Creatine Monohydrate

BACKGROUND: Creatine monohydrate is a widely used dietary supplement with proven benefits in athletic performance and potential therapeutic applications in clinical populations. However, concerns regarding its impact on renal function persist, largely due to elevated serum creatinine levels associated with creatine intake. METHODS: A comprehensive literature search was conducted in PubMed, Scopus, Web of Science, and Google Scholar for studies published between January 2000 and March 2025. Primary outcomes were serum creatinine and glomerular filtration rate (GFR). Meta-analyses were performed using a random-effects model, with subgroup analysis by supplementation duration. RESULTS: Twenty-one studies were included in the systematic review, and 12 studies (177 participants in the creatine group and 263 in control) were eligible for meta-analysis of serum creatinine levels. Creatine supplementation was associated with a small but statistically significant increase in serum creatinine (MD: 0.07 µmol/L; 95% CI: 0.01 to 0.12; p = 0.03). Subgroup analysis of the creatinine outcome based on follow-up duration revealed that the intervention effect was significant in studies with a follow-up of ≤ 1 week (MD = 0.12; 95% CI: 0.03 to 0.21). However, no significant effect was observed in studies with a follow-up of 1 to 12 weeks (MD = 0.04; 95% CI: - 0.09 to 0.17). The effect became significant again in studies with a follow-up of more than 12 weeks. The meta-analysis revealed a non-statistically significant differences in GFR following creatine supplementation compared to control. CONCLUSION: Creatine supplementation is associated with a modest, transient increase in serum creatinine levels, likely due to metabolic turnover rather than renal impairment. No significant changes were observed in GFR, suggesting preserved kidney function. CLINICAL TRIAL NUMBER: Not applicable. © 2025. The Author(s).

BACKGROUND: There is robust evidence that creatine monohydrate supplementation can enhance short-term high-intensity exercise in athletes. However, the effect of creatine monohydrate supplementation on aerobic performance and its role during aerobic activities is still controversial. OBJECTIVE: The purpose of this systematic review and meta-analysis was to evaluate the supplementation effects of creatine monohydrate on endurance performance in a trained population. METHODS: The search strategy in this systematic review and meta-analysis was designed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and PubMed/MEDLINE, Web of Science, and Scopus databases were explored from inception until 19 May, 2022. Only human experimental trials, controlled with a placebo group, evaluating the effects of creatine monohydrate supplementation on endurance performance in a trained population were analyzed in this systematic review and meta-analysis. The methodological quality of included studies was evaluated using the Physiotherapy Evidence Database (PEDro) scale. RESULTS: A total of 13 studies satisfied all the eligibility criteria and were included in this systematic review and meta-analysis. The results for the pooled meta-analysis showed a non-significant change in endurance performance after creatine monohydrate supplementation in a trained population (p = 0.47), with a trivial negative effect (pooled standardized mean difference = - 0.07 [95% confidence interval - 0.32 to 0.18]; I2 = 34.75%). Further, after excluding the studies not evenly distributed around the base of the funnel plot, the results were similar (pooled standardized mean difference = - 0.07 [95% confidence interval - 0.27 to 0.13]; I2 = 0%; p = 0.49). CONCLUSIONS: Creatine monohydrate supplementation was shown to be ineffective on endurance performance in a trained population. CLINICAL TRIAL REGISTRATION: The study protocol was registered in the Prospective Register of Systematic Review (PROSPERO) with the following registration number: CRD42022327368. © 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

BACKGROUND: The association between diet, symptoms and health related quality of life in children and young people with Juvenile idiopathic arthritis (JIA) is not clearly understood. The objectives of this systematic review and meta-analysis were to explore the evidence for a relationship between nutritional status, dietary intake, arthritis symptoms, disease activity and health-related quality of life in children and young people with JIA considering both observational and interventional studies separately. METHOD: The databases PubMed, CINAHL, PsycINFO, Web of Science and Cochrane were searched in October 2019, updated in September 2020 and October 2021. Searches were restricted to English language, human and age (2-18 years old). Studies were included if they measured the effect of dietary supplements, vitamins or minerals, or diet in general, on quality of life and/ or arthritis symptom management. Two researchers independently screened titles and abstracts. Full texts were sourced for relevant articles. PRISMA guidelines were used for extracting data. For variables (vitamin D and disease activity), a random-effects meta-analysis model was performed. Two authors using a standardized data extraction form, extracted data independently. RESULTS: 11,793 papers were identified through database searching, 26 studies met our inclusion criteria with 1621 participants. Overall studies quality were fair to good. Results from controlled trial and case control studies with total 146 JIA patients, found that Ɯ-3 PUFA improved the mean active joint count (p < 0.001), Juvenile Arthritis Disease Activity Score (JADAS-27) (p < 0.001) and immune system (≤ 0.05). Furthermore, n-3 and n-6 PUFAs have a negative correlation with CRP (C-reactive protein) and ESR (erythrocyte sedimentation rate) (p < 0.05). Improvement in JIA symptoms were observed in one case, one pilot and one exploratory study with overall 9 JIA patients after receiving Exclusive Enteral Nutrition (EEN) which contains protein and what is required for a complete nutrition, A clinical trial study found Kre-Celazine nutrition (composed of a proprietary alkali buffered, creatine monohydrate and fatty acids mixture)

Comment in Nutr Rev. 2023 Oct 10;81(11):1495-1496. doi: 10.1093/nutrit/nuac108. 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 Author(s) 2022. Published by Oxford University Press on behalf of the International Life Sciences Institute.

BACKGROUND: Several studies have examined the effect of creatine monohydrate (CrM) on indirect muscle damage markers and muscle performance, although pooled data from several studies indicate that the benefits of CrM on recovery dynamics are limited. OBJECTIVE: This systematic review and meta-analysis determined whether the ergogenic effects of CrM ameliorated markers of muscle damage and performance following muscle-damaging exercises. METHODS: In total, 23 studies were included, consisting of 240 participants in the CrM group (age 23.9 ± 10.4 years, height 178 ± 5 cm, body mass 76.9 ± 7.6 kg, females 10.4%) and 229 participants in the placebo group (age 23.7 ± 8.5 years, height 177 ± 5 cm, body mass 77.0 ± 6.6 kg, females 10.0%). These studies were rated as fair to excellent following the PEDro scale. The outcome measures were compared between the CrM and placebo groups at 24-36 h and 48-90 h following muscle-damaging exercises, using standardised mean differences (SMDs) and associated p-values via forest plots. Furthermore, sub-group analyses were conducted by separating studies into those that examined the effects of CrM as an acute training response (i.e., after one muscle-damaging exercise bout) and those that examined the chronic training response (i.e., examining the acute response after the last training session following several weeks of training). RESULTS: According to the meta-analysis, the CrM group exhibited significantly lower indirect muscle damage markers (i.e., creatine kinase, lactate dehydrogenase, and/or myoglobin) at 48-90 h post-exercise for the acute training response (SMD - 1.09; p = 0.03). However, indirect muscle damage markers were significantly greater in the CrM group at 24 h post-exercise (SMD 0.95; p = 0.04) for the chronic training response. Although not significant, a large difference in indirect muscle damage markers was also found at 48 h post-exercise (SMD 1.24) for the chronic training response. The CrM group also showed lower inflammation for the acute training response at 24-36 h post-exercise and 48-90 h post-exercise with a large effect size (SMD - 1.38 ≤ d ≤ - 1.79). Similarly, the oxidative stress markers were lower fo

Creatine Monohydrate (CrM) is a dietary supplement routinely used as an ergogenic aid for sport and training, and as a potential therapeutic aid to augment different disease processes. Despite its increased use in recent years, studies reporting potential adverse outcomes of CrM have been mostly derived from male or mixed sex populations. A systematic search was conducted, which included female participants on CrM, where adverse outcomes were reported, with meta-analysis performed where appropriate. Six hundred and fifty-six studies were identified where creatine supplementation was the primary intervention; fifty-eight were female only studies (9%). Twenty-nine studies monitored for adverse outcomes, with 951 participants. There were no deaths or serious adverse outcomes reported. There were no significant differences in total adverse events, (risk ratio (RR) 1.24 (95% CI 0.51, 2.98)), gastrointestinal events, (RR 1.09 (95% CI 0.53, 2.24)), or weight gain, (mean difference (MD) 1.24 kg pre-intervention, (95% CI -0.34, 2.82)) to 1.37 kg post-intervention (95% CI -0.50, 3.23)), in CrM supplemented females, when stratified by dosing regimen and subject to meta-analysis. No statistically significant difference was reported in measures of renal or hepatic function. In conclusion, mortality and serious adverse events are not associated with CrM supplementation in females. Nor does the use of creatine supplementation increase the risk of total adverse outcomes, weight gain or renal and hepatic complications in females. However, all future studies of creatine supplementation in females should consider surveillance and comprehensive reporting of adverse outcomes to better inform participants and health professionals involved in future trials.

BACKGROUND: Creatine transporter deficiency (CTD) is an X-linked inborn error of creatine metabolism characterized by reduced intra-cerebral creatine, developmental delay/intellectual disability, (ID), behavioral disturbance, seizures, and hypotonia in individuals harboring mutations in the SLC6A8 gene. Treatment for CTD includes supplementation with creatine, either alone or in combination with creatine precursors (arginine or glycine). Unlike other disorders of creatine metabolism, the efficacy of its treatment remains controversial. METHODS: We present our systematic literature review (2001-2013) comprising 7 publications (case series/reports), collectively describing 25 patients who met the inclusion criteria, and 3 additional cases treated at our institution. Definitions were established and extracted data analyzed for cognitive ability, psychiatric and behavioral disturbances, epilepsy, and cerebral proton magnetic resonance spectroscopy measurements at pre- and post-treatment. RESULTS: Treatment regimens varied among the 28 cases: 2 patients received creatine-monohydrate supplementation; 7 patients received L-arginine; 2 patients received creatine-monohydrate and L-arginine; and 17 patients received a combination of creatine-monohydrate, L-arginine and glycine. Median treatment duration was 34.6 months (range 3 months-5 years). Level of evidence was IV. A total of 10 patients (36%) demonstrated response to treatment, manifested by either an increase in cerebral creatine, or improved clinical parameters. Seven of the 28 patients had quantified pre- and post-treatment creatine, and it was significantly increased post-treatment. All of the patients with increased cerebral creatine also experienced clinical improvement. In addition, the majority of patients with clinical improvement had detectable cerebral creatine prior to treatment. 90% of the patients who improved were initiated on treatment before nine years of age. CONCLUSIONS: Acknowledging the limitations of this systematic review, we conclude that a proportion of CTD patients show amenability to treatment-particularly milder cases with residual brain creatine, and therefore probable residual protein f

BACKGROUND: Mitochondrial respiratory chain disorders are the most prevalent group of inherited neurometabolic diseases. They present with central and peripheral neurological features usually in association with other organ involvement including the eye, the heart, the liver, and kidneys, diabetes mellitus and sensorineural deafness. Current treatment is largely supportive and the disorders progress relentlessly causing significant morbidity and premature death. Vitamin supplements, pharmacological agents and exercise therapy have been used in isolated cases and small clinical trials, but the efficacy of these interventions is unclear. The first review was carried out in 2003, and identified six clinical trials. This major update was carried out to identify new studies and grade the original studies for potential bias in accordance with revised Cochrane Collaboration guidelines. OBJECTIVES: To determine whether there is objective evidence to support the use of current treatments for mitochondrial disease. SEARCH METHODS: We searched the Cochrane Neuromuscular Disease Group Specialized Register (4 July 2011), CENTRAL (2011, Issue 2, MEDLINE (1966 to July 2011), and EMBASE (January 1980 to July 2011), and contacted experts in the field. SELECTION CRITERIA: We included randomised controlled trials (including cross-over studies). Two of the authors independently selected abstracts for further detailed review. Further review was performed independently by all five authors to decide which trials fit the inclusion criteria and graded risk of bias. Participants included males and females of any age with a confirmed diagnosis of mitochondrial disease based upon muscle histochemistry, respiratory chain complex analysis of tissues or cell lines or DNA studies. Interventions included any pharmacological agent, dietary modification, nutritional supplement, exercise therapy or other treatment. The review authors excluded studies at high risk of bias in any category. The primary outcome measures included an change in muscle strength and/or endurance, or neurological clinical features. Secondary outcome measures included quality of life assessments, biochemical markers of disea

Background/Objectives: Creatine is a supplement that, beyond its physiological effects, has been shown to have positive effects on cognitive abilities. In our previous study, we showed that a single dose of 0.35 g/kg creatine induces changes in brain metabolism during sleep deprivation and reduces deterioration in cognitive performance. The present study investigates whether supplementation of a lower dose is associated with cognitive effects during sleep deprivation, focusing exclusively on cognitive performance outcomes. Methods: Twenty-nine healthy subjects performed cognitive tests at the evening baseline and 3, 5.5, and 7.5 h after receiving a single dose of creatine monohydrate (0.2 g/kg) or a placebo during a total of 21 h of sleep deprivation (SD). Results: The results show a mitigating effect of creatine on sleep deprivation-induced deterioration in logical and numerical tasks, language-related processing speed, and the Psychomotor Vigilance Test (PVT). Compared to males, females benefit more in logic, PVT and processing speed in language and logic tasks. Conclusions: Our results show that a dose of 0.2 g/kg creatine is associated with a reduced deterioration in cognitive performance during sleep deprivation. Although the effect is less pronounced than with a high dose of 0.35 g/kg, there is still an improvement of up to 12%.

BACKGROUND: While the long-term ergogenic benefits of creatine monohydrate (CrM) supplementation are well-documented, the potential advantages of acute ingestion followed by short-term consumption remain relatively underexplored. This double-blind, randomized crossover study investigated the acute and short-term effects of CrM supplementation on strength performance, heart rate variability (HRV) responses, and recovery of lower limbs strength and muscle soreness in resistance-trained males. METHODS: A total of eleven physically active participants were recruited; however, due to incomplete data, one participant was excluded, and ten participants (age: 21.3 ± 1.9 years) were analyzed. Participants ingested either creatine monohydrate (CrM: 0.3 g·kg-1·d-1) or a placebo (PLA) for three days, with the first day's dose consumed 2 h pre-test and subsequent doses divided into three daily doses. Participants completed two test sessions in a randomized order, separated by a seven-day washout period. Each session included bench press (BP) and back squat (BS) tests performed at 60%, 70%, and 80% of one-repetition maximum (1RM) under either CrM or PLA conditions. Strength performances (repetitions, velocity, power), HRV and peak heart rate (HR), jump tests (Countermovement Jump (CMJ) and Squat Jump (SJ)), and delayed-onset muscle soreness (DOMS) were assessed. RESULTS: Compared to PLA, CrM supplementation significantly increased repetitions completed at 60-80% 1RM in BP and BS (p ≤ 0.041, d = 0.72-1.6) during both test sessions. CrM reported higher velocity compared to PLA at all intensities (60-80% 1RM) for both exercises and sessions (p ≤ 0.035, d = 0.78-4.09). CrM reduced cardiovascular strain compared to PLA at 60% 1RM during back squat (p = 0.017, d = 1.05). Peak HR increased with intensity for both conditions (d = 1.1-4.28), with CrM showing lower HR at 60% (p = 0.017, d = 1.05) and higher HR at 80% (p = 0.047, d = 0.82) compared to PLA. CrM enhanced post-exercise parasympathetic reactivation in the 1st session demonstrating higher favorable response in RMSSD (p = 0.015, d = 2.99) and HF power (p = 0.022, d = 2.76) compared to PLA. CMJ performance was higher in CrM co

Background/Objectives: Creatine monohydrate (CrM) supplementation is well-established for enhancing physical performance and accelerating recovery in several sporting contexts. However, beyond these traditional performance benefits, its effects on sleep metrics and cognitive function have not been thoroughly investigated. This investigation aimed to determine the effect of a loading phase of CrM on sleep metrics, physical performance, psycho-cognitive aspects, and recovery in physically active men. Methods: In a randomized, double-blind, placebo-controlled crossover design, 14 physically active men ingested 20 g/day of CrM or placebo (PL) for 7 days, during which their habitual exercise routines were maintained and standardized across both intervention phases. Sleep metrics were monitored throughout the interventions using wrist-worn actigraphy. On the day following the completion of each supplementation phase, participants rated their sleep quality using the Sleep Subjective Quality (SSQ) scale, and the Hooper questionnaire was used to monitor participants' well-being status. Physical performance was assessed using the 5 m shuttle run test (5mSRT), which measured total distance (TD), best distance (BD), performance decrement (PD), fatigue index (FI), and the rating of perceived exertion (RPE). Affective valence was determined using the feeling scale (FS) and cognitive function was evaluated using the digit cancellation test (DCT). Recovery and muscle soreness perceptions were evaluated at multiple time points (pre-exercise, 5 min, 24 h, 48 h, and 72 h post-exercise) using the perceived recovery status (PRS) and the delayed onset muscle soreness (DOMS) scales, respectively. Results: During the supplementation, CrM improved sleep quality compared to PL, as measured with the SSQ scale (d = 0.81, p = 0.009), and was associated with an earlier in-bed time (r = 0.60; p = 0.026). However, CrM did not affect sleep latency (t = 0.98; p = 0.35), sleep efficiency (t = 0.018; p = 0.98), or total sleep time (t = 0.25; p = 0.81). After the supplementation phase, CrM resulted in significantly lower muscle soreness scores, as measured by the Hooper questionnaire (d = -0.59; p

Athletes use creatine monohydrate (CM) to enhance high-intensity exercise performance by increasing creatine phosphate availability. While CM supplementation is known to raise muscle creatine levels in vegans and vegetarians, its impact on exercise performance remains uncertain. We examined the effects of CM supplementation on muscle creatine content and exercise performance in vegans and vegetarians. In a randomized, double-blind placebo-controlled design, 15 healthy vegans and vegetarians consumed CM (0.3 g/kg/day, n = 7) or placebo (PLA, 0.3 g maltodextrin/kg/day, n = 8) four times a day for 7 days. Before and after supplementation, repeated sprint capacity was determined. Body mass and fat-free mass (FFM) were assessed by dual-energy x-ray absorptiometry. The CM group increased body mass (1.56 ± 0.57 kg, p < 0.01) and FFM (1.15 ± 0.94 kg, p < 0.05), while the PLA group showed no changes. In the CM group, muscle creatine (Cr) and total muscle creatine (TCr) increased by 18.8 ± 13.1 mmol/kg (p < 0.05) and 30.8 ± 21.2 mmol/kg (p < 0.01), respectively. The PLA group showed no changes in Cr and TCr (-4.6 ± 13.1 mmol/kg and 2.9 ± 11.6 mmol/kg, respectively). Phosphocreatine levels remained consistent within and between groups. There were no observed changes in peak and mean power output during repeated sprints. A seven-day CM supplementation in healthy vegans and vegetarians increased Cr and TCr whereas Phosphocreatine, peak and mean power output during repeated sprints was unchanged. © 2025 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.

BACKGROUND AND AIMS: Elevated plasma levels of total homocysteine (Hcy) and S-Adenosylhomocysteine (SAH) are associated with increased risks of neurological and cardiovascular diseases (CVD). Whilst elevated plasma levels of Hcy can be managed through supplementation with B-group vitamins, there are no effective therapies for managing SAH in patients with elevated SAH and normal Hcy. SAH, a by-product of cellular methylation reactions, is considered a more sensitive biomarker for CVD than homocysteine (Hcy). The aim of this study was to determine if a test product containing ashwagandha extract, alpha-glycerylphosphorylcholine and creatine monohydrate, could lower plasma SAH levels in adults with elevated SAH and normal Hcy. METHODS AND RESULTS: In this prospective, randomized, single-blind, placebo-controlled clinical trial, 40 participants with elevated SAH (≥20 nmol/L) and normal Hcy (≤13 μmol/L) were randomized into two groups: 15 participants received the placebo, and 25 participants received the test product. The test product significantly lowered plasma SAH levels by approximately 12% and increased S-Adenosylmethionine (SAM): SAH ratio by approximately 26% after 12 weeks of supplementation compared to baseline. The test product was safe and well-tolerated, with no serious adverse events. No clinically relevant changes in vital signs and safety laboratory parameters were detected. CONCLUSION: This is the first demonstration of a nutritional product's effectiveness in decreasing plasma levels of SAH in otherwise healthy individuals with elevated SAH and normal Hcy. Hence, this test product offers a unique opportunity for investigating the impact of lowering plasma SAH on the risk of developing CVD and other diseases. Clincaltrial.gov registration: NCT05994794, 2023-08-16.

BACKGROUND: Basketball games involve numerous cognitive-motor dual-task (CMDT) situations, where athletes must execute technical skills while processing complex on-court information. However, adolescent athletes often experience performance declines under CMDT conditions due to increased cognitive load. Creatine supplementation has been shown to enhance both physical and cognitive functions, but its acute effects on basketball skill performance under CMDT conditions remain unclear. This study investigates the impact of acute creatine supplementation on the technical performance of adolescent basketball players under single-task (ST) and CMDT conditions. METHODS: A randomized counterbalanced crossover design with a Latin square arrangement was used to recruit 40 male adolescent basketball players (13-14 years old) with provincial-level competitive experience. Participants received either creatine monohydrate (0.3 g/kg/day for 5 days, plus 0.1 g/kg pretest) or placebo, with a 4-week washout period between phases. To minimize learning and order effects, a standardized familiarization session was conducted prior to testing, and the sequence of ST and CMDT conditions was counterbalanced using a Latin square design. The CMDT condition required players to perform a continuous subtraction task while executing dribbling, passing, and shooting tasks. Performance metrics, subtraction task accuracy, heart rate, and ratings of perceived exertion (RPE) were collected. Two-way repeated measures ANOVA and paired t-tests were conducted for statistical analysis (α = 0.05, Bonferroni-corrected). RESULTS: Under CMDT conditions, creatine supplementation significantly improved performance in dribbling, passing, and shooting tasks (all p < 0.05), while only dribbling and shooting performance improved under ST conditions (p < 0.05). Dual-task cost significantly decreased in dribbling and passing (p < 0.05), but not in shooting (p > 0.05). Subtraction task accuracy improved only during shooting (p = 0.013). Additionally, creatine supplementation significantly reduced heart rate and RPE scores across all tasks and both conditions (p < 0.05). CONCLUSION: Acute creatine supplementation enh

Tactical athletes and military personnel engaged in intense exercise need to consume enough quality protein in their diet to maintain protein balance and promote recovery. Plant-based protein sources contain fewer essential amino acids (EAAs), while pork loin contains a higher concentration of EAAs and creatine than most other animal protein sources. This study aimed to determine whether the ingestion of plant-based or pork-based military-style meals ready-to-eat (MREs) affects recovery from and subsequent Army Combat Fitness Test (ACFT) performance. Methods: Twenty-three (n = 23) University Corps of Cadets members participated in a randomized, double-blind, placebo-controlled, and crossover-designed study. Diets were prepared by a dietitian, food scientist, and chef to have similar taste, appearance, texture, and macronutrient content. The chef also labeled the meals for double-blind administration. Participants refrained from intense exercise for 48 h before reporting to the lab in a fasted condition with a 24 h urine sample. Participants donated a blood sample, completed questionnaires and cognitive function tests, and consumed a pre-exercise meal. After four hours, participants performed the ACFT according to military standards. Participants were fed three MREs daily while returning to the lab in a fasted condition at 0600 with 24 h urine samples after 24, 48, and 72 h of recovery. On day 3, participants repeated the ACFT four hours after consuming an MRE for breakfast. Participants resumed normal training and returned to the lab after 2-3 weeks to repeat the experiment while consuming the alternate diet. Data were analyzed using general linear model statistics with repeated measures and percent changes from baseline with 95% confidence intervals. Results: Results revealed that 3 days were sufficient for participants to replicate ACFT performance. However, those consuming the pork-based diet experienced less muscle soreness, urinary urea excretion, cortisol, inflammation, and depression scores while experiencing a higher testosterone/cortisol ratio and appetite satisfaction. There was also evidence of more favorable changes in red and white blood cells. Conv

Although creatine monohydrate (CM), leucine, and polyphenols have been independently researched, there is a lack of research on the effects of a supplementation blend containing trisodium citrate, CM, leucine, and blueberry extract (TCLB) on muscle strength, endurance, and size. This study compared the effects of 8 wk of supplementation with TCLB versus CM and placebo (PLA) combined with resistance training on leg extension strength, endurance, and muscle size. Twenty-eight recreationally active men ingested either TCLB (n = 10), CM (n = 10), or PLA (n = 8) during 8 wk of resistance training. Leg extension 1-repetition maximum (1RM), leg extension repetitions-to-failure at ∼80% of pre-training 1RM, individual quadriceps cross-sectional area (CSA) values, and the sum of the CSA values (CSAsum) were assessed at pre-training and post-training. Separate one-way ANCOVAs covaried for pre-training values were used to analyze differences in adjusted post-training means. Separate Chi-squared tests were used to analyze differences between groups in the proportion of subjects that exceeded the minimal important difference (MID). There were no group differences (p > 0.05) for leg extension 1RM, leg extension repetitions-to-failure, rectus femoris CSA, vastus lateralis CSA, or vastus medialis CSA. The TCLB group demonstrated greater (p ≤ 0.05) adjusted post-training means and proportions of subjects who exceeded the MID for the CSAsum and vastus intermedius CSA than the PLA group, but the TCLB group did not differ (p > 0.05) from the CM group for those variables. The CM group (p ≤ 0.05) exhibited a greater proportion of subjects who exceeded the MID for the CSAsum than the PLA group. These findings indicated that 8 wk of supplementation with TCLB and CM combined with resistance training increased the overall quadriceps muscle size greater than the PLA, but TCLB did not differ from CM. Furthermore, the groups did not differ in the training-induced increases in leg extension strength and endurance.

Background/Objectives: In this study, we aimed to examine the effect of creatine monohydrate (CrM) supplementation on recovery from eccentric exercise-induced muscle damage (EIMD) in diverse populations, including different sexes and age groups. EIMD decreases maximal voluntary contraction (MVC), restricts the range of motion (ROM), and increases muscle stiffness and delayed-onset muscle soreness, all of which negatively impact athletic performance. Therefore, developing effective recovery strategies is essential. Methods: A double-blind, randomized, placebo-controlled trial was conducted with 40 healthy male and female participants. After 33 days of supplementation with either CrM or placebo (crystalline cellulose), the participants performed eccentric exercises. Recovery indices, including MVC, muscle stiffness, subjective muscle extensive soreness, fatigue, and upper arm circumference, were measured at baseline, immediately after exercise, 48 h post-exercise, and 96 h post-exercise. Results: The creatine supplementation group (CRE) demonstrated a significantly quicker recovery of MVC than the placebo group (PLA). Furthermore, reductions in shear modulus and muscle fatigue were observed in the CRE group. Notably, females in the CRE group exhibited a significant suppression of post-exercise edema, suggesting a sex-specific response. Conclusions: These findings indicate that CrM supplementation may enhance recovery from EIMD, contributing to the maintenance of muscle function and the reduction of discomfort after exercise. CrM has the potential to serve as a practical nutritional strategy to promote recovery, not only for athletes, but also for a broader population.

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is a rare, progressive muscle disease with no available disease-modifying therapy. Creatine monohydrate (CrM) has been shown to improve muscle strength in individuals with muscular dystrophies but has not been tested in young people with FSHD. This study aimed to explore the efficacy of CrM on motor function in children with FSHD. METHODS: In a randomized placebo-controlled double-blind crossover trial, powdered CrM at a dose of 100 mg/kg/day (maximum 10 g daily) was compared with placebo in two 12-week treatment periods with a 6-week washout between crossover arms. The primary outcome measure was the Motor Function Measure for Neuromuscular Disease (MFM-32) with secondary outcomes assessing safety, endurance, strength, patient-reported outcome measures, and muscle morphology measurements as assessed by whole-body magnetic resonance imaging (MRI). RESULTS: Thirteen children were enrolled (mean (standard deviation, SD) 12.2 (2.67) years of age) and 11 patients completed both trial treatment periods. In an intention-to-treat analysis, no clinically meaningful difference was seen between treatment groups as measured by the mean difference in MFM-32 (0.19, 95% confidence interval (CI) -0.71 to 1.08). However, there was an improvement in 6-minute walk distance of 27.74 m (95% CI -1.41 to 56.88) and trends to improvement in the FSHD-Composite Outcome Measure for Pediatrics (FSHD-COM Peds), 10 meter walk/run, and in MRI measures. There were no serious adverse events. Serum creatinine increased by a mean 12.63 μmol/L (95% CI 1.14 to 24.12) post-CrM treatment, though this was presumed to reflect increased creatinine production. No participants discontinued CrM due to adverse events. CONCLUSION: CrM is safe and well tolerated in children with FSHD. Although CrM had no effect on motor function as measured by the MFM-32 compared with placebo, there were trends toward improvement in the 6-minute walk distance and other secondary outcome measures. This study confirms the feasibility of conducting clinical trials in children with FSHD. Further assessment of the efficacy of CrM in pediatric FSHD is warranted in a larger

BACKGROUND: Rates of major depressive disorder (MDD) increase with living at altitude. In our model, rats housed at moderate altitude (in hypobaric hypoxia) exhibit increased depression-like behavior, altered brain serotonin and a lack of antidepressant response to most selective serotonin reuptake inhibitors (SSRIs). A forebrain deficit in the bioenergetic marker creatine is noted in people living at altitude or with MDD. METHODS: Rats housed at 4500 ft were given dietary creatine monohydrate (CRMH, 4% w/w, 5 weeks) vs. un-supplemented diet, and impact on depression-like behavior, brain bioenergetics, serotonin and SSRI efficacy assessed. RESULTS: CRMH significantly improved brain creatine in a sex-based manner. At altitude, CRMH increased serotonin levels in the female prefrontal cortex and striatum but reduced male striatal and hippocampal serotonin. Dietary CRMH was antidepressant in the forced swim test and anti-anhedonic in the sucrose preference test in only females at altitude, with motor behavior unchanged. CRMH improved fluoxetine efficacy (20 mg/kg) in only males at altitude: CRMH + SSRI significantly improved male striatal creatine and serotonin vs. CRMH alone. CONCLUSIONS: Dietary CRMH exhibits sex-based efficacy in resolving altitude-related deficits in brain biomarkers, depression-like behavior and SSRI efficacy, and may be effective clinically for SSRI-resistant depression at altitude. This is the first study to link CRMH treatment to improving brain serotonin.

BACKGROUND: The effects of creatine on brain metabolism and the potential cognitive enhancing properties of this compound raise the possibility of developing a new augmentation therapeutic strategy in schizophrenia especially in patients demonstrating negative and cognitive symptomatology. METHODS: Seven inpatients with chronic schizophrenia presenting with treatment resistant negative symptoms were enrolled into exploratory treatment study with creatine monohydrate augmentation at a daily high-dose of 10 grams, administered for 6 months. Several clinical rating scales and a computerized cognitive assessment battery were applied. RESULTS: Creatine treatment mildly improved the schizophrenia symptomatology but there were no significant changes in cognitive functions. Several ward behaviors were also improved. Tardive parkinsonism improved numerically by above 40% in 4 out of 6 patients. CONCLUSION: This small, open design study of high dose creatine add-on for 6 months in chronic inpatients with schizophrenia demonstrated only mild positive effects on the patients' symptomatology and behavior and might have beneficial effect on tardive parkinsonism.

Creatine is an antioxidant, neuromodulator and key regulator of energy metabolism shown to improve depressive symptoms in humans and animals, especially in females. To better understand the pharmacological effects of creatine, we examined its influence on depression-related hippocampal gene expression and behaviors in the presence and absence of sex steroids. Sham-operated and gonadectomized male and female rats were fed chow alone or chow blended with either 2% or 4% w/w creatine monohydrate for five weeks before forced swim, open field, and wire suspension tests, or seven weeks total. Before supplementation, males were chronically implanted with an empty or a testosterone-filled (T) capsule (10-mm surface release), and females were administered progesterone (P, 250 μg), estradiol benzoate (EB, 2.5 μg), EB+P, or sesame oil vehicle weekly. Relative to non-supplemented shams, all hippocampal plasticity-related mRNAs measured, including brain-derived neurotrophic factor (BDNF), tyrosine kinase B, doublecortin, calretinin, and calbindin, were downregulated in sham males given 4% creatine, and BDNF, doublecortin, and calbindin mRNAs were downregulated in sham females given 4% creatine. In contrast, combined 4% creatine+T in castrates prevented downregulation of BDNF, doublecortin, and calretinin mRNAs. Similarly, combined 4% creatine+EB+P in ovariectomized females attenuated downregulation of BDNF and calbindin mRNA levels. Moderate antidepressant and anxiolytic-like behaviors were observed in EB+P-treated ovariectomized females fed creatine, with similar trends in T-treated castrates fed creatine. Altogether, these data show that chronic, high-dose creatine has opposing effects on neuroplasticity-related genes and depressive behavior in intact and gonadectomized male and female rats. The dose and schedule of creatine used negatively impacted hippocampal neuronal integrity in otherwise healthy brains, possibly through negative compensatory changes in energy metabolism, whereas combined creatine and sex steroids acted in a neuroprotective manner in gonadectomized rats, potentially by reducing metabolic complications associated with castration or ovariectomy.

Creatine's effects on brain energy metabolism raise the possibility of developing a new therapeutic strategy in depression focusing on the treatment of metabolic hypoactive brain areas. Previous creatine augmentation studies in patients with major depression showed a beneficial effect. Eighteen patients (14 women) with major depression not responding to previous 3 weeks of antidepressant treatment were enrolled into a pilot, dose finding, 4-week double-blind parallel augmentation study where creatine monohydrate 5 or 10 g daily or placebo was added to ongoing SSRIs/SNRIs/NASA treatment. Rating scales included the Hamilton Depression Rating Scale and the Clinical Global Impression Severity scale. Overall, there was no difference between creatine administered at 5 or 10 g daily and its corresponding placebos. Two female patients on creatine augmentation, but none on the placebo, showed early improvement of more than 50% reduction in Hamilton Depression Rating Scale after 2 weeks of creatine treatment. No clinically relevant side effects were reported. This preliminary study seems to suggest that the strategy using creatine augmentation in major depressive women showing no 'real-life response' to 3 weeks of treatment with SSRIs/SNRIs/NASA treatment is of no advantage compared with placebo. However, such creatine augmentation may still induce a more rapid response in a small subgroup of these female patients.

The potential role of metabolic impairments in the pathophysiology of depression is motivating researchers to evaluate the treatment efficacy of creatine, a naturally occurring energetic and neuroprotective compound found in brain and muscle tissues. Growing evidence is demonstrating the benefit of oral creatine supplements for reducing depressive symptoms in humans and animals. A novel question is whether dietary creatine, when combined with antidepressant drug therapy, would be more effective than either compound alone. To answer this question, four studies were conducted to investigate the behavioral effects of combined creatine and low-dose fluoxetine treatment using the forced swim test in male and female rats. Sprague-Dawley rats were fed powdered rodent chow supplemented with 0%, 2% or 4% w/w creatine monohydrate for 5 weeks. Rats were injected with fluoxetine (5.0 or 10.0 mg/kg) or saline according to a sub-acute dosing schedule. Female rats maintained on a 4% creatine diet displayed antidepressant-like effects compared to non-supplemented females prior to fluoxetine treatment. In contrast, creatine did not alter behavior reliably in males. Following drug treatment and a second forced swim trial, the antidepressant-like profile of creatine remained significant only in females co-administered 5.0 mg/kg fluoxetine. Moreover, in females only, supplementation with 4% creatine produced a more robust antidepressant-like behavioral profile compared to either dose of fluoxetine alone. Estrous cycle data indicated that ovarian hormones influenced the antidepressant-like effects of creatine. Addressing the issue of sex differences in response to treatment may affect our understanding of creatine, its relationship with depressive behavior, and may lead to sex-specific therapeutic strategies.

PURPOSE: The authors examined the combined effects of conjugated linoleic acid (CLA), creatine (C), and whey protein (P) supplementation during strength training. METHODS: Sixty-nine participants (52 men, 17 women; M +/- SD age 22.5 +/-2.5 yr) were randomly assigned (double-blind) to 1 of 3 groups: CCP (6 g/d CLA + 9 g/d C + 36 g/d P; n = 22), CP (C + P + placebo oil; n = 25), or P (P + placebo oil; n = 22) during 5 wk of strength training (4-5 sets, 6-12 repetitions, 6 d/wk). Measurements were taken for body composition (air-displacement plethysmography), muscle thickness (ultrasound) of the flexors and extensors of the elbow and knee, 1-repetition-maximum (1-RM) strength (leg press and bench press), urinary markers of bone resorption (N-telopeptides, NTx), myofibrillar protein catabolism (3-methylhistidine; 3-MH), oxidative stress (8-isoprostanes), and kidney function (microalbumin) before and after training. RESULTS: Contrast analyses indicated that the CCP group had a greater increase in bench-press (16.2% +/- 11.3% vs. 9.7% +/- 17.0%; p < .05) and leg-press (13.1% +/- 9.9% vs. 7.7% +/-14.2%; p < .05) strength and lean-tissue mass (2.4% +/- 2.8% vs. 1.3% +/-4.1%; p < .05) than the other groups combined. All groups increased muscle thickness over time (p < .05). The relative change in 3-MH (CCP -4.7% +/- 70.2%, CP -0.4% +/- 81.4%, P 20.3% +/- 75.2%) was less in the groups receiving creatine (p < .05), with the difference for NTx also close to significance (p = .055; CCP -3.4% +/- 66.6%, CP -3.9% +/- 64.9%, P 26.0% +/- 63.8%). There were no changes in oxidative stress or kidney function. CONCLUSION: Combining C, CLA, and P was beneficial for increasing strength and lean-tissue mass during heavy resistance training.

Alpha-lipoic acid has been found to enhance glucose uptake into skeletal muscle in animal models. Studies have also found that the co-ingestion of carbohydrate along with creatine increases muscle creatine uptake by a process related to insulin-stimulated glucose disposal. The purpose of this study was to determine the effect of alpha-lipoic acid on human skeletal muscle creatine uptake by directly measuring intramuscular concentrations of creatine, phosphocreatine, and adenosine triphosphate when creatine monohydrate was co-ingested with alpha-lipoic acid. Muscle biopsies were acquired from the vastus lateralis m. of 16 male subjects (18-32 y) before and after the experimental intervention. After the initial biopsy, subjects ingested 20 g x d(-1) of creatine monohydrate, 20 g x d(-1) of creatine monohydrate + 100 g x d(-1) of sucrose, or 20 g x d(-1) of creatine monohydrate + 100 g x d(-1) of sucrose + 1000 mg x d(-1) of alpha-lipoic acid for 5 days. Subjects refrained from exercise and consumed the same balanced diet for 7 days. Body weight increased by 2.1% following the nutritional intervention, with no differences between the groups. There was a significant increase in total creatine concentration following creatine supplementation, with the group ingesting alpha-lipoic acid showing a significantly greater increase (p < .05) in phosphocreatine (87.6 --> 106.2 mmol x kg(-1) dry mass [dm]) and total creatine (137.8 --> 156.8 mmol x kg(-1) dm). These findings indicate that co-ingestion of alpha-lipoic acid with creatine and a small amount of sucrose can enhance muscle total creatine content as compared to the ingestion of creatine and sucrose or creatine alone.

Comment in Nutr Rev. 2026 Oct 1;84(10):2213. doi: 10.1093/nutrit/nuaf239. Nutr Rev. 2026 Oct 1;84(10):2215-2218. doi: 10.1093/nutrit/nuaf240. CONTEXT: Creatine is a well-studied dietary supplement that is known to benefit aging muscle and bone, especially when combined with resistance training. Some studies suggest that creatine may also be favorable for cognitive function, yet these independent effects have not been thoroughly reviewed in older adults. OBJECTIVE: The objective of this study was to systematically examine the current literature on creatine and cognition in older adults. DATA SOURCES: A comprehensive search was conducted across eight electronic databases. DATA EXTRACTION: Original peer-reviewed studies investigating creatine supplementation and/or estimations of dietary creatine intake in older adults (aged 55+ years) with cognition assessed as an outcome were included. Studies not examining creatine and cognition exclusively, only in combination with another intervention (e.g., resistance training), were excluded. The methodological quality of each study was evaluated using a modified version of the Downs and Black (1998) checklist. DATA ANALYSIS: Six studies were included, with a total of 1542 participants (55.7% female). Most participant samples included healthy community-dwelling older adults, with the exception of one study examining overweight older women. Two studies were double-blind interventions in which participants were supplemented with creatine monohydrate. Four studies were cross-sectional and estimated creatine consumption through dietary recall. Five of the six (83.3%) studies reported a positive relationship between creatine and cognition in older adults, particularly in the domains of memory and attention. One study achieved a methodological quality rating of "good", two "fair", and three "poor". CONCLUSION: The current limited evidence suggests that creatine may be associated with benefits for cognition in generally healthy older adults. However, high-quality clinical trials are warranted to further validate this relationship. Future research should investigate creatine supplementation in older clinical populations with notabl

BACKGROUND: Wrestling is a popular combat sport that requires muscular strength, power, agility, and endurance. Weight classes have motivated wrestlers to compete at a lower weight to optimise power-to-weight ratio and performance. To achieve these characteristics, athletes may use dietary supplements, however, their efficacy in wrestlers has not been systematically evaluated. OBJECTIVE: The purpose was to systematically review the literature to determine the efficacy of dietary supplements to improve body composition, physiological status, and performance in wrestlers. METHODS: A systematic search was conducted in PubMed, ProQuest Medline, Web of Science, Cochrane Library, and Scopus on the 21st of January 2024 and updated on the 6th of January 2025. Studies were included if the participants were healthy wrestlers ingesting any type of dietary supplement in comparison to a control. Data associated with intervention type and characteristics, target populations, outcomes, and analysis methods were extracted. RESULTS: A total of 24 eligible original articles were included that assessed various supplementation strategies on body composition, exercise performance, and metabolic markers in wrestlers. Individual studies revealed significant effects of sodium citrate, creatine monohydrate, spirulina, green tea and oolong tea extracts, and branched-chain amino acids on body mass or composition. β-Hydroxy-β-methylbutyrate (HMB-FA), creatine monohydrate, and iron supplementation improved recovery and may improve exercise performance. Beet-root juice supplementation enhanced muscular strength and balance. BCAA supplementation produced mixed results on muscle damage biomarkers and performance, while sodium citrate, creatine, and spirulina can act as buffering agents. Thyme tea appears to improve antioxidant capacity. CONCLUSIONS: Overall, individual studies show some promise for several dietary supplements to alter body mass and body composition, improve exercise recovery and performance, delay fatigue, and modify serum biomarkers; nevertheless, effect sizes were often small, and results were often mixed. © 2025. The Author(s).

BACKGROUND: Patients with end-stage renal disease undergoing dialysis suffer from muscle cramps, a prevalent and burdensome symptom for which there is a paucity of efficient and safe treatments. AIM: What is the efficacy and safety of pharmacological interventions for the treatment of dialysis-related muscle cramps? DESIGN: A systematic review was conducted in OVID, CINAHL, PubMed, Web of Science, and Central Cochrane databases up to August 25, 2023. DATA SOURCES: Experimental studies reporting on a pharmacological intervention for the treatment of dialysis-related muscle cramps were included. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis, and the studies quality was assessed with the RoB2 tool. RESULTS: A total of 4660 studies were retrieved, and 13 articles were included. The studies reported on nine interventions: vitamin C, vitamin E, vitamin K2, vitamin B7, dextrose solutions, gabapentin, sodium chloride, creatine monohydrate, and L-carnitine. The studies testing L-carnitine and creatine monohydrate were the only ones deemed to have a low risk of bias. Side effects were reported in only two trials, consisting primarily of gastrointestinal discomfort and hyperglycemia. Vitamins C and E are the two most studied interventions that showed positive results in reducing the frequency, severity, and duration of dialysis-related muscle cramps. L-carnitine is a promising intervention that warrants further investigation. CONCLUSION: Our review consolidates the existing evidence, elucidating the range of treatments along with their potential benefits and limitations. Future studies should uphold high-quality standards, incorporate patient-reported outcomes, and utilize well-defined, robust samples to improve patient care. © 2024 Wiley Periodicals LLC.

It is estimated that three to five million sports injuries occur worldwide each year. The highest incidence is reported during competition periods with mainly affectation of the musculoskeletal tissue. For appropriate nutritional management and correct use of nutritional supplements, it is important to individualize based on clinical effects and know the adaptive response during the rehabilitation phase after a sports injury in athletes. Therefore, the aim of this PRISMA in Exercise, Rehabilitation, Sport Medicine and Sports Science PERSiST-based systematic integrative review was to perform an update on nutritional strategies during the rehabilitation phase of musculoskeletal injuries in elite athletes. After searching the following databases: PubMed/Medline, Scopus, PEDro, and Google Scholar, a total of 18 studies met the inclusion criteria (Price Index: 66.6%). The risk of bias assessment for randomized controlled trials was performed using the RoB 2.0 tool while review articles were evaluated using the AMSTAR 2.0 items. Based on the main findings of the selected studies, nutritional strategies that benefit the rehabilitation process in injured athletes include balanced energy intake, and a high-protein and carbohydrate-rich diet. Supportive supervision should be provided to avoid low energy availability. The potential of supplementation with collagen, creatine monohydrate, omega-3 (fish oils), and vitamin D requires further research although the effects are quite promising. It is worth noting the lack of clinical research in injured athletes and the higher number of reviews in the last 10 years. After analyzing the current quantitative and non-quantitative evidence, we encourage researchers to conduct further clinical research studies evaluating doses of the discussed nutrients during the rehabilitation process to confirm findings, but also follow international guidelines at the time to review scientific literature.

Fazio, C, Elder, CL, and Harris, MM. Efficacy of alternative forms of creatine supplementation on improving performance and body composition in healthy subjects: a systematic review. J Strength Cond Res 36(9): 2663-2670, 2022-Novel forms of creatine have appeared in the marketplace with substantial claims of improved efficacy compared to creatine monohydrate (CrM). The purpose of this study was to conduct a systematic review on alternative forms of creatine to determine (a) whether they are effective ergogenic aids and (b) whether they outperform CrM. A separate comparison was conducted to determine average cost of various forms of creatine. Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Medline, and Google Scholar were systematically reviewed according to PRISMA guidelines. The design of the review was set to answer the PICOS model (subjects, interventions, comparators, outcomes, and study design). Seventeen randomized placebo controlled clinical trials examining exercise performance outcomes and body composition were included in the analysis. Magnesium-creatine chelate and creatine citrate, malate, ethyl ester, nitrate, and pyruvate were the only forms researched in the literature. Of these studies, only 3 studies compared the alternative creatine form to CrM, making it difficult to compare efficacy to CrM. There were no consistent findings of performance enhancement among alternative forms of creatine when compared to placebo. A review of the marketplace shows that CrM is the lowest cost form of creatine. Due to the paucity of studies on alternative forms of creatine as well as high prices on the market of these alternative forms, CrM remains as the most extensively studied form of creatine that shows efficacy, safety, and lowest cost to consumer.