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

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, 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. 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/ ).

Is It Time for a Requiem for Creatine Supplementation-Induced Kidney Failure? A Narrative Review.

Creatine has become one of the most popular dietary supplements among a wide range of healthy and clinical populations. However, its potential adverse effects on kidney health are still a matter of concern. This is a narrative review of the effects of creatine supplementation on kidney function. Despite a few case reports and animal studies suggesting that creatine may impair kidney function, clinical trials with controlled designs do not support this claim. Creatine supplementation may increase serum creatinine (Crn) concentration for some individuals, but it does not necessarily indicate kidney dysfunction, as creatine is spontaneously converted into Crn. Based on studies assessing kidney function using reliable methods, creatine supplements have been shown to be safe for human consumption. Further studies with people who have pre-existing kidney disease remain necessary.

Influence of CReatine supplementation on mUScle mass and strength after stroke (ICaRUS Stroke Trial): study protocol for a randomized controlled trial.

BACKGROUND: Stroke is a leading cause of mortality and disability, and its sequelae are associated with inadequate food intake which can lead to sarcopenia. The aim of this study is to verify the effectiveness of creatine supplementation on functional capacity, strength, and changes in muscle mass during hospitalization for stroke compared to usual care. An exploratory subanalysis will be performed to assess the inflammatory profiles of all participants, in addition to a follow-up 90 days after stroke, to verify functional capacity, muscle strength, mortality, and quality of life. METHODS: Randomized, double-blind, unicenter, parallel-group trial including individuals with ischemic stroke in the acute phase. The duration of the trial for the individual subject will be approximately 90 days, and each subject will attend a maximum of three visits. Clinical, biochemical, anthropometric, body composition, muscle strength, functional capacity, degree of dependence, and quality of life assessments will be performed. Thirty participants will be divided into two groups: intervention (patients will intake one sachet containing 10g of creatine twice a day) and control (patients will intake one sachet containing 10g of placebo [maltodextrin] twice a day). Both groups will receive supplementation with powdered milk protein serum isolate to achieve the goal of 1.5g of protein/kg of body weight/day and daily physiotherapy according to the current rehabilitation guidelines for patients with stroke. Supplementation will be offered during the 7-day hospitalization. The primary outcomes will be functional capacity, strength, and changes in muscle mass after the intervention as assessed by the Modified Rankin Scale, Timed Up and Go test, handgrip strength, 30-s chair stand test, muscle ultrasonography, electrical bioimpedance, and identification of muscle degradation markers by D3-methylhistidine. Follow-up will be performed 90 days after stroke to verify functional capacity, muscle strength, mortality, and quality of life. DISCUSSION: The older population has specific nutrient needs, especially for muscle mass and function maintenance. Considering that stroke is a potentially disabling event that can lead the affected individual to present with numerous sequelae, it is crucial to study the mechanisms of muscle mass loss and understand how adequate supplementation can help these patients to better recover. TRIAL REGISTRATION: The Brazilian Clinical Trials Registry (ReBEC) RBR-9q7gg4 . Registered on 21 January 2019.

Creatine Supplementation to Improve Sarcopenia in Chronic Liver Disease: Facts and Perspectives.

Creatine supplementation has been one of the most studied and useful ergogenic nutritional support for athletes to improve performance, strength, and muscular mass. Over time creatine has shown beneficial effects in several human disease conditions. This review aims to summarise the current evidence for creatine supplementation in advanced chronic liver disease and its complications, primarily in sarcopenic cirrhotic patients, because this condition is known to be associated with poor prognosis and outcomes. Although creatine supplementation in chronic liver disease seems to be barely investigated and not studied in human patients, its potential efficacy on chronic liver disease is indirectly highlighted in animal models of non-alcoholic fatty liver disease, bringing beneficial effects in the fatty liver. Similarly, encephalopathy and fatigue seem to have beneficial effects. Creatine supplementation has demonstrated effects in sarcopenia in the elderly with and without resistance training suggesting a potential role in improving this condition in patients with advanced chronic liver disease. Creatine supplementation could address several critical points of chronic liver disease and its complications. Further studies are needed to support the clinical burden of this hypothesis.

Bioavailability, Efficacy, Safety, and Regulatory Status of Creatine and Related Compounds: A Critical Review.

In 2011, we published a paper providing an overview about the bioavailability, efficacy, and regulatory status of creatine monohydrate (CrM), as well as other "novel forms" of creatine that were being marketed at the time. This paper concluded that no other purported form of creatine had been shown to be a more effective source of creatine than CrM, and that CrM was recognized by international regulatory authorities as safe for use in dietary supplements. Moreover, that most purported "forms" of creatine that were being marketed at the time were either less bioavailable, less effective, more expensive, and/or not sufficiently studied in terms of safety and/or efficacy. We also provided examples of several "forms" of creatine that were being marketed that were not bioavailable sources of creatine or less effective than CrM in comparative effectiveness trials. We had hoped that this paper would encourage supplement manufacturers to use CrM in dietary supplements given the overwhelming efficacy and safety profile. Alternatively, encourage them to conduct research to show their purported "form" of creatine was a bioavailable, effective, and safe source of creatine before making unsubstantiated claims of greater efficacy and/or safety than CrM. Unfortunately, unsupported misrepresentations about the effectiveness and safety of various "forms" of creatine have continued. The purpose of this critical review is to: (1) provide an overview of the physiochemical properties, bioavailability, and safety of CrM; (2) describe the data needed to substantiate claims that a "novel form" of creatine is a bioavailable, effective, and safe source of creatine; (3) examine whether other marketed sources of creatine are more effective sources of creatine than CrM; (4) provide an update about the regulatory status of CrM and other purported sources of creatine sold as dietary supplements; and (5) provide guidance regarding the type of research needed to validate that a purported "new form" of creatine is a bioavailable, effective and safe source of creatine for dietary supplements. Based on this analysis, we categorized forms of creatine that are being sold as dietary supplements as either having strong, some, or no evidence of bioavailability and safety. As will be seen, CrM continues to be the only source of creatine that has substantial evidence to support bioavailability, efficacy, and safety. Additionally, CrM is the source of creatine recommended explicitly by professional societies and organizations and approved for use in global markets as a dietary ingredient or food additive.

Timing of Creatine Supplementation around Exercise: A Real Concern?

Creatine has been considered an effective ergogenic aid for several decades; it can help athletes engaged in a variety of sports and obtain performance gains. Creatine supplementation increases muscle creatine stores; several factors have been identified that may modify the intramuscular increase and subsequent performance benefits, including baseline muscle Cr content, type II muscle fibre content and size, habitual dietary intake of Cr, aging, and exercise. Timing of creatine supplementation in relation to exercise has recently been proposed as an important consideration to optimise muscle loading and performance gains, although current consensus is lacking regarding the ideal ingestion time. Research has shifted towards comparing creatine supplementation strategies pre-, during-, or post-exercise. Emerging evidence suggests greater benefits when creatine is consumed after exercise compared to pre-exercise, although methodological limitations currently preclude solid conclusions. Furthermore, physiological and mechanistic data are lacking, in regard to claims that the timing of creatine supplementation around exercise moderates gains in muscle creatine and exercise performance. This review discusses novel scientific evidence on the timing of creatine intake, the possible mechanisms that may be involved, and whether the timing of creatine supplementation around exercise is truly a real concern.

Treatment efficacy of high-dose creatine supplementation in a child with creatine transporter (SLC6A8) deficiency.

BACKGROUND: Creatine transporter deficiency is an inborn error of metabolism caused by a deficiency in the creatine transporter protein encoded by the SLC6A8 gene. Previous treatment with creatine supplementation, either alone or in combination with creatine precursors (arginine or glycine), has been attempted; the efficacy of therapy, however, remains controversial. METHODS AND RESULTS: To analyze the treatment efficacy of high-dose creatine supplementation on creatine transporter deficiency, we reported a child diagnosed with creatine transporter deficiency, who was treated with a conventional dose of creatine (400 mg/kg/d) for 1 month, then twice the dose (800 mg/kg/d) for 2 months, and finally 3 times the dose (1200 mg/kg/d) for 3 months. The patient tolerated the treatment well and showed improvements in muscle mass and strength when the creatine dose was gradually increased to 1200 mg/kg/d. However, when assessed by proton magnetic resonance spectroscopy (H-MRS), the brain creatine concentration did not increase, and there was no improvement in speech and neurodevelopmental symptoms. CONCLUSION: We conclude that high-dose creatine supplementation (1200 mg/kg/d) alone improved muscular symptoms, but did not improve cognitive symptoms and brain creatine concentration assessed using H-MRS. Therefore, new treatment strategies are required for the management of creatine transporter deficiency.

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

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.

Associations between legal performance-enhancing substance use and future cardiovascular disease risk factors in young adults: A prospective cohort study.

BACKGROUND: Legal performance-enhancing substances (PES), such as creatine, are commonly used by adolescents and young adults. As PES are mostly unregulated by the US Food and Drug Administration, there has been limited empirical attention devoted to examining their long-term safety and health outcomes. Preliminary studies have demonstrated associations between PES use and severe medical events, including hospitalizations and death. PES could be linked to cardiovascular disease (CVD), the most common cause of mortality in the US, by altering the myocardium, vasculature, or metabolism. The objective of this study was to examine prospective associations between the use of legal PES in young adulthood and CVD risk factors at seven-year follow-up. MATERIALS AND METHODS: Nationally representative longitudinal cohort data from the National Longitudinal Study of Adolescent to Adult Health, Waves III (2001-2002) and IV (2008), were analyzed. Regression models determined the prospective association between the use of legal PES (e.g. creatine monohydrate) and CVD risk factors (e.g. body mass index, diabetes, hypertension, hyperlipidemia), adjusting for relevant covariates. RESULTS: Among the diverse sample of 11,996 male and female participants, no significant differences by PES use in body mass index, diabetes, hypertension, or hyperlipidemia were noted at Wave III. In unadjusted comparisons, legal PES users (versus non-users) were more likely to be White, be male, be college educated, drink alcohol, and engage in weightlifting, exercise, individual sports, team sports, and other strength training. There were no significant prospective associations between legal PES use at Wave III and body mass index, hemoglobin A1c, systolic and diastolic blood pressure, and cholesterol (total, HDL, LDL, triglycerides) deciles at seven-year follow-up (Wave IV), adjusting for demographics, health behaviors, and Wave III CVD risk factors. Similarly, there were no significant prospective associations between legal PES use and diabetes, hypertension, or hyperlipidemia based on objective measures or self-reported medications and diagnoses, adjusting for demographics, health behaviors, and Wave III CVD risk. CONCLUSIONS: We do not find evidence for a prospective association between legal PES use and CVD risk factors in young adults over seven years of follow-up, including BMI, diabetes, hypertension, or hyperlipidemia. It should be noted that legal PES use was operationalized dichotomously and as one broad category, which did not account for frequency, amount, or duration of use. Given the lack of regulation and clinical trials data, observational studies can provide much needed data to inform the safety and long-term health associations of legal PES use and, in turn, inform clinical guidance and policy.

Legal Performance-Enhancing Substances and Substance Use Problems Among Young Adults.

BACKGROUND: Legal performance-enhancing substance(s) (PES) (eg, creatine) are widely used among adolescent boys and young men; however, little is known about their temporal associations with substance use behaviors. METHODS: We analyzed prospective cohort data from the National Longitudinal Study of Adolescent to Adult Health, Waves I to IV (1994-2008). Logistic regressions were used to first assess adolescent substance use (Wave I) and use of legal PES (Wave III) and second to assess use of legal PES (Wave III) and subsequent substance use-associated risk behaviors (Wave IV), adjusting for potential confounders. RESULTS: Among the sample of 12 133 young adults aged 18 to 26 years, 16.1% of young men and 1.2% of young women reported using legal PES in the past year. Adolescent alcohol use was prospectively associated with legal PES use in young men (odds ratio 1.39; 95% confidence interval [CI] 1.13-1.70). Among young men, legal PES use was prospectively associated with higher odds of problematic alcohol use and drinking-related risk behaviors, including binge drinking (adjusted odds ratio [aOR] 1.35; 95% CI 1.07-1.71), injurious and risky behaviors (aOR 1.78; 95% CI 1.43-2.21), legal problems (aOR 1.52; 95% CI 1.08-2.13), cutting down on activities and socialization (aOR 1.91; 95% CI 1.36-2.78), and emotional or physical health problems (aOR 1.44; 95% CI 1.04-1.99). Among young women, legal PES use was prospectively associated with higher odds of emotional or physical health problems (aOR 3.00; 95% CI 1.20-7.44). CONCLUSIONS: Use of legal PES should be considered a gateway to future problematic alcohol use and drinking-related risk behaviors, particularly among young men.

Risk of Adverse Outcomes in Females Taking Oral Creatine Monohydrate: A Systematic Review and Meta-Analysis.

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.

Creatine supplementation improves performance, but is it safe? Double-blind placebo-controlled study.

BACKGROUND: Creatine represents a natural supplement and ergogenic aid for sport performance, but there are several concerns regarding its safety for health. The present double-blind placebo-controlled study evaluated the effect of creatine monohydrate supplementation on a panel of blood and urine health indicators in resistance training practitioners. METHODS: Eighteen males performing resistance training three times per week were supplemented with 0.3 g/kg per day creatine monohydrate for 7 days and compared with matched controls supplemented with dextrosol. Blood and urine samples were collected pre- and 30 days post-supplementation to evaluate 41 biochemical parameters and renal function. RESULTS: Creatine monohydrate supplementation did not cause adverse events and, as expected, promoted an increase of the performance and body weight. No modification of red blood cells parameters, white blood cells profile, blood lipid profile, metabolic and urine markers, hepatic and renal function were observed in the supplemented group. CONCLUSIONS: Despite the expected weight increase, the creatine monohydrate supplementation is safe for health and no detrimental effects on different organs and physiological systems were observed in our cohort of volunteers.

Selection design phase II trial of high dosages of tamoxifen and creatine in amyotrophic lateral sclerosis.

Objective: To conduct a phase-II trial using a ranking and selection paradigm where multiple treatments are compared with limited sample size and the best is chosen for a subsequent efficacy trial versus placebo. This strategy can find an effective treatment faster than traditional strategy of conducting larger trials against placebo. Methods: Sixty amyotrophic lateral sclerosis (ALS) participants were randomized 1:1:1 to creatine 30 g/day (CRE), tamoxifen 40 mg/day (T40), or tamoxifen 80 mg/day (T80), with matching placebo. The primary outcome was 38-week change in ALS Functional Rating Scale-Revised (ALSFRS-R), analyzed in a repeated-measures ANOVA. Secondary outcomes included slow vital capacity (SVC), quantitative muscle strength, early drug discontinuation (EDD), adverse events (AEs), and survival. Results: CRE participants experienced higher rates of drug-related AEs (82% vs. 43% T40, 47% T80) and EDD (50% vs. 24% T40, 29% T80). T80 participants experienced slower adjusted mean decline in ALSFRS-R in points/month (-0.80 vs. -0.84 T40, -0.85 CRE) and quantitative muscle strength but not in SVC and higher rates of mortality. Conclusion: Efficacy of T80 ranked numerically superior to CRE and T40 with respect to ALSFRS-R decline. Following the selection paradigm, T80 would be chosen to test against placebo. The approach was not designed to distinguish among treatments that are nearly equally effective or ineffective. If treatments are equivalent, then under the paradigm, it does not matter which treatment is selected. Newer approaches for increasing trial efficiency, including an adaptive platform trial design, may mitigate limitations of the selection design.

Does Creatine Supplementation Affect Renal Function in Patients with Peripheral Artery Disease? A Randomized, Double Blind, Placebo-controlled, Clinical Trial.

BACKGROUND: Case studies and reviews have shown that creatine supplementation can affect kidney function. The objective of this study is to verify the effects of 8 weeks of creatine supplementation on renal function (creatinine clearance: primary outcome) in patients with symptomatic peripheral arterial disease. METHODS: Twenty-nine patients, of both genders, 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 4 equal doses (loading phase), followed by single daily doses of 5 g in the subsequent 7 weeks (maintenance phase). Before and after the supplementation period, markers of renal function, serum creatinine, creatinine excretion rate, and creatinine clearance were evaluated. The Generalized Estimation Equation Model was used for comparison between groups. The level of significance was P < 0.05. RESULTS: No significant differences were found between groups before and after the intervention for serum creatinine (Cr: pre 1.00 ± 0.15 mL/dL vs. post 1.07 ± 0.16 mL/dL; PLA: pre 1.30 ± 0.53 mL/dL vs. post 1.36 ± 0.47 mL/dL, P = 0.590), creatinine excretion rate (Cr: pre 81.73 ± 43.80 mg/dL vs. post 102.92 ± 59.57 mg/dL; PLA: pre 74.37 ± 38.90 mg/dL vs. post 86.22 ± 39.94 mg/dL, P = 0.560), or creatinine clearance (Cr; pre 108 ± 59 mL/min/1.73 m2 vs. post 117 ± 52 mL/min/1.73 m2; PLA: pre 88 ± 49 mL/min/1.73 m2 vs. post 82 ± 47 mL/min/1.73 m2, P = 0.366). CONCLUSIONS: Eight weeks of creatine supplementation is safe and does not compromise the renal function of patients with peripheral arterial disease.

[Effects of creatine supplementation on renal function]. / Efectos en la función renal de la suplementación de creatina con fines deportivos.

Creatine supplements may transitorily rise serum creatinine levels and mimic a kidney disease. If its use is associated with a high protein diet, the resulting increase in blood urea nitrogen will increase the confusion. Since clinical laboratories usually inform the estimated glomerular filtration rate based on serum creatinine, its elevation may lead to over diagnose a chronic renal failure, with the inherent personal and public health consequences. Creatine supplements are safe and do not cause renal disease. Reports of kidney damage associated with its use are scanty. However, creatine supplements should not be used in people with chronic renal disease or using potentially nephrotoxic medications.

Effects of Creatine Supplementation on Renal Function: A Systematic Review and Meta-Analysis.

Creatine supplements are intended to improve performance, but there are indications that it can overwhelm liver and kidney functions, reduce the quality of life, and increase mortality. Therefore, this is the first systematic review and meta-analysis study that aimed to investigate creatine supplements and their possible renal function side effects. After evaluating 290 non-duplicated studies, 15 were included in the qualitative analysis and 6 in the quantitative analysis. The results of the meta-analysis suggest that creatine supplementation did not significantly alter serum creatinine levels (standardized mean difference = 0.48, 95% confidence interval 0.24-0.73, P = .001, I2 = 22%), and did not alter plasma urea values (standardized mean difference = 1.10, 95% confidence interval 0.34-1.85, P = .004, I2 = 28%). The findings indicate that creatine supplementation does not induce renal damage in the studied amounts and durations.

Efectos en la función renal de la suplementación de creatina con fines deportivos / Effects of creatine supplementation on renal function

Creatine supplements may transitorily rise serum creatinine levels and mimic a kidney disease. If its use is associated with a high protein diet, the resulting increase in blood urea nitrogen will increase the confusion. Since clinical laboratories usually inform the estimated glomerular filtration rate based on serum creatinine, its elevation may lead to over diagnose a chronic renal failure, with the inherent personal and public health consequences. Creatine supplements are safe and do not cause renal disease. Reports of kidney damage associated with its use are scanty. However, creatine supplements should not be used in people with chronic renal disease or using potentially nephrotoxic medications.

Effect of Creatine Supplementation on the Airways of Youth Elite Soccer Players.

INTRODUCTION: Owing to its well-established ergogenic potential, creatine is a highly popular food supplement in sports. As an oral supplement, creatine is considered safe and ethical. However, no data exist on the safety of creatine on lung function in athletes. The aim of this project was to evaluate the effects of a standard course of creatine on the airways of youth elite athletes. METHODS: Nineteen elite soccer players, 16-21 yr old, completed a stratified, randomized, double-blind, placebo-controlled, parallel-group trial. The creatine group (n = 9) ingested 0.3 g·kg⋅d of creatine monohydrate (CM) for 1 wk (loading phase) and 5 g·d for 7 wk (maintenance phase), and the placebo group (n = 10) received the same dosages of maltodextrin. Airway inflammation (assessed by exhaled nitric oxide, FENO) and airway responsiveness (to dry air hyperpnoea) were measured pre- and postsupplementation. RESULTS: Mild, unfavorable changes in FENO were noticed by trend over the supplementation period in the CM group only (P = 0.056 for interaction, η = 0.199), with a mean group change of 9 ± 13 ppb in the CM group versus -5 ± 16 ppb in the placebo group (P = 0.056, d = 0.695). Further, the maximum fall in forced expiratory volume in 1 s after dry air hyperpnoea was larger by trend postsupplementation in the CM group compared with the placebo group: 9.7% ± 7.5% vs 4.4% ± 1.4%, respectively (P = 0.070, d = 0.975). These adverse effects were more pronounced when atopic players only (n = 15) were considered. CONCLUSION: On the basis of the observed trends and medium to large effect sizes, we cannot exclude that creatine supplementation has an adverse effect on the airways of elite athletes, particularly in those with allergic sensitization. Further safety profiling of the ergogenic food supplement is warranted.

Potential Adverse Effects of Creatine Supplement on the Kidney in Athletes and Bodybuilders.

INTRODUCTION: Nowadays, creatine is one of the most common oral supplements used by professional athletes for boosting their strength and muscle mass. In this review, we collect available experimental and clinical data about renal safety of both short-term and long-term use of creatine. MATERIALS AND METHODS: Scientific literature was critically searched by keywords "creatine," "renal insufficiency," and "renal dysfunction" and their synonyms in medical databases (Scopus, MEDLINE, EMBase, and ISI Web of Knowledge). Overall, 19 relevant clinical and experimental articles were selected for this review. RESULTS: Short- and long-term creatine supplementations (range, 5 days to 5 years) with different doses (range, 5 g/d to 30 g/d) had no known significant effects on different studied indexes of kidney function such as glomerular filtration rate at least in healthy athletes and bodybuilders with no underlying kidney diseases. In addition, although short-term (range, 5 days to 2 weeks) high-dose oral creatine supplementation (range, 20 g/d to 0.3 g/kg/d) stimulated the production of methylamine and formaldehyde (as potential cytotoxic metabolites of creatine) in the urine of healthy humans, there was currently no definite clinical evidence about their adverse effects on the kidney function. CONCLUSIONS: Although creatine supplementation appears to have no detrimental effects on kidney function of individuals without underlying kidney diseases, it seems more advisable to suggest that creatine supplementation not to be used by sportsmen or women with pre-existing kidney disease or those with a potential risk for kidney dysfunction.