiological adaptations. Among the most commonly used supplements is creatine (CR), a non-essential nitrogenous compound formed by three amino acids: glycine, arginine, and methionine, whose main benefit lies in improving performance in high-intensity activities. The consumption of CR along with carbohydrate (CHO) sources promotes supplement absorption compared to isolated consumption due to increased plasma insulin levels. The human body can absorb approximately 25% more CR when ingested with a CHO source. This review aimed to provide an expanded outlook on the consumption of CR combined with CHO sources and its relationship with increased CR transport into muscle cells in individuals engaging in strength exercises. Studies have shown that the increase or improvement in CR absorption by muscle cells may be related to increased blood glucose levels and consequent insulin release, which acts in a co-dependent and direct manner on the membrane transporter that regulates the entry of CR together with sodium into the intracellular environment, demonstrating that CHO supplementation is not necessary every time CR is consumed, but instead that this improvement consists of increased serum glucose and insulin release.

Effects of Creatine Supplementation on the Myostatin Pathway and Myosin Heavy Chain Isoforms in Different Skeletal Muscles of Resistance-Trained Rats

Creatine has been used to maximize resistance training effects on skeletal muscles, including muscle hypertrophy and fiber type changes. This study aimed to evaluate the impact of creatine supplementation on the myostatin pathway and myosin heavy chain (MyHC) isoforms in the slow- and fast-twitch muscles of resistance-trained rats. Twenty-eight male Wistar rats were divided into four groups: a sedentary control (Cc), sedentary creatine supplementation (Cr), resistance training (Tc), and resistance training combined with creatine supplementation (Tcr). Cc and Tc received standard commercial chow; Cr and Tcr received a 2% creatine-supplemented diet. Tc and Tcr performed a resistance training protocol on a ladder for 12 weeks. Morphology, MyHC isoforms, myostatin, follistatin, and ActRIIB protein expressions were analyzed in soleus and white gastrocnemius portion samples. The results were analyzed using two-way ANOVA and Tukey’s test. Tc and Tcr exhibited higher performance than their control counterparts. Resistance training increased the ratio between muscle and body weight, the cross-sectional area, as well as the interstitial collagen fraction. Resistance training alone increased MyHC IIx and follistatin while reducing myostatin (p &lt; 0.001) and ActRIIB (p = 0.040) expressions in the gastrocnemius. Resistance training induced skeletal muscle hypertrophy and interstitial remodeling, which are more evident in the gastrocnemius muscle. The effects were not impacted by creatine supplementation.

Creatine in the fetal brain: A regional investigation of acute global hypoxia and creatine supplementation in a translational fetal sheep model.

Creatine supplementation during pregnancy is a promising prophylactic treatment for perinatal hypoxic brain injury. Previously, in near-term sheep we have shown that fetal creatine supplementation reduces cerebral metabolic and oxidative stress induced by acute global hypoxia. This study investigated the effects of acute hypoxia with or without fetal creatine supplementation on neuropathology in multiple brain regions. Near-term fetal sheep were administered continuous intravenous infusion of either creatine (6 mg kg-1 h-1) or isovolumetric saline from 122 to 134 days gestational age (dGA; term is approx. 145 dGA). At 131 dGA, global hypoxia was induced by a 10 min umbilical cord occlusion (UCO). Fetuses were then recovered for 72 h at which time (134 dGA) cerebral tissue was collected for either RT-qPCR or immunohistochemistry analyses. UCO resulted in mild injury to the cortical gray matter, thalamus and hippocampus, with increased cell death and astrogliosis and downregulation of genes involved in regulating injury responses, vasculature development and mitochondrial integrity. Creatine supplementation reduced astrogliosis within the corpus callosum but did not ameliorate any other gene expression or histopathological changes induced by hypoxia. Of importance, effects of creatine supplementation on gene expression irrespective of hypoxia, including increased expression of anti-apoptotic (BCL-2) and pro-inflammatory (e.g., MPO, TNFa, IL-6, IL-1β) genes, particularly in the gray matter, hippocampus, and striatum were identified. Creatine treatment also effected oligodendrocyte maturation and myelination in white matter regions. While supplementation did not rescue mild neuropathology caused by UCO, creatine did result in gene expression changes that may influence in utero cerebral development.

Effects of creatine supplementation on brain in the healthy population

Introduction and purpose: Creatine supplementation is playing an increasingly important role not only in sports, but is beneficial in the context of brain health (e.g., cognitive processing, brain function and recovery from injury). This is a growing field of research, and the purpose of this brief review is to provide an update on the effects of creatine supplementation on brain health in healthy people.&#x0D; Description of the state of knowledge: Creatine, is an organic compound produced mainly by the liver and kidneys. From the liver, kidneys and gastrointestinal tract, creatine enters through the bloodstream into skeletal muscle, where a total of about 95% of the body's total creatine is stored. It is stored in the muscles, heart and brain.&#x0D; Summary: There is potential for creatine supplementation to improve cognitive processing, especially in conditions characterized by creatine deficits in the brain, which can be triggered by acute stress factors (e.g., exercise, lack of sleep) or chronic, pathological conditions (e.g., creatine synthesis enzyme deficiencies, mild traumatic brain injury, aging, Alzheimer's disease). People with depression, the elderly, people with diseases associated with certain genetic defects (where creatine production and storage in the brain is impaired) are just some of the groups of people in whom creatine supplementation may be helpful. More research is needed to determine the clinical impact of long-term creatine supplementation dosing strategies on brain function and health.

Letter to the Editor: Double-counting due to inadequate statistics leads to false-positive findings in "Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials".

Prokopidis et al have conducted a meta-analysis of randomized, placebo-controlled clinical trials to assess the effects of oral creatine supplementation on memory performance of healthy individuals. However, concerns were raised regarding the validity of their statistical analyses, which may have led to misleading conclusions. In this letter, we describe the statistical issue at hand and its potential implications.

Author's reply: Letter to the Editor: Double counting due to inadequate statistics leads to false-positive findings in "Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials".

Author's reply: Letter to the Editor: Double counting due to inadequate statistics leads to false-positive findings in "Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials".

The Effects of Creatine Supplementation on Markers of Muscle Damage and Inflammation Following Exercise in Older Adults: A Brief Narrative Review

Exercise induced muscle damage occurs following strenuous and unfamiliar exercise and results in biomarkers of muscle damage and inflammation in the circulation. Creatine (Cr) is a commonly utilized nutritional supplement which has been proposed to enhance post-exercise recovery and has been suggested to decrease exercise induced inflammation. Exercise is well recognized to be beneficial for older adults to maintain skeletal muscle mass and strength as well as promote health for other biological systems. However, older adults can experience chronic low-grade inflammation, sometimes referred to as ‘inflammaging’. Therefore, it may be prudent to limit post-exercise induced skeletal muscle damage and inflammation for the older adult population who may already be in a pro-inflammatory state and at risk of age-related muscle loss (sarcopenia). The purpose of this brief narrative review is to outline the current research on Cr and its effects on biomarkers of muscle damage and inflammation in older adults. Further, the review will suggest areas of research that are required to fully understand how Cr supplementation may affect muscle damage and inflammatory biomarkers in older adults who exercise.

Effects of Creatine Supplementation on Histopathological and Biochemical Parameters in the Kidney and Pancreas of Streptozotocin-Induced Diabetic Rats.

Diabetes mellitus (DM) is a worldwide health concern, and projections state that cases will reach 578 million by 2030. Adjuvant therapies that can help the standard treatment and mitigate DM effects are necessary, especially those using nutritional supplements to improve glycemic control. Previous studies suggest creatine supplementation as a possible adjuvant therapy for DM, but they lack the evaluation of potential morphological parameters alterations and tissue injury caused by this compound. The present study aimed to elucidate clinical, histomorphometric, and histopathological consequences and the cellular oxidative alterations of creatine supplementation in streptozotocin (STZ)-induced type 1 DM rats. We could estimate whether the findings are due to DM or the supplementation from a factorial experimental design. Although creatine supplementation attenuated some biochemical parameters, the morphological analyses of pancreatic and renal tissues made clear that the supplementation did not improve the STZ-induced DM1 injuries. Moreover, creatine-supplemented non-diabetic animals were diagnosed with pancreatitis and showed renal tubular necrosis. Therefore, even in the absence of clinical symptoms and unaltered biochemical parameters, creatine supplementation as adjuvant therapy for DM should be carefully evaluated.

Effect of Creatine Supplementation on Last Spurt Performance in Long-distance run.

Effect of Creatine Supplementation on Last Spurt Performance in Long-distance run.

Effects of Creatine Supplementation and Progressive Resistance Training in Stroke Survivors

Effects of Creatine Supplementation and Progressive Resistance Training in Stroke Survivors

Creatine supplementation and muscles: From metabolism to medical practice

Creatine has become the most popular dietary supplement in sport and exercise physiology. In humans creatine is synthesized by the kidneys, pancreas and liver and transported mainly into brain, skeletal and cardiac muscle. Phosphocreatine is a high-energy content molecule, essential for the ADP to ATP conversion during intensive physical activity. Creatine and phosphocreatine are crucial in the energy shuttle system of high-energy phosphates between the mitochondrial ATP production and the cytosolic ATP consumption. Creatine supplementation increases lean body mass acting on myogenic regulatory factors. During muscular recovery, creatine supplementation regulates the regeneration process by reduction of muscle damage-induced inflammation and oxidative stress, activation and proliferation of satellite cells and regulation of calcium transport in muscle. The effects of creatine supplementation on muscle physiology are beneficial in anaerobic/aerobic exercises. In several muscle disorders (muscular dystrophies, in idiopathic inflammatory myopathies) creatine improved functional performance, but apparently not in metabolic myopathies; in McArdle diseases it may even have paradoxical effects. More research is warranted to better understand the short and long-term effects and safety of creatine supplementation among adolescents or elderly, as well as in different types of muscle diseases; for the two enzymatic genetic defects of creatine biosynthesis – arginine: glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), respectively – normal neurodevelopment has been achieved in early initiation of creatine therapy.

The Application of Creatine Supplementation in Medical Rehabilitation.

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 Supplementation, Physical Exercise and Oxidative Stress Markers: A Review of the Mechanisms and Effectiveness.

Oxidative stress is the result of an imbalance between the generation of reactive oxygen species (ROS) and their elimination by antioxidant mechanisms. ROS degrade biogenic substances such as deoxyribonucleic acid, lipids, and proteins, which in turn may lead to oxidative tissue damage. One of the physiological conditions currently associated with enhanced oxidative stress is exercise. Although a period of intense training may cause oxidative damage to muscle fibers, regular exercise helps increase the cells’ ability to reduce the ROS over-accumulation. Regular moderate-intensity exercise has been shown to increase antioxidant defense. Endogenous antioxidants cannot completely prevent oxidative damage under the physiological and pathological conditions (intense exercise and exercise at altitude). These conditions may disturb the endogenous antioxidant balance and increase oxidative stress. In this case, the use of antioxidant supplements such as creatine can have positive effects on the antioxidant system. Creatine is made up of two essential amino acids, arginine and methionine, and one non-essential amino acid, glycine. The exact action mechanism of creatine as an antioxidant is not known. However, it has been shown to increase the activity of antioxidant enzymes and the capability to eliminate ROS and reactive nitrogen species (RNS). It seems that the antioxidant effects of creatine may be due to various mechanisms such as its indirect (i.e., increased or normalized cell energy status) and direct (i.e., maintaining mitochondrial integrity) mechanisms. Creatine supplement consumption may have a synergistic effect with training, but the intensity and duration of training can play an important role in the antioxidant activity. In this study, the researchers attempted to review the literature on the effects of creatine supplementation and physical exercise on oxidative stress.

Creatine Supplementation and Brain Health.

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.

Effect of Creatine Supplementation on Functional Capacity and Muscle Oxygen Saturation in Patients with Symptomatic Peripheral Arterial Disease: A Pilot Study of a Randomized, Double-Blind Placebo-Controlled Clinical Trial.

The aim of the study was to verify the effects of creatine (Cr) supplementation on functional capacity (walking capacity; primary outcome) and calf muscle oxygen saturation (StO2) (secondary outcome) in symptomatic peripheral arterial disease (PAD) patients. Twenty-nine patients, of both sexes, were randomized (1:1) in a double-blind manner for administration of placebo (PLA, n = 15) or creatine monohydrate (Cr, n = 14). The supplementation protocol consisted of 20 g/day for 1 week divided into four equal doses (loading phase), followed by single daily doses of 5 g in the subsequent 7 weeks (maintenance phase). Functional capacity (total walking distance) was assessed by the 6 min walk test, and calf muscle StO2 was assessed through near infrared spectroscopy. The measurements were collected before and after loading and after the maintenance phase. The level of significance was p < 0.05. No significant differences were found for function capacity (total walking distance (PLA: pre 389 ± 123 m vs. post loading 413 ± 131 m vs. post maintenance 382 ± 99 m; Cr: pre 373 ± 149 m vs. post loading 390 ± 115 m vs. post maintenance 369 ± 115 m, p = 0.170) and the calf muscle StO2 parameters (p > 0.05). Short- and long-term Cr supplementation does not influence functional capacity and calf muscle StO2 parameters in patients with symptomatic PAD.