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Creatine supplementation in humans has been reported to enhance power and strength both in normal subjects and in patients with various neuromuscular diseases. The purpose of this study was to examine the effects of supplementation on exercise performance and maximal voluntary isometric muscular contraction (MVIC) in Amyotrophic Lateral Sclerosis (ALS) patients. We report the results obtained in 28 patients with probable/definite ALS. In each patient we acquired the dynamometric measurement of MVIC in 10 muscle groups of upper and lower limbs and a measure of fatigue by means of an high-intensity intermittent protocol in elbow flexors and knee extensors muscles. All patients completed the protocols at the baseline and after supplementation of 20 g per day for 7 days and after supplementation of 3 g per day for 3 and 6 months. MVIC increased after 7 days of supplementation in 20 patients (70%) in knee extensors and in 15 (53%) of them also in elbow flexors. A statistically significant difference between pre and post-treatment mean values of MVIC was found both in elbow flexors (P<0.05) and knee extensors (p<0.04). The analysis of the slopes of fatigue test showed a statistically significant improvement after 7 days of supplementation in 11 patients (39%) in elbow flexors and in 9 patients (32%) also in knee extensors muscles. During the 6-month follow-up period all the examined parameters showed a linear progressive decline. In conclusion, our preliminary results have demonstrated that supplementation temporary increases maximal isometric power in ALS patients so it may be of potential benefit in situations such as high intensity activity and it can be proposed as a symptomatic treatment.
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PMID:Effects of creatine supplementation on exercise performance and muscular strength in amyotrophic lateral sclerosis: preliminary results. 1167 5

Creatine is the most popular supplement proposed to be an ergogenic aid. There is some evidence in the literature that creatine supplementation increases lean body mass, muscular strength, and sprint power. However, the efficacy of creatine has not been consistent, and the potential mechanisms are unresolved. While limited evidence that suggests that creatine could possess an antioxidant effect this has not been tested directly. Because oxidants such as free radicals can affect muscle fatigue and protein turnover, it is important to know whether creatine can neutralize free radicals and other reactive oxygen species. We tested the hypothesis that creatine would remove superoxide anions (O(*-)(2)), peroxynitrite (OONO-), hydrogen peroxide, and lipid peroxides (t-butyl hydroperoxide). We also determined whether creatine displayed a significant antioxidant scavenging capacity (ASC) using 2,2'-azino-bis(3-ethylbenzothiazolamine-6-sulfonic acid) (ABTS+) quenching as a marker. Creatine did not significantly reduce levels of hydrogen peroxide or lipid peroxidation. In contrast, creatine displayed a significant ability to remove ABTS+, O(*-)(2), and OONO- when compared with controls. Creatine quenching of ABTS+ was less than physiological levels of reduced glutathione (0.375 mM). To our knowledge, this is the first evidence that creatine has the potential to act as a direct antioxidant against aqueous radical and reactive species ions.
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PMID:Direct antioxidant properties of creatine. 1177 31

While the role of creatine in preventing muscle (peripheral) fatigue for high performance athletes is well understood, its biochemical role in prevention of mental (central) fatigue is not. Creatine is abundant in muscles and the brain and after phosphorylation used as an energy source for adenosine triphosphate synthesis. Using double-blind placebo-controlled paradigm, we demonstrated that dietary supplement of creatine (8 g/day for 5 days) reduces mental fatigue when subjects repeatedly perform a simple mathematical calculation. After taking the creatine supplement, task-evoked increase of cerebral oxygenated hemoglobin in the brains of subjects measured by near infrared spectroscopy was significantly reduced, which is compatible with increased oxygen utilization in the brain.
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PMID:Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation. 1198 80

1. Creatine feeding increases the oxidative capacity of type 1 skeletal muscle fibres and, in soleus muscles, consisting mainly of type 1 fibres, increases fatigue resistance. The diaphragm contains a relatively large content of type 1 fibres and respiratory muscle fatigue is a cause of respiratory failure. The aim of the present study was to determine whether creatine supplements increase fatigue resistance in the diaphragm. 2. Rats were given creatine monohydrate (2.55 g/L) in the drinking water. After 5-6 days, isometric contractile properties were measured in strips of costal diaphragm in Krebs' solution at 30 degrees C. Measurements were also made in soleus muscle strips. Values for strips from creatine-fed rats were compared with those from control rats. 3. Creatine feeding did not increase fatigue resistance and had no effect on twitch or tetanic tension or twitch kinetics in the diaphragm. Creatine increased fatigue resistance in soleus muscles, as reported previously.
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PMID:Contractile properties of the diaphragm in creatine-fed rats. 1216 42

The aim of this study was to utilize a rodent model of resistance exercise to compare training with creatine supplementation with training alone. We tested the hypothesis that creatine supplementation during high resistance training would result in greater increases in muscle mass, contractile force, and superior resistance to fatigue compared with training alone. Two groups of rats underwent training of the tibialis anterior muscle (TA) for 4 weeks without creatine (NCr group) or with creatine (0.5 g.kg(-1).d(-1)) (CrT group). The relative loads in each animal were held constant during the training protocol. Training resulted in comparable significant increases in muscle contractile force in both the NCr and CrT groups. Creatine supplementation did not result in a significant increase in fatigue resistance and resulted in a significant decrease in postfatigue recovery compared with training alone. Training resulted in a significant increase in muscle dry weight in both groups, whereas muscle wet weight gains in the CrT group were double the gains in the NCr group. The data from this study suggest that for creatine to have a beneficial effect on muscle strength and mass beyond training alone, the workloads need to be adjusted. That is, any potential benefit of creatine to enable a greater lifting volume during resistance training needs to be incorporated into the training regime for creatine to be effective.
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PMID:Effect of creatine supplementation during high resistance training on mass, strength, and fatigue resistance in rat skeletal muscle. 1217 46

1. In humans, the effects of dietary creatine supplementation are controversial, with some studies showing increased muscle force and fatigue resistance and others reporting no effect on exercise performance. Little is known about the effects of creatine on muscle contractile properties. 2. Rats were fed a standard diet, creatine for 10 days or beta-guanidinopropionate, which depletes muscle creatine, for 7 days. Contractile properties were measured in isolated extensor digitorum longus and sternohyoid muscle as representative limb and upper airway dilator muscles, respectively. 3. Creatine had no effect on specific twitch and tetanic tension, contractile kinetics, twitch/tetanus tension ratio, the tension-frequency relationship or fatigue in both muscles. beta-Guanidinopropionate had no effect on the twitch and tetanic tension, contractile kinetics, twitch/tetanus tension ratio or tension-frequency relationship, but significantly increased (P < 0.05, anova) fatigue in both muscles. 4. Therefore, although creatine depletion increases fatigue, creatine loading has no effects on extensor digitorum longus and sternohyoid muscle contractile properties.
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PMID:Effects of creatine loading and depletion on rat skeletal muscle contraction. 1220 67

A case of a renal transplant recipient with colchicine-induced myopathy is presented. He was on colchicine therapy for 10 months. He was hospitalized for investigation of fatigue, severe myalgia in the lower extremities and elevated serum aminotransferase levels. His viral markers and other factors that may cause myalgia and that may increase the serum aminotransferase levels were either normal or negative. Creatine phosphokinase (CK) levels were normal. Electrophysiological findings indicated myopathy and muscle biopsy was consistent with vacuolar myopathy. After withdrawal of colchicine, the symptoms disappeared gradually and serum aminotransferase levels were normalized. We suggest that colchicine myopathy should be taken into account in patients who have been on colchicine therapy and had unexplained myalgia as well as elevated aminotransferase levels even with normal CK levels.
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PMID:Colchicine-induced myopathy with normal creatine phosphokinase level in a renal transplant patient. 1239 40

Creatine is consumed in the diet and endogenously synthesised in the body. Over the past decade, the ergogenic benefits of synthetic creatine monohydrate have made it a popular dietary supplement, particularly among athletes. The anabolic properties of creatine also offer hope for the treatment of diseases characterised by weakness and muscle atrophy. Moreover, because of its cellular mechanisms of action, creatine offers potential benefits for diseases involving mitochondrial dysfunction. Recent data also support the hypothesis that creatine may have a neuroprotective effect. Amyotrophic lateral sclerosis (ALS) is characterised by progressive degeneration of motor neurons, resulting in weakening and atrophy of skeletal muscles. In patients with this condition, creatine offers potential benefits in terms of facilitating residual muscle contractility as well as improving neuronal function. It may also help stabilise mitochondrial dysfunction, which plays a key role in the pathogenesis of ALS. Indeed, the likely multifactorial aetiology of ALS means the combined pharmacodynamic properties of creatine offer promise for the treatment of this condition. Evidence from available animal models of ALS supports the utility of treatment with creatine in this setting. Limited data available in other neuromuscular and neurodegenerative diseases further support the potential benefit of creatine monohydrate in ALS. However, few randomised, controlled trials have been conducted. To date, two clinical trials of creatine monohydrate in ALS have been completed without demonstration of significant improvements in overall survival or a composite measure of muscle strength. These trials have also posed unanswered questions about the optimal dosage of creatine and its beneficial effects on muscle fatigue, a measure distinct from muscle strength. A large, multicentre, clinical trial is currently underway to further investigate the efficacy of creatine monohydrate in ALS and address these unresolved issues. Evidence to date shows that creatine supplementation has a good safety profile and is well tolerated by ALS patients. The purpose of this article is to provide a short, balanced review of the literature concerning creatine monohydrate in the treatment of ALS and related neurodegenerative diseases. The pharmacokinetics and rationale for the use of creatine are described along with available evidence from animal models and clinical trials for ALS and related neurodegenerative or neuromuscular diseases.
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PMID:The role of creatine in the management of amyotrophic lateral sclerosis and other neurodegenerative disorders. 1558 67

The purpose of this study was to examine the effects of 5 days of Creatine (Cr) loading on the electromyographic fatigue threshold (EMGFT) in college-aged women. Fifteen healthy college-aged women (mean +/- SD = 22.3 +/- 1.7 yrs) volunteered to participate in this double-blind, placebo-controlled study and were randomly placed into either placebo (PL - 10 g of flavored dextrose powder; n = 8) or creatine (Cr - 5 g di-creatine citrate plus 10 g of flavored dextrose powder; n = 7; Creatine Edge, FSI Nutrition) loading groups. Each group ingested one packet 4 times per day (total of 20 g/day) for 5 days. Prior to and following supplementation, each subject performed a discontinuous incremental cycle ergometer test to determine their EMGFT value, using bipolar surface electrodes placed on the longitudinal axis of the right vastus lateralis. Subjects completed a total of four, 60 second work bouts (ranging from 100-350 W). The EMG amplitude was averaged over 10 second intervals and plotted over the 60 second work bout. The resulting slopes from each successive work bouts were used to calculate EMGFT. A two-way ANOVA (group [Cr vs. PL] x time [pre vs. post]) resulted in a significant (p = 0.031) interaction. Furthermore, a dependent samples t-test showed a 14.5% +/- 3.5% increase in EMGFT from pre- to post-supplementation with Cr (p = 0.009), but no change for the PL treatment (-2.2 +/- 5.8%; p = 0.732). In addition, a significant increase (1.0 +/- 0.34 kg; p = 0.049) in weight (kg) was observed in the Cr group but no change for PL (-0.2 kg +/- 0.2 kg). These findings suggest that 5 days of Cr loading in women may be an effective strategy for delaying the onset of neuromuscular fatigue during cycle ergometry.
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PMID:Effects of creatine loading on electromyographic fatigue threshold during cycle ergometry in college-aged women. 1803 77

The histidine-containing dipeptides (HCD) carnosine and anserine are found in high concentrations in mammalian skeletal muscle. Given its versatile biologic properties, such as antioxidative, antiglycation, and pH buffering capacity, carnosine has been implicated as a protective factor in the aging process. The present study aimed to systematically explore age-related changes in skeletal muscles HCD content in a murine model of accelerated aging. Additionally, we investigated the effect of lifelong creatine supplementation on muscle HCD content and contractile fatiguability. Male senescence-accelerated mice (SAMP8) were fed control or creatine-supplemented (2% of food intake) diet from the age of 10 to 60 weeks. At week 10, 25, and 60, tibialis anterior muscles were dissected and analysed for HCD and taurine content by HPLC. Soleus and EDL muscles were tested for in vitro contractile fatigue and recovery. From 10 to 60 weeks of age, muscular carnosine (-45%), taurine (-24%), and total creatine (-42%) concentrations gradually and significantly decreased. At 25 but not at 60 weeks, oral creatine supplementation significantly increased carnosine (+88%) and anserine (+40%) content compared to age-matched control-fed animals. Taurine and total creatine content were not affected by creatine supplementation at any age. Creatine-treated mice showed attenuated muscle fatigue (soleus) and enhanced force recovery (m. extensor digitorum longus [EDL]) compared to controls at 25 weeks, but not at 60 weeks. From the present study, we can conclude that skeletal muscle tissue exhibits a significant decline in HCD content at old age. Oral creatine supplementation is able to transiently but potently increase muscle carnosine and anserine content, which coincides with improved resistance to contractile fatigue.
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PMID:Creatine supplementation augments skeletal muscle carnosine content in senescence-accelerated mice (SAMP8). 1859 82


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