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Acute creatine loading increases fat-free mass, but does not affect blood pressure, plasma creatinine, or CK activity in men and women

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Abstract

Creatine monohydrate (CrM) administration may enhance high intensity exercise performance and increase body mass, yet few studies have examined for potential adverse effects, and no studies have directly considered potential gender differences. The purpose of this study was to examine the effect of acute creatine supplementation upon total and lean mass and to determine potential side effects in both men and women. The effect of acute CrM (20 g x d(-1) x 5 d) administration upon systolic, diastolic, and mean BP, plasma creatinine, plasma CK activity, and body composition was examined in 15 men and 15 women in a randomized, double-blind experiment. Additionally, ischemic isometric handgrip strength was measured before and after CrM or placebo (PL). CrM did not affect blood pressure, plasma creatinine, estimated creatinine clearance, plasma CK activity, or handgrip strength (P > 0.05). In contrast, CrM significantly increased fat-free mass (FFM) and total body mass (P < 0.05) as compared with PL, with no changes in body fat. The observed mass changes were greater for men versus women. These findings suggest that acute CrM administration does not affect blood pressure, renal function, or plasma CK activity, but increases FFM. The effect of CrM upon FFM may be greater in men as compared with that in women.

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... Cr in combination with HIIT increases ventilatory threshold (VT; Graef et al., 2009) and critical power in young males ; however, the effects of Cr with HIIT in young females are unknown. There are potential sex-based differences in response to Cr (Johannsmeyer et al., 2016;Mihic et al., 2000). Mihic et al. (2000) demonstrated that the effect of Cr combined with resistance training on gains in fat free mass were greater in men compared to women. ...
... There are potential sex-based differences in response to Cr (Johannsmeyer et al., 2016;Mihic et al., 2000). Mihic et al. (2000) demonstrated that the effect of Cr combined with resistance training on gains in fat free mass were greater in men compared to women. Johannsmeyer et al. (2016) found that males increased strength to a greater extent than females following Cr and resistance training and males ingesting Cr were able to train at a greater capacity compared to males in the placebo condition; whereas, there was no differences in training volume between females ingesting Cr or placebo. ...
... Recently, Johannsmeyer et al., (2016) demonstrated greater gains in strength in males compared to females in response to Cr combined with resistance training on strength. Mihic et al., (2000) similarly found that males had greater gains in fat free mass following Cr supplementation compared to females. Kendall et al. (2009) and Graef et al. (2009) examined recreationally active males. ...
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High-intensity interval training (HIIT) has been shown to improve cardiorespiratory fitness, performance, body composition, and insulin sensitivity. Creatine (Cr) supplementation may augment responses to HIIT, leading to even greater physiological adaptations. The purpose of this study was to determine the effects of four weeks of HIIT (three sessions/week) combined with Cr supplementation in recreationally active females. Seventeen females (age = 23 ± 4 yrs; BMI = 23.4 ± 2.4) were randomly assigned to either Cr (Cr; 0.3 g·kg(-1)·d(-1) for 5 d followed by 0.1 g·kg(-1)·d(-1) for 23 days; n=9) or placebo (PLA; n=8). Before and after the intervention, VO2peak, ventilatory threshold (VT), time- trial performance, lean body mass and fat mass, and insulin sensitivity were assessed. HIIT improved VO2peak (Cr = +10.2%; PLA = +8.8%), VT (Cr = +12.7%; PLA = +9.9%), and time- trial performance (Cr = -11.5%; PLA = -11.6%) with no differences between groups (time main effects, all p<0.001). There were no changes over time for fat mass (Cr = -0.3%; PLA = +4.3%), whole-body lean mass (Cr = +0.5%; PLA = -0.9%), or insulin resistance (Cr = +3.9%; PLA = +18.7%). In conclusion, HIIT is an effective way to improve cardiorespiratory fitness, VT, and time-trial performance. The addition of Cr to HIIT did not augment improvements in cardiorespiratory fitness, performance or body composition in recreationally active females.
... The use of dietary creatine supplementation as an ergogenic aid for exercise performance, and as a targeted therapeutic for a wide range of conditions where mitochondrial demise and depleted ATP underlie the pathology has been widely studied (see reviews , Feldman 1999;Gualano et al. 2010;Wallimann et al. 2011). Despite the fundamental role this phosphagen circuit plays at a cellular level, from time-to-time studies into creatine homeostasis and the benefits of dietary creatine supplementation for exercise performance and disorders of metabolism have identified differences in the sex-specific responses to creatine loading, with the benefits for women, particularly in regard to exercise physiology, being less than those reported for men (Mihic et al. 2000). ...
... Concerns about the ergogenic potential of supplementary creatine in women have been raised, as a higher resting total creatine content in skeletal muscle could diminish the capacity for creatine loading prior to exercise, and a lower total muscle mass has been correlated to lower CK activity (Norton et al. 1985;Forsberg et al. 1991). A study conducted by Mihic et al. (2000) directly assessed potential sex differences of acute dietary creatine loading on fat-free mass, blood pressure, plasma creatinine and CK activity, and concluded that increased creatine consumption increased total body mass and fat free mass for males and females, but that the effect was significantly greater in men (Mihic et al. 2000). In addition, only creatine supplementation in men has been shown to reduce amino acid oxidation and protein breakdown following strenuous exercise (Parise et al. 2001). ...
... Concerns about the ergogenic potential of supplementary creatine in women have been raised, as a higher resting total creatine content in skeletal muscle could diminish the capacity for creatine loading prior to exercise, and a lower total muscle mass has been correlated to lower CK activity (Norton et al. 1985;Forsberg et al. 1991). A study conducted by Mihic et al. (2000) directly assessed potential sex differences of acute dietary creatine loading on fat-free mass, blood pressure, plasma creatinine and CK activity, and concluded that increased creatine consumption increased total body mass and fat free mass for males and females, but that the effect was significantly greater in men (Mihic et al. 2000). In addition, only creatine supplementation in men has been shown to reduce amino acid oxidation and protein breakdown following strenuous exercise (Parise et al. 2001). ...
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The creatine/phosphocreatine/creatine kinase circuit is instrumental in regulating high-energy phosphate metabolism, and the maintenance of cellular energy turnover. The mechanisms by which creatine is able to buffer and regulate cellular energy balance, maintain acid-base balance, and reduce the effects of oxidative stress have led to a large number of studies into the use of creatine supplementation in exercise performance and to treat diseases associated with cellular energy depletion. Some of these studies have identified sex-specific responses to creatine supplementation, as such; there is the perception, that females might be less receptive to the benefits of creatine supplementation and therapy, compared to males. This review will describe the differences in male and female physique and physiology that may account for such differences, and discuss the apparent endocrine modulation of creatine metabolism in females. Hormone-driven changes to endogenous creatine synthesis, creatine transport and creatine kinase expression suggest that significant changes in this cellular energy circuit occur during specific stages of a female's reproductive life, including pregnancy and menopause. Recent studies suggest that creatine supplementation may be highly beneficial for women under certain conditions, such as depression. A greater understanding of these pathways, and the consequences of alterations to creatine bioavailability in females are needed to ensure that creatine is used to full advantage as a dietary supplement to optimize and enhance health outcomes for women.
... Our findings support other published literature that found no evidence of a significant effect on GIT symptoms, muscle cramping, or renal and hepatic changes across placebo-controlled trials [15,19,90,94,[134][135][136][137][138]. This included studies in middle to older age male, or mixed sex populations treated with creatine [94,[139][140][141][142][143] and in younger mixed sex populations [25,135,144]. ...
... Serum creatinine remains the most commonly used biomarker of renal function and this corresponds to our review. Previous studies have shown no significant change in serum creatinine levels [94,135,[144][145][146][147][148][149], or a mild to modest change of up to 13% with creatine supplementation [150][151][152], which correlates with the ranges reported in our studies. Serum creatinine remained within normal range across all studies over the time of supplementation, and this finding corresponds with a previous review that found 91% of studies reported no change or change that remained within normal limits [87]. ...
... There have been no systematic reviews on blood pressure changes or adverse cardiovascular effects of creatine supplementation in relatively healthy male or mix-sex populations. However, our finding is consistent with no reported blood pressure effect in three published male only placebo-controlled trials with creatine [160][161][162] and one mix-sex study [144]. There has been one systematic review on the use of creatine and creatine analogues in hypertension and cardiovascular disease, which also concluded no change in blood pressure with creatine supplementation in myocardial infarction or heart failure trials [163]. ...
Article
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Creatine Monohydrate (CrM) is a dietary supplement routinely used as an ergogenic aid for sport and training, and as a potential therapeutic aid to augment different disease processes. Despite its increased use in recent years, studies reporting potential adverse outcomes of CrM have been mostly derived from male or mixed sex populations. A systematic search was conducted, which included female participants on CrM, where adverse outcomes were reported, with meta-analysis performed where appropriate. Six hundred and fifty-six studies were identified where creatine supplementation was the primary intervention; fifty-eight were female only studies (9%). Twenty-nine studies monitored for adverse outcomes, with 951 participants. There were no deaths or serious adverse outcomes reported. There were no significant differences in total adverse events, (risk ratio (RR) 1.24 (95% CI 0.51, 2.98)), gastrointestinal events, (RR 1.09 (95% CI 0.53, 2.24)), or weight gain, (mean difference (MD) 1.24 kg pre-intervention, (95% CI −0.34, 2.82)) to 1.37 kg post-intervention (95% CI −0.50, 3.23)), in CrM supplemented females, when stratified by dosing regimen and subject to meta-analysis. No statistically significant difference was reported in measures of renal or hepatic function. In conclusion, mortality and serious adverse events are not associated with CrM supplementation in females. Nor does the use of creatine supplementation increase the risk of total adverse outcomes, weight gain or renal and hepatic complications in females. However, all future studies of creatine supplementation in females should consider surveillance and comprehensive reporting of adverse outcomes to better inform participants and health professionals involved in future trials.
... Supplement efficacy based on sex has been suggested to be related to initial muscular creatine concentrations, because they are often lower in men than in women (13,17). Men often show greater increases in lean tissue mass than women (5,25) when performing exercise while supplementing with creatine for either 20 g·kg 21 for 5 days (25) or 0.2 g·kg 21 for 6 weeks (5). Therefore, sexspecific muscular power changes in response to acute, short-term application and oral creatine supplementation should be considered. ...
... Supplement efficacy based on sex has been suggested to be related to initial muscular creatine concentrations, because they are often lower in men than in women (13,17). Men often show greater increases in lean tissue mass than women (5,25) when performing exercise while supplementing with creatine for either 20 g·kg 21 for 5 days (25) or 0.2 g·kg 21 for 6 weeks (5). Therefore, sexspecific muscular power changes in response to acute, short-term application and oral creatine supplementation should be considered. ...
... Our sex-specific results for the topical creatine support past research that suggests creatine supplementation is more effective in men than women (5,17,27). Previous work has demonstrated that men have greater changes in intramuscular total creatine content during supplementation, which could lead to the improvements observed in our male subjects (17,25). Women have higher resting total muscular creatine content compared with their male counterparts (17,26,27), minimizing the likelihood of detecting or deriving a performance benefit from exogenous supplementation (3,39) as they are closer to the "ceiling" of 160 nmol·kg 21 dry mass in an individual (17). ...
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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.
... 65 Moreover, some anecdotes report hypertensive effects upon supplementing with Cr, though acute (5 d, 20 g·day -1 ) and longer-duration (6 wk, 20 g·day -1 (3 d), 10 g·day -1 maintenance) interventions have been shown to have no effects on blood pressure (systolic, diastolic, and mean). 66,67 More commonly anecdotally reported non-severe adverse effects accompany counterpart. 87 Following, Gufford and colleagues reported that when Cr ethyl ester was placed in a highly acidic state (HCl), with the pH stabilized at pH 1.0, the amount of Cr absorbed by the intestines consequently increased 60%, due to the enhanced solubility and greater permeability characteristics under these acidic conditions, in comparison to ...
... 120 There have also been anecdotes of hypertension among those who supplement with Cr. 26 However, Mihic and colleagues found via double-blind procedures that shortterm Cr supplementation (20 g·d -1 , 5 d) among young male and female participants had no effects on mean, systolic, or diastolic blood pressures. 66 Peeters et al. found in a similar study that the same supplemental Cr protocol yielded no blood pressure effects over a longer duration of time (6 wk, 20 g·d -1 (3 d), 10 g·d -1 maintenance). 67 Two more studies found that blood pressure was not affected among participants with congestive heart failure who supplemented with Cr (20 g·d -1 , 5 d and 20 g·d -1 , 10 d). ...
... Both Robinson et al. [133] and Mihic et al. [134] reported no effect of high-dose short-term (20 g/day for 5 days) and low-dose longer-term (3 g/day for 8 weeks) creatine supplementation on blood CK activity in physically unstressed subjects. Additionally, Robinson et al. [133] found no increase in serum CK activity in a group that performed 8 weeks of resistance training in addition to creatine ingestion (20 g/day for 5 days followed by 3 g/day for 8 weeks). ...
... Collectively, these data indicate that creatine supplementation has no effect on bio-markers of muscle damage. The effects of creatine supplementation on markers of muscle damage at rest are summarized in Table 1 [133][134][135][136]. ...
Article
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Exertional (exercise-induced) rhabdomyolysis is a potentially life threatening condition that has been the subject of research, intense discussion, and media attention. The causes of rhabdomyolysis are numerous and can include direct muscle injury, unaccustomed exercise, ischemia, extreme temperatures, electrolyte abnormalities, endocrinologic conditions, genetic disorders, autoimmune disorders, infections, drugs, toxins, and venoms. The objective of this article is to review the literature on exertional rhabdomyolysis, identify precipitating factors, and examine the role of the dietary supplement creatine monohydrate. PubMed and SPORTDiscus databases were searched using the terms rhabdomyolysis, muscle damage, creatine, creatine supplementation, creatine monohydrate, and phosphocreatine. Additionally, the references of papers identified through this search were examined for relevant studies. A meta-analysis was not performed. Although the prevalence of rhabdomyolysis is low, instances still occur where exercise is improperly prescribed or used as punishment, or incomplete medical history is taken, and exertional rhabdomyolysis occurs. Creatine monohydrate does not appear to be a precipitating factor for exertional rhabdomyolysis. Healthcare professionals should be able to recognize the basic signs of exertional rhabdomyolysis so prompt treatment can be administered. For the risk of rhabdomyolysis to remain low, exercise testing and prescription must be properly conducted based on professional standards.
... In accordance, creatine supplementation was shown to effectively augment athletic performance during various exercise tasks characterized by repeated high-intensity exercise and has since become common practice among many athletes [12][13][14]. Besides increasing high-intensity exercise performance, creatine supplementation has also been reported to increase muscle mass and strength in the presence as well as in the absence of prolonged resistance-type exercise training [9,15,16]. The increase in lean mass following creatine supplementation has, at least partly, been attributed to water retention in muscle tissue [11,17]. ...
... We also observed an increase in body weight in the responders to creatine supplementation, ranging from 0.4 to 1.9 kg, which is in line with findings of previous studies [9,10,29]. The increase in body weight with creatine loading has been found to result from water retention due to the increased cellular osmolarity [11,17] or the increase in fat-free mass [9,15,16]. The fact that the individuals with an increase in muscle total creatine content also show an increase in body weight supports that these subjects are responders to creatine supplementation. ...
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Background: A short period of leg immobilization leads to rapid loss of muscle mass and strength. Creatine supplementation has been shown to increase lean body mass in active individuals and can be used to augment gains in muscle mass and strength during prolonged resistance-type exercise training. Objective: Our objective was to investigate whether creatine loading can attenuate the loss of muscle mass and strength during short-term leg immobilization. Methods: Healthy young men (n = 30; aged 23 ± 1 years; body mass index [BMI] 23.3 ± 0.5 kg/m(-2)) were randomly assigned to either a creatine or a placebo group. Subjects received placebo or creatine supplements (20 g/d) for 5 days before one leg was immobilized by means of a full-leg cast for 7 days. Muscle biopsies were taken before creatine loading, prior to and immediately after leg immobilization, and after 7 days of subsequent recovery. Quadriceps cross-sectional area (CSA) (computed tomography [CT] scan) and leg muscle strength (one-repetition maximum [1-RM] knee extension) were assessed before and immediately after immobilization and after 1 week of recovery. Data were analyzed using repeated measures analysis of variance (ANOVA). Data are presented consistently as mean ± standard error of the mean (SEM). Results: There was a significant overall increase in muscle total creatine content following the 5-day loading phase (p = 0.049), which appeared driven by an increase in the creatine group (from 90 ± 9 to 107 ± 4 mmol/kg(-1) dry muscle) with no apparent change in the placebo group (from 88 ± 4 to 90 ± 3 mmol/kg(-1); p = 0.066 for time × treatment interaction). Quadriceps muscle CSA had declined by 465 ± 59 and 425 ± 69 mm(2) (p < 0.01) in the creatine and placebo group, respectively, with no differences between groups (p = 0.76). Leg muscle strength decreased from 56 ± 4 to 53 ± 4 kg in the creatine and from 59 ± 3 to 53 ± 3 kg in the placebo group, with no differences between groups (p = 0.20). Muscle fiber size did not change significantly over time in either group (p > 0.05). When non-responders to creatine loading were excluded (n = 6), responders (n = 8; total creatine content increasing from 70 to 106 mmol/kg(-1)) showed similar findings, with no signs of preservation of muscle mass or strength during immobilization. During the subsequent recovery phase, no differences in muscle mass or strength were found between the two groups (p > 0.05). Conclusion: Creatine supplementation prior to and during leg immobilization does not prevent or attenuate the loss of muscle mass or strength during short-term muscle disuse. NIH Clinical Trial Registration Number: NCT01894737 ( http://www.clinicaltrials.gov/ ).
... Administration of CrM may enhance high intensity exercises performance and increase body mass as well as fat free mass [8,9]. Another study observed that CrM supplementation did not increase total body mass or fat free mass [10,11]. However, it has been noted that acute creatine supplementation favorably affected repeated sprint performance in highly trained soccer players [12]. ...
... Further, it has been noted that short term supplementation of creatine monohydrate has no significant effect on body mass or fat free mass [24]. Although it has been reported that short-term oral creatine ingestion is accompanied by increase in body mass, this weight gain has been explained by water retention [10,11,25]. ...
Article
Creatine has beneficial effect on strength training athletes, but it is not clear whether it has any effect on endurance sport. Present study has been designed to investigate the effect of creatine supplementation on cardiovascular adaptation to sub maximal exercise and endurance performance. A total of 60 male athletes (age range 16-19 years) were selected and randomly divided into experimental group (EG, n = 30) and control group (CG, n = 30) and supplemented with 5 g per day of creatine monohydrate (CrM) and moltodextrine, respectively for 4 weeks. A treadmill test was performed to determine the heart rate responses to sub maximal exercise and maximal endurance performance. Blood lactate was measured at the end of exercise. Body mass, body fat and fat free mass were also measured. Repeated measure ANOA followed by t-test was applied to analyze the data. Significant decreases in heart rates were noted in the experimental group during sub maximal exercise when compared to the control group. Moreover, the maximal endurance time was increase in the experimental group after supplementation of CrM when compared to control group. However, no significant change has been observed in resting heart, maximal heart rate, recovery heart rate, body mass, body fat, fat free mass and blood lactate level.
... Females may have higher intramuscular creatine concentrations [158] possibly due to lower skeletal muscle mass [159]. Potentially, the higher resting intramuscular creatine concentration in females (based on the upper limit of intramuscular creatine storage) may help explain some research showing diminished responsiveness and/or performance effects on females [160,161]. ...
... Furthermore, in college-aged females (20 yrs), creatine supplementation (0.5 g/kg of fat-free mass for 5 days) improved knee extension muscle performance compared to placebo [179]. In contrast, not all data show improved performance in females [89,160,161]. Additionally, Smith-Ryan et al. [180] reported no significant effects of creatine loading on neuromuscular properties of fatigue in young adult females. ...
Article
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Supplementing with creatine is very popular amongst athletes and exercising individuals for improving muscle mass, performance and recovery. Accumulating evidence also suggests that creatine supplementation produces a variety of beneficial effects in older and patient populations. Furthermore, evidence-based research shows that creatine supplementation is relatively well tolerated, especially at recommended dosages (i.e. 3-5 g/day or 0.1 g/kg of body mass/day). Although there are over 500 peer-refereed publications involving creatine supplementation, it is somewhat surprising that questions regarding the efficacy and safety of creatine still remain. These include, but are not limited to: 1. Does creatine lead to water retention? 2. Is creatine an anabolic steroid? 3. Does creatine cause kidney damage/renal dysfunction? 4. Does creatine cause hair loss / baldness? 5. Does creatine lead to dehydration and muscle cramping? 6. Is creatine harmful for children and adolescents? 7. Does creatine increase fat mass? 8. Is a creatine ‘loading-phase’ required? 9. Is creatine beneficial for older adults? 10. Is creatine only useful for resistance / power type activities? 11. Is creatine only effective for males? 12. Are other forms of creatine similar or superior to monohydrate and is creatine stable in solutions/beverages? To answer these questions, an internationally renowned team of research experts was formed to perform an evidence-based scientific evaluation of the literature regarding creatine supplementation.
... Methyl guanidino acetic acid, commonly known as creatine (Cr), is a naturally occurring compound found predominantly in skeletal muscle (Myers and Fine 1915;Hunter 1922). Cr supplementation has been reported to improve physical performance during a variety of different exercise modalities, intensities, and durations, and to promote greater gains in strength, muscle mass, bone mineral density, and neuromuscular function in populations ranging from trained healthy individuals to the elderly with sarcopenia undergoing exercise rehabilitation (Bosco et al. 1997;Grindstaff et al. 1997;Mihic et al. 2000;Metzl et al. 2001;Mihic et al. 2000;Hespel et al. 2001;Volek et al. 2004;Pearlman and Fielding 2006;Bazzucchi et al. 2009;Bemben et al. 2010;Devries and Phillips 2014;Gualano et al. 2011Gualano et al. , 2014Candow et al. 2015;Chilibeck et al. 2015;Griffen et al. 2015;Martone et al. 2015;Ramirez-Campillo et al. 2015;Wilkinson et al. 2015, Phillips 2015) (see Table 1). The mechanism(s) responsible for these effects range from Cr-induced increases in intramuscular phosphocreatine (PCr) levels and the PCr/ATP energy charge ratio, as well as a greater resynthesis rate of PCr following intense exercise, leading to a higher efficiency of ATP utilization (Wallimann et al. 2011) and to attenuated cardiovascular and thermoregulatory responses during prolonged exercise in the heat (Demant and Rhodes 1999;Terjung et al. 2000;Lopez et al. 2009). ...
... Methyl guanidino acetic acid, commonly known as creatine (Cr), is a naturally occurring compound found predominantly in skeletal muscle (Myers and Fine 1915;Hunter 1922). Cr supplementation has been reported to improve physical performance during a variety of different exercise modalities, intensities, and durations, and to promote greater gains in strength, muscle mass, bone mineral density, and neuromuscular function in populations ranging from trained healthy individuals to the elderly with sarcopenia undergoing exercise rehabilitation (Bosco et al. 1997;Grindstaff et al. 1997;Mihic et al. 2000;Metzl et al. 2001;Mihic et al. 2000;Hespel et al. 2001;Volek et al. 2004;Pearlman and Fielding 2006;Bazzucchi et al. 2009;Bemben et al. 2010;Devries and Phillips 2014;Gualano et al. 2011Gualano et al. , 2014Candow et al. 2015;Chilibeck et al. 2015;Griffen et al. 2015;Martone et al. 2015;Ramirez-Campillo et al. 2015;Wilkinson et al. 2015, Phillips 2015) (see Table 1). The mechanism(s) responsible for these effects range from Cr-induced increases in intramuscular phosphocreatine (PCr) levels and the PCr/ATP energy charge ratio, as well as a greater resynthesis rate of PCr following intense exercise, leading to a higher efficiency of ATP utilization (Wallimann et al. 2011) and to attenuated cardiovascular and thermoregulatory responses during prolonged exercise in the heat (Demant and Rhodes 1999;Terjung et al. 2000;Lopez et al. 2009). ...
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Creatine (Cr) is produced endogenously in the liver or obtained exogenously from foods, such as meat and fish. In the human body, 95 % of Cr is located in the cytoplasm of skeletal muscle either in a phosphorylated (PCr) or free form (Cr). PCr is essential for the immediate rephosphorylation of adenosine diphosphate to adenosine triphosphate. PCr is rapidly degraded at the onset of maximal exercise at a rate that results in muscle PCr reservoirs being substantially depleted. A well-established strategy followed to increase muscle total Cr content is to increase exogenous intake by supplementation with chemically pure synthetic Cr. Most Cr supplementation regimens typically follow a well-established loading protocol of 20 g day(-1) of Cr for approximately 5-7 days, followed by a maintenance dose at between 2 and 5 g day(-1) for the duration of interest, although more recent studies tend to utilize a 0.3-g kg(-1) day(-1) supplementation regimen. Some studies have also investigated long-term supplementation of up to 1 year. Uptake of Cr is enhanced when taken together with carbohydrate and protein and/or while undertaking exercise. Cr supplementation has been shown to augment muscle total Cr content and enhance anaerobic performance; however, there is also some evidence of indirect benefits to aerobic endurance exercise through enhanced thermoregulation. While there is an abundance of data supporting the ergogenic effects of Cr supplementation in a variety of different applications, some individuals do not respond, the efficacy of which is dependent on a number of factors, such as dose, age, muscle fiber type, and diet, although further work in this field is warranted. Cr is increasingly being used in the management of some clinical conditions to enhance muscle mass and strength. The application of Cr in studies of health and disease has widened recently with encouraging results in studies involving sleep deprivation and cognitive performance.
... Females have also been reported to consume significantly lower amounts of dietary creatine compared to males [3], indicating that females may benefit from creatine supplementation as a strategy/means to increase endogenous stores. Interestingly, females have higher reported (~10%) resting levels of intramuscular creatine concentrations compared to males [4], which could theoretically lower their responsiveness to supplementation and require higher dosages compared to males [5]. In addition, creatine supplementation has not been shown to effectively reduce amino acid oxidation and measures of protein breakdown following exercise in females, which has been reported in males [6]. ...
... A considerable amount of evidence indicates that creatine is an effective ergogenic aid for increasing strength, power, and athletic performance in females without marked changes in body weight [5,[19][20][21]. The reluctance among females to use creatine may be due to a fear of weight gain or other adverse side effects, which are largely unfounded, particularly in women [20]. ...
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Despite extensive research on creatine, evidence for use among females is understudied. Creatine characteristics vary between males and females, with females exhibiting 70–80% lower endogenous creatine stores compared to males. Understanding creatine metabolism pre- and post-menopause yields important implications for creatine supplementation for performance and health among females. Due to the hormone-related changes to creatine kinetics and phosphocreatine resynthesis, supplementation may be particularly important during menses, pregnancy, post-partum, during and post-menopause. Creatine supplementation among pre-menopausal females appears to be effective for improving strength and exercise performance. Post-menopausal females may also experience benefits in skeletal muscle size and function when consuming high doses of creatine (0.3 g·kg−1·d−1); and favorable effects on bone when combined with resistance training. Pre-clinical and clinical evidence indicates positive effects from creatine supplementation on mood and cognition, possibly by restoring brain energy levels and homeostasis. Creatine supplementation may be even more effective for females by supporting a pro-energetic environment in the brain. The purpose of this review was to highlight the use of creatine in females across the lifespan with particular emphasis on performance, body composition, mood, and dosing strategies.
... Kambis e Pizzedas [27] mostraram uma melhora na força muscular de membros inferiores de mulheres adultas não treinadas, suplementadas com 0,5g/kg de peso de creatina monoidratada, durante 5 dias. Candow et al. [28] conduziram estudo com amostra de homens e mulheres, e os dois grupos obtiveram melhora na força dos membros inferiores no leg press, apesar dos ganhos terem sido maiores nos homens. Gualano et al. [29] encontraram melhora da força no leg press em seu estudo com mulheres idosas e vulneráveis, depois da suplementação crônica com creatina. ...
... No trabalho de Forbes et al. [35], as mulheres suplementadas durante cinco dias com creatina seguidos de um período de manutenção de 23 dias com doses menores, submetidas a 4 semanas de HIIT, também não obtiveram mudanças na composição corporal. Os autores acreditam que não houve resposta hipertrófica devido à ausência do treinamento de força e pelo fato das participantes serem mulheres, pois alguns estudos sugerem que mulheres possuem menor resposta à suplementação de creatina em comparação aos homens [28,36]. Em contrapartida, a maioria dos trabalhos com a suplementação creatina mostra aumento de massa magra em homens, em geral, relacionada a fatores como modulação na transcrição de fatores regulatórios miogênicos; eficiência na tradução de proteínas; ativação, proliferação e diferenciação de células satélite; aumento do volume ou intensidade do treino em decorrência do efeito ergogênico [37]. ...
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Introdução: A creatina tem sido considerada agente ergogênico para indivíduos onívoros e vegetarianos, porém, nota-se lacuna importante sobre o efeito dessa suplementação sobre a performance de veganos, grupo que apresenta maiores restrições nutricionais dentre os vegetarianos. Objetivo: Analisar o efeito da suplementação de creatina sobre performance em teste de força e composição corporal de veganas. Métodos: Quatorze veganas não-atletas foram randomicamente distribuídas em grupo creatina (n = 7) e placebo (n = 7). Antes e depois da suplementação (0,3 g kg-1 d-1 por 7 dias) foram realizados testes de performance em leg press (3 séries de repetições máximas até falha, a 80% de uma repetição máxima, 60 segundos de intervalo), e antropometria. Resultados: Após suplementação, houve diferenças significativa no número de repetições na primeira série e no somatório das três séries para ambos grupos, porém, com o o tamanho do efeito (effect size) e delta percentual superiores para grupo creatina. Na segunda série, não houve diferenças significativas entre grupos e momentos, porém, effect size e delta percentual também foram superiores para grupo creatina. Não foi observada alteração significativa na composição corporal. Conclusão: A suplementação de creatina apresentou maior efeito sobre performance em teste de força para membros inferiores, quando comparadas ao placebo, sem alterar composição corporal.
... Under non-supplemental conditions, anterior compartment muscle volume can increase by 20% during exercise [13]. Creatine supplementation also has been found to increase intracellular fluid by 2-3 % [14]. Coupled together, this augmented pressure could theoretically create an ischemic environment within the osteofascial compartment, resulting in clinical and subclinical related issues such as cramping, tightness, and/or pain within the anterior compartment muscle group. ...
... One to two weeks of creatine supplementation has been shown to increase total body mass by approximately 1 kg, predominately in the form of fat free mass [14,33,34]. Most of this weight gain is attributed to intra-myofibrillar water retention mediated by the sodium and amino acid concentration gradient across the sarcolemma created by creatine transportation into the muscle fiber [35]. ...
... Dietary creatine supplementation increases the phosphocreatine stores in the muscles, and has been shown to enhance performance during high-intensity, short duration activities or repeated bouts of high-intensity exercise with short rest periods such as jumping, sprinting, and strength training [26,[31][32][33][34][35][36][37][38][39]. It is estimated that 27-78% of all college athletes have used creatine supplements [40][41][42][43] and the proportion of individuals using creatine is likely much higher in athletes participating in sports such as football, track, wrestling, and soccer [26,[31][32][33][34]44]. ...
... As shown in Fig. 1, creatine is the substrate for the creatine kinase reaction, resulting in the generation of phosphocreatine, which comprises 60% of the creatine in skeletal muscle (~60% of muscle creatine is stored as phosphocreatine and 40% as free creatine) [2]. As previously mentioned, phosphocreatine is responsible for the re-phosphorylation of ADP to ATP during bursts of high intensity movements, thus resulting in an increased availability of energy during short periods of explosive exercise [35][36][37][38][39]64]. As phosphocreatine levels decline due to the re-phosphorylation of ADP, phosphofructokinase production is stimulated, thereby increasing the rate of glycolysis [39]. ...
Article
Creatine is widely used by both elite and recreational athletes as an ergogenic aid to enhance anaerobic exercise performance. Older individuals also use creatine to prevent sarcopenia and, accordingly, may have therapeutic benefits for muscle wasting diseases. Although the effect of creatine on the musculoskeletal system has been extensively studied, less attention has been paid to its potential effects on other physiological systems. Because there is a significant pool of creatine in the brain, the utility of creatine supplementation has been examined in vitro as well as in vivo in both animal models of neurological disorders and in humans. While the data are preliminary, there is evidence to suggest that individuals with certain neurological conditions may benefit from exogenous creatine supplementation if treatment protocols can be optimized. A small number of studies that have examined the impact of creatine on the immune system have shown an alteration in soluble mediator production and the expression of molecules involved in recognizing infections, specifically toll-like receptors. Future investigations evaluating the total impact of creatine supplementation are required to better understand the benefits and risks of creatine use, particularly since there is increasing evidence that creatine may have a regulatory impact on the immune system.
... better values of FCR [20], reported Creatine monohydrate wassignificant improvement in FCR. [10,24] showed Creatine the significant improvement in feed efficiency. In this study at T2, T3 and T4 had no significant (p>0.05) ...
... We demonstrated that creatine supplementation did not affect hand grip (right and left hand) and back strength results. Our results are consistent with similar studies (Mihic at al., 2000;Gotshalk at al., 2008;Urbanski at al., 1999) that investigated the effects of Cr supplementation on isometric hand grip strength. In our study, a lack of meaningful differences in hand grip and back strength values of the futsal players could be due to the more intense use of the muscles of the upper extremities in comparison to the upper extremities during a 15-day creatine supplementation. ...
... Our findings are discordant from some past literature. For instance, creatine supplementation in women has shown to increase fat-free mass and total body mass but not alter fat mass [20] . Others have also reported that creatine supplementation decreases body fat percentage in male and female track and field athletes [21] . ...
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Aims: We performed a pilot study examining the effects of whey protein and creatine supplementation (PRO + CRE group) versus whey protein supplementation (PRO group) alone on body composition and performance variables in a limited number of resistance-trained women. Methods: Seventeen resistance-trained women (21 ± 3 years, 64.7 ± 8.2 kg, 23.5 kg/m2, 26.6 ± 4.8% body fat, >6 months of training) performed a 4-day per week split-body resistance training program for 8 weeks. Subjects ingested either 24 g PRO (n = 9) or 24 g whey plus 5 g creatine monohydrate (PRO + CRE, n = 8) following each exercise bout. At baseline (T1), 4 weeks (T2) and 8 weeks (T3), body composition was measured by dual X-ray absorptiometry (DXA), strength measures (leg press and bench press one repetition maximum) and lower-body power measures were determined. Results: DXA lean mass increased from T1 to T3 in both groups (PRO: +2.5 kg, p < 0.001; PRO + CRE: +2.5 kg, p < 0.001), although no differences between groups were observed. Compared to T1 values, performance measures similarly increased in both groups from T1 to T3 although, no between-group differences were observed. Conclusions: PRO + CRE did not enhance training adaptations compared to PRO, albeit studies employing longer-term interventions with larger sample sizes are needed in order to confirm or disprove our findings.
... Moreover, such a CA protocol has not yet been replicated for PAPE in the lower limbs or on female athletes. According to acknowledged studies, males present higher motor unit firing frequency [19,20] along with a greater cross-sectional area of type II fibers [19,21] and relatively lower oxidative capacity [20], which could lead to a faster rise in fatigue levels compared to females. Furthermore, the neuromuscular responses of females appear to be delayed, [22,23] which, along with a lower level of muscular strength compared to males, may affect PAPE response. ...
Article
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Although velocity control in resistance training is widely studied, its utilization in eliciting post-activation performance enhancement (PAPE) responses receives little attention. Therefore, this study aimed to evaluate the effectiveness of heavy-loaded barbell squats (BS) with velocity loss control conditioning activity (CA) on PAPE in subsequent countermovement jump (CMJ) performance. Sixteen resistance-trained female volleyball players participated in this study (age: 24 ± 5 yrs.; body mass: 63.5 ± 5.2 kg; height: 170 ± 6 cm; relative BS one-repetition maximum (1RM): 1.45 ± 0.19 kg/body mass). Each participant performed two different conditions: a set of the BS at 80% 1 RM with repetitions performed until a mean velocity loss of 10% as the CA or a control condition without CA (CNTRL). To assess changes in jump height (JH) and relative mean power output (MP), the CMJ was performed 5 min before and throughout the 10 min after the CA. The two-way analysis of variance with repeated measures showed a significant main effect of condition (p = 0.008; η2 = 0.387) and time (p < 0.0001; η2 = 0.257) for JH. The post hoc test showed a significant decrease in the 10th min in comparison to the value from baseline (p < 0.006) for the CNTRL condition. For the MP, a significant interaction (p = 0.045; η2 = 0.138) was found. The post hoc test showed a significant decrease in the 10th min in comparison to the values from baseline (p < 0.006) for the CNTRL condition. No significant differences were found between all of the time points and the baseline value for the CA condition. The CA used in the current study fails to enhance subsequent countermovement jump performance in female volleyball players. However, the individual analysis showed that 9 out of the 16 participants (56%) responded positively to the applied CA, suggesting that the PAPE effect may be individually dependent and should be carefully verified before implementation in a training program.
... 11,12,15 Not surprisingly, because creatine is a natural compound and is present in the daily diet, the side effects of creatine supplementation were shown in phase I trials to be very few, both for healthy persons and patients. [16][17][18] Creatine supplementation to HD patients was shown to be safe in dosages up to 30 mg per day and to reduce the levels of the DNA damage marker 8hydroxy-2'-deoxyguanosine(8OH2'dG). 19 A phase III clinical trial of creatine supplementation in HD was completed this year (with 650 participants enrolled, ClinicalTrials.gov ...
Article
Background and Objective: Mitochondrial dysfunction has been implicated in several neurodegenerative diseases. Creatine administration increases concentration of the energy buffer phosphocreatine, exerting protective effects in the brain. We evaluate whether a creatine‐enriched diet would be beneficial for a mouse model of spinocerebellar ataxia type 3, a genetically defined neurodegenerative disease for which no treatment is available. Methods: We performed 2 independent preclinical trials using the CMVMJD135 mouse model (treating 2 groups of animals with different disease severity) and wild‐type mice, to which 2% creatine was provided for 19 (preclinical trial 1) or 29 (preclinical trial 2) weeks, starting at a presymptomatic age. Motor behavior was evaluated at several time points from 5 to 34 weeks of age, and neuropathological studies were performed at the end of each trial. Results: Creatine supplementation led to an overall improvement in the motor phenotype of CMVMJD135 mice in both trials, rescuing motor balance and coordination and also restored brain weight, mitigated astrogliosis, and preserved Calbindin‐positive cells in the cerebellum. Moreover, a reduction of mutant ataxin‐3 aggregates occurred despite maintained steady‐state levels of the protein and the absence of autophagy activation. Creatine treatment also restored the expression of the mitochondrial mass marker Porin and reduced the expression of antioxidant enzymes Heme oxygenase 1 (HO1) and NAD(P)H Quinone Dehydrogenase 1 (NQO1), suggesting a beneficial effect at the level of mitochondria and oxidative stress. Conclusions: Creatine slows disease progression and improves motor dysfunction as well as ameliorates neuropathology of the CMVMJD135 animals, supporting this as a useful strategy to slow the progression of spinocerebellar ataxia type 3. © 2018 International Parkinson and Movement Disorder Society
... One study implied that single exhaustive exercise sessions can significantly decrease the GAA level in circulation postexercise in both healthy men and women (Stajer et al. 2016). The effect of creatine supplementation on exercise performance enhancement in women was found to be less than that in in men, as proven in studies conducted by Mihic et al. (2000) and Parise et al. (2001). However, deeper insight into gender-dependent differences in PCr metabolism after creatine and creatine-like substance administration in a HIIT scenario are necessary, since there are no studies considering sex hormones and menstrual cycle influence in HIIT conditions. ...
Article
This study aimed to determine how guanidinoacetic acid (GAA) or its combined administration with betaine (B) or creatine (C) influences the cardiac function, morphometric parameters, and redox status of rats subjected to high-intensity interval training (HIIT). This research was conducted on male Wistar albino rats exposed to HIIT for 4 weeks. The animals were randomly divided into five groups: HIIT, HIIT + GAA, HIIT + GAA + C, HIIT + GAA + B, and HIIT + GAA + C + B. After completing the training protocol, GAA (300 mg/kg), C (280 mg/kg), and B (300 mg/kg) were applied daily per os for 4 weeks. GAA supplementation in combination with HIIT significantly decreased the level of both systemic and cardiac prooxidants ( O 2 - , H2O2, NO 2 - , and thiobarbituric acid reactive substances) compared with nontreated HIIT (p < 0.05). Also, GAA treatment led to an increase in glutathione and superoxide dismutase levels. None of the treatment regimens altered cardiac function. A larger degree of cardiomyocyte hypertrophy was observed in the HIIT + GAA group, which was reflected through an increase of the cross-sectional area of 27% (p < 0.05) and that of the left ventricle wall thickness of 27% (p < 0.05). Since we showed that GAA in combination with HIIT may ameliorate oxidative stress and does not alter cardiac function, the present study is a basis for future research exploring the mechanisms of cardioprotection induced by this supplement in an HIIT scenario.
... 36 Additionally, studies have reported mixed results of creatine's effect on creatinine (CREA) excretion in humans with some studies showing an increase [39][40][41][42] and others showing no increase. 37,[43][44][45][46] In the current 90-day study, we provide the beginnings of evidence supporting the safety of CLL. ...
Article
A battery of toxicological studies was conducted to investigate the genotoxicity and repeated-dose oral toxicity of creatyl-l-leucine, a synthetic compound, in rats in accordance with internationally accepted guidelines. There was no evidence of mutagenicity in a bacterial reverse mutation test and in an in vitro mammalian chromosomal aberration test. There was no genotoxic activity observed in an in vivo mammalian micronucleus test at concentrations up to the limit dose of 2,000 mg/kg bw/d. Creatyl-l-leucine did not cause mortality or toxic effects in Hsd.Han Wistar rats in a 90-day repeated-dose oral (gavage) toxicity study at doses of 1,250, 2,500, and 5,000 mg/kg bw/d. The no observed adverse effect level from the 90-day study was determined to be 5,000 mg/kg bw/d, the highest dose tested, for both male and female rats.
... 14 In line with these findings, in a randomized, double-blinded placebo-controlled trial on both sexes in 2000, this recent creatine supplementation regimen did not either affect plasma creatinine or creatinine clearance, but it increased total body mass and free fat mass. 15 In contrast to the aforementioned results, some other clinical studies demonstrated that short-time creatine administration could affect the concentration of creatinine level or creatinine clearance. For example, 20 g/d of creatine supplementation for 6 days increased total creatine concentration in the muscle. ...
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Introduction. Nowadays, creatine is one of the most common oral supplements used by professional athletes for boosting their strength and muscle mass. In this review, we collect available experimental and clinical data about renal safety of both short-term and long-term use of creatine. Materials and Methods. Scientific literature was critically searched by keywords "creatine," "renal insufficiency," and "renal dysfunction" and their synonyms in medical databases (Scopus, MEDLINE, EMBase, and ISI Web of Knowledge). Overall, 19 relevant clinical and experimental articles were selected for this review. Results. Short- and long-term creatine supplementations (range, 5 days to 5 years) with different doses (range, 5 g/d to 30 g/d) had no known significant effects on different studied indexes of kidney function such as glomerular filtration rate at least in healthy athletes and bodybuilders with no underlying kidney diseases. In addition, although short-term (range, 5 days to 2 weeks) high-dose oral creatine supplementation (range, 20 g/d to 0.3 g/kg/d) stimulated the production of methylamine and formaldehyde (as potential cytotoxic metabolites of creatine) in the urine of healthy humans, there was currently no definite clinical evidence about their adverse effects on the kidney function. Conclusions. Although creatine supplementation appears to have no detrimental effects on kidney function of individuals without underlying kidney diseases, it seems more advisable to suggest that creatine supplementation not to be used by sportsmen or women with pre-existing kidney disease or those with a potential risk for kidney dysfunction.
... A ingestão de creatina, em curto prazo, é acompanhada de um aumento da massa corpórea, principalmente em atletas do sexo masculino, cujo ganho gira em torno de 0,7 a 2,0 kg de peso após 1 a 2 semanas de suplementação com altas doses (20-25 g/d) [20,35]. Este ganho de peso pode ser justifi cado por duas hipóteses; a) ocorrência de retenção hídrica devido ao alto poder osmótico da creatina, fenômeno este supostamente consequente de uma suplementação aguda, consiste em um potente estimulador da síntese protéica, motivo para constante crítica na literatura, porém, esta é uma hipótese a espera de ser confi rmada [3], b) ocorrência de um aumento da taxa de síntese de proteínas contráteis [36]. ...
Article
Enquanto o consumo de creatina por atletas e praticantes de atividade física que desejam aumentar a massa muscular e o desempenho físico tem crescido vertiginosamente, os efeitos adversos desse suplemento continuam sendo alvos de debates. O objetivo desta revisão é descrever aspectos gerais da creatina, seu metabolismo e impacto na composição corporal. Enfatizam-se possíveis efeitos colaterais prejudiciais, em especial sobre a função renal e hepática. Há muitas contradições e lacunas na literatura, fatores que contribuem para a divergência do tema, uma vez que os resultados disponíveis são contraditórios. Levando-se em conta que estudos sobre possíveis efeitos tóxicos da suplementação com creatina são escassos, sugere-se investimento adicional para avaliar a relação custo-benefício de sua suplementação.
... Another supplement that should be mentioned is creatine monohydrate, as it is one of the best-studied supplements with well-documented benefits. However, despite anecdotal reports, creatine monohydrate does not increase the prevalence of hypertension [83][84][85]. ...
Article
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Purpose of Review We reviewed most current medical literature in order to describe the epidemiology, clinical manifestation, outcome, and management of hypertension in athletes. Recent Findings An estimated quarter of the world’s population is suffering from hypertension and this prevalence is also reflected in athletes and in individuals involved in leisure time sport activities. Several studies found an inverse relationship between physical activity and blood pressure. Therefore, physical exercise is recommended to prevent, manage, and treat hypertension. On the other hand, the prevalence of hypertension may vary by sport and in some cases may even be higher in athletes competing in certain disciplines than in the general population. Hypertension is the most common medical condition in athletes and may raise concerns about its management and the individual’s eligibility for competitive sports. A thorough clinical evaluation should be performed to correctly diagnose or rule out hypertension in athletes, describe the individual’s risk profile, rule out secondary causes, and detect possible hypertension-mediated organ damage caused by hypertension at an early stage. Based on most recent clinical research and international consensus documents, we propose a diagnostic algorithm as well the non-pharmacological and pharmacological management of hypertension in athletes. Summary Although elevated blood pressure levels are less common in the active population, athletes are not protected from hypertension. A thorough diagnostic approach may help to identify individual at risk for adverse cardiovascular events and to address the optimal treatment as well as sport recommendations.
... This loss is replaced by both dietary and endogenous CR synthesis, which is approximately 1 g d −1 . Therefore, many athletes utilize CR supplementation (most often in the form of CR monohydrate [11][12][13]) to increase intramuscular stores of CR and phosphocreatine [8,[11][12][13][14][15][16][17][18][19][20][21][22][23]. Many different CR loading paradigms have been used [24], but the most commonly used dosing strategy occurs in two phases. ...
Article
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The use of dietary supplements has become increasingly common over the past 20 years. Whereas supplements were formerly used mainly by elite athletes, age and fitness status no longer dictates who uses these substances. Indeed, many nutritional supplements are recommended by health care professionals to their patients. Creatine (CR) is a widely used dietary supplement that has been well-studied for its effects on performance and health. CR also aids in recovery from strenuous bouts of exercise by reducing inflammation. Although CR is considered to be very safe in recommended doses, a caveat is that a preponderance of the studies have focused upon young athletic individuals; thus there is limited knowledge regarding the effects of CR on children or the elderly. In this review, we examine the potential of CR to impact the host outside of the musculoskeletal system, specifically, the immune system, and discuss the available data demonstrating that CR can impact both innate and adaptive immune responses, together with how the effects on the immune system might be exploited to enhance human health.
... These studies have been conducted in both athletic and general populations and range from as short as a few days to as long as 5 years without any adverse changes in markers of clinical health (12,13). Multiple studies have assessed and reported that creatine supplementation has no adverse impact on clinical health markers in competitive athletes (13)(14)(15)(16)(17), non-athletic populations (18)(19)(20)(21)(22)(23)(24)(25), and in clinical populations (26)(27)(28)(29). Furthermore, recent evidence suggests that creatine supplementation is unrelated to the formation of carcinogenic heterocyclic amines in humans, which was a long-standing concern due to creatine's potential role as a precursor of the compounds (30). ...
Article
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Creatine has been extensively researched and is well-supported as one of the most effective dietary supplements available. There is overwhelming support within the literature regarding the ability of creatine to augment performance following short term (5–7 days) and long-duration supplementation periods. There is also strong support for creatine regarding its safety profile and minimal risk for adverse events or any negative influence on markers of clinical health and safety. Recent research has also highlighted the ability of creatine to confer several health-related benefits in select clinical populations in addition to offering cognitive benefits. Creatine is also a popular supplement of choice for adolescent athletes; however, research in this area is extremely limited, particularly when examining the safety and efficacy of creatine supplementation in this population. Therefore, the purpose of this review was to highlight the limited number of studies available in adolescent populations and systematically discuss the topic of safety of creatine supplementation in a younger population.
... With significant success as an ergogenic aid, the potential application of creatine supplementation in clinical populations has gained attention. Creatine supplementation has been shown to impart a variety of benefits upon skeletal muscle, such as the enhancement of force output during skeletal Nutrients 2020, 12, 2834 5 of 23 muscle contraction [45], the augmentation of lean body mass [46], fatigue resistance [41,42], and the improvement of intracellular calcium handling [47]. Furthermore, it has been proposed that creatine supplementation may impart further favorable effects on skeletal muscle physiology and metabolism, such as enhancing growth and hypertrophy through direct modulation of components of the mammalian target of rapamycin (mTOR), secretion of myokines such as myostatin and insulin-like growth factor-1, and increasing the expression of myogenic regulatory factors which can stimulate satellite cell mitotic activity [48][49][50]. ...
Article
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Creatine is a naturally occurring compound, functioning in conjunction with creatine kinase to play a quintessential role in both cellular energy provision and intracellular energy shuttling. An extensive body of literature solidifies the plethora of ergogenic benefits gained following dietary creatine supplementation; however, recent findings have further indicated a potential therapeutic role for creatine in several pathologies such as myopathies, neurodegenerative disorders, metabolic disturbances, chronic kidney disease and inflammatory diseases. Furthermore, creatine has been found to exhibit non-energy-related properties, such as serving as a potential antioxidant and anti-inflammatory. Despite the therapeutic success of creatine supplementation in varying clinical populations, there is scarce information regarding the potential application of creatine for combatting the current leading cause of mortality, cardiovascular disease (CVD). Taking into consideration the broad ergogenic and non-energy-related actions of creatine, we hypothesize that creatine supplementation may be a potential therapeutic strategy for improving vascular health in at-risk populations such as older adults or those with CVD. With an extensive literature search, we have found only four clinical studies that have investigated the direct effect of creatine on vascular health and function. In this review, we aim to give a short background on the pleiotropic applications of creatine, and to then summarize the current literature surrounding creatine and vascular health. Furthermore, we discuss the varying mechanisms by which creatine could benefit vascular health and function, such as the impact of creatine supplementation upon inflammation and oxidative stress.
... Several studies have reported no effect of high-dose short-term or low-dose long-term creatine use in physically unstressed subjects or power athletes on high-dose creatine. [35][36][37] Despite these studies, there are few cases reported of rhabdomyolysis in the setting of creatine supplement use. The majority were involved in extreme exercise regimens. ...
Article
In addition to liver injury, elevation of aminotransferases can be caused by strenuous exercise and use of muscle-building and weight-loss supplements. The purpose of this review is to discuss the various mechanisms of elevation of aminotransferases related to body building. A literature review was performed on clinical trials and case reports involving exercise or supplement use and their effects on aminotransferases. Normal aminotransferase levels varied according to gender, age, body mass index, and comorbidities. Strenuous exercise and weight lifting, especially in the unaccustomed, can cause elevated aminotransferases in the absence of liver damage. Supplements such as anabolic steroids, ephedra, and LipoKinetix, amongst others, have also been associated with aminotransferase elevations. The pattern of elevation of aminotransferases is not helpful in distinguishing liver from muscle injury. Other associated muscle enzymes can be useful in making that distinction. To prevent aminotransferase elevations, subjects not accustomed to moderate-high intensity workouts, are recommended to undertake gradual increase in intensity. When causes of liver injury have been ruled out, investigation into bodybuilding, extreme exercise, and supplement use is warranted.
... In addition, the effect of creatine supplementation, especially during pregnancy, has been virtually ignored. There is some evidence to suggest gender-specific differences in creatine homeostasis under normal dietary conditions, including higher intramuscular creatine concentrations relative to lean muscle mass in women, and gender specific responses to creatine supplementation, particularly with regard to changes in body composition (Forsberg et al. 1991;Mihic et al. 2000). ...
Article
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Recent evidence obtained from a rodent model of birth asphyxia shows that supplementation of the maternal diet with creatine during pregnancy protects the neonate from multi-organ damage. However, the effect of increasing creatine intake on creatine homeostasis and biosynthesis in females, particularly during pregnancy, is unknown. This study assessed the impact of creatine supplementation on creatine homeostasis, body composition, capacity for de novo creatine synthesis and renal excretory function in non-pregnant and pregnant spiny mice. Mid-gestation pregnant and virgin spiny mice were fed normal chow or chow supplemented with 5 % w/w creatine for 18 days. Weight gain, urinary creatine and electrolyte excretion were assessed during supplementation. At post mortem, body composition was assessed by Dual-energy X-ray absorptiometry, or tissues were collected to assess creatine content and mRNA expression of the creatine synthesising enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT) and the creatine transporter (CrT1). Protein expression of AGAT and GAMT was also assessed by Western blot. Key findings of this study include no changes in body weight or composition with creatine supplementation; increased urinary creatine excretion in supplemented spiny mice, with increased sodium (P < 0.001) and chloride (P < 0.05) excretion in pregnant dams after 3 days of supplementation; lowered renal AGAT mRNA (P < 0.001) and protein (P < 0.001) expressions, and lowered CrT1 mRNA expression in the kidney (P < 0.01) and brain (P < 0.001). Creatine supplementation had minimal impact on creatine homeostasis in either non-pregnant or pregnant spiny mice. Increasing maternal dietary creatine consumption could be a useful treatment for birth asphyxia.
... Atualmente, os verdadeiros e possíveis efeitos da suplementação de creatina em atletas e desportistas sobre a massa corpórea vêm sendo muito discutidos em diferentes estudos. Alguns estudos demonstraram que o consumo de creatina em curto prazo é acompanhado de um aumento da massa corporal, principalmente, em atletas do sexo masculino, cujo ganho gira em torno de 0,7 a 2,0 kg de peso após 1 a 2 semanas de suplementação com altas doses (20-25 g/d) [14][15][16]. segundo os autores, este ganho de peso pode ser justificado através de duas hipóteses: a retenção hídrica decorrente do alto poder de osmolaridade da creatina e o aumento da taxa de síntese de proteínas contráteis. ...
Article
Atualmente, a creatina é considerada um dos poucos suplementos cujo efeito ergogênico comprovado é mais conhecido pelo aumento de força muscular ou ressíntese de adenosina trifosfato (ATP), a qual é utilizada em exercícios de força e curta duração. Entretanto, novas pesquisas sugerem outros benefícios da creatina como ação antioxidante, hipoglicemiante e como tampão energético, além de funções terapêuticas com uso e aplicação promissora em indivíduos com diabetes mellitus, insuficiência cardíaca congestiva (ICC) e distrofias musculares. Este estudo tem como objetivo explanar as principais funções da creatina e sua utilização sob seus parâmetros bioquímicos e fisiológicos, desde seu surgimento até aspectos atuais, que será apresentado através de atualizações dos principais estudos que surgiram relatando novos benefícios.Palavras-chave: saúde, desempenho, exercício, substâncias ergogênicas.
... In particular, Cr was used for the first time in the Olympic Games in Barcelona by successful sprinters and, subsequently, has been used to enhance the physical performance in healthy individuals and athletes. At present, a huge body of evidence, from more than 25 years of research in the field, corroborates the efficacy of Cr supplementation to promote physiological function in many types of exercise of varying duration and intensity, and to aid improvements in strength, skeletal muscle mass, and bone mineral density, in healthy individuals and those with neuromuscular diseases (Bazzucchi et al., 2009;Bemben et al., 2010;Bosco et al., 1997;Candow et al., 2015;Chilibeck et al., 2015;D'Antona et al., 2014;Devries and Phillips, 2014;Griffen et al., 2015;Grindstaff et al., 1997;Gualano et al., 2011Gualano et al., , 2014Hespel et al., 2001;Martone et al., 2015;Metzl et al., 2001;Mihic et al., 2000;Pearlman and Fielding, 2006;Phillips, 2015;Ramirez-Campillo et al., 2015;Volek et al., 2004;Wilkinson et al., 2016). Indeed, Cr has also been recently recognized as playing a role as an antioxidant, antinflammatory, and immunomodulatory compound (Riesberg et al., 2016), as well as having interesting physiological effects on thermoregulation and cognitive performance (Twycross-Lewis et al., 2016). ...
Article
With regard to athletes attempting to improve their performance, at the present time creatine monohydrate is clearly the most widely used dietary supplement or ergogenic aid. Loading doses as high as 20 g/d are typical among athletes. The majority (> 90%) of the creatine ingested is removed from the plasma by the kidney and excreted in the urine. Despite relatively few isolated reports of renal dysfunction in persons taking creatine, the studies completed to date suggest that in normal healthy individuals the kidneys are able to excrete creatine, and its end product creatinine, in a manner that does not adversely alter renal function. This situation would be predicted to be different in persons with impaired glomerular filtration or inherent renal disease. The question of whether long-term creatine supplementation (ie, months to years) has any deleterious affects on renal structure or function can not be answered at this time. The limited number of studies that have addressed the issue of the chronic use of creatine have not seen remarkable changes in renal function. However, physicians should be aware that the safety of long-term creatine supplementation, in regard to the effects on the kidneys, cannot be guaranteed. More information is needed on possible changes in blood pressure, protein/albumin excretion, and glomerular filtration in athletes who are habitual users of this compound.
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Without question, since its over the counter availability to consumers in 1992, creatine has become one of the most popular nutritional supplements among exercise and sport populations. In addition to its popularity, creatine has become one of the most extensively studied and research validated products that have been experimentally dissected in a multitude of ways. Specifically, investigators have evaluated topics such as muscle-creatine content and phosphocreatine resynthesis, short-and long-term ergogenic effects of creatine ingestion, gender issues associated with creatine ingestion, age-specific issues related to creatine ingestion, ethical considerations of creatine ingestion, viable clinical and medical applications of creatine ingestion, health and safety concerns regarding creatine ingestion, and more recently relevant biochemical mechanisms regarding the creatine transport system. Although each of these research approaches have greatly contributed to the body of creatine literature, it is first imperative to grasp various foundational aspects associated with understanding this controversial nutritional supplement. With these considerations in mind, the purpose of this chapter is to set the stage for a creatine overview regarding the following information: (1) creatine facts, fallacies, and safety (2) creatine quality, purity, and formulations, (3) creatine dosage protocols, (4) creatine nutritional supplement combinations, (5) foundational creatine ergogenic efficacy, (6) future creatine research options, and (7) common creatine practical applications.
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Creatine has become increasingly popular as a nutritional supplement among athletes both on a competitive and recreational level due to its potential "ergogenic" effects. This paper reviews the biochemical and scientific aspects of the creatine supplementation. Over the past several years many studies have suggested an improvement in performance during repetitive maximal and submaximal activities. On the contrary only few studies support the ability to improve performance measurably during competition. Recommendations for athletes considering creatine supplementation are described in a survey. Both clinicians and athletes should be aware thet the long term effects of creatine supplementation are unknown. At present, creatine is not listed as a banned substance by the International Olympic Committee (IOC).
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Anecdotal reports suggest that creatine supplementation during intense training and competition may increase the incidence of muscle cramping and injury. This study examined the effects of creatine supplementation on cramping and injury during collegiate baseball training and competition. Thirty-nine Division I baseball players participated in this study. Twenty-one (54.0%) of the thirty-nine athletes ingested 15 to 25g/d of creatine for 5 days followed by 5 g/day of creatine that was mixed with sports drinks or water. Athletes who were non-creatine users had access to a carbohydrate drink that contained no creatine (placebo) during the training/competition period. Injuries treated by the athletic training staff were recorded and categorized as cramping, heat/dehydration, muscle tightness, muscle strains, non-contact injuries joint injuries, contact injuries, and illness. The number of practices missed due to injury and illness were also recorded. While no heat/dehydration events were reported by either group, results revealed that creatine-users had significantly fewer total injuries, ?2 (1)=4.69, p=0.03 than non-creatine users (p<0.05). However, there were no significant differences between groups regarding cramping, ?2 (1)=2.94, p=0.08, muscle tightness, ? 2 (1)=3.01, p=0.08, muscle strains, ?2 (1)=2.92, p=0.08, non-contact joint injuries, ?2 (1)=1.04, p=0.31, contact injuries, ?2 (1)=0.009, p=.92, illness, ?2 (1)=0.02, p=0.95, missed practices due to injury, ?2 (1)=.103, p=0.74, and players lost for the season, ?2 (1)=2.45, p=0.11. Based on the findings in this investigation, creatine supplementation during collegiate baseball training and competition does not appear to increase the incidence of injury or cramping. Additional research is warranted to evaluate the effect of creatine supplementation on athletes training in hot/humid climates.
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Member States requested the European Food Safety Authority (EFSA) to provide opinions relating to the food ingredient creatine and a range of health claims. The EFSA Panel provided a positive opinion on creatine and exercise performance, stating it was effective for 'increasing physical performance during short-term, high intensity, repeated exercise bouts'. However, some data relating to creatine's effects on strength and muscle mass were not addressed in this assessment. Hence the only authorised EU health claim for creatine is: 'Creatine increases physical performance in successive bursts of short-term, high intensity exercise'.
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Background: In an age of highly competitive sports, whether it be the high school student, the weekend warrior, or the professional athlete, more individuals are using "performance-enhancing" nutritional supplements. Many feel they are gaining a "competitive edge," without thinking of the potential consequences. Consumers are inundated with claims of strength, weight loss, and improved body definition, but they are rarely given information on the potentially harmful side effects. There are few large, multicenter, randomized trials of these various nutritional supplements that look at the purported claims and potential side effects. study: We reviewed the available studies, including case reports, and researched data on five of the most popular performance-enhancing supplements, including androstenedione, creatine, chromium, ephedra, and protein and amino acid supplements. Conclusions: Of the reviewed supplements, only creatine may be marginally beneficial. The potential benefit would probably only be useful to the professional athlete and not the average person. All of the supplements reviewed have potentially harmful side effects; however, certain supplements clearly show harmful effects, and use should strongly be cautioned. In addition, ephedra should be withdrawn from the marketplace. At this time, without better-designed studies, these agents cannot be recommended.
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One of the most common-sought after goals in athletic performance is attaining and maintaining muscle mass. From protein to creatine, arginine to human growth hormone, how is one to determine what really works, what is legitimate, and what is merely another gimmick in the supplement industry? Coupling the array of supplements with the unique performance needs of an athlete creates an infinite amount of possible combinations. How do you know what is the right combination for successfully building the desired amount of muscle mass, maintaining an “optimal” body composition, and (during periods when additional body mass is desired) ensuring lean mass is gained over fat mass? It is with great time, research, and a foundation laid for us by our predecessors in the field of sports nutrition that we write this chapter on muscle building and optimizing lean body mass. By the end of this chapter you should be able to: Describe the muscle building process Define and determine net protein balance Describe how genetics play a role in muscle growth Know the recommended amounts of protein for gaining muscle Know the suggested protein: carbohydrate ratio for optimal muscle hypertrophy Define nutrient timing and its role in muscle hypertrophy Explain the difference between whey, casein, egg, soy, and vegan protein supplements Explain why and when supplementing with BCAAs are important to muscle growth Explain the major hormones that play a role in muscle growth Explain the potential benefits and drawbacks of anabolic steroids Define the role of IGF in muscle growth Describe the creatine-phosphate system and why creatine is used for muscle hypertrophy Explain why supplements that promote the production of nitric oxide are used by athletes Explain how resistance training stimulates muscle hypertrophy
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Creatine monohydrate (CrH2O) supplementation has been demonstrated to increase skeletal muscle power output in men. However, its effect upon women is not as clearly defined. This study investigated the effect of oral creatine supplementation upon muscle function, thigh circumference, and body weight in women. Twenty-two consenting college-age women were assigned to 1 of 2 groups matched for dietary and exercise habits, phase of menstrual cycle, and fat-free mass (FFM). After familiarization with testing procedures, pretrial measures of muscle function (5 repetitions 60 deg (.) s(-1) and 50 repetitions 180 deg (.) s(-1)) were conducted during maximal voluntary concentric contraction of the preferred quadriceps muscle using an isokinetic dynamometer. Subjects then ingested 0.5 g (.) kg(-1) FFM of either CrH2O or placebo (one fourth dosage 4 times daily) in a double-blind design for 5 days. Resistance exercise was prohibited. After the ingestion phase was completed, all measures were repeated at the same time of day as during pretrials. Statistical analysis revealed time to peak torque in quadriceps extension decreased from pre-test values of 255 +/-11 ms (mean +/- SEM to post-test values of 223 +/- 3 ms; average power in extension increased from 103 +/- 7 W pre-test to 112 +/- 7 W post-test; and, during flexion, average power increased from 59 +/- 5 W pre-test to 65 +/- 5 W post-test in the creatine group as compared to controls (p less than or equal to .05). FFM, percent body fat, midquadriceps circumference, skinfold thickness of the measured thigh, and total body weight did not change for both groups between trials. We conclude that CrH2O improves muscle performance in women without significant gains in muscle volume or body weight.
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Creatine is a substance occurring naturally in the, human body. The major proportion of the total Creatine pool is found in skeletal muscle (circa 90 %), heart and brain. The total creatine content in a normal, healthy person of TO kg is approximately 120 g. Creatine and its phosphorylated form, phospho-creatine, play an important role for cellular energy storage, buffering, and transport. Due to these properties, Creatine supplementation has become very popular in sports among athletes to enhance muscle performance and muscle mass. For this purpose, Creatine is usually taken during a loading phase at 20 g per day for one week and during a maintenance phase at 5-10 g, per day during extended periods of training. According to numerous publications, such a supplementation scheme is well tolerated and does not lead to significant side effects. Occasionally slight gastrointestinal discomfort or muscle cramping were reported. in those reports where liver and kidney functions of healthy athletes were examined specifically, no indications for adverse effects of Creatine an these organs have been noticed. Systematic studies on the clinical toxicology of creatine, however, are not available at present. Since no reports about experimental toxicity studies have been published so far, a series of toxicological examinations was thus performed, the results of which are reported within the scope of this publication. Based on these new data, Creatine did not reveal acute nor subacute toxic effects. The substance is well tolerated locally, as well. Furthermore, Creatine does not act as a sensitizing agent. Finally, no mutagenic effects were observed with Creatine in standardized bacterial mutagenicity tests. Since a significant proportion of the Creatine, taken at the dose levels mentioned above, is immediately excreted via the kidneys and since there is no evidence that very high dosages of Creatine are more beneficial, a loading dosage of 10 g per day for the first 8 days, to fill-up endogenous creatine pools, and a maintenance dose of 4-5 g per day, during the time after, are thus recommended. In addition, as a precautionary measure, it is advisable, after a prolonged period of Creatine intake (e.g. during 3 months), to take a break for several weeks (e, g. 4 weeks which is the wash-out time to return to original Creatine levels).
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Objectivo: Défices ou excessos nutricionais podem impedir o máximo rendimento de um desportista. Assim, estudamos a ingestão nutricional de um maratonista de elite, analisando o grau de adequação às exigências de treino e competição. Material e métodos: Maratonista de elite (32 anos, 1,69m, 55 kg), 4º lugar no Campeonato do Mundo de Atletismo, (2h09’28” - melhor marca pessoal). Realiza 12 a 14 treinos por semana. Os dados nutricionais foram obtidos por registo de sete dias. A conversão dos alimentos em nutrientes foi realizada pelo programa informático The Food Processor Plus 7.0. Estatística: Utilizaram-se as medidas descritivas, média, desvio-padrão e valores máximo e mínimo dos sete dias. Resultados: Aporte diários médios: calorias - 2296 ± 639 Kcal; carbohidratos – 40,6 ± 10,2% (4,42 ± 1,98 g/kg/dia); proteínas - 22,9 ± 6,7% (2,1 ± 0,3 g/kg/dia); gorduras – 36,5 ± 6,3%; colesterol – 488,1 ± 102,3 mg; fibras – 8,1 ± 2,8 g; vitamina C – 24,9 ± 12,5 mg; vitamina A – 211,0 ± 130,5 μg ER; Betacaroteno – 163,4 ± 265,5 μg; vitamina D – 3,7 ± 4,1 μg; vitamina E – 7,02 ± 3,4 mg ET. Reduzido aporte de cálcio (387,4 ± 154,5 mg), magnésio (222,6 ± 22,3 mg), molibdénio (2,46 ± 3,42 μg) e iodo (58,6 μg). Conclusão: Este maratonista apresenta um perfil nutricional incompatível com as elevadas exigências do treino e competição, caracterizado pelo reduzido aporte de energia, carboidratos, vitaminas antioxidantes e fibras, com excessivo consumo de colesterol. Este maratonista deve alterar o seu perfil de ingestão nutricional.Palavras-chave: perfil nutricional, esportes, provas de rendimento.
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The purpose of this study was to determine the effect of long-term Cr supplementation on blood parameters reflecting liver and kidney function. Twenty-three members of an NCAA Division 11 American football team (ages = 19-24 years) with at least 2 years of strength training experience were divided into a Cr monohydrate group (CrM, n = 10) in which they voluntarily and spontaneously ingested creatine, and a control group (n = 13) in which they took no supplements. Individuals in the CrM group averaged regular daily consumption of 5 to 20 g (mean +/- SD = 13.9 +/- 5.8 g) for 0.25 to 5.6 years (2.9 +/- 1.8 years). Venous blood analysis for serum albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, urea, and creatinine produced no significant differences between groups. Creatinine clearance was estimated from serum creatinine and was not significantly different between groups. Within the CrM group, correlations between all blood parameters and either daily dosage or duration of supplementation were nonsignificant. Therefore, it appears that oral supplementation with CrM has no long-term detrimental effects on kidney or liver functions in highly trained college athletes in the absence of other nutritional supplements.
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Over the past few years there has been considerable interest in both the use of creatine (Cr) supplementation by athletes and the documentation of its effects by scientists. Some believe that this nitrogen-containing compound found in meat and fish has a performance-enhancing capability as important for brief intense exercise efforts as dietary carbohydrate is for activities where glycogen supplies limit performance. The mechanisms thought to be responsible for any ergogenic effect of acute (few d) Cr supplementation include: increased stores of muscle phosphocreatine (PCr), faster regeneration of PCr during exercise recovery, enhanced adenosine triphosphate (ATP) production from glycolysis secondary to increased hydrogen ion buffering, and/or possible shortened post contraction muscle relaxation time. With chronic (wk & mo) supplementation when combined with strength training, Cr may alter muscle protein metabolism directly (via decreasing protein breakdown or increasing synthesis) and/or indirectly as a result of a greater training load made possible by its acute ergogenic effects on strength and power Cr supplementation is not banned by the International Olympic Committee and, with the exception of a small increase in body mass (similar to1 kg) over the initial 3-6 d, does not appear to have any adverse side effects, at least with short-term use. Few scientific data are available for more prolonged use (mo or y) but considering the large numbers of athletes using Cr over the past 6(+) y and the absence of reported problems, it may be that the often discussed somewhat nebulous long term adverse effects are presently being overestimated. Intakes of 285-300 mg Cr/kg body mass (.) d(-1) over 3-6 d or 30-50 mg/kg body mass (.) d(-1) over similar to4 wk are sufficient to produce benefits (muscle mass and high intensity power gains); however not all study results are consistent. The focus of this review is to outline some possible explanations for the inconsistent observations reported in the literature. Clearly, if proven to be consistent the benefits of Cr supplementation could extend far beyond the athletic arena to include individuals who experience muscle weakness for a variety of other reasons (e.g., age/disease, muscle disease, exposure to microgravity, etc).
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In football, the use of supplements is rather fewer than have been reported from some athletes of other sports. The decision to use a supplement should be made after careful consideration of several issues. It should be assessed if the supplement is safe, legal, and effective. Then, it is important to weigh the benefits (assistance to meet nutritional goals and placebo effect) and the risks (expense, side effects, contamination causing inadvertent doping outcome, and redirection of resources from real performance-enhancing factors) of using the supplement. Dietary supplements should be consumed alongside with a daily diet balanced in macronutrients and micronutrients. There is consolidated evidence about several dietary supplements that may be of interest for use in specific situations in football players. Supplementation with caffeine, carnitine, creatine, omega-3, buffers like β-alanine and sodium bicarbonate, antioxidants, probiotics, vitamin D, and whey protein may be used in football players with distinct goals. Nevertheless, dietary supplements should be used in individualized protocols under the direction of an appropriate sports physician/nutritionist.
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ZET Derleme Kullanımı çok yaygın olan kreatin suplementasyonu ile ilgili araştırmalar ve bilgiler sürekli artmakta, literatürü hızla büyümektedir. Bu derlemenin amacı özellikle farklı sportif branşlarda, cinsiyet, yaş grubu, antrenman düzeyi farklı araştırmaları gözden geçirmek, uzun süreli ve kısa süreli kreatin kullanımının bugün için bilinen etkilerini (sportif performans, yan etki, fizyolojik değişimler) sunmaktır. Kısa süreli kreatin suplementasyonu genellikle 5-7 gün süre ile vücut ağırlığıx0,3gram veya 20-30gram/gün şeklinde uygulanmaktadır. Uzun süreli kreatin suplementasyonu ise 5-7 gün 20 gram /gün kullanımın devamında 3-5 hafta 0,03 g x vücut ağırlığı/gün şeklinde yaygın olarak kullanılmaktadır. Bu yükleme miktarları içerisinde yapılan çalışmalarda yan etki bildirilmemiştir. Ancak uzun süreli, farklı suplementlerle kombine edilmiş tavsiye edilen dozlardan daha yüksek dozlarda kullanımın karaciğer ve böbrek fonksiyonlarında zararlar oluşturduğu gösterilmiştir. Yan etkiler açısından bakıldığında, önerilen sınırlar içinde kreatin suplementasyonu güvenli ve doğal bir ergojenik yardımcıdır. Belirtilen limitler içerisinde yapılan farklı yükleme miktarları, yöntem ve kombinasyonlardaki çalışmalarda kreatinin performans artışına katkı sağladığı görülmektedir. Kreatin suplementasyonu özellikle yüksek şiddetli antrenman evrelerinde artmış antrenman yüküne hızlı adaptasyona, branşa özgü hareket kalitesinin artmasına ve sakatlık riskinin azalmasına katkı sağlayabilir. Gelecekteki çalışmalar farklı spor branşlarında, egzersiz türlerinde, farklı cinsiyet (özellikle kadın) ve popülasyonda kreatin kullanımı hakkında daha etkili sonuçlar elde etmek için daha geniş bilgi sağlayacaktır. ABSTRACT Compilation Research and information on creatine supplementation, which is very common in use, is constantly increasing and the literature about creatine supplementation is growing rapidly. The aim of this review is to examine the recent researches especially held in different sports branches, different gender, population and training level and to present known effects (on sportive performance, side effects, physiological changes, etc…) of long-term and short-term supplementation. Short-term creatine supplementation is usually administered in 5-7 days at a dose of 0,3xbody weight or 20-30g / day. Long-term creatine supplementation is widely used as 5-7 days 20 g / day loading followed at a dose of 0.03g x body weight / day for 3-5 weeks. No serious side effects have been reported in studies carried out within these loading quantities. However, long term use with higher doses than recommended doses and combinations with different
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A formula has been developed to predict creatinine clearance (Ccr) from serum creatinine (Scr) in adult males: (see article)(15% less in females). Derivation included the relationship found between age and 24-hour creatinine excretion/kg in 249 patients aged 18-92. Values for Ccr were predicted by this formula and four other methods and the results compared with the means of two 24-hour Ccr's measured in 236 patients. The above formula gave a correlation coefficient between predicted and mean measured Ccr's of 0.83; on average, the difference predicted and mean measured values was no greater than that between paired clearances. Factors for age and body weight must be included for reasonable prediction.
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Our purpose was to determine the effect of oral creatine supplementation on exercise performance during high-intensity short-duration bicycle sprinting. Power output was recorded for 12 healthy untrained males (age 24.08 +/- 0.53 yr, weight 81.22 +/- 1.32 kg) before and after 5 days of creatine (n = 6) or placebo (n = 6) supplementation. A double-blind research design was employed. Subjects performed maximal sprints against a constant load (111.8 N) for 15 s. Each one-half pedal revolution was magnetically counted, and subsequent measurements of peak power, time to peak power, total work, and the fatigue index were digitized and stored on disk. Mean values for peak power, time to peak power, total work, and fatigue index were 958.01 +/- 40.66 W, 4.09 +/- 0.82 s, 11.28 +/- 0.46 kJ, and 32.1 +/- 1.58% decline from peak power, respectively. No significant differences were observed within or between groups before or after supplementation for any of the mechanical parameters measured (P > 0.05). These findings suggest that oral creatine supplementation does not positively affect power output or fatigue during continuous high-intensity bicycle exercise in untrained men.
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1. The present experiment was undertaken to investigate: (a) the effect of nitric oxide synthase (NOS) inhibition, mediated by oral supplementation of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on measures of myocardial energy metabolism and function: (b) the effect of oral creatine supplementation on these variables, in the absence and presence of L-NAME. 2. In one series of experiments, 4 weeks oral administration of L-NAME (0.05 mg ml-1 day-1 in the drinking water) to Brattleboro rats caused significant reductions in myocardial ATP, creatine, and total creatine concentrations and an accumulation of tissue lactate when compared with control animals. Administration of creatine (0.63 mg ml-1 day-1 in the drinking water) for 4 weeks elevated myocardial creatine and total creatine concentrations and reduced lactate accumulation, but did not significantly affect ATP or phosphocreatine (PCr). Concurrent treatment with creatine and L-NAME prevented the reduction in creatine and total creatine concentrations, and significantly attenuated the accumulation of lactate and the reduction in ATP seen with L-NAME alone. 3. In a second series of experiments, 4 weeks treatment with L-NAME and creatine plus L-NAME increased mean arterial blood pressure in conscious Brattleboro rats. Hearts isolated from these animals showed decreased coronary flow and left ventricular developed pressure (LVDP), and total mechanical performance. Treatment with creatine alone had no measurable effect on either mean arterial blood pressure or coronary flow in isolated hearts. However, there was an increase in LVDP, but not in total mechanical performance, because there was a bradycardia. 4. These results indicate that creatine supplementation can attenuate the metabolic stress associated with L-NAME administration and that this effect occurs as a consequence of the action of creatine on myocardial energy metabolism.
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To determine the effects of 28 d of creatine supplementation during training on body composition, strength, sprint performance, and hematological profiles. In a double-blind and randomized manner, 25 NCAA division IA football players were matched-paired and assigned to supplement their diet for 28 d during resistance/agility training (8 h x wk[-1]) with a Phosphagen HP (Experimental and Applied Sciences, Golden, CO) placebo (P) containing 99 g x d(-1) of glucose, 3 g x d(-1) of taurine, 1.1 g x d(-1) of disodium phosphate, and 1.2 g x d(-1) of potassium phosphate (P) or Phosphagen HP containing the P with 15.75 g x d(-1) of HPCE pure creatine monohydrate (HP). Before and after supplementation, fasting blood samples were obtained; total body weight, total body water, and body composition were determined; subjects performed a maximal repetition test on the isotonic bench press, squat, and power clean; and subjects performed a cycle ergometer sprint test (12 x 6-s sprints with 30-s rest recovery). Hematological parameters remained within normal clinical limits for active individuals with no side effects reported. Total body weight significantly increased (P < 0.05) in the HP group (P 0.85 +/- 2.2; HP 2.42 +/- 1.4 kg) while no differences were observed in the percentage of total body water. DEXA scanned body mass (P 0.77 +/- 1.8; HP 2.22 +/- 1.5 kg) and fat/bone-free mass (P 1.33 +/- 1.1; HP 2.43 +/- 1.4 kg) were significantly increased in the HP group. Gains in bench press lifting volume (P -5 +/- 134; HP 225 +/- 246 kg), the sum of bench press, squat, and power clean lifting volume (P 1,105 +/- 429; HP 1,558 +/- 645 kg), and total work performed during the first five 6-s sprints was significantly greater in the HP group. The addition of creatine to the glucose/taurine/electrolyte supplement promoted greater gains in fat/bone-free mass, isotonic lifting volume, and sprint performance during intense resistance/agility training.
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Sixty-nine patients with muscle hypotonotrophy of the thigh due to knee osteoarticular lesions underwent a rehabilitative training with of without the addition of creatine phosphate. An isokinetic dynamometer was used for the diagnostic evaluation and rehabilitative training. During physiokinesitherapy, the 38 patients treated with creatine phosphate showed a faster and greater muscle recovery of strength and power than the 31 control patients, with statistically significant differences. After 30 days of treatment the difference between the two groups was 13% in flexion and 18% in extension. Creatine phospate appeared to aid muscle strength recovery in patients with hypotrophy of the lower extremity.
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Fatigue in patients with mitochondrial cytopathies is associated with decreased basal and postactivity muscle phosphocreatine (PCr). Creatine monohydrate supplementation has been shown to increase muscle PCr and high-intensity power output in healthy subjects. We studied the effects of creatine monohydrate administration (5 g PO b.i.d. × 14 days → 2 g PO b.i.d. × 7 days) in 7 mitochondrial cytopathy patients using a randomized, crossover design. Measurements included: activities of daily living (visual analog scale); ischemic isometric handgrip strength (1 min); basal and postischemic exercise lactate; evoked and voluntary contraction strength of the dorsiflexors; nonischemic, isometric, dorsiflexion torque (NIDFT, 2 min); and aerobic cycle ergometry with pre- and post-lactate measurements. Creatine treatment resulted in significantly (P < 0.05) increased handgrip strength, NIDFT, and postexercise lactate, with no changes in the other measured variables. We concluded that creatine monohydrate increased the strength of high-intensity anaerobic and aerobic type activities in patients with mitochondrial cytopathies but had no apparent effects upon lower intensity aerobic activities. © 1997 John Wiley & Sons, Inc. Muscle Nerve20: 1502–1509, 1997
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A human creatine transporter (hCRT-BS2M) cDNA clone was isolated from a human brainstem/spinal cord using a PCR and phage plaque hybridization based technique. This clone included an open reading frame of 1,905 base pairs(bp) within a 2,283bp cDNA. Northern blot hybridization detected the expression of corresponding mRNAs most prominently in the skeletal muscle, heart and kidney. Peptide sequence analysis of the hCRT-BS2M protein product revealed 12 putative transmembrane domains. The predicted protein sequence further demonstrates that the hCRT-BS2M has highly conserved amino acid identity with the other members of the sodium dependent plasma membrane transporter family. Transient expression of the hCRT-BS2M in COS-7 cells demonstrates sodium dependent [14C]creatine uptake with a KM value of 14.9 ± 3.0 μM (n=5) that is attenuated by creatine and selective structural analogues of creatine.
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The microelectrode technique of intracellular constant current application and intracellular transmembrane voltage recording was used to study the effects of procaine amide (PA) on cardiac excitability. We measured the effect of PA in a concentration equivalent to clinically effective antiarrhythmic plasma levels (5 mug/ml), on nonnormalized and normalized strength-duration and charge-duration curves, membrane characteristics, and cable properties in long sheep Purkinje fibers in normal Tyrode's solution with [K+]0 = 4.0 mM. PA exerted a complex action and influenced passive resistance-capacitance (RC) and active generator properties by decreasing membrane conductance, primarily membrane sodium conductance. Whether PA increased or decreased excitability depended on the relative contribution of the drug-induced alterations in passive and active membrane properties. These findings may explain, in part, the conflicting results of studies on cardiac excitability in the whole animal, as well as the clinical observation that PA may exert both artiarrhythmic and arrhythmogenic effects. The primary mechanism by which PA modifies excitability would seem to differ considerably from that of the structurally similar local anesthetic agent lidocaine.
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The observation that increased muscular activity leads to muscle hypertrophy is well known, but identification of the biochemical and physiological mechanisms by which this occurs remains an important problem. The hypothesis has been proposed that creatine, an end product of contraction, may be the chemical signal coupling increased muscular activity and increased contractile mass. Two muscle models have been used in experimental tests of this hypothesis: differentiating skeletal muscle cells in culture and the fetal mouse heart in organ culture. Using these culture models, it is possible to alter the intracellular creatine concentration and to measure the effect of increased creatine concentrations on the rates of synthesis and accumulation of both muscle-specific and nonspecific proteins. The results show that muscle-specific protein synthesis in both skeletal and cardiac muscle is selectively stimulated by creatine.
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1. The present study was undertaken to test whether creatine given as a supplement to normal subjects was absorbed, and if continued resulted in an increase in the total creatine pool in muscle. An additional effect of exercise upon uptake into muscle was also investigated. 2. Low doses (1 g of creatine monohydrate or less in water) produced only a modest rise in the plasma creatine concentration, whereas 5 g resulted in a mean peak after 1 h of 795 (sd 104) μmol/l in three subjects weighing 76–87 kg. Repeated dosing with 5 g every 2 h sustained the plasma concentration at around 1000 μmol/l. A single 5 g dose corresponds to the creatine content of 1.1 kg of fresh, uncooked steak. 3. Supplementation with 5 g of creatine monohydrate, four or six times a day for 2 or more days resulted in a significant increase in the total creatine content of the quadriceps femoris muscle measured in 17 subjects. This was greatest in subjects with a low initial total creatine content and the effect was to raise the content in these subjects closer to the upper limit of the normal range. In some the increase was as much as 50%. 4. Uptake into muscle was greatest during the first 2 days of supplementation accounting for 32% of the dose administered in three subjects receiving 6 × 5 g of creatine monohydrate/day. In these subjects renal excretion was 40, 61 and 68% of the creatine dose over the first 3 days. Approximately 20% or more of the creatine taken up was measured as phosphocreatine. No changes were apparent in the muscle ATP content. 5. No side effects of creatine supplementation were noted. 6. One hour of hard exercise per day using one leg augmented the increase in the total creatine content of the exercised leg, but had no effect in the collateral. In these subjects the mean total creatine content increased from 118.1 (sd 3.0) mmol/kg dry muscle before supplementation to 148.5 (sd 5.2) in the control leg, and to 162.2 (sd 12.5) in the exercised leg. Supplementation and exercise resulted in a total creatine content in one subject of 182.8 mmol/kg dry muscle, of which 112.0 mmol/kg dry muscle was in the form of phosphocreatine.
Article
1. A method is described enabling the determination of fat, water, electrolytes, protein, DNA, RNA and total creatine in a single sample of human muscle obtained by the percutaneous needle-biopsy technique. The amino acid content can also be analysed in the same muscle sample. 2. Fifty healthy subjects were studied: 29 between 19 and 40 years of age, 11 between 41 and 60 years of age, and 10 between 61 and 85 years of age. The two groups aged less than 60 years showed only marginal differences in muscle composition, whereas the highest age group showed increases in muscle fat content in relation to tissue weight and decreases in alkali-soluble protein content in relation to both tissue weight and tissue DNA content. Also, potassium, magnesium, total creatine and RNA contents were decreased in this age group when related to tissue DNA content. When alkali-soluble protein was used as a reference base, only magnesium content was decreased. 3. A comparison was also made between female (n = 23) and male (n = 18) subjects in the age groups below 60 years. Differences observed included a higher fat content in female muscle, and an increase in total creatine content in relation to tissue weight. The alkali-soluble protein content was lower per muscle cell in the females when calculated on the basis of DNA content. 4. The results show that in the assessment of muscle constituents, age and sex must be taken into account.
Article
The accuracy of blood pressure values obtained by continuous noninvasive finger blood pressure recording via the FINAPRES device was evaluated by comparison with simultaneous intraarterial monitoring both at rest and during performance of tests known to induce fast and often marked changes in blood pressure. The comparison was performed in 24 normotensive or essential hypertensive subjects. The average discrepancy between finger and intra-arterial blood pressure recorded over a 30-minute rest period was 6.5 +/- 2.6 mm Hg and 5.4 +/- 2.9 mm Hg for systolic and diastolic blood pressure, respectively; a close between-method correspondence was also demonstrated by linear regression analysis. The beat-to-beat changes in finger systolic and diastolic blood pressure were on average similar to those measured intra-arterially during tests that induced a pressor or depressor response (hand-grip, cold pressor test, diving test, Valsalva maneuver, intravenous injections of phenylephrine and trinitroglycerine) as well as during tests that caused vasomotor changes without major variations in blood pressure (application of lower body negative pressure, passive leg raising). The average between-method discrepancy in the evaluation of blood pressure changes was never greater than 4.3 and 2.0 mm Hg for systolic and diastolic blood pressure, respectively; the corresponding standard deviations ranged between 4.6 and 1.6 mm Hg. Beat-to-beat computer analysis of blood pressure variability over the 30-minute rest period provided standard deviations almost identical when calculated by separate consideration of intra-arterial and finger blood pressure tracings (3.7 and 3.8 mm Hg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Article
We recorded finger arterial blood pressure (FINAP) in 50 male patients during various types of surgical operations. Three different types of cuffs were used on four fingers of each patient. Measurements were made by the arterial volume-clamp method of Penaz. The FINAP measurements were compared with pressure data obtained ipsilaterally from a radial artery catheter-transducer system (intraarterial pressure [IAP]) to find optimal recording conditions and to document factors affecting FINAP readings. The thumb, with a specially designed cuff, gave the most accurate results. The mean FINAP - IAP difference for the thumb was -4.8 mm Hg for systolic pressure, 1.49 mm Hg for diastolic pressure, and 0.29 mm Hg for mean pressure. The differences were statistically significant for systolic and diastolic pressure but not for mean pressure. The regression slope for thumb systolic FINAP/IAP was 0.979, that for thumb diastolic FINAP/IAP was 0.963, and that for mean thumb FINAP/IAP was 0.996, whereas the intercepts were 7.499 for systolic pressure, 0.802 for diastolic pressure, and 0.083 for mean pressure. The correlation coefficients were 0.945 (systolic), 0.884 (diastolic), and 0.949 (mean). The correlation coefficients with the other fingers ranged from 0.502 to 0.922 for systolic pressure, 0.757 to 0.932 for diastolic pressure, and 0.767 to 0.892 for mean pressure. The slopes for the various finger-cuff combinations ranged from 0.537 to 0.996, and the intercepts ranged from 0.083 to 32.387 from mean pressure. In 3 patients (6%) the FINAP measurement was not possible because of insufficient peripheral circulation. In 9 other patients (18%) the FINAP measurements were not accurate during some periods of time.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
This study examined the differences in male and female resting serum creatine kinase (CK) activity and assessed the relationship of resting CK activity and body composition. Two serum samples were obtained from sixty-five college age subjects (thirty-five males and thirty females) and assayed for CK activity. Body density, percentage of body fat, and kilograms of lean body mass were calculated from hydrostatic weighing. The mean serum CK activity was significantly greater for males (161.0 mU/ml) than females (87.7 mU/ml) (p < .05). The lean body mass and percent body fat for males (65.4 kg and 13.4%) were significantly different than the corresponding values for females (46.0 kg and 23.8%) (p < .01). When CK activity was covaried with lean body mass, the difference between the sexes for CK was still significant. No significant correlations for CK with measures of body composition were found for the males or for the females. Thus, the differences in resting CK activity between males and females are not solely due to differences in body composition.
Article
Gyrate atrophy of the choroid and retina (GA) is an autosomal recessive chorioretinal degeneration with a 10-20-fold elevation of plasma ornithine due to deficient activity of ornithine aminotransferase. Type II fibres of the skeletal muscle are atrophic and contain tubular aggregates in electron microscopy. Deficient creatine and creatine phosphate formation have been postulated to be involved in the pathogenesis of GA. The five-year follow-up results of oral creatine supplementation in 13 patients are presented. Visual function tests and fundus photographs showed progression of GA during the treatment. The velocity of the progression varied considerably between individuals. Generally, the progression was rapid in the young patients and slow in the more advanced stages. Abnormalities in the skeletal muscle decreased or disappeared rapidly. They reappeared in the few patients who discontinued the medication. The difference in the therapeutic effect on the skeletal muscle and eye is discussed.
Article
Seven male subjects performed repeated bouts of high-intensity exercise, on a cycle ergometer, before and after 6 d of creatine supplementation (20 g Cr H2O day-1). The exercise protocol consisted of five 6-s exercise periods performed at a fixed exercise intensity, interspersed with 30-s recovery periods (Part I), followed (40 s later) by one 10 s exercise period (Part II) where the ability to maintain power output was evaluated. Muscle biopsies were taken from m. vastus lateralis at rest, and immediately after (i) the fifth 6 s exercise period in Part I and (ii) the 10 s exercise period in Part II. In addition, a series of counter movement (CMJ) and squat (SJ) jumps were performed before and after the administration period. As a result of the creatine supplementation, total muscle creatine [creatine (Cr) + phosphocreatine (PCr)] concentration at rest increased from (mean +/- SEM) 128.7 (4.3) to 151.5 (5.5) mmol kg-1 dry wt (P < 0.05). This was accompanied by a 1.1 (0.5) kg increase in body mass (P < 0.05). After the fifth exercise bout in Part I of the exercise protocol, PCr concentration was higher [69.7 (2.3) vs. 45.6 (7.5) mmol kg-1 dry wt, P < 0.05], and muscle lactate was lower [26.2 (5.5) vs. 44.3 (9.9) mmol kg-1 dry wt, P < 0.05] after vs. before supplementation. In Part II, after creatinine supplementation, subjects were better able to maintain power output during the 10-s exercise period (P < 0.05). There was no change in jump performance as a result of the creatine supplementation (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Cardiac creatine levels are depressed in chronic heart failure. Oral supplementation of creatine to healthy volunteers has been shown to increase physical performance. To evaluate the effects of creatine supplementation on ejection fraction, symptom-limited physical endurance and skeletal muscle strength in patients with chronic heart failure. With a double-blind, placebo-controlled design 17 patients (age 43-70 years, ejection fraction < 40) were supplemented with creatine 20 g daily for 10 days. Before and on the last day of supplementation ejection fraction was determined by radionuclide angiography as was symptom-limited 1-legged knee extensor and 2-legged exercise performance on the cycle ergometer. Muscle strength as unilateral concentric knee extensor performance (peak torque, Nm at 180 degrees/s) was also evaluated. Skeletal muscle biopsies were taken for the determination of energy-rich phosphagens. Ejection fraction at rest and at work did not change. Performance before creatine supplementation did not differ between placebo and creatine groups. While no change was seen in the placebo group compared to baseline, creatine supplementation increased skeletal muscle total creatine and creatine phosphate by 17 +/- 4% (P < 0.05) and 12 +/- 4% (P < 0.05), respectively. Increments were seen only in patients with < 140 mmol total creatine/kg d.w. (P < 0.05). One-legged performance (21%, P < 0.05), 2-legged performance (10%, P < 0.05), and peak torque, Nm (5%, P < 0.05) increased. Both peak torque and 1-legged performance increased linearly with increased skeletal muscle phosphocreatine (P < 0.05). The increments in 1-legged, 2-legged and peak torque were significant compared to the placebo group, (P < 0.05). One week of creatine supplementation to patients with chronic heart failure did not increase ejection fraction but increased skeletal muscle energy-rich phosphagens and performance as regards both strength and endurance. This new therapeutic approach merits further attention.
The effect of dietary creatine (Cr) supplementation on performance during 3, 30 s bouts maximal isokinetic cycling and on plasma ammonia and blood lactate accumulation during exercise was investigated. Placebo (P) ingestion had no effect on peak power output (PPO), mean power output (MPO) and total work output during each bout of exercise. Cr ingestion (4 x 5 g.day-1 for 5 days) significantly increased PPO in exercise bout 1 (p < 0.05) and MPO and total work output in exercise bouts 1 (p < 0.05, p < 0.05, respectively) and 2 (p < 0.05, p < 0.05, respectively). Cr ingestion had no effect on any of the measures of performance during exercise bout 3. No difference was observed in peak plasma ammonia accumulation before (146 + 30 mumol.l-1) and after (122 +/- 17 mumol.l-1) P ingestion, however the corresponding concentration was lower following Cr ingestion (129 +/- 22 mumol.l-1) compared with before Cr ingestion (160 +/- 18 mumol.l-1, p < 0.05), despite subjects performing more work. No difference in peak blood lactate accumulation was observed before and after P or Cr ingestion. The results demonstrate that Cr ingestion can increase whole body exercise performance during the initial two, but not a third, successive bout of maximal exercise lasting 30 s. The lower accumulation of plasma ammonia under these conditions suggests this response is achieved by an effect on muscle ATP turnover.
Article
There is evidence that cellular hydration state is an important factor controlling cellular protein turnover; protein synthesis and protein degradation are affected in opposite directions by cell swelling and shrinking. An increase in cellular hydration (swelling) acts as an anabolic proliferative signal, whereas cell shrinkage is catabolic and antiproliferative. The cellular hydration state is mainly determined by the activity of ion and substrate transport systems in the plasma membrane. Hormones, substrates, and oxidative stress can change the cellular hydration state within minutes, thereby affecting protein turnover. We postulate that a decrease in cellular hydration in liver and skeletal muscle triggers the protein catabolic states that accompany various diseases.
Article
Biopsy samples were obtained from the vastus lateralis muscle of eight subjects after 0, 20, 60, and 120 s of recovery from intense electrically evoked isometric contraction. Later (10 days), the same procedures were performed using the other leg, but subjects ingested 20 g creatine (Cr)/day for the preceding 5 days. Muscle ATP, phosphocreatine (PCr), free Cr, and lactate concentrations were measured, and total Cr was calculated as the sum of PCr and free Cr concentrations. In five of the eight subjects, Cr ingestion substantially increased muscle total Cr concentration (mean 29 +/- 3 mmol/kg dry matter, 25 +/- 3%; range 19-35 mmol/kg dry matter, 15-32%) and PCr resynthesis during recovery (mean 19 +/- 4 mmol/kg dry matter, 35 +/- 6%; range 11-28 mmol/kg dry matter, 23-53%). In the remaining three subjects, Cr ingestion had little effect on muscle total Cr concentration, producing increases of 8-9 mmol/kg dry matter (5-7%), and did not increase PCr resynthesis. The data suggest that a dietary-induced increase in muscle total Cr concentration can increase PCr resynthesis during the 2nd min of recovery from intense contraction.
Article
1. The present experiment was undertaken to investigate the influence of oral creatine supplementation, shown previously to increase the total creatine content of human skeletal muscle (Harris RC, Soderlund K, Hultman E. Clin Sci 1992; 83: 367–74), on skeletal muscle isokinetic torque and the accumulation of plasma ammonia and blood lactate during five bouts of maximal exercise. 2. Twelve subjects undertook five bouts of 30 maximal voluntary isokinetic contractions, interspersed with 1 min recovery periods, before and after 5 days of placebo (4 × 6 g of glucose/day, n = 6) or creatine (4 × 5 g of creatine plus 1 g of glucose/day, n = 6) oral supplementation. Muscle torque production and plasma ammonia and blood lactate accumulation were measured during and after exercise on each treatment 3. No difference was seen when comparing muscle peak torque production during exercise before and after placebo ingestion. After creatine ingestion, muscle peak torque production was greater in all subjects during the final 10 contractions of exercise bout 1 (P <0.05), throughout the whole of exercise bouts 2 (P <0.01), 3 (P <0.05) and 4 (P = 0.057) and during contractions 11–20 of the final exercise bout (P <0.05), when compared with the corresponding measurements made before creatine ingestion. Plasma ammonia accumulation was lower during and after exercise after creatine ingestion. No differences were found when comparing blood lactate levels. 4. There is evidence to suggest that the decrease in the degree of muscle torque loss after dietary creatine supplementation may be a consequence of a creatine-induced acceleration of skeletal muscle phosphocreatine resynthesis. It is postulated that an increased availability of phosphocreatine would maintain better the required rate of ATP demand during contraction. This is supported by the observed lower accumulation of plasma ammonia during exercise after creatine ingestion.
Article
The aim of the present study was to ascertain whether or not phosphocreatine (PC) could produce electrophysiological and inotropic effects in isolated rabbit cardiac preparations. Exogenous PC (50 mmol/l) was introduced into many cells simultaneously by the "cut-end" and "saponinated-end" methods. PC that entered the cells (opened by cutting or chemical disruption of the sarcolemma) in the loading region, passed through the preparation intercellularly and evoked the following effects in the test region. PC enhanced the spontaneous rate and probably shifted the pacemaker in sinus node strips. On the other hand, PC elevated the action potential amplitude and duration and increased the isometric tension in atrial and ventricular strips. Furthermore, PC applied into ventricular cells partially prevented the effects of hypoxia. These findings suggest that PC may act in cardiac muscle as an intercellular energy carrier. The effects of PC introduced intracellularly resembled these evoked by O-benzyl-phosphocreatine--a permanent synthetic phosphagen--applied via superfusion.
Article
This study examined the effect of (a) creatine supplementation on exercise metabolism and performance and (b) changes in intramuscular total creatine stores following a 5 day supplementation period and a 28 day wash-out period. Six men performed four exercise trials, each consisting of four 1 min cycling bouts, punctuated by 1 min of rest followed by a fifth bout to fatigue, all at a workload estimated to require 115 or 125% VO2,max. After three familiarization trials, one trial was conducted following a creatine monohydrate supplementation protocol (CREAT); the other after 28 d without creatine supplementation, in which the last 5 d involved placebo ingestion (CON). Intramuscular TCr was elevated (P < 0.05) in CREAT compared with the final familiarization trial (FAM 3) and CON. Concentrations of this metabolite in these latter trials were not different. In addition, a main effect (P < 0.05) for treatment was observed for PCr when the data from CREAT were compared with CON. In contrast, no differences were observed in the total adenine nucleotide pool (ATP+ADP+AMP), inosine 5'-monophosphate, ammonia, lactate or glycogen when comparing CREAT with CON. Despite the differences in TCr and PCr concentrations when comparing CREAT with other trials, no difference was observed in exercise duration in the fifth work bout. These data demonstrate that creatine supplementation results in an increase in TCr but this has no effect on performance during exercise of this nature, where the creatine kinase system is not the principal energy supplier. In addition 28 d without supplementation is a sufficient time to return intramuscular TCr stores to basal levels.
Article
The effect of dietary creatine and supplementation on skeletal muscle creatine accumulation and subsequent degradation and on urinary creatinine excretion was investigated in 31 male subjects who ingested creatine in different quantities over varying time periods. Muscle total creatine concentration increased by approximately 20% after 6 days of creatine supplementation at a rate of 20 g/day. This elevated concentration was maintained when supplementation was continued at a rate of 2 g/day for a further 30 days. In the absence of 2 g/day supplementation, total creatine concentration gradually declined, such that 30 days after the cessation of supplementation the concentration was no different from the presupplementation value. During this period, urinary creatinine excretion was correspondingly increased. A similar, but more gradual, 20% increase in muscle total creatine concentration was observed over a period of 28 days when supplementation was undertaken at a rate of 3 g/day. In conclusion, a rapid way to "creatine load" human skeletal muscle is to ingest 20 g of creatine for 6 days. This elevated tissue concentration can then be maintained by ingestion of 2 g/day thereafter. The ingestion of 3 g creatine/day is in the long term likely to be as effective at raising tissue levels as this higher dose.
Article
This study was conducted to examine the effects of creatine (Cr) supplementation on sprint swimming performance and energy metabolism. Twenty highly trained swimmers (9 female, 11 male) were tested for blood ammonia and for blood lactate after the 25-, 50-, and 100-m performance in their best stroke on two occasions 7 d apart. After the first trial, subjects were evenly and randomly assigned to either a creatine (5 g creatine monohydrate 4 times per day for 5 d) or a placebo group (same dosage of a lactose placebo) in a double-blind research design. No significant differences in performance times were observed between trials. Post-exercise blood ammonia concentration decreased in the 50- and 100-m trials in the creatine group and in the 50-m trial in the placebo group. The supplementation period had no effect on post-exercise blood lactate. Therefore, creatine supplementation cannot be considered as an ergogenic aid for sprint performance in highly trained swimmers although adenine nucleotide degradation may be reduced during sprint exercise after 5 d of creatine ingestion.
Article
Our purpose was to determine the effect of creatine supplementation on power output during a 30-s maximal cycling (Wingate) test. Nine males underwent 3 randomly ordered tests following ingestion of a creatine supplementation (CRE), placebo (PLA), and control (CON) CRE was ingested as creatine monohydrate (CrH2O) dissolved in a flavored drink (20g.d-1 for 3 d), while PLA consisted of the drink only. Tests were performed 14 d apart on a Monarch ergometer modified for immediate resistance loading. Needle biopsies were taken from the vastus lateralis at the end of each treatment period and before the exercise test. No difference was found between conditions for peak, mean 10-s, and mean 30-s power output, percent fatigue, or post-exercise blood lactate concentration. Similarly, no difference between conditions was observed for ATP, phosphocreatine (PCr), or total creatine (TCr); however, the TCr/ATP was higher in the CRE condition (P < 0.05) than in the CON and PLA conditions. Findings suggest that 3 d of oral Cr supplementation does not increase resting muscle PCr concentration and has no effect on performance during a single short-term maximal cycling task.
There is an increasing utilisation of oral creatine (Cr) supplementation among athletes who hope to enhance their performance but it is not known if this ingestion has any detrimental effect on the kidney. Five healthy men ingested either a placebo or 20 g of creatine monohydrate per day for 5 consecutive days. Blood samples and urine collections were analysed for Cr and creatinine (Crn) determination after each experimental session. Total protein and albumin urine excretion rates were also determined. Oral Cr supplementation had a significant incremental impact on arterial content (3.7 fold) and urine excretion rate (90 fold) of this compound. In contrast, arterial and urine Crn values were not affected by the Cr ingestion. The glomerular filtration rate (Crn clearance) and the total protein and albumin excretion rates remained within the normal range. In conclusion, this investigation showed that short-term oral Cr supplementation does not appear to have any detrimental effect on the renal responses of healthy men.
Article
The gene defect in Huntington's disease (HD) may result in an impairment of energy metabolism. Malonate and 3-nitropropionic acid (3-NP) are inhibitors of succinate dehydrogenase that produce energy depletion and lesions that closely resemble those of HD. Oral supplementation with creatine or cyclocreatine, which are substrates for the enzyme creatine kinase, may increase phosphocreatine (PCr) or phosphocyclocreatine (PCCr) levels and ATP generation and thereby may exert neuroprotective effects. We found that oral supplementation with either creatine or cyclocreatine produced significant protection against malonate lesions, and that creatine but not cyclocreatine supplementation significantly protected against 3-NP neurotoxicity. Creatine and cyclocreatine increased brain concentrations of PCr and PCCr, respectively, and creatine protected against depletions of PCr and ATP produced by 3-NP. Creatine supplementation protected against 3-NP induced increases in striatal lactate concentrations in vivo as assessed by 1H magnetic resonance spectroscopy. Creatine and cyclocreatine protected against malonate-induced increases in the conversion of salicylate to 2,3- and 2,5-dihydroxybenzoic acid, biochemical markers of hydroxyl radical generation. Creatine administration protected against 3-NP-induced increases in 3-nitrotyrosine concentrations, a marker of peroxynitrite-mediated oxidative injury. Oral supplementation with creatine or cyclocreatine results in neuroprotective effects in vivo, which may represent a novel therapeutic strategy for HD and other neurodegenerative diseases.
Article
This study investigated the effect of insulin on plasma and muscle creatine accumulation and limb blood flow in humans after creatine administration. Seven men underwent a 300-min euglycemic insulin clamp combined with creatine administration on four separate occasions. Insulin was infused at rates of 5, 30, 55, or 105 mU. m-2. min-1, and on each occasion 12.4 g creatine was administered. During infusion of insulin at rates of 55 and 105 mU. m-2. min-1, muscle total creatine concentration increased by 4.5 +/- 1.4 (P < 0. 05) and 8.3 +/- 1.0 mmol/kg dry mass (P < 0.05), and plasma creatine concentrations were lower at specific time points compared with the 5 mU. m-2. min-1 infusion rate. The magnitude of increase in calf blood flow (plethysmography) was the same irrespective of the rate of insulin infusion, and forearm blood flow increased to the same extent as the three highest infusion rates. These findings demonstrate that insulin can enhance muscle creatine accumulation in humans but only when present at physiologically high or supraphysiological concentrations. This response is likely to be the result of an insulin-mediated increase in muscle creatine transport rather than creatine delivery.
  • Pritchard