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The creatine kinase system is crucial for maintaining cellular energy homeostasis and plays a role in regulating locomotor behavior in organisms, but its significance in the regulating the motionless behavior in olive flounder is limited. In the first experiment of this study, elevated levels of creatine kinase (CK) activity in the spinal cord were detected in the juvenile group (JG) flounder compared to the adult group (AG) flounder. In the second experiment, to further confirm the involvement of CK in the locomotor behavior, the adult flounder was given an intraperitoneal injection of creatine (150 mg/kg), while the flounder in the control group received a saline solution. After one week post-injection, the behavioral analysis revealed that the flounder in the creatine-treated group displayed higher levels of locomotor activity and a greater number of escape attempts in response to external stimuli when compared to the control group. However, the acute stress response, induced by intraperitoneal injection and characterized by tail beating, was significantly alleviated in the flounder in the creatine-treated group. Additionally, there was an upregulation of the UII and AchR genes in the spinal cord, as well as increased levels of UII and AchR in the muscle tissues of the creatine-treated flounder. However, a reduction in UI mRNA levels was observed in the brain of the flounder. Collectively, our data provide the evidence that the elevated enzyme activity and gene expression of creatine kinase play important roles in off-bottom swimming behavior in the JG flounder. Furthermore, administration of creatine improved the locomotor activity and alleviated the stress response in flounder, which is associated with regulation of the locomotor- and stress-related gene in the brain, spinal cord, and muscle., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the study in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Creatine supplementation is ubiquitously consumed by fitness enthusiasts due to its perceived advantages in enhancing athletic performance. Although there is an increasing concern within this demographic regarding its possible impact on renal function, there is still a lack of rigorous scientific investigations into this alleged association., Methods: Data were collected through an online survey on the participants' demographics, creatine usage and concerns related to renal function. The reliability and validity of the survey were assessed using SPSS software. A total of 1129 participants responded to the survey, and chi-square tests were utilized for data analysis. To explore the potential association between creatine levels (as the exposure) and renal function (as the outcome), we utilized open-access genetic databases, and Mendelian randomization (MR) techniques were used to confirm this correlation., Results: Chi-square analysis revealed no significant association between creatine usage and renal function among the participants. Our MR analysis further supported this finding, demonstrating no significant association between creatine levels and six indicators assessing renal function (IVW, all with p values exceeding 0.05). Similar p values were consistently observed across other MR methods, confirming the absence of a statistical correlation., Conclusions: This MR study offers compelling evidence indicating that creatine levels are not statistically associated with renal function, suggesting the potential to alleviate concerns within the fitness community and emphasizing the significance of evidence-based decision-making when considering nutritional supplementation.

Background: Gym-goers usually seek methods to improve performance, muscle gain, and overall health. One of the main strategies is including food supplements (FS) into their routine as aids to enhance their athletic capabilities and satisfy their nutritional needs. Thus, this study aimed to investigate and characterize the main FS and Sports Foods (SF) currently consumed, as well as the main reasons for their use and the source of advice in a group of gym-goers in the Lisbon Metropolitan Area (Portugal)., Methods: A cross-sectional study was conducted, including 303 gym-goers from Lisbon, Portugal, who were 133 women and 170 males (30.8 ± 12.9 years old). Face-to-face interviews were used by qualified researchers to gather data., Results: Most of the interviewed athletes (71.95 %) took FS/SF, being men the main consumers. On average, 1.59 supplements were consumed per athlete. Logistic regression models indicated significant associations between age, gender, and motivations for gym attendance. While men and younger groups attended mainly for hypertrophy, women and older groups were focused on well-being. Protein (59.17 %) was the most used FS/SF, followed by creatine (41.28 %) and multivitamins (27.06 %). Men and younger individuals preferred protein and creatine, while older individuals focused more on specific vitamins and minerals. Women seemed to prefer L-carnitine and protein yogurts. Main sources of information included the internet, friends, and dietitians with notable gender and age-based preferences. Online stores were the main place of purchase. Monthly expenditures on FS/SF were not significantly affected by age or gender, but motivations for use had an influence., Conclusion: Most of the athletes interviewed took FS/SF, being men the major consumers. Protein was the principal FS/SF used, with online stores being the main place of purchase and the internet the primary source of information. Age and gender were key factors in adopted training, in the FS/SF chosen, and in the source of information selected. It is crucial that health professionals take primary responsibility for providing this guidance.

Background: Despite the robust evidence demonstrating positive effects from creatine supplementation (primarily when associated with resistance training) on measures of body composition, there is a lack of a comprehensive evaluation regarding the influence of creatine protocol parameters (including dose and form) on body mass and estimates of fat-free and fat mass., Methods: Randomized controlled trials (RCTs) evaluating the effect of creatine supplementation on body composition were included. Electronic databases, including PubMed, Web of Science, and Scopus were searched up to July 2023. Heterogeneity tests were performed. Random effect models were assessed based on the heterogeneity tests, and pooled data were examined to determine the weighted mean difference (WMD) with a 95% confidence interval (CI)., Results: From 4831 initial records, a total of 143 studies met the inclusion criteria. Creatine supplementation increased body mass (WMD: 0.86 kg; 95% CI: 0.76 to 0.96, I 2  = 0%) and fat-free mass (WMD: 0.82 kg; 95% CI: 0.57 to 1.06, I 2  = 0%) while reducing body fat percentage (WMD: -0.28 %; 95% CI: -0.47 to -0.09; I 2  = 0%). Studies that incorporated a maintenance dose of creatine or performed resistance training in conjunction with supplementation had greater effects on body composition., Conclusion: Creatine supplementation has a small effect on body mass and estimates of fat-free mass and body fat percentage. These findings were more robust when combined with resistance training.

Purpose of Review: Sarcopenia, generally characterized by the age-related reduction in muscle strength, lean/muscle mass and functional ability, is also associated with reduced bone mass and strength and impaired brain health and function. One potential intervention which has received much 'hype' over the past few decades to countermeasure these negative consequences of biological aging is creatine monohydrate supplementation., Recent Findings: From a skeletal muscle perspective, the combination of creatine monohydrate supplementation and resistance training provides 'hope' for older adults as it improves measures of lean mass, regional (limb) muscle thickness, upper- and lower-body muscle strength and functional ability. Further, there is some evidence that creatine (supplementation or habitual diet) provides a ray of 'hope' for improving some aspects of cognitive function. The majority of research suggests that creatine is more 'hype' than 'hope' for improving measures of bone mass in older adults. Creatine monohydrate supplementation provides some anti-sarcopenic benefits for older adults., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Skeletal muscle satellite cells (SC) contribute to the adaptive process of resistance exercise training (RET) and may be influenced by nutritional supplementation. However, little research exists on the impact of multi-ingredient supplementation on the SC response to RET., Purpose: We tested the effect of a multi-ingredient supplement (MIS) including whey protein, creatine, leucine, calcium citrate, and vitamin D on SC content and activity as well as myonuclear accretion, SC and myonuclear domain compared with a collagen control (COL) throughout a 10-wk RET program., Methods: Twenty-six participants underwent a 10-wk linear RET program while consuming either the MIS or COL supplement twice daily. Muscle biopsies were taken from the vastus lateralis at baseline and 48 h after a bout of damaging exercise, before and after RET. Muscle tissue was analyzed for SC and myonuclear content, domain, acute SC activation, and fiber cross-sectional area (fCSA)., Results: MIS resulted in a greater increase in type II fCSA following 10 wk of RET (effect size (ES) = 0.89) but not myonuclear accretion or SC content. Change in myonuclei per fiber was positively correlated with type I and II and total fiber hypertrophy in the COL group only, indicating a robust independent effect of MIS on fCSA. Myonuclear domain increased similarly in both groups, whereas SC domain remained unchanged following RET. SC activation was similar between groups for all fiber types in the untrained state but showed a trend toward greater increases with MIS after RET (ES = 0.70)., Conclusions: SC responses to acute damaging exercise and long-term RET are predominantly similar in MIS and COL groups. However, MIS can induce greater increases in type II fCSA with RET and potentially SC activation following damage in the trained state., (Copyright © 2024 by the American College of Sports Medicine.)

Background: Numerous meta-analyses have assessed the efficacy of creatine supplementation in increasing muscle strength. However, most have not considered the effect of the participants' age, training duration, or other confounding variables on strength outcomes. Therefore, the purpose of this study was to consider the effect of these variables on the potential efficacy of creatine supplementation and resistance training for improving measures of muscle strength., Methods: Four databases were searched (MEDLINE, Scopus, Embase, and SPORTDiscus) with a search end date of 22 May 2024. Twenty-three studies were included, with 20 studies involving males (447 male participants), 2 studies involving females (40 female participants), and 1 study involving both males and females (13 male participants and 9 female participants)., Results: In comparison with a placebo, creatine supplementation combined with resistance training significantly increased upper-body (WMD = 4.43 kg, p < 0.001) and lower-body strength (WMD = 11.35 kg, p < 0.001). Subgroup analyses showed a trend for greater upper-body strength improvements for males on creatine compared with females on creatine ( p = 0.067, Q = 3.366). Additionally, males who consumed creatine combined with resistance training significantly increased both upper- and lower-body strength, whereas females showed no significant gains. There was a trend indicating greater lower-body strength gains from high-dose creatine compared with lower doses ( p = 0.068, Q = 3.341). No other variables influenced the effect of creatine supplementation. In conclusions, creatine supplementation with resistance training enhances upper- and lower-body muscle strength in adults aged < 50, with greater benefits likely to be seen in males than females.

Background: This study examines whether creatine supplementation combined with strength training mitigates muscle mass loss in women during early rehabilitation post-bariatric surgery, as its effectiveness remains untested in this context., Methods: Fifteen women (37.8 ± 9.6 years; BMI, 38.8 ± 5.6 kg/m 2 ) completed the intervention (creatine group = 7; placebo group = 8). Both groups followed a strength training program three times a week for 8 weeks. The dosage for both the creatine and placebo was 8 g prior to each exercise session. Body weight, skeletal muscle mass, fat mass, handgrip strength, and physical activity levels were measured before and after the intervention., Results: The creatine group showed a reduction of 9.5 ± 1.5 kg in body weight, with a 0.72 ± 0.6 kg decrease in muscle mass and an 8.64 ± 1.2 kg reduction in fat mass. The placebo group had a reduction of 9.6 ± 3.5 kg in body weight, with a 0.6 ± 1.2 kg decrease in muscle mass and an 8.88 ± 3.2 kg reduction in fat mass, without significant differences between groups (p > 0.05)., Conclusion: The pre-session strength exercise training creatine supplementation is not superior to placebo regarding body weight and fat mass losses and the attenuation of muscle mass loss during the first weeks of rehabilitation following bariatric surgery., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: In the recent years creatine has been shown promising results in patients with neurodegenerative diseases, myopathies and dystrophies. Cardiovascular diseases could be another pathology that can benefit from creatine supplementation, considering the influence on the risk factors associated with the development of cardiovascular diseases including reduction in chronic inflammation, and improved control of hyperglycemia and dyslipidemia The aim of the present study was to investigate the impact of short-term creatine supplementation on cardiac and vascular health in older adults., Methods: Males between the ages of 55-80 were randomly assigned to three groups: creatine, placebo and control. Creatine or placebo was provided for 7-day supplementation, at a dose of 20 g/day. Testing was performed at the same time of the day at baseline and on the eighth day. Vascular responses were assessed using an arterial pulse wave velocity equipment, while cardiac assessment was performed using an impedance cardiography device., Results: The placebo group was older (71.1 ± 8.2 yr) compared to creatine (61.4 ± 5.2 yr) and control (62.5 ± 7.1 yr). Cardio-ankle vascular index improved just in the creatine group (8.7 ± 0.5 to 8.2 ± 0.5, p = 0.03). While the upstroke time of the placebo and control groups did not change after 7 days, the creatine group had a nonsignificant reduction, 178.9 ± 26.5 ms to 158.4 ± 28.6 ms, p = 0.07. Similar tendency was seen with the systolic blood pressures, while the placebo and control did not change, the creatine group showed nonsignificant improvement, especially on the right, 144.0 ± 12.7 mmHg to 136.1 ± 13.4 mmHg, p = 0.08. All three groups had similar responses in stroke volume (p = 0.61), contractility index (p = 0.64) and ejection fraction (p = 0.72)., Conclusions: In older adults, acute creatine supplementation can positively affect vascular parameters of arterial stiffness and atherosclerosis. Creatine supplementation has the potential to serve as a potent adjuvant in the management of CVD for older adults., Clinical Trial Registration: clinicaltrials.gov; ID: NCT05329480., Competing Interests: Declaration of competing interest Eric S. Rawson has conducted industry sponsored research involving creatine supplementation and received creatine donations for scientific studies and travel support for presentations involving creatine supplementation at scientific conferences. In addition, Eric S. Rawson serves on the Scientific Advisory Board for Alzchem (a company that manufactures creatine) and as an expert witness/consultant in legal cases involving creatine supplementation. All other authors declare no conflict of interest., (Published by Elsevier Ltd.)

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic medical condition with no specific pharmacological treatment. Creatine, a nutrient essential for maintaining energy homeostasis in the cells, is a candidate for interventions in ME/CFS., Methods: Fourteen participants with ME/CFS received supplementation with 16 g creatine monohydrate for 6 weeks. Before starting creatine and on the last day of treatment, participants underwent brain magnetic resonance spectroscopy (MRS) scanning of the pregenual anterior cingulate cortex (pgACC) and dorsolateral prefrontal cortex (DLPFC), followed by symptom, cognition, and hand-grip strength assessments., Results: Eleven participants completed the study. Creatine treatment increased creatine concentration in both the pgACC and DLPFC ( p = 0.004 and 0.012, respectively), decreased fatigue and reaction time (RT) on congruent and incongruent trials of the Stroop test ( p = 0.036 and 0.014, respectively), and increased hand-grip strength ( p = 0.0004). There was a positive correlation between increases in pgACC creatine and changes in RT on Stroop congruent and incongruent trials ( p = 0.048 and p = 0.022, respectively). Creatine was well tolerated, and none of the participants stopped treatment., Conclusion: Creatine supplementation over six weeks in ME/CFS patients increased brain creatine and improved fatigue and some aspects of cognition. Despite its methodological limitations, this study encourages placebo-controlled investigations of creatine treatment in ME/CFS.

Background/Objectives: Firefighters, tactical police officers, and warriors often engage in periodic, intermittent, high-intensity physical work in austere environmental conditions and have a heightened risk of premature mortality. In addition, tough decision-making challenges, routine sleep deprivation, and trauma exacerbate this risk. Therefore, identifying strategies to bolster these personnel's health and occupational performance is critical. Creatine monohydrate (CrM) supplementation may offer several benefits to firefighters and tactical athletes (e.g., police, security, and soldiers) due to its efficacy regarding physical performance, muscle, cardiovascular health, mental health, and cognitive performance. Methods: We conducted a narrative review of the literature with a focus on the benefits and application of creatine monohydrate among firefighters. Results: Recent evidence demonstrates that CrM can improve anaerobic exercise capacity and muscular fitness performance outcomes and aid in thermoregulation, decision-making, sleep, recovery from traumatic brain injuries (TBIs), and mental health. Emerging evidence also suggests that CrM may confer an antioxidant/anti-inflammatory effect, which may be particularly important for firefighters and those performing tactical occupations exposed to oxidative and physiological stress, which can elicit systemic inflammation and increase the risk of chronic diseases. Conclusions: This narrative review highlights the potential applications of CrM for related tactical occupations, with a particular focus on firefighters, and calls for further research into these populations.

Background/Objectives: Sports supplements have become popular among fitness enthusiasts for enhancing the adaptive response to exercise. This review analyzes five of the most effective ergogenic aids: creatine, beta-alanine, nitrates, caffeine, and protein. Methods: We conducted a narrative review of the literature with a focus on the sport supplements with the most robust evidence for efficacy and safety. Results: Creatine, one of the most studied ergogenic aids, increases phosphocreatine stores in skeletal muscles, improving ATP production during high-intensity exercises like sprinting and weightlifting. Studies show creatine supplementation enhances skeletal muscle mass, strength/power, and muscular endurance. The typical dosage is 3-5 g per day and is safe for long-term use. Beta-alanine, when combined with the amino acid histidine, elevates intramuscular carnosine, which acts as a buffer in skeletal muscles and delays fatigue during high-intensity exercise by neutralizing hydrogen ions. Individuals usually take 2-6 g daily in divided doses to minimize paresthesia. Research shows significant performance improvements in activities lasting 1-4 min. Nitrates, found in beetroot juice, enhance aerobic performance by increasing oxygen delivery to muscles, enhancing endurance, and reducing oxygen cost during exercise. The recommended dosage is approximately 500 milligrams taken 2-3 h before exercise. Caffeine, a central nervous system stimulant, reduces perceived pain while enhancing focus and alertness. Effective doses range from 3 to 6 milligrams per kilogram of body weight, typically consumed an hour before exercise. Protein supplementation supports muscle repair, growth, and recovery, especially after resistance training. The recommended intake for exercise-trained men and women varies depending on their specific goals. Concluions: In summary, creatine, beta-alanine, nitrates, caffeine, and protein are the best ergogenic aids, with strong evidence supporting their efficacy and safety.

Females historically experience sleep disturbances and overall poor sleep compared to males. Creatine has been proposed to impact sleep; however, the effects are not well known. The purpose of this study was to examine the effects of creatine supplementation on sleep among naturally menstruating females. Twenty-one participants completed a double-blind, randomized controlled trial in which they consumed 5 g creatine + 5 g maltodextrin or placebo, 10 g maltodextrin, daily for 6 weeks. Participants completed resistance training 2x/week using the TONAL ® (Tonal Systems Inc., San Francisco, CA, USA) at-home gym. Pre- and post-testing assessed body composition, Pittsburgh Sleep Quality Index (PSQI), dietary intake, and muscular strength. Sleep was assessed nightly using an ŌURA ® (Oulu, Finland) ring. Compared to the placebo group, those consuming creatine experienced significant increases in total sleep on training days ( p = 0.013). No significant changes in chronic sleep and PSQI (pre-post) were observed. There was a significant increase in TONAL ® strength score over time ( p < 0.001), with no between-group differences. Participants reduced their total calorie (kcal) ( p = 0.039), protein (g/kg) ( p = 0.009), carbohydrate (g/kg) ( p = 0.023), and fat (g) ( p = 0.036) intake over time. Creatine supplementation increases sleep duration on resistance training days in naturally menstruating females.

Background: Warfighters, often called tactical athletes, seek dietary supplementation to enhance training and recovery. Roughly 69% of active-duty US military personnel have reported consuming dietary supplements. The objective of this systematic review was to examine the impact of dietary supplements on muscle-related physical performance and recovery in active-duty military personnel., Methods: Randomized controlled trials and quasi-experimental controlled trials of oral dietary supplementation in active-duty military members were examined. A protocol was registered (PROSPERO CRD42023401472), and a systematic search of MEDLINE and CINAHL was undertaken. Inclusion criteria consisted of studies published between 1990-2023 with outcomes of muscle performance and recovery among active-duty military populations. The risk of bias was assessed with the McMaster University Guidelines and Critical Review Form for Quantitative Studies., Results: Sixteen studies were included. Four were conducted on protein or carbohydrate; four on beta-alanine alone, creatine alone, or in combination; two on mixed nutritional supplements; two on probiotics alone or in combination with beta hydroxy-beta methylbutyrate calcium; and four on phytonutrient extracts including oregano, beetroot juice, quercetin, and resveratrol. Ten examined outcomes related to physical performance, and six on outcomes of injury or recovery. Overall, protein, carbohydrate, beta-alanine, creatine, and beetroot juice modestly improved performance, while quercetin did not. Protein, carbohydrates, beta-alanine, probiotics, and oregano reduced markers of inflammation, while resveratrol did not., Conclusions: Nutrition supplementation may have small benefits on muscle performance and recovery in warfighters. However, there are significant limitations in interpretation due to the largely inconsistent evidence of ingredients and comparable outcomes. Thus, there is inadequate practical evidence to suggest how dietary supplementation may affect field performance.

Low creatine availability may be linked to an elevated risk of neuronal damage, yet this association remains inadequately explored at the population level. Utilizing 2013-2014 National Health and Nutrition Examination Survey data, the current study found a negative correlation between dietary creatine intake and serum levels of neurofilament light chain (NfL; a biomarker for neuronal damage) in a cohort of 1912 individuals (52.2% females) aged 20-75 years. This inverse association persisted even after adjusting for other nutritional variables known to influence neuronal viability. The observed pattern, where increased dietary creatine intake was associated with reduced circulating NfL levels, suggests potential protective effects of creatine against neuronal injury., Competing Interests: SMO serves as a member of the Scientific Advisory Board on Creatine in Health and Medicine (AlzChem LLC). SMO co-owns patent “Supplements Based on Liquid Creatine” at the European Patent Office (WO2019150323 A1) and patent application “Composition Comprising Creatine for Use in Telomere Lengthening” at the U.S. Patent and Trademark Office (# 63/608,850). SMO has received research support related to creatine during the past 36 months from the Serbian Ministry of Education, Science, and Technological Development; Provincial Secretariat for Higher Education and Scientific Research; Alzchem GmbH; ThermoLife International; and Hueston Hennigan LLP. SMO does not own stocks and shares in any organization. EG, SB, and JC declare no known competing financial interests or personal relationships that could have appeared to influence the authorship of this paper.

Background: In recent years, the study of creatine supplementation in professional athletes has been of great interest. However, the genetics involved in response to supplementation is unknown. The aim of this study was to analyse, for the first time, the relationship between muscle performance-related genes and the risk of an increased body mass index (BMI) and muscle mass and a decrease in fat mass in professional football players after creatine supplementation., Methods: For this longitudinal study, one hundred and sixty-one men's professional football players were recruited. The polymorphisms ACE I/D, ACTN3 c.1729C>T, AMPD1 c.34C>T, CKM c.*800A>G, and MLCK (c.49C>T and c.37885C>A) were genotyped using Single-Nucleotide Primer Extension (SNPE). To assess the combined impact of these six polymorphisms, a total genotype score (TGS) was calculated. The creatine supplementation protocol consisted of 20 g/day of creatine monohydrate for 5 days (loading dose) and 3-5 g/day for 7 weeks (maintenance dose). Anthropometric characteristics (body mass index (BMI), fat, and muscle mass) were recorded before and after the creatine supplementation protocol. Characteristics of non-contact muscle injuries during the 2022/2023 season were classified according to a consensus statement for injury recording. The results showed that the allelic frequencies of ACE and AMPD1 differed between responders and non-responders in muscle mass increase (all p < 0.05). Players with a TGS exceeding 54.16 a.u. had an odds ratio (OR) of 2.985 (95%CI: 1.560-5.711; p = 0.001) for muscle mass increase. By contrast, those with a TGS below 54.16 a.u. had an OR of 9.385 (95%CI: 4.535-19.425; p < 0.001) for suffering non-contact muscle injuries during the season., Conclusions: The increase in BMI and muscle mass in response to creatine supplementation in professional football players was influenced by a TGS derived from the combination of favourable genotypes linked to muscle performance. The CC genotype and C allele of AMPD1 were particularly associated with a higher likelihood of muscle mass increase under creatine supplementation in this group of professional football players.

There is evidence that both intra-serial variable resistance (I-sVR), as pre-activation within the post-activation performance enhancement cycle (PAPE), and creatine and caffeine supplementation increase athletic performance in isolation. However, the effect of the three conditioning factors on 30 m repeated sprint ability (RSA) performance in young soccer players is unknown. This study determined the summative and isolation effect of ergogenic aids and pre-activation in half-back squats (HBSs) with I-sVR on performance in an RSA test in young soccer players. Twenty-eight young soccer players were randomly assigned to either EG 1 ( n = 7, creatine + caffeine + I-sVR), EG 2 ( n = 7, creatine + placebo 2 + I-sVR), EG 3 ( n = 7, placebo 1 + caffeine + I-sVR), or EG 4 ( n = 7, placebo 1 + placebo 2 + I-sVR), using a factorial, four-group-matched, double-blind, placebo-controlled design. Creatine supplementation included 0.3 g/kg/day for 14 days, caffeine supplementation included 0.3 mg/kg per day, and pre-activation in HBS with I-sVR (1 × 5 at 30% 1RM [1.0-1.1 m/s] + 1 × 4 at 60% 1RM [0.6-0.7 m/s]). The RSA test and HBS outcomes were evaluated. Three-way ANOVA showed non-significant differences for the RSA test and HBS outcomes ( p > 0.05). At the end of this study, it was found that the three ergogenic aids, together, do not generate a summative effect on the physical performance of young soccer players. However, it is important to analyze individual responses to these specific protocols.

This systematic review aimed to evaluate the effectiveness of the independent or combined use of nutritional ergogenic aids belonging to Group A of the ABCD classification by the Australian Institute of Sport (AIS) in the context of cycling (caffeine, creatine, sodium bicarbonate, beta-alanine, nitrates, and glycerol). A comprehensive search was carried out using three databases: PubMed, Scopus, and Web of Science. All the databases were searched for Randomized Controlled Trials or crossover design studies assessing the effects of supplementation on cycling performance in comparison with placebos in healthy adults. The methodological quality of each study was evaluated using the Physiotherapy Evidence Database scale. Thirty-six articles involving 701 participants were included in this review, examining supplementation with caffeine (n = 5), creatine (n = 2), sodium bicarbonate (n = 6), beta-alanine (n = 3), and nitrates (n = 8). Additionally, supplemental combinations of caffeine and creatine (n = 3), caffeine and sodium bicarbonate (n = 3), caffeine and nitrates (n = 1), creatine and sodium bicarbonate (n = 1), and sodium bicarbonate and beta-alanine (n = 4) were analyzed. A benefit for cyclists' athletic performnce was found when consuming a caffeine supplement, and a potential positive effect was noted after the consumption of sodium bicarbonate, as well as after the combination of caffeine and creatine. However, no statistically significant effects were identified for the remaining supplements, whether administered individually or in combination.

First-week survival and egg hatchability are lower in chicks from younger broiler breeder hen flocks. Creatine is a naturally occurring compound synthesised from the amino acid arginine or obtained from the diet and is important in the storage and transport of energy. Previous research found an improvement in the hatch rate but no posthatch performance improvements when fertile eggs from young breeder hens were injected with creatine monohydrate (CrM) on embryonic day 14. This pilot study aimed to further investigate the possibility of early posthatch improvements by examining the activity of chicks during the 1st week posthatch. Behaviours were broadly classified as active or inactive, the pen was split into three areas, and the amount of time spent in the heat lamp, feed hopper, or drinker line areas was recorded. Chicks given in ovo CrM spent less time in the heat lamp area over the whole 7 days compared to saline (t = 2.352, P = 0.021) and control groups (t = 3.336, P = 0.003) and more time in the feed hopper area during the first 4 days compared to the control group (t = 2.174, P = 0.033). This finding suggests that creatine may improve energy reserves in young chicks allowing them to spend more time away from the heat lamp., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Creatine supplementation has been put forward as a possible aid to cognition, particularly for vegans, vegetarians, the elderly, sleep deprived and hypoxic individuals. However, previous narrative reviews have only provided limited support for these claims. This is despite the fact that research has shown that creatine supplementation can induce increased brain concentrations of creatine, albeit to a limited extent. We carried out a systematic review to examine the current state of affairs. The review supported claims that creatine supplementation can increases brain creatine content but also demonstrated somewhat equivocal results for effects on cognition. It does, however, provide evidence to suggest that more research is required with stressed populations, as supplementation does appear to significantly affect brain content. Issues with research design, especially supplementation regimens, need to be addressed. Future research must include measurements of creatine brain content., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Creatine is consumed by athletes to increase strength and gain muscle. The aim of this study was to evaluate the effects of creatine supplementation on maximal strength and strength endurance. Twelve strength-trained men (25.2 ± 3.4 years) supplemented with 20 g Creatina + 10g maltodextrin or placebo (20g starch + 10g maltodextrin) for five days in randomized order. Maximal strength and strength endurance (4 sets 70% 1RM until concentric failure) were determined in the bench press. In addition, blood lactate, rate of perceived effort, fatigue index, and mood state were evaluated. All measurements were performed before and after the supplementation period. There were no significant changing in maximal strength, blood lactate, RPE, fatigue index, and mood state in either treatment. However, the creatine group performed more repetitions after the supplementation (Cr: Δ = +3.4 reps, p = 0.036, g = 0.53; PLA: Δ = +0.3reps, p = 0.414, g = 0.06), and higher total work (Cr: Δ = +199.5au, p = 0.038, g = 0.52; PLA: Δ = +26.7au, p = 0.402, g = 0.07). Creatine loading for five days allowed the subjects to perform more repetitions, resulting in greater total work, but failed to change the maximum strength.

Background: The efficacy of creatine replacement through supplementation for the optimization of physical function in the population at risk of functional disability is unclear., Methods: We conducted a systematic literature search of MEDLINE, EMBASE, the Cochrane Library, and CINAHL from inception to November 2022. Studies included were randomized controlled trials (RCTs) comparing creatine supplementation with placebos in older adults and adults with chronic disease. The primary outcome was physical function measured by the sit-to-stand test after pooling data using random-effects modeling. We also performed a Bayesian meta-analysis to describe the treatment effect in probability terms. Secondary outcomes included other measures of physical function, muscle function, and body composition. The risk of bias was assessed using the Cochrane risk-of-bias tool., Results: We identified 33 RCTs, comprising 1076 participants. From six trials reporting the primary outcome, the pooled standardized mean difference (SMD) was 0.51 (95% confidence interval [CI]: 0.01-1.00; I 2  = 62%; P = 0.04); using weakly informative priors, the posterior probability that creatine supplementation improves physical function was 66.7%. Upper-body muscle strength (SMD: 0.25; 95% CI: 0.06-0.44; I 2  = 0%; P = 0.01), handgrip strength (SMD 0.23; 95% CI: 0.01-0.45; I 2  = 0%; P = 0.04), and lean tissue mass (MD 1.08 kg; 95% CI: 0.77-1.38; I 2  = 26%; P < 0.01) improved with creatine supplementation. The quality of evidence for all outcomes was low or very low because of a high risk of bias., Conclusion: Creatine supplementation improves sit-to-stand performance, muscle function, and lean tissue mass. It is crucial to conduct high-quality prospective RCTs to confirm these hypotheses (PROSPERO number, CRD42023354929)., (© 2024 The Authors. Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

The use of creatine monohydrate (Cr) in professional soccer is widely documented. However, the effect of low doses of Cr on the physical performance of young soccer players is unknown. This study determined the effect of a low dose of orally administered Cr on muscle power after acute intra-session fatigue in young soccer players. Twenty-eight young soccer players (mean age = 17.1 ± 0.9 years) were randomly assigned to either a Cr (n = 14, 0.3 g·kg -1 ·day -1 for 14 days) or placebo group (n = 14), using a two-group matched, double-blind, placebo-controlled design. Before and after supplementation, participants performed 21 repetitions of 30 m (fatigue induction), and then, to measure muscle power, they performed four repetitions in half back squat (HBS) at 65% of 1RM. Statistical analysis included a two-factor ANOVA ( p ˂ 0.05). Bar velocity at HBS, time: p = 0.0006, ŋp2 = 0.22; group: p = 0.0431, ŋp2 = 0.12, time × group p = 0.0744, ŋp2 = 0.02. Power at HBS, time: p = 0.0006, ŋp2 = 0.12; group: p = 0.16, ŋp2 = 0.06, time × group: p = 0.17, ŋp2 = 0.009. At the end of the study, it was found that, after the induction of acute intra-session fatigue, a low dose of Cr administered orally increases muscle power in young soccer players.

Abstract: Eight long-COVID patients with moderate fatigue that had lasted for ≥3 months were recruited. All patients were allocated in a double-blind parallel-group design to receive either 4 g of creatine per day plus breathing exercises (study group) or breathing exercises only (control group) for 3 months. Creatine induced a significant increase in tissue total creatine levels for all 14 locations evaluated in the present study ( P < 0.05), while its levels significantly dropped in the right frontal gray matter and left parietal mesial gray matter at follow-up in the control group ( P < 0.05). No change in time to exhaustion was demonstrated in the control group (P > 0.05), while the mean time to exhaustion was significantly improved for 54 s in the study group post-administration (P = 0.05). These preliminary findings suggest that creatine is as an effective adjuvant therapeutic to breathing exercises for tackling the clinical features in long-COVID., (Copyright © 2023 Copyright: © 2023 Journal of Postgraduate Medicine.)

Background: Athletes commonly use creatine, caffeine, and sodium bicarbonate for performance enhancement. While their isolated effects are well-described, less is known about their potential additive effects., Methods: Following a baseline trial, we randomized 12 endurance-trained males (age: 25 ± 5 years, VO 2max : 56.7 ± 4.6 mL kg -1  min -1 ; mean ± SD) and 11 females (age: 25 ± 3 years, VO 2max : 50.2 ± 3.4 mL kg -1  min -1 ) to 5 days of creatine monohydrate (0.3 g kg -1  per day) or placebo loading, followed by a daily maintenance dose (0.04 g kg -1 ) throughout the study. After the loading period, subjects completed four trials in randomized order where they ingested caffeine (3 mg kg -1 ), sodium bicarbonate (0.3 g kg -1 ), placebo, or both caffeine and sodium bicarbonate before a maximal voluntary contraction (MVC), 15-s sprint, and 6-min time trial., Results: Compared to placebo, mean power output during 15-s sprint was higher following loading with creatine than placebo (+34 W, 95% CI: 10 to 58, p = 0.008), but with no additional effect of caffeine (+10 W, 95% CI: -7 to 24, p = 0.156) or sodium bicarbonate (+5 W, 95% CI: -4 to 13, p = 0.397). Mean power output during 6-min time trial was higher with caffeine (+12 W, 95% CI: 5 to 18, p = 0.001) and caffeine + sodium bicarbonate (+8 W, 95% CI: 0 to 15, p = 0.038), whereas sodium bicarbonate (-1 W, 95% CI: -7 to 6, p = 0.851) and creatine (-6 W, 95% CI: -15 to 4, p = 0.250) had no effects., Conclusion: While creatine and caffeine can enhance sprint- and time trial performance, respectively, these effects do not seem additive. Therefore, supplementing with either creatine or caffeine appears sufficient to enhance sprint or short intense exercise performance., (© 2024 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Preliminary studies demonstrated beneficial effects of dietary creatine across different post-viral fatigue syndromes. Creatine is often co-administered with glucose to improve its potency yet whether glucose boost the efficacy of creatine in long COVID remains currently unknown. In this report, we investigate the effects of 8-wk creatine intake with and without glucose on patient-reported outcomes, exercise tolerance, and tissue creatine levels in patients with long COVID. Fifteen male and female long COVID adult patients (age 39.7±16.0 y; 9 women) with moderate fatigue and at least one of additional long COVID-related symptoms volunteered to participate in this randomized controlled parallel-group interventional trial. All patients were allocated in a double-blind parallel-group design (1 : 1 : 1) to receive creatine (8 g of creatine monohydrate per day), a mixture of creatine and glucose (8 g of creatine monohydrate and 3 g of glucose per day), or placebo (3 g of glucose per day) t.i.d. during an 8-wk intervention interval. Two-way ANOVA with repeated measures (treatment vs. time interaction) revealed significant differences in changes in total creatine levels between the groups, showing an interaction effect at two brain locations (right precentral white matter F=34.740, p=0.008; partial η 2 =0.72; left paracentral grey matter F=19.243, p=0.019; partial η 2 =0.88), with creatine and creatine-glucose outcompeted placebo to elevate creatine levels at these two locations. Several long COVID symptoms (including body aches, breathing problems, difficulties concentrating, headache, and general malaise) were significantly reduced in creatine-glucose group at 8-wk follow-up (p≤0.05); the effect sizes for reducing body aches, difficulties concentrating, and headache were 1.33, 0.80, and 1.12, respectively, suggesting a large effect of creatine-glucose mixture for these outcomes. Our preliminary findings suggest that supplying exogenous creatine with glucose could be recommended as an effective procedure in replenishing brain creatine pool and alleviating long COVID features in this prevalent condition.

Near-term acute hypoxia in utero can result in significant fetal brain injury, with some brain regions more vulnerable than others. As mitochondrial dysfunction is an underlying feature of the injury cascade following hypoxia, this study is aimed at characterizing mitochondrial function at a region-specific level in the near-term fetal brain after a period of acute hypoxia. We hypothesized that regional differences in mitochondrial function would be evident, and that prophylactic creatine treatment would mitigate mitochondrial dysfunction following hypoxia; thereby reducing fetal brain injury. Pregnant Border-Leicester/Merino ewes with singleton fetuses were surgically instrumented at 118 days of gestation (dGa; term is ~145 dGA). A continuous infusion of either creatine ( n = 15; 6 mg/kg/h) or isovolumetric saline ( n = 16; 1.5 ml/kg/h) was administered to the fetuses from 121 dGa. After 10 days of infusion, a subset of fetuses (8 saline-, 7 creatine-treated) were subjected to 10 minutes of umbilical cord occlusion (UCO) to induce a mild global fetal hypoxia. At 72 hours after UCO, the fetal brain was collected for high-resolution mitochondrial respirometry and molecular and histological analyses. The results show that the transient UCO-induced acute hypoxia impaired mitochondrial function in the hippocampus and the periventricular white matter and increased the incidence of cell death in the hippocampus. Creatine treatment did not rectify the changes in mitochondrial respiration associated with hypoxia, but there was a negative relationship between cell death and creatine content following treatment. Irrespective of UCO, creatine increased the proportion of cytochrome c bound to the inner mitochondrial membrane, upregulated the mRNA expression of the antiapoptotic gene Bcl2, and of PCG1-α, a driver of mitogenesis, in the hippocampus. We conclude that creatine treatment prior to brief, acute hypoxia does not fundamentally modify mitochondrial respiratory function, but may improve mitochondrial structural integrity and potentially increase mitogenesis and activity of antiapoptotic pathways., Competing Interests: SJE serves as a member of the Scientific Advisory Broad on creatine in health and medicine (AlzChem LLC). The company had no oversight of the experimental design or reporting of this study., (Copyright © 2022 Anna Maria Muccini et al.)

Background: The fasting and stress associated with road transportation contributes to a lack of energy and a decline in the immune system of beef cattle. Therefore, it is essential for beef cattle to enhance energy reserves before transportation. Creatine pyruvate (CrPyr) is a new multifunctional nutrient that can provide both pyruvate and creatine, which are two intermediate products of energy metabolism. To investigate the effects of transport and rumen-protected (RP)-CrPyr on the blood biochemical parameters and rumen fluid characteristics of beef cattle, twenty male Simmental crossbred cattle (659 ± 16 kg) aged 18 months were randomly allocated to four groups (n = 5) using a 2 × 2 factorial arrangement with two RP-CrPyr supplemental levels (0 or 140 g/d) and two transport treatments (5 min or 12 h): T&#95;CrPyr140, T&#95;CrPyr0, NT&#95;CrPyr140, and NT&#95;CrPyr0. After feeding for 30 days, three cattle per treatment were slaughtered., Results: Compared with nontransport, transport decreased the total antioxidant capacity, catalase activity, contents of IgA, interferon γ, interleukin-1β (IL-1β), and IL-6 in serum, and the amounts of total volatile fatty acids (TVFA), acetate, and butyrate in rumen (P < 0.05); increased the serum lipopolysaccharide (LPS) level, contents of rumen LPS and ammonia nitrogen (P < 0.05). RP-CrPyr supplementation decreased the levels of cortisol and LPS in serum and the butyrate concentration in the rumen of beef cattle compared with those in the unsupplemented groups (P < 0.05). RP-CrPyr and transport interaction had a significant effect on the contents of serum tumour necrosis factor-α, IL-6, LPS, ruminal pH, acetate content, and acetate/propionate (P < 0.05). In terms of ruminal bacterial composition, group T&#95;CrPyr0 increased the Prevotella genus abundance compared with group NT&#95;CrPyr0 (P < 0.05), while group T&#95;CrPyr140 increased Firmicutes phylum abundance and decreased Bacteroidetes phylum and genus Prevotella abundance compared with group T&#95;CrPyr0 (P < 0.05). Moreover, Bacteroidetes was positively correlated with serum LPS., Conclusions: These results indicated that dietary supplementation with RP-CrPyr might be beneficial to alleviate transport stress by decreasing serum cortisol and LPS levels and promoting the restoration of the rumen natural flora., (© 2022. The Author(s).)

A high volume of fluid can strongly reduce a drug's concentration in urine. Therefore, to detect diluted samples, the concentration of creatinine in urine is determined during testing drugs of abuse. If the concentration is below 20 mg creatinine/dl urine, the urine sample is usually rejected for drug testing. It should be examined whether creatine or creatinine ingestion can mask urine dilution by increasing the creatinine concentration. A total of 18 subjects drank 1.3 L of water and 0.2 L of orange juice on each of the three testing days: (1) without creatine, (2) with 20 g of creatine, and (3) with 20 g of creatine following incubation for 4 days in orange juice at room temperature; an acidic environment should promote conversion of creatine to creatinine. The lowest creatinine concentrations in urine were observed on average 2 h after fluid intake. At that time, ingestion of fluid without creatine, with creatine, and with creatine(ine)-orange juice mixture resulted in mean values of 11.6, 22.5, and 28.3 mg creatinine/dl urine, respectively. It can be concluded that ingestion of creatine or creatinine can increase the concentration of creatinine in urine and thus mask dilution of a sample. The conversion of creatine in orange juice further increases availability of creatinine as it is obvious from urine creatinine concentration. Therefore, creatine ingestion during drug testing will give rise to negative results due to matrix adulteration. In a case of suspected creatine supplementation, the creatine content of the sample should be determined in addition to creatinine., (© 2021 John Wiley & Sons, Ltd.)

Sports participation is not without risk, and most athletes incur at least one injury throughout their careers. Combat sports are popular all around the world, and about one-third of their injuries result in more than 7 days of absence from competition or training. The most frequently injured body regions are the head and neck, followed by the upper and lower limbs, while the most common tissue types injured are superficial tissues and skin, followed by ligaments and joint capsules. Nutrition has significant implications for injury prevention and enhancement of the recovery process due to its effect on the overall physical and psychological well-being of the athlete and improving tissue healing. In particular, amino acid and protein intake, antioxidants, creatine, and omega-3 are given special attention due to their therapeutic roles in preventing muscle loss and anabolic resistance as well as promoting injury healing. The purpose of this review is to present the roles of various nutritional strategies in reducing the risk of injury and improving the treatment and rehabilitation process in combat sports. In this respect, nutritional considerations for muscle, joint, and bone injuries as well as sports-related concussions are presented. The injury risk associated with rapid weight loss is also discussed. Finally, preoperative nutrition and nutritional considerations for returning to a sport after rehabilitation are addressed.

Purpose: To examine the efficacy of creatine (Cr) supplementation and any sex differences during supervised whole-body resistance training (RT) on properties of bone and muscle in older adults., Methods: Seventy participants (39 men, 31 women; mean age ± standard deviation: 58 ± 6 yr) were randomized to supplement with Cr (0.1 g·kg-1·d-1) or placebo (Pl) during RT (3 d·wk-1 for 1 yr). Bone geometry (radius and tibia) and muscle area and density (forearm and lower leg) were assessed using peripheral quantitative computed tomography., Results: Compared with Pl, Cr increased or maintained total bone area in the distal tibia (Cr, Δ +17 ± 27 mm2; Pl, Δ -1 ± 22 mm2; P = 0.031) and tibial shaft (Cr, Δ 0 ± 9 mm2; Pl, Δ -5 ± 7 mm2; P = 0.032). Men on Cr increased trabecular (Δ +28 ± 31 mm2; P < 0.001) and cortical bone areas in the tibia (Δ +4 ± 4 mm2; P < 0.05), whereas men on Pl increased trabecular bone density (Δ +2 ± 2 mg·cm-3; P < 0.01). There were no bone changes in the radius (P > 0.05). Cr increased lower leg muscle density (Δ +0.83 ± 1.15 mg·cm-3; P = 0.016) compared with Pl (Δ -0.16 ± 1.56 mg·cm-3), with no changes in the forearm muscle., Conclusions: One year of Cr supplementation and RT had some favorable effects on measures of bone area and muscle density in older adults., (Copyright © 2021 by the American College of Sports Medicine.)

Sarcopenia refers to the age-related loss of muscle strength and muscle mass, which is associated with a reduced quality of life, particularly in older females. Resistance training (RT) is well established to be an effective intervention to counter indices of sarcopenia. Accumulating research indicates that the addition of creatine supplementation (Cr) to RT augments gains in muscle strength and muscle mass, compared to RT alone. However, some evidence indicates that sex differences may alter the effectiveness of Cr. Therefore, we systematically reviewed randomized controlled trials (RCTs) investigating the efficacy of Cr + RT on measures of upper- and lower-body strength and muscle mass in older females. A systematic literature search was performed in nine electronic databases. Ten RCTs ( N = 211 participants) were included the review. Overall, Cr significantly increased measures of upper-body strength (7 studies, n = 142, p = 0.04), with no effect on lower-body strength or measures of muscle mass. Sub-analyses revealed that both upper-body (4 studies, n = 97, p = 0.05) and lower-body strength (4 studies, n = 100, p = 0.03) were increased by Cr, compared to placebo in studies ≥ 24 weeks in duration. In conclusion, older females supplementing with Cr experience significant gains in muscle strength, especially when RT lasts for at least 24 weeks in duration. However, given the level of evidence, future high-quality studies are needed to confirm these findings.

Sprague-Dawley rats ( n  = 32) underwent 8-weeks of creatine monohydrate (CM) supplementation (0, 2.5, 5, and 10 g/L). Total creatine (TCr) concentrations in female white fibre-dominant gastrocnemius (WGAS) and cardiac muscle (HRT) were significantly higher compared with males ( p  < 0.05). CM supplementation increased TCr concentrations in female WGAS ( p  < 0.05) and HRT ( p  < 0.01) and in male red fibre-dominant gastrocnemius muscle (RGAS) ( p  < 0.05). Future research should further investigate sex-differences in basal levels of TCr and the response to CM supplementation. Novelty: There is a sex- and tissue-dependant response to CM supplementation in rats.

Creatine improves flesh quality on mammalian but studies on crustaceans are scarce. In the present study, diets with six levels of creatine (1.23, 2.58, 5.12, 8.28, 14.12, 24.49 g kg -1 diet) were hand-fed to juvenile Litopenaeus vannamei (IBW: 1.50 ± 0.02 g) reared in freshwater for 46 days. Results showed creatine supplementation did not affect the growth performance (FBW: 17.04 ± 1.28 g) or the content of guanidinoacetic acid in muscle and hepatopancreas whereas significantly increased muscular creatine content. Diet with 8.28 g kg -1 creatine significantly increased muscular hardness and chewiness by decreasing myofiber diameter and increasing myofiber density. Additionally, creatine downregulated the mRNA expression of fast sMyHC1, sMyHC2, sMyHC6a and upregulated slow sMyHC5 and sMyHC15 mRNA expression. Muscular protein, collagen, total amino acid and flavor amino acid contents increased with creatine supplementation. In conclusion, the diet with 8.28 g kg -1 creatine improved the flesh quality of L. vannamei., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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.

Mild cognitive impairment (MCI) designates the boundary area between cognitive function in natural aging and dementia, and this is viewed as a therapeutic window to prevent the occurrence of dementia. The current study investigated the neurocognitive effects of oral creatine (Cr) supplementation in young female Wistar rats that received intracerebroventricular injections of lipopolysaccharide (LPS) to mimic MCI. Neuromolecular changes within the dentate gyrus were analyzed following behavioral testing. We also investigated both neurocognitive and neuromolecular changes following Cr supplementation in the absence of LPS in young female Wistar rats to further investigate mechanisms. Interestingly, based on trial 2 of Barnes maze test, Cr supplementation ameliorated spatial learning and memory deficit induced by LPS, shown by decreased latency time and errors to reach the escape box ( p < 0.0001, n = 12). Cr supplementation also attenuated recognition memory deficit induced by LPS, shown by increased amount of time taken to explore the new object ( p = 0.002, n = 12) during novel object recognition testing. Within the dentate gyrus, Cr supplementation in LPS injected rats upregulated mTORC1 signaling ( p = 0.026 for mTOR phosphorylation, p = 0.002 for p70S6K phosphorylation, n = 8) as well as the synapsin ( p = 0.008) and PSD-95 synaptic proteins ( p = 0.015), in comparisons to LPS injected rats. However, Cr supplementation failed to further enhance spatial memory and recognition memory in the absence of LPS. In conclusion, Cr ameliorates LPS-induced cognitive impairment in a rodent MCI model. Mechanistically, these phenotypic effects may, in part, be mitigated via an upregulation of mTORC1 signaling, and an enhancement in synaptogenesis in the dentate gyrus. While preliminary, these findings may inform future research investigating neurocognitive effects of Cr for MCI patients.

There is great need for the identification of new, potentially modifiable risk factors for the poor health-related quality of life (HRQoL) and of the excess risk of mortality in dialysis-dependent chronic kidney disease patients. Creatine is an essential contributor to cellular energy homeostasis, yet, on a daily basis, 1.6-1.7% of the total creatine pool is non-enzymatically degraded to creatinine and subsequently lost via urinary excretion, thereby necessitating a continuous supply of new creatine in order to remain in steady-state. Because of an insufficient ability to synthesize creatine, unopposed losses to the dialysis fluid, and insufficient intake due to dietary recommendations that are increasingly steered towards more plant-based diets, hemodialysis patients are prone to creatine deficiency, and may benefit from creatine supplementation. To avoid problems with compliance and fluid balance, and, furthermore, to prevent intradialytic losses of creatine to the dialysate, we aim to investigate the potential of intradialytic creatine supplementation in improving outcomes. Given the known physiological effects of creatine, intradialytic creatine supplementation may help to maintain creatine homeostasis among dialysis-dependent chronic kidney disease patients, and consequently improve muscle status, nutritional status, neurocognitive status, HRQoL. Additionally, we describe the rationale and design for a block-randomized, double-blind, placebo-controlled pilot study. The aim of the pilot study is to explore the creatine uptake in the circulation and tissues following different creatine supplementation dosages.

Background: Sarcopenia plays a central role in the development of frailty syndrome. Nutrition and exercise are cornerstone strategies to mitigate the transition to frailty; however, there is a paucity of evidence for which dietary and exercise strategies are effective., Objective: This large, multifactorial trial investigated the efficacy of different dietary strategies to enhance the adaptations to resistance training in pre-frail and frail elderly., Methods: This was a single-site 16-week, double-blind, randomized, placebo-controlled trial conducted at the Clinical Hospital, School of Medicine - University of São Paulo, Sao Paulo, Brazil. Four integrated, sub-investigations were conducted to compare: 1) leucine vs. placebo; 2) whey vs. soy vs. placebo; 3) creatine vs. whey vs. creatine plus whey vs. placebo; 4) women vs. men in response to whey. Sub-investigations 1 to 3 were conducted in women, only. Two-hundred participants (154 women/46 men, mean age 72 ± 6 years) underwent a twice-a-week, resistance training program. The main outcomes were muscle function (assessed by dynamic and isometric strength and functional tests) and lean mass (assessed by DXA). Muscle cross-sectional area, health-related quality of life, bone and fat mass, and biochemical markers were also assessed., Results: We observed that leucine supplementation was ineffective to improve muscle mass and function. Supplementation with whey and soy failed to enhance resistance-training effects. Similarly, supplementation with neither whey nor creatine potentiated the adaptations to resistance training. Finally, no sex-based differences were found in response to whey supplementation. Resistance exercise per se increased muscle mass and function in all sub-investigations. There were no adverse effects., Conclusion: Neither protein (whey and soy), leucine, nor creatine supplementation enhanced resistance training-induced adaptations in pre-frail and frail elderly, regardless of sex. These findings do not support the notion that some widely used supplement-based interventions can add to the already potent effects of resistance exercise to counteract frailty-related muscle wasting and dynapenia., Clinical Trial Registry: NCT01890382; https://clinicaltrials.gov/ct2/show/NCT01890382., Data Sharing: Data described in the manuscript will be made available upon request pending application., Competing Interests: Conflict of interest SMP reports personal fees from Enhanced Recovery, equity from Exerkine, personal fees from Dairy Farmers of Canada, personal fees from US National Dairy Export Council, grants from Alliance for Potato Research and Education, grants from US National Dairy Council, outside the submitted work; In addition, SMP has a patent 3052324 issued to Exerkine, and a patent 16/182891 pending to Exerkine., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

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.

Creatine (Cr) and phosphocreatine (PCr) are physiologically essential molecules for life, given they serve as rapid and localized support of energy- and mechanical-dependent processes. This evolutionary advantage is based on the action of creatine kinase (CK) isozymes that connect places of ATP synthesis with sites of ATP consumption (the CK/PCr system). Supplementation with creatine monohydrate (CrM) can enhance this system, resulting in well-known ergogenic effects and potential health or therapeutic benefits. In spite of our vast knowledge about these molecules, no integrative analysis of molecular mechanisms under a systems biology approach has been performed to date; thus, we aimed to perform for the first time a convergent functional genomics analysis to identify biological regulators mediating the effects of Cr supplementation in health and disease. A total of 35 differentially expressed genes were analyzed. We identified top-ranked pathways and biological processes mediating the effects of Cr supplementation. The impact of CrM on miRNAs merits more research. We also cautiously suggest two dose-response functional pathways (kinase- and ubiquitin-driven) for the regulation of the Cr uptake. Our functional enrichment analysis, the knowledge-based pathway reconstruction, and the identification of hub nodes provide meaningful information for future studies. This work contributes to a better understanding of the well-reported benefits of Cr in sports and its potential in health and disease conditions, although further clinical research is needed to validate the proposed mechanisms.

Introduction: We described here the annual variations in mean dietary creatine intake from 1999 to 2018 in U.S. children and adults using National Health and Nutrition Examination Survey (NHANES) database., Methods: Dietary intake information from ten consecutive rounds of NHANES (from 1999 to 2000 to 2017-2018) was extracted for a total of 89,161 respondents aged 0-85 years. Individual values for total grams of creatine consumed per day were computed using the average amount of creatine (3.88 g/kg) across all creatine-containing food sources., Results: The average daily intake of creatine across the entire sample was 0.70 ± 0.78 g (95% confidence interval [CI], from 0.69 to 0.71) and 13.1 ± 16.5 mg/kg body weight (95% CI, from 13.0 to 13.2). A significant negative trend for dietary creatine intake was found in infants (r = - 0.019; P = 0.042), and children and adolescents (r = - 0.024; P < 0.001)., Conclusions: Our findings suggest a variation in dietary creatine intake in the U.S. population during the past 20 years, with young persons tend to consume fewer grams of creatine per day from 1999 onwards. Long-running studies are highly warranted to assess possible health consequences of variable creatine intake in human nutrition.

Background: This study aimed to investigate the effect of multi-ingredient intra- (BA) versus extra- (ALK) cellular buffering factor supplementation, combined with the customary intake of branched-chain amino acids (BCAA) and creatine malate (TCM), on body composition, exercise variables, and biochemical and hematological parameters in 9 elite taekwondo athletes., Methods: Eight-week randomized double-blind crossover BA (5.0 g·day -1 of β-alanine) versus ALK (0.07 g·kg FFM -1 ·day -1 of sodium bicarbonate) supplementation combined with BCAA (0.2 g·kg FFM -1 ·day -1 ) and TCM (0.05 g·kg FFM -1 ·day -1 ) during a standard 8-week taekwondo training period was implemented. In the course of the experiment, body composition (dual X-ray absorptiometry), aerobic capacity (ergospirometric measurements during an incremental treadmill test until exhaustion), and exercise blood biomarkers concentrations were measured. Data were analyzed using repeated measures within-between interaction analysis of variance with the inclusion of experimental supplementation order., Results: The maximum post-exercise blood ammonia concentration decreased in both groups after supplementation (from 80.3 ± 10.6 to 72.4 ± 10.2 µmol∙L -1 , p = 0.013 in BA; from 81.4 ± 8.7 to 74.2 ± 8.9 µmol∙L -1 , p = 0.027 in ALK), indicating reduced exercise-related adenosine triphosphate degradation. However, no differences were found in body composition, aerobic capacity, blood lactate concentration, and hematological parameters after neither BA (combined with BCAA and TCM) nor ALK (combined with BCAA and TCM) supplementation., Conclusions: In highly trained taekwondo athletes, neither extra- nor intracellular buffering enhancement resulting from BA and ALK supplementation, combined with BCAA and TCM treatment, affects body mass and composition, maximum oxygen uptake, and hematological indices, even though certain advantageous metabolic adaptations can be observed.

Creatine supplementation in conjunction with resistance training (RT) augments gains in lean tissue mass and strength in aging adults; however, there is a large amount of heterogeneity between individual studies that may be related to creatine ingestion strategies. Therefore, the purpose of this review was to (1) perform updated meta-analyses comparing creatine vs. placebo (independent of dosage and frequency of ingestion) during a resistance training program on measures of lean tissue mass and strength, (2) perform meta-analyses examining the effects of different creatine dosing strategies (lower: ≤5 g/day and higher: >5 g/day), with and without a creatine-loading phase (≥20 g/day for 5-7 days), and (3) perform meta-analyses determining whether creatine supplementation only on resistance training days influences measures of lean tissue mass and strength. Overall, creatine (independent of dosing strategy) augments lean tissue mass and strength increase from RT vs. placebo. Subanalyses showed that creatine-loading followed by lower-dose creatine (≤5 g/day) increased chest press strength vs. placebo. Higher-dose creatine (>5 g/day), with and without a creatine-loading phase, produced significant gains in leg press strength vs. placebo. However, when studies involving a creatine-loading phase were excluded from the analyses, creatine had no greater effect on chest press or leg press strength vs. placebo. Finally, creatine supplementation only on resistance training days significantly increased measures of lean tissue mass and strength vs. placebo.

The unfolded protein response (UPR) plays a pivotal role in some exercise training-induced physiological adaptation. Our aim was to evaluate the changes in the protein kinase R-like endoplasmic reticulum kinase (PERK) arm of the UPR and hypertrophy signaling pathway following 8 weeks of resistance training and creatine (Cr) supplementation in rats. Thirty-two adult male Wistar rats (8 weeks old) were randomly divided into 4 groups of 8: untrained + placebo (UN+P), resistance training + placebo (RT+P), untrained + Cr (UN+Cr), and resistance training + Cr (RT+Cr). Trained animals were submitted to the ladder-climbing exercise training 5 days per week for a total of 8 weeks. Cr supplementation groups received creatine diluted with 1.5 ml of 5% dextrose orally. The flexor hallucis longus (FHL) muscle was extracted 48 h after the last training session and used for western blotting. After training period, the RT+Cr and RT+P groups presented a significant increase in phosphorylated and phosphorylated/total ratio hypertrophy indices, phosphorylated and phosphorylated/total ratio PERK pathway proteins, and other downstream proteins of the PERK cascade compared with their untrained counterparts (P < 0.05). The increase in hypertrophy indices were higher but PERK pathway proteins were lower in the RT-Cr group than in the RT+P group (P < 0.05). There was no significant difference between the untrained groups (P > 0.05). Our study suggests that resistance training in addition to Cr supplementation modifies PERK pathway response and improves skeletal muscle hypertrophy.

Background: The rate of accrual of muscle mass in neonates has not been assessed. We describe the D 3 -creatine (D 3 Cr) dilution method, a noninvasive assessment of muscle mass in neonates., Methods: A total of 76 neonates >26-week-old corrected gestational age were enrolled and measured at 2-week intervals while admitted to a neonatal intensive care unit (NICU). Additional measures at 6 and 12-20 months after initial measurement were obtained if available. An enteral dose of 2 mg D 3 Cr in 0.5 mL 20% 2 H 2 O was used to determine muscle mass and total body water (TBW)., Results: Muscle mass by the D 3 Cr method was strongly associated with TBW and body weight (r = 0.9272, p < 0.0001 and r = 0.9435, p < 0.0001 for all time points and r = 0.6661, p < 0.0001 and r = 0.8634, p < 0.0001, respectively, while in the NICU). Change in muscle mass vs. change in body weight, TBW, and length were also strongly correlated., Conclusions: The D 3 Cr dilution method provides a noninvasive assessment of muscle mass accrual in neonates, which has not been previously possible and may be an important new tool for the evaluation of nutritional status and normal growth patterns., Impact: We describe a noninvasive method for the measurement of skeletal muscle mass neonates. At the present time, there is no direct measurement of muscle mass in infants available. The D 3 Cr dilution method is a direct and noninvasive measurement of muscle mass. Using a single enteral dose of D 3 Cr in 2 H 2 O followed by urine and saliva samples, rapid and substantial accrual of muscle mass and TBW is assessed. Assessment of muscle mass accrual in premature infants may be a strong indicator of nutritional status. Change in muscle mass is strongly related to change in weight and TBW.

This systematic review and meta-analysis examined the effects of creatine supplementation on recovery from exercise-induced muscle damage, and is reported according to the PRISMA guidelines. MEDLINE and SPORTDiscus were searched for articles from inception until April 2020. Inclusion criteria were adult participants (≥18 years); creatine provided before and/or after exercise versus a noncreatine comparator; measurement of muscle function recovery, muscle soreness, inflammation, myocellular protein efflux, oxidative stress; range of motion; randomized controlled trials in humans. Thirteen studies (totaling 278 participants; 235 males and 43 females; age range 20-60 years) were deemed eligible for analysis. Data extraction was performed independently by both authors. The Cochrane Collaboration Risk of Bias Tool was used to critically appraise the studies; forest plots were generated with random-effects model and standardized mean differences. Creatine supplementation did not alter muscle strength, muscle soreness, range of motion, or inflammation at each of the five follow-up times after exercise (<30 min, 24, 48, 72, and 96 hr; p > .05). Creatine attenuated creatine kinase activity at 48-hr postexercise (standardized mean difference: -1.06; 95% confidence interval [-1.97, -0.14]; p = .02) but at no other time points. High (I2; >75%) and significant (Chi2; p < .01) heterogeneity was identified for all outcome measures at various follow-up times. In conclusion, creatine supplementation does not accelerate recovery following exercise-induced muscle damage; however, well-controlled studies with higher sample sizes are warranted to verify these conclusions. Systematic review registration (PROSPERO CRD42020178735).

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., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)