Short term creatine loading improves strength endurance even without changing maximal strength, RPE, fatigue index, blood lactate, and mode state.

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.

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

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.

Impact of Short-Term Creatine Supplementation on Muscular Performance among Breast Cancer Survivors.

Breast cancer (BC) is one of the most common cancers in the United States. Advances in detection and treatment have resulted in an increased survival rate, meaning an increasing population experiencing declines in muscle mass and strength. Creatine supplementation has consistently demonstrated improvements in strength and muscle performance in older adults, though these findings have not been extended to cancer populations. PURPOSE: The purpose of this study was to investigate the effects of short-term creatine supplementation on muscular performance in BC survivors. METHODS: Using a double-blind, placebo-controlled, randomized design, 19 female BC survivors (mean ± SD age = 57.63 ± 10.77 years) were assigned to creatine (SUPP) (n = 9) or dextrose placebo (PLA) (n = 10) groups. The participants completed two familiarization sessions, then two test sessions, each separated by 7 days, where the participants supplemented with 5 g of SUPP or PLA 4 times/day between sessions. The testing sessions included sit-to-stand power, isometric/isokinetic peak torque, and upper/lower body strength via 10 repetition maximum (10RM) tests. The interaction between supplement (SUPP vs. PLA) and time (Pre vs. Post) was examined using a group × time ANOVA and effect sizes. RESULTS: No significant effects were observed for sit-to-stand power (p = 0.471; ηp2 = 0.031), peak torque at 60°/second (p = 0.533; ηp2 = 0.023), peak torque at 120°/second (p = 0.944; ηp2 < 0.001), isometric peak torque (p = 0.905; ηp2 < 0.001), 10RM chest press (p = 0.407; ηp2 = 0.041), and 10RM leg extension (p = 0.932; ηp2 < 0.001). However, a large effect size for time occurred for the 10RM chest press (ηp2 = 0.531) and leg extension (ηp2 = 0.422). CONCLUSION: Seven days of creatine supplementation does not influence muscular performance among BC survivors.

No additive effect of creatine, caffeine, and sodium bicarbonate on intense exercise performance in endurance-trained individuals.

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, VO2max: 56.7 ± 4.6 mL kg-1 min-1; mean ± SD) and 11 females (age: 25 ± 3 years, VO2max: 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.

Creatine supplementation and resistance training to preserve muscle mass and attenuate cancer progression (CREATINE-52): a protocol for a double-blind randomized controlled trial.

BACKGROUND: Muscle mass is important for metastatic prostate cancer survival and quality of life (QoL). The backbone of treatment for men with metastatic castration sensitive prostate cancer (mCSPC) is androgen deprivation therapy (ADT) with an androgen signaling inhibitor. ADT is an effective cancer treatment, but it facilitates significant declines in muscle mass and adverse health outcomes important to mCSPC survivors, such as fatigue, and reductions in physical function, independence, insulin sensitivity, and QoL. In non-metastatic CSPC survivors, resistance training (RT) preserves muscle mass and improves these related health outcomes, but the biggest barrier to RT in CSPC survivors of all stages is fatigue. Creatine monohydrate supplementation coupled with RT (Cr + RT) may address this barrier since creatine plays a critical role in energy metabolism. Cr + RT in cancer-free older adults and other clinical populations improves muscle mass and related health outcomes. Evidence also suggests that creatine supplementation can complement cancer treatment. Thus, Cr + RT is a strategy that addresses gaps in survivorship needs of people with mCSPC. The purpose of this parallel, double-blind randomized controlled trial is to test the effects of 52-weeks of Cr + RT compared with placebo (PLA) and RT (PLA + RT) on muscle mass, other related health outcomes, and markers of cancer progression. METHODS: We will carry out this trial with our team's established, effective, home-based, telehealth RT program in 200 mCSPC survivors receiving ADT, and evaluate outcomes at baseline, 24-, and 52-weeks. RT will occur twice weekly with elastic resistance bands, and an established creatine supplementation protocol will be used for supplementation delivery. Our approach addresses a major facilitator to RT in mCSPC survivors, a home-based RT program, while utilizing a supervised model for safety. DISCUSSION: Findings will improve delivery of comprehensive survivorship care by providing a multicomponent, patient-centered lifestyle strategy to preserve muscle mass, improve health outcomes, and complement cancer treatment (NCT06112990).

The Effect of Prior Creatine Intake for 28 Days on Accelerated Recovery from Exercise-Induced Muscle Damage: A Double-Blind, Randomized, Placebo-Controlled Trial.

Despite the known beneficial effects of creatine in treating exercise-induced muscle damage (EIMD), its effectiveness remains unclear. This study investigates the recovery effect of creatine monohydrate (CrM) on EIMD. Twenty healthy men (21-36 years) were subjected to stratified, randomized, double-blind assignments. The creatine (CRE) and placebo (PLA) groups ingested creatine and crystalline cellulose, respectively, for 28 days. They subsequently performed dumbbell exercises while emphasizing eccentric contraction of the elbow flexors. The EIMD was evaluated before and after exercise. The range of motion was significantly higher in the CRE group than in the PLA group 24 h (h) post exercise. A similar difference was detected in maximum voluntary contraction at 0, 48, 96, and 168 h post exercise (p = 0.017-0.047). The upper arm circumference was significantly lower in the CRE group than in the PLA group at 48, 72, 96, and 168 h post exercise (p = 0.002-0.030). Similar variation was observed in the shear modulus of the biceps brachii muscle at 96 and 168 h post exercise (p = 0.003-0.021) and in muscle fatigue at 0 and 168 h post exercise (p = 0.012-0.032). These findings demonstrate CrM-mediated accelerated recovery from EIMD, suggesting that CrM is an effective supplement for EIMD recovery.

The Effect of Creatine Nitrate and Caffeine Individually or Combined on Exercise Performance and Cognitive Function: A Randomized, Crossover, Double-Blind, Placebo-Controlled Trial.

This study examined the effect of creatine nitrate and caffeine alone and combined on exercise performance and cognitive function in resistance-trained athletes. In a double-blind, randomized crossover trial, twelve resistance-trained male athletes were supplemented with 7 days of creatine nitrate (5 g/day), caffeine (400 mg/day), and a combination of creatine nitrate and caffeine. The study involved twelve resistance-trained male athletes who initially provided a blood sample for comprehensive safety analysis, including tests for key enzymes and a lipid profile, and then performed standardized resistance exercises-bench and leg press at 70% 1RM-and a Wingate anaerobic power test. Cognitive function and cardiovascular responses were also examined forty-five minutes after supplementation. Creatine nitrate and caffeine that were co-ingested significantly enhanced cognitive function, as indicated by improved scores in the Stroop Word-Color Interference test (p = 0.04; effect size = 0.163). Co-ingestion was more effective than caffeine alone in enhancing cognitive performance. In contrast, no significant enhancements in exercise performance were observed. The co-ingestion of creatine nitrate and caffeine improved cognitive function, particularly in cognitive interference tasks, without altering short-term exercise performance. Furthermore, no adverse events were reported. Overall, the co-ingestion of creatine nitrate and caffeine appears to enhance cognition without any reported side effects for up to seven days.

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

The inverse effects of creatine supplementation and sleep deprivation on high energy phosphates, neural creatine, and cognitive performances suggest that creatine is a suitable candidate for reducing the negative effects of sleep deprivation. With this, the main obstacle is the limited exogenous uptake by the central nervous system (CNS), making creatine only effective over a long-term diet of weeks. Thus far, only repeated dosing of creatine over weeks has been studied, yielding detectable changes in CNS levels. Based on the hypothesis that a high extracellular creatine availability and increased intracellular energy consumption will temporarily increase the central creatine uptake, subjects were orally administered a high single dose of creatinemonohydrate (0.35 g/kg) while performing cognitive tests during sleep deprivation. Two consecutive 31P-MRS scans, 1H-MRS, and cognitive tests were performed each at evening baseline, 3, 5.5, and 7.5 h after single dose creatine (0.35 g/kg) or placebo during sub-total 21 h sleep deprivation (SD). Our results show that creatine induces changes in PCr/Pi, ATP, tCr/tNAA, prevents a drop in pH level, and improves cognitive performance and processing speed. These outcomes suggest that a high single dose of creatine can partially reverse metabolic alterations and fatigue-related cognitive deterioration.

Creatine supplementation with exercise reduces α-synuclein oligomerization and necroptosis in Parkinson's disease mouse model.

Parkinson's disease (PD) is an incurable neurological disorder that causes typical motor deficits. In this study, we investigated the effects of creatine supplementation and exercise in the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. We found that 2% creatine supplementation and/or exercise intervention for 4 weeks elicited neurobehavioral recovery and neuroprotective effects regarding dopaminergic cell loss in MPTP-treated mice; this effect implies functional preservation of dopaminergic cells in the substantia nigra, as reflected by tyrosine hydroxylase expression recovery. Creatine and exercise reduced necroptotic activity in dopaminergic cells by lowering mixed lineage kinase domain-like protein (MLKL) modification to active phenotypes (phosphorylation at Ser345 and oligomerization) and phosphorylated receptor-interacting protein kinase 1 (RIPK1) (Ser166-p) and RIPK3 (Ser232-p) levels. In addition, creatine and exercise reduced the MPTP-induced increase in pathogenic α-synuclein forms, such as Ser129 phosphorylation and oligomerization. Furthermore, creatine and exercise had anti-inflammatory and antioxidative effects in MPTP mice, as evidenced by a decrease in microglia activation, NF-κB-dependent pro-inflammatory molecule expression, and increase in antioxidant enzyme expression. These phenotypic changes were associated with the exercise/creatine-induced AMP-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (Nrf2) and sirtuin 3 (SIRT3)/forkhead box O3 (FoxO3a) signaling pathways. In all experiments, combining creatine with exercise resulted in considerable improvement over either treatment alone. Consequently, these findings suggest that creatine supplementation with exercise has anti-inflammatory, antioxidative, and anti-α-synucleinopathy effects, thereby reducing necroptotic cell death in a PD mouse model.

Creatine Supplementation and Resistance Training in Patients With Breast Cancer (CaRTiC Study): Protocol for a Randomized Controlled Trial.

BACKGROUND: Creatine supplementation is an effective ergogenic nutrient for athletes, as well as for people starting a health or fitness program. Resistance training has previously been identified as an important method of increasing muscle mass and strength, especially in people with cancer to avoid sarcopenia. The potential of creatine supplementation for adaptations produced by resistance training in patients with cancer is still unknown. The primary aim of this study is to evaluate the effectiveness of a supervised resistance training program intervention with and without creatine supplementation in patients with breast cancer. METHODS: Is a multicentre, randomized, blind, placebo-controlled study. Patients will be randomly assigned to a control group and 2 experimental groups. The first training resistance group (RG) will perform resistance training, while the second experimental resistance-creatine group will perform the same resistance training as the RG and will also receive a 5 g/d creatine supplementation during the intervention. RG participants will follow the same daily dosing protocol, but in their case, with dextrose/maltodextrin. Resistance training will be a 16-week supervised workout that will consist of a series of resistance exercises (leg press, knee extension, knee bends, chest press, sit-ups, back extensions, pull-ups, and shoulder press) that involve the largest muscle groups, performed 3 times a week on nonconsecutive days. Both the RG and the resistance-creatine group will receive a supplement of soluble protein powder (20 to 30 g) daily. CONCLUSION: This intervention will help to better understand the potential of nonpharmacological treatment for improving strength and well-being values in patients with breast cancer with and without creatine supplementation.

The Effects of Protein and Carbohydrate Supplementation, with and without Creatine, on Occupational Performance in Firefighters.

BACKGROUND: The purpose of this study was to assess the effects of protein and carbohydrate supplementation, with and without creatine, on occupational performance in firefighters. METHODS: Using a randomized, double-blind approach, thirty male firefighters (age: 34.4 ± 8.4 yrs., height: 1.82 ± 0.07 m; weight: 88.6 ± 12.5 kg; BF%: 17.2 ± 5.8%) were randomized to receive either (A.) 25 g of whey protein isolate + 25 g of carbohydrate powder (ProCarb group); or (B.) ProCarb + 5 g of creatine (Creatine group) in a double-blind fashion over a period of 21-26 days (depending on shift rotations) to evaluate the impact of supplementation on occupation-specific performance. At baseline and following supplementation, firefighters completed a battery of tests. These tests included an aerobic speed test on an air-braked cycle ergometer followed by the hose carry, body drag, stair climb, and Keiser sled hammer for time. RESULTS: No significant differences in measures of performance were observed at baseline (p > 0.05). There was a significant main effect for time observed for rescue, stair climb, total time to completion, and time trial performance (p < 0.05). There was a significant group × time (p < 0.05) interaction for rescue and forcible entry. Independent sample t-tests indicated that the Creatine group experienced a greater reduction (from baseline) in completion time for the rescue (1.78 ± 0.57 s, 95% CI: 0.61, 2.95 s, p = 0.004) and forcible entry (2.66 ± 0.97 s, 95% CI: 0.68, 4.65 s, p = 0.01) tests compared to the ProCarb group. No significant group × time interactions were observed for the hose line advance, stair climb, total time to completion, and time trial performance (p > 0.05). CONCLUSIONS: The addition of supplemental creatine to a protein and carbohydrate supplement to the diet of career firefighters throughout a three week period improves occupational performance in firefighters in specific areas of high-intensity, repetitive actions.

Creatine supplementation enhances anti-tumor immunity by promoting adenosine triphosphate production in macrophages.

Creatine is an indispensable organic compound utilized in physiological environments; however, its role in immunity is still poorly understood. Here, we show that creatine supplementation enhances anti-tumor immunity through the functional upregulation of macrophages by increasing adenosine triphosphate (ATP) production. Creatine supplementation significantly suppressed B16-F10-originated tumor growth in mice compared with the control treatment. Under these conditions, intratumor macrophages polarized towards the M1 phenotype rather than the M2 phenotype, and there was an increase in tumor antigen-specific CD8+ T cells in the mice. The cytokine production and antigen-presenting activity in the macrophages were enhanced by creatine supplementation, resulting in a substantial increase in tumor antigen-specific CD8+ T cells. ATP upregulation was achieved through the cytosolic phosphocreatine (PCr) system via extracellular creatine uptake, rather than through glycolysis and mitochondrial oxidative phosphorylation in the macrophages. Blockade of the creatine transporter (CrT) failed to upregulate ATP and enhance the immunological activity of macrophages in creatine supplementation, which also impaired CD8+ T cell activity. Consequently, CrT blockade failed to suppress tumor growth in the creatine-supplemented mice. Thus, creatine is an important nutrient that promotes macrophage function by increasing ATP levels, ultimately contributing to enhanced anti-tumor immunity orchestrated by CD8+ T cells.

The Effect of Skeletal Muscle-Specific Creatine Treatment on ALS NMJ Integrity and Function.

Although skeletal muscle (hSKM) has been proven to be actively involved in Amyotrophic Lateral Sclerosis (ALS) neuromuscular junction (NMJ) dysfunction, it is rarely considered as a pharmacological target in preclinical drug discovery. This project investigated how improving ALS hSKM viability and function effects NMJ integrity. Phenotypic ALS NMJ human-on-a-chip models developed from patient-derived induced pluripotent stem cells (iPSCs) were used to study the effect of hSKM-specific creatine treatment on clinically relevant functional ALS NMJ parameters, such as NMJ numbers, fidelity, stability, and fatigue index. Results indicated comparatively enhanced NMJ numbers, fidelity, and stability, as well as reduced fatigue index, across all hSKM-specific creatine-treated systems. Immunocytochemical analysis of the NMJs also revealed improved post-synaptic nicotinic Acetylcholine receptor (AChR) clustering and cluster size in systems supplemented with creatine relative to the un-dosed control. This work strongly suggests hSKM as a therapeutic target in ALS drug discovery. It also demonstrates the need to consider all tissues involved in multi-systemic diseases, such as ALS, in drug discovery efforts. Finally, this work further establishes the BioMEMs NMJ platform as an effective means of performing mutation-specific drug screening, which is a step towards personalized medicine for rare diseases.

Efficacy of creatine nitrate supplementation on redox status and mitochondrial function in pectoralis major muscle of preslaughter transported broilers.

This study was purposed to investigate the efficacy of dietary creatine nitrate (CrN) supplementation on redox status and mitochondrial function in pectoralis major (PM) muscle of broilers that experienced preslaughter transport. A total of 288 Arbor Acres broilers (28-day-old) were randomly assigned into five dietary treatments, including a basal diet or the basal diet supplemented with 600 mg/kg guanidinoacetic acid (GAA), 300, 600, or 900 mg/kg CrN for 14 days, respectively. On the transportation day, the basal diet group was divided into two groups on average, resulting in six groups. The control group was transported for 0.5 h and the other groups for 3 h (identified as Control, T3h, GAA600, CrN300, CrN600, and CrN900 group, respectively), and all crates were randomly placed on the truck travelling at an average speed of 80 km/h. Our results showed that GAA600 and CrN treatments decreased the muscle ROS level and MDA content (P < 0.05) and increased the mitochondrial membrane potential (P < 0.001), as well as a higher mRNA expression of avUCP (P < 0.001) and lower mRNA expressions of Nrf2 (P < 0.001), Nrf2 and PGC-1α (P < 0.05) compared with T3h group. Meanwhile, the mRNA and protein expressions of Nrf1, TFAM, and PGC-1α in CrN600 and CrN900 groups were lower than those in the T3h group (P < 0.05). Conclusively, dietary supplementation with GAA and CrN decreased muscle oxidative products and enhanced mitochondrial uncoupling mechanism and mtDNA copy number, which relieved muscle oxidative damage and maintained mitochondrial function.

The Effects of Creatine Monohydrate Loading on Exercise Recovery in Active Women throughout the Menstrual Cycle.

Creatine supplementation improves anaerobic performance and recovery; however, to date, these outcomes have not been well explored in females. This study evaluated the effect of creatine monohydrate loading on exercise recovery, measured by heart rate variability (HRV) and repeated sprint performance, in women across the menstrual cycle. In this randomized, double-blind, cross-over study, 39 women (mean ± standard deviation: age: 24.6 ± 5.9 years, height: 172.5 ± 42.3 cm, weight: 65.1 ± 8.1 kg, BF: 27.4 ± 5.8%) were randomized to a creatine monohydrate (n = 19; 20 g per day in 4 × 5 g doses) or non-caloric PL group (n = 20). HRV was measured at rest and after participants completed a repeated sprint cycling test (10 × 6 s maximal sprints). Measurements were conducted before and after supplementation in the follicular/low hormone and luteal/high hormone phases. Creatine monohydrate supplementation did not influence HRV values, as no significant differences were seen in HRV values at rest or postexercise. For repeated sprint outcomes, there was a significant phase × supplement interaction (p = 0.048) for fatigue index, with the greatest improvement seen in high hormone in the creatine monohydrate group (-5.8 ± 19.0%) compared to changes in the PL group (0.1 ± 8.1%). Sprint performance and recovery were reduced by the high hormone for both groups. Though not statistically significant, the data suggests that creatine monohydrate could help counteract performance decrements caused by the high hormone. This data can help inform creatine monohydrate loading strategies for females, demonstrating potential benefits in the high hormone phase.

Effects of dietary supplements on athletic performance in elite soccer players: a systematic review.

Dietary supplements are widely used among athletes, and soccer players are no exception. Nevertheless, evidence supporting the use of dietary supplements aiming to enhance performance in soccer is somewhat contradictory, scarce, or even nonexistent. Thus, the present study aimed to systematically review and synthesize the effects of dietary supplements on athletic performance (e.g. distance covered, sprinting, jump performance) in elite soccer players. Studies enrolling highly trained, elite, and world-class soccer players using dietary supplements were searched in MEDLINE/PubMed, Web of Science, Scopus, and EBSCO databases in June 2022. In total, 1043 studies were identified, and 18 met the eligibility criteria. The studies evaluated the impacts on athletic performance of several dietary supplements, including caffeine, creatine, protein, beverages with carbohydrates and electrolytes, tart cherry juice, nitrate-rich beetroot juice, sodium bicarbonate with minerals, yohimbine, and a proprietary nutraceutical blend. Caffeine supplementation in doses between 3 and 6 mg/kg of body mass may improve jump height and sprint ability, particularly in female players, but individual response to caffeine must be considered. Creatine may improve sprint, agility, and in female players, jump performance. Protein supplementation can improve sprint and jump performance between matches, especially if protein ingested from food is not up to recommendations. Beverages containing carbohydrates and electrolytes can be used as part of the strategies to achieve carbohydrate intake during training and match-days but used alone do not benefit athletic performance. Tart cherry juice might be useful for maintaining athletic performance after matches that produce higher force loss and exercise-induced muscle damage, although polyphenols from the diet might attenuate the effects of tart cherry supplementation. Nitrate-rich beetroot concentrate can attenuate performance decrease in the days following matches. Further investigation with sodium bicarbonate alone is necessary, as supplementation protocols with elite players included other substances. Finally, the available data does not support yohimbine supplementation or the use of Resurgex Plus® to improve athletic performance in elite soccer players. Still, more well-designed research with elite soccer players is needed to improve support and advice regarding the use of dietary supplements for athletic performance enhancement.

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

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

Intranasal creatine administration increases brain creatine level and improves Barnes maze performance in rats.

While skeletal muscle creatine levels can be enhanced by exogenous creatine supplementation, the elevation of brain creatine levels with oral creatine administration remains a challenge due to a lack of effective transportation of creatine through the blood-brain barrier. Intranasal administration can bypass the blood-brain barrier and deliver drugs directly to the brain. The purpose of this study was to assess the effect of intranasal administration of creatine on brain creatine level and cognitive performance. Rats were randomly assigned into three groups intranasal administration group, oral administration group, and control group. The intranasal group exhibited fewer errors and shorter primary latency compared to the control and oral groups, respectively, during the acquisition phase of the Barnes maze. The intranasal group spent a higher percentage of time in the target quadrant during the probe trial compared to the control group. Biochemical measurements showed that the concentration of creatine in the olfactory bulbs, medial prefrontal cortex, and hippocampus of the rats in the intranasal group was higher than in the oral, and control groups. These results indicate that intranasal administration of creatine hydrochloride increases the creatine level in the rat's brain's and improves their performance in the Barnes maze.

Creatine supplementation protects spatial memory and long-term potentiation against chronic restraint stress.

Stress contributes to numerous psychopathologies, including memory impairment, and threatens one's well-being. It has been reported that creatine supplementation potentially influences cognitive processing. Hence, in this study, we examined the effects of creatine supplementation on memory, synaptic plasticity, and neuronal arborization in the CA1 region of the hippocampus in rats under chronic restraint stress (CRS). Thirty-two adult male Wistar rats (8 weeks old) weighing 200-250 g were randomly divided into four groups (n = 8/per group): control, stress, creatine, and stress + creatine. CRS was induced for 6 h per day for 14 days, and creatine supplementation was carried out by dissolving creatine (2 g/kg body weight per day) in the animals' drinking water for 14 days. We used the Barnes maze and shuttle box for spatial and passive avoidance memory examination. The in-vivo field potential recording and Golgi-Cox staining were also used to investigate long-term potentiation (LTP) and dendrite arborization in the CA1 pyramidal neurons. Chronic stress impaired spatial memory, dysregulated LTP parameters, and decreased the number of dendrites in the CA1 pyramidal neurons of stressed rats, and creatine supplementation modified these effects in stressed rats. It seems that creatine supplementation can improve spatial memory deficits and synaptic plasticity loss induced by CRS in hippocampal CA1 neurons, possibly by reducing the dendrite arborization damages. However, understanding its mechanism needs further investigation.

"Heads Up" for Creatine Supplementation and its Potential Applications for Brain Health and Function.

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