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 combined with breathing exercises reduces respiratory discomfort and improves creatine status in patients with long-COVID.

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.

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.

Exploring the relationship between creatine supplementation and renal function: insights from Mendelian randomization analysis.

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.

Effects of rumen-protected creatine pyruvate on blood biochemical parameters and rumen fluid characteristics in transported beef cattle.

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_CrPyr140, T_CrPyr0, NT_CrPyr140, and NT_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-1ß (IL-1ß), 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_CrPyr0 increased the Prevotella genus abundance compared with group NT_CrPyr0 (P < 0.05), while group T_CrPyr140 increased Firmicutes phylum abundance and decreased Bacteroidetes phylum and genus Prevotella abundance compared with group T_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.

Vitreous metabolomics profiling of proliferative diabetic retinopathy.

AIMS/HYPOTHESIS: Proliferative diabetic retinopathy (PDR) with retinal neovascularisation (NV) is a leading cause of vision loss. This study identified a set of metabolites that were altered in the vitreous humour of PDR patients compared with non-diabetic control participants. We corroborated changes in vitreous metabolites identified in prior studies and identified novel dysregulated metabolites that may lead to treatment strategies for PDR. METHODS: We analysed metabolites in vitreous samples from 43 PDR patients and 21 non-diabetic epiretinal membrane control patients from Japan (age 27-80 years) via ultra-high-performance liquid chromatography-mass spectrometry. We then investigated the association of a novel metabolite (creatine) with retinal NV in mouse oxygen-induced retinopathy (OIR). Creatine or vehicle was administered from postnatal day (P)12 to P16 (during induced NV) via oral gavage. P17 retinas were quantified for NV and vaso-obliteration. RESULTS: We identified 158 metabolites in vitreous samples that were altered in PDR patients vs control participants. We corroborated increases in pyruvate, lactate, proline and allantoin in PDR, which were identified in prior studies. We also found changes in metabolites not previously identified, including creatine. In human vitreous humour, creatine levels were decreased in PDR patients compared with epiretinal membrane control participants (false-discovery rate <0.001). We validated that lower creatine levels were associated with vascular proliferation in mouse retina in the OIR model (p = 0.027) using retinal metabolomics. Oral creatine supplementation reduced NV compared with vehicle (P12 to P16) in OIR (p = 0.0024). CONCLUSIONS/INTERPRETATION: These results suggest that metabolites from vitreous humour may reflect changes in metabolism that can be used to find pathways influencing retinopathy. Creatine supplementation could be useful to suppress NV in PDR. Graphical abstract.

Nutritional interventions to improve neurophysiological impairments following traumatic brain injury: A systematic review.

Traumatic brain injury (TBI) accounts for significant global health burden. Effects of TBI can become chronic even following mild injury. There is a need to develop effective therapies to attenuate the damaging effects of TBI and improve recovery outcomes. This literature review using a priori criteria (PROSPERO; CRD42018100623) summarized 43 studies between January 1998 and July 2019 that investigated nutritional interventions (NUT) delivered with the objective of altering neurophysiological (NP) outcomes following TBI. Risk of bias was assessed for included studies, and NP outcomes recorded. The systematic search resulted in 43 of 3,748 identified studies met inclusion criteria. No studies evaluated the effect of a NUT on NP outcomes of TBI in humans. Biomarkers of morphological changes and apoptosis, oxidative stress, and plasticity, neurogenesis, and neurotransmission were the most evaluated NP outcomes across the 43 studies that used 2,897 animals. The risk of bias was unclear in all reviewed studies due to poorly detailed methodology sections. Taking these limitations into account, anti-oxidants, branched chain amino acids, and ω-3 polyunsaturated fatty acids have shown the most promising pre-clinical results for altering NP outcomes following TBI. Refinement of pre-clinical methodologies used to evaluate effects of interventions on secondary damage of TBI would improve the likelihood of translation to clinical populations.

D3-creatine dilution for the noninvasive measurement of skeletal muscle mass in premature infants.

BACKGROUND: The rate of accrual of muscle mass in neonates has not been assessed. We describe the D3-creatine (D3Cr) 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 D3Cr in 0.5 mL 20% 2H2O was used to determine muscle mass and total body water (TBW). RESULTS: Muscle mass by the D3Cr 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 D3Cr 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 D3Cr dilution method is a direct and noninvasive measurement of muscle mass. Using a single enteral dose of D3Cr in 2H2O 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.

The Effect of Creatine Supplementation on Markers of Exercise-Induced Muscle Damage: A Systematic Review and Meta-Analysis of Human Intervention Trials.

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).

Sex-Based Impact of Creatine Supplementation on Depressive Symptoms, Brain Serotonin and SSRI Efficacy in an Animal Model of Treatment-Resistant Depression.

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 supplementation attenuates the rate of fatigue development during intermittent isometric exercise performed above end-test torque.

NEW FINDINGS: What is the central question of this study? Does creatine supplementation augment the total torque impulse accumulated above end-test torque (IET) during severe-intensity knee-extensor exercise by attenuating the rate of decrease in peak potentiated twitch torque (PT)? What is the main finding and its importance? Creatine augmented the IET and attenuated the rate of decrease in both voluntary activation and PT during severe-intensity exercise. The IET was related to the rate of decrease in PT. These findings reveal an important role for the rates of neuromuscular fatigue development as key determinants of exercise tolerance within the severe domain. ABSTRACT: This study investigated the effect of creatine supplementation on exercise tolerance, total torque impulse accumulated above end-test torque (total IET) and neuromuscular fatigue development of the knee extensors during severe-intensity intermittent isometric exercise. Sixteen men were randomly allocated into Creatine (n = 8, 20 g day-1 for 5 days) or Placebo (n = 8) groups and performed knee-extensor maximal voluntary contraction (MVC) testing, all-out testing to determine end-test torque (ET) and the finite torque impulse accumulated above end-test torque (IET'), and three submaximal tests at ET + 10%: (i) time to task failure without supplementation (Baseline); (ii) time to task failure after creatine or placebo supplementation; and (iii) time matched to Baseline after creatine (Creatine-Isotime) or placebo (Placebo-Isotime) supplementation. Creatine supplementation significantly increased the time to task failure (Baseline = 572 ± 144 s versus Creatine = 833 ± 221 s) and total IET (Baseline = 5761 ± 1710  N m s versus Creatine = 7878 ± 1903 N m s), but there were no significant differences within the Placebo group. The percentage change pre- to postexercise in MVC, voluntary activation, peak potentiated twitch torque and integrated EMG during MVC were not significantly different between Baseline and Creatine but were all significantly attenuated in Creatine-Isotime compared with Baseline. There were no significant differences in these variables within the placebo group. The total IET was significantly correlated with the rates of change in potentiated twitch torque peak (r = 0.83-0.87) and rate of torque development (r = -0.83 to -0.87) for the submaximal tests to task failure. These findings reveal an important role for the rates of neuromuscular fatigue development as key determinants of exercise tolerance during severe-intensity intermittent isometric exercise.

Creatine supplementation in Walker-256 tumor-bearing rats prevents skeletal muscle atrophy by attenuating systemic inflammation and protein degradation signaling.

PURPOSE: The aim of this study was to investigate the effects of creatine supplementation on muscle wasting in Walker-256 tumor-bearing rats. METHODS: Wistar rats were randomly assigned into three groups (n = 10/group): control (C), tumor bearing (T), and tumor bearing supplemented with creatine (TCr). Creatine was provided in drinking water for a total of 21 days. After 11 days of supplementation, tumor cells were implanted subcutaneously into T and TCr groups. The animals' weight, food and water intake were evaluated along the experimental protocol. After 10 days of tumor implantation (21 total), animals were euthanized for inflammatory state and skeletal muscle cross-sectional area measurements. Skeletal muscle components of ubiquitin-proteasome pathways were also evaluated using real-time PCR and immunoblotting. RESULTS: The results showed that creatine supplementation protected tumor-bearing rats against body weight loss and skeletal muscle atrophy. Creatine intake promoted lower levels of plasma TNF-α and IL-6 and smaller spleen morphology changes such as reduced size of white pulp and lymphoid follicle compared to tumor-bearing rats. In addition, creatine prevented increased levels of skeletal muscle Atrogin-1 and MuRF-1, key regulators of muscle atrophy. CONCLUSION: Creatine supplementation prevents skeletal muscle atrophy by attenuating tumor-induced pro-inflammatory environment, a condition that minimizes Atrogin-1 and MuRF-1-dependent proteolysis.

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

BACKGROUND: Case studies and reviews have shown that creatine supplementation can affect kidney function. The objective of this study is to verify the effects of 8 weeks of creatine supplementation on renal function (creatinine clearance: primary outcome) in patients with symptomatic peripheral arterial disease. METHODS: Twenty-nine patients, of both genders, were randomized (1:1) in a double-blind manner for administration of Placebo (PLA; n = 15) or creatine monohydrate (Cr; n = 14). The supplementation protocol consisted of 20 g/day for 1 week divided into 4 equal doses (loading phase), followed by single daily doses of 5 g in the subsequent 7 weeks (maintenance phase). Before and after the supplementation period, markers of renal function, serum creatinine, creatinine excretion rate, and creatinine clearance were evaluated. The Generalized Estimation Equation Model was used for comparison between groups. The level of significance was P < 0.05. RESULTS: No significant differences were found between groups before and after the intervention for serum creatinine (Cr: pre 1.00 ± 0.15 mL/dL vs. post 1.07 ± 0.16 mL/dL; PLA: pre 1.30 ± 0.53 mL/dL vs. post 1.36 ± 0.47 mL/dL, P = 0.590), creatinine excretion rate (Cr: pre 81.73 ± 43.80 mg/dL vs. post 102.92 ± 59.57 mg/dL; PLA: pre 74.37 ± 38.90 mg/dL vs. post 86.22 ± 39.94 mg/dL, P = 0.560), or creatinine clearance (Cr; pre 108 ± 59 mL/min/1.73 m2 vs. post 117 ± 52 mL/min/1.73 m2; PLA: pre 88 ± 49 mL/min/1.73 m2 vs. post 82 ± 47 mL/min/1.73 m2, P = 0.366). CONCLUSIONS: Eight weeks of creatine supplementation is safe and does not compromise the renal function of patients with peripheral arterial disease.

Do multi-ingredient protein supplements augment resistance training-induced gains in skeletal muscle mass and strength? A systematic review and meta-analysis of 35 trials.

OBJECTIVE: To determine the effects of multi-ingredient protein (MIP) supplements on resistance exercise training (RT)-induced gains in muscle mass and strength compared with protein-only (PRO) or placebo supplementation. DATA SOURCES: Systematic search of MEDLINE, Embase, CINAHL and SPORTDiscus. ELIGIBILITY CRITERIA: Randomised controlled trials with interventions including RT ≥6 weeks in duration and a MIP supplement. DESIGN: Random effects meta-analyses were conducted to determine the effect of supplementation on fat-free mass (FFM), fat mass, one-repetition maximum (1RM) upper body and 1RM lower body muscular strength. Subgroup analyses compared the efficacy of MIP supplementation relative to training status and chronological age. RESULTS: The most common MIP supplements included protein with creatine (n=17) or vitamin D (n=10). Data from 35 trials with 1387 participants showed significant (p<0.05) increases in FFM (0.80 kg (95% CI 0.44 to 1.15)), 1RM lower body (4.22 kg (95% CI 0.79 to 7.64)) and 1RM upper body (2.56 kg (95% CI 0.79 to 4.33)) where a supplement was compared with all non-MIP supplemented conditions (means (95% CI)). Subgroup analyses indicated a greater effect of MIP supplements compared with all non-MIP supplements on FFM in untrained (0.95 kg (95% CI 0.51 to 1.39), p<0.0001) and older participants (0.77 kg (95% CI 0.11 to 1.43), p=0.02); taking MIP supplements was also associated with gains in 1RM upper body (1.56 kg (95% CI 0.80 to 2.33), p=0.01) in older adults. SUMMARY/CONCLUSIONS: When MIP supplements were combined with resistance exercise training, there were greater gains in FFM and strength in healthy adults than in counterparts who were supplemented with non-MIP. MIP supplements were not superior when directly compared with PRO supplements. The magnitude of effect of MIP supplements was greater (in absolute values) in untrained and elderly individuals undertaking RT than it was in trained individuals and in younger people. TRIAL REGISTRATION NUMBER: CRD42017081970.

Repeated Application of a Novel Creatine Cream Improves Muscular Peak and Average Power in Male Subjects.

Whinton, AK, Donahoe, K, Gao, R, Thompson, KMA, Aubry, R, Saunders, TJ, Johnston, A, Chilibeck, PD, and Burr, JF. Repeated application of a novel creatine cream improves muscular peak and average power in male subjects. J Strength Cond Res 34(9): 2482-2491, 2020-Using a multicenter, randomized controlled trial, (N = 123, age 23 ± 4 years) we sought to determine whether administration of a novel, topical creatine supplement could improve muscular performance after acute and repeated (7-day) exposure. To study the acute performance enhancing effects of the supplement, subjects completed 5 sets of 15 maximal concentric single-leg knee extensions with and without the application of a low- (low dose [LD]-3.5 ml) or high-dose (high dose [HD]-7 ml) topical creatine cream. After a wash-out period, subjects had one leg randomized to receive either the creatine or placebo cream, with further randomization into an oral creatine or placebo supplement group. Subjects completed 5 sets of 15 maximal concentric single leg knee extensions before and after the supplementation protocol. After acute application, no significant differences in peak power (LD: 252 ± 93 W, HD: 261 ± 100 W, p = 0.21), average power (LD: 172 ± 65 W, HD: 177 ± 69 W, p = 0.78), or fatigue index (LD: 13.4 ± 10.6%, HD: 14 ± 11.9%, p = 0.79) were observed between experimental and placebo creams (peak power: LD: 244 ± 76 W, HD: 267 ± 109 W; average power: LD: 168 ± 57 W, HD: 177 ± 67 W; fatigue index: LD: 12.4 ± 9.6%, HD: 12.8 ± 10.6%) or when controlling for sex. After the 7-day supplementation protocol, a significant increase in average power (creatine: 203 ± 61-220 ± 65 W, placebo: 224 ± 61-214 ± 61 W) and peak power (creatine: 264 ± 73-281 ± 80 W, placebo: 286 ± 79-271 ± 73 W) in the leg receiving creatine cream was observed in male subjects. No differences were observed in female subjects. The topical creatine cream did not enhance measures of muscle performance after acute application, but was able to improve peak and average power in male subjects after 7 consecutive days of application.

Beyond sports: Efficacy and safety of creatine supplementation in pathological or paraphysiological conditions of brain and muscle.

Creatine is pivotal in energy metabolism of muscle and brain cells, both in physiological and in pathological conditions. Additionally, creatine facilitates the differentiation of muscle and neuronal cells. Evidence of effectiveness of creatine supplementation in improving several clinical conditions is now substantial, and we review it in this paper. In hereditary diseases where its synthesis is impaired, creatine has a disease-modifying capacity, especially when started soon after birth. Strong evidence, including a Cochrane meta-analysis, shows that it improves muscular strength and general well-being in muscular dystrophies. Significant evidence exists also of its effectiveness in secondary prevention of statin myopathy and of treatment-resistant depression in women. Vegetarians and vegans do not consume any dietary creatine and must synthesize all they need, spending most of their methylation capacity. Nevertheless, they have a lower muscular concentration of creatine. Creatine supplementation has proved effective in increasing muscular and neuropsychological performance in vegetarians or vegans and should, therefore, be recommended especially in those of them who are athletes, heavy-duty laborers or who undergo intense mental effort. Convincing evidence also exists of creatine effectiveness in muscular atrophy and sarcopenia in the elderly, and in brain energy shortage (mental fatigue, sleep deprivation, environmental hypoxia as in mountain climbing, and advanced age). Furthermore, we review more randomized, placebo-controlled trials showing that creatine supplementation is safe up to 20 g/d, with a possible caveat only in people with kidney disease. We trust that the evidence we review will be translated into clinical practice and will spur more research on these subjects.

Creatine supplementation improves performance above critical power but does not influence the magnitude of neuromuscular fatigue at task failure.

NEW FINDINGS: What is the central question of this study? Does the magnitude of neuromuscular fatigue depend on the amount of work done (W') at task failure when cycling above critical power (CP)? What is the main finding and its importance? Creatine supplementation increases W' and enhances supra-CP performance, but induces similar magnitudes of neuromuscular fatigue at task failure compared to placebo. Increased W' does not lead to higher levels of neuromuscular fatigue. This supports the notion of a critical level of neuromuscular fatigue at task failure and challenges a direct causative link between W' depletion and neuromuscular fatigue. ABSTRACT: The present study examined the effect of creatine supplementation on neuromuscular fatigue and exercise tolerance when cycling above critical power (CP). Eleven males performed an incremental cycling test with four to five constant-load trials to task failure (TTF) to obtain asymptote (CP) and curvature constant (W') of the power-duration relationship, followed by three constant-load supra-CP trials: (1) one TTF following placebo supplementation (PLA); (2) one TTF following creatine supplementation (CRE); and (3) one trial of equal duration to PLA following creatine supplementation (ISO). Neuromuscular assessment of the right knee extensors was performed pre- and post-exercise to measure maximal voluntary contraction (MVC), twitch forces evoked by single (Qpot ) and paired high- (PS100) and low- (PS10) frequency stimulations and voluntary activation. Creatine supplementation increased TTF in CRE vs. PLA by ∼11% (P = 0.017) and work done above CP by ∼10% (P = 0.015), with no difference (P > 0.05) in reductions in MVC (-24 ± 8% vs. -20 ± 9%), Qpot (-39 ± 13% vs. -32 ± 14%), PS10 (-42 ± 14% vs. -36 ± 13%), PS100 (-25 ± 10% vs. -18 ± 12%) and voluntary activation (-7 ± 8% vs. -5 ± 7%). No significant difference was found between ISO and either PLA or CRE (P > 0.05). These findings suggest similar levels of neuromuscular fatigue can be found following supra-CP cycling despite increases in performance time and amount of work done above CP, supporting the notion of a critical level of neuromuscular fatigue and challenging a direct causative link between W' depletion and neuromuscular fatigue.

Is vegetarianism healthy for children?

According to the Academy of Nutrition and Dietetics' influential position statement on vegetarianism, meat and seafood can be replaced with milk, soy/legumes, and eggs without any negative effects in children. The United States Department of Agriculture endorses a similar view. The present paper argues that the Academy of Nutrition and Dietetics ignores or gives short shrift to direct and indirect evidence that vegetarianism may be associated with serious risks for brain and body development in fetuses and children. Regular supplementation with iron, zinc, and B12 will not mitigate all of these risks. Consequently, we cannot say decisively that vegetarianism or veganism is safe for children.

Chronic dietary creatine enhances hippocampal-dependent spatial memory, bioenergetics, and levels of plasticity-related proteins associated with NF-κB.

The brain has a high demand for energy, of which creatine (Cr) is an important regulator. Studies document neurocognitive benefits of oral Cr in mammals, yet little is known regarding their physiological basis. This study investigated the effects of Cr supplementation (3%, w/w) on hippocampal function in male C57BL/6 mice, including spatial learning and memory in the Morris water maze and oxygen consumption rates from isolated mitochondria in real time. Levels of transcription factors and related proteins (CREB, Egr1, and IκB to indicate NF-κB activity), proteins implicated in cognition (CaMKII, PSD-95, and Egr2), and mitochondrial proteins (electron transport chain Complex I, mitochondrial fission protein Drp1) were probed with Western blotting. Dietary Cr decreased escape latency/time to locate the platform (P < 0.05) and increased the time spent in the target quadrant (P < 0.01) in the Morris water maze. This was accompanied by increased coupled respiration (P < 0.05) in isolated hippocampal mitochondria. Protein levels of CaMKII, PSD-95, and Complex 1 were increased in Cr-fed mice, whereas IκB was decreased. These data demonstrate that dietary supplementation with Cr can improve learning, memory, and mitochondrial function and have important implications for the treatment of diseases affecting memory and energy homeostasis.

Creatine enhances the duration of sperm capacitation: a novel factor for improving in vitro fertilization with small numbers of sperm.

STUDY QUESTION: Why are many sperm required for successful fertilization of oocytes in vitro, even though fertilization occurs in vivo when only a few sperm reach the oocyte? SUMMARY ANSWER: Creatine produced in the ovary promotes efficient fertilization in vivo; however, in vitro, creatine is not contained in the in vitro fertilization (IVF) medium. WHAT IS KNOWN ALREADY: The IVF medium enables capacitation of sperm. However, the IVF medium does not fully mimic the in vivo environment during fertilization. Consequently, fertilization in vitro is more inefficient than in the oviduct. STUDY DESIGN, SIZE, DURATION: Follicular and oviductal fluids were collected and then analyzed for creatine and glucose levels. To determine the physiological functions of creatine, the creatine antagonist 3-guanidinopropionic acid (GPA) was injected into hormonally primed mice. Using conventional IVF protocols, sperm were pre-incubated in IVF medium with creatine and then co-cultured with 10 ovulated cumulus-oocyte complexes (1-1000 per oocyte) in 50 µl medium droplets. PARTICIPANTS/MATERIALS, SETTING, METHODS: Glucose and creatine levels were measured using commercial enzymatic assay kits. The effect of creatine in vivo was assessed by mating experiments using mice treated with or without GPA just before ovulation. To assess the functions of sperm incubated in IVF medium containing creatine, we analyzed (1) the motility of sperm using computer-assisted sperm assay, (2) the capacitation level of sperm by western blot analyses, and (3) the condition of sperm acrosomes by peanut agglutinin lectin-FITC staining. MAIN RESULTS AND THE ROLE OF CHANCE: Oviductal creatine levels were significantly increased following ovulation. Injecting mice with GPA just before ovulation significantly reduced the number of fertilized oocytes. The addition of creatine to IVF medium enhanced sperm capacitation by increasing ATP levels. Successful fertilization was achieved with as few as five sperm/oocyte in the creatine group, and the number of fertilized oocytes was significantly higher than in the control without creatine (P < 0.01). LIMITATIONS, REASONS FOR CAUTION: In the present study, a pharmacological approach, creatine antagonist (GPA) treatment, but not a knockout mouse model, was used to understand the role of creatine in vivo. The role of creatine in fertilization processes can only be shown in a mouse model. WIDER IMPLICATIONS OF THE FINDINGS: A modified IVF technique using creatine-containing medium was developed and shown to markedly improve fertilization with small numbers of sperm. This approach has the potential to be highly beneficial for human assisted reproductive technologies, especially for patients with a limited number of good quality sperm. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by JSPS KAKENHI Grant numbers JP24688028, JP16H05017 (to M.S.), and JP15J05331 (to T.U.), the Japan Agency for Medical Research and Development (AMED) (16gk0110015h0001 to M.S.), and National Institutes of Health (NIH-HD-076980 to J.S.R). The authors have nothing to disclose.