Creatina...

[Eagle]

Qualche studio che ho raccimolato in un quarto d'ora ... ogniuno poi tragge le proprio conclusioni... volevo farmi un'idea dei rischi e degli usi extra sportivi, visto che Master diceva che la usano su vecchi, bambini e malati ...

Avevo evidenziato e commentato alcune frasi ... ma non mi ha copiato la colorazione ... pazienza


Eagle



J Herb Pharmacother. 2004;4(1):1-7. Links
Effects of creatine supplementation on renal function.
Yoshizumi WM, Tsourounis C.
Cedars-Sinai Medical Center, Los Angeles, CA., USA.
Creatine is a popular supplement used by athletes in an effort to increase muscle performance. The purpose of this review was to assess the literature evaluating the effects of creatine supplementation on renal function. A PubMed search was conducted to identify relevant articles using the keywords, creatine, supplementation, supplements, renal dysfunction, ergogenic aid and renal function. Twelve pertinent articles and case reports were identified. According to the existing literature, creatine supplementation appears safe when used by healthy adults at the recommended loading (20 gm/day for five days) and maintenance doses (</=3 gm/day). In people with a history of renal disease or those taking nephrotoxic medications, creatine may be associated with an increased risk of renal dysfunction. One case report of acute renal failure was reported in a 20-year-old man taking 20 gm/day of creatine for a period of four weeks. There are few trials investigating the long-term use of creatine supplementation in doses exceeding 10 gm/day. Furthermore, the safety of creatine in children and adolescents has not been established. Since creatine supplementation may increase creatinine levels, it may act as a false indicator of renal dysfunction. Future studies should include renal function markers other than serum creatinine and creatinine clearance.

Ann Pharmacother. 2005 Jun;39(6):1093-6. Epub 2005 May 10.Links
The effect of creatine intake on renal function.
Pline KA, Smith CL.
College of Pharmacy, Ferris State University, Big Rapids, MI, USA.
OBJECTIVE: To examine the effect of creatine supplementation on renal function and estimates of creatinine clearance. DATA SOURCES: A MEDLINE search was conducted (1966-September 2004) using the key terms creatine, creatinine, kidney function tests, drug toxicity, and exercise. Relevant articles were cross-referenced to screen for additional information. DATA SYNTHESIS: Supplementation with creatine, an unregulated dietary substance, is increasingly common in young athletes. To date, few studies have evaluated the impact of creatine on renal function and estimates of creatinine clearance. Because creatine is converted to creatinine in the body, supplementation with large doses of creatine may falsely elevate creatinine concentrations. Five studies have reported measures of renal function after acute creatine ingestion and 4 after chronic ingestion. All of these studies were completed in young healthy populations. Following acute ingestion (4-5 days) of large amounts of creatine, creatinine concentrations increased slightly, but not to a clinically significant concentration. Creatinine is also only minimally affected by longer creatine supplementation (up to 5.6 y). CONCLUSIONS: Creatine supplementation minimally impacts creatinine concentrations and renal function in young healthy adults. Although creatinine concentrations may increase after long periods of creatine supplementation, the increase is extremely limited and unlikely to affect estimates of creatinine clearance and subsequent dosage adjustments. Further studies are required in the elderly and patients with renal insufficiency.
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Questo e’ pesantino … pero’ sono ratti …

Med Sci Sports Exerc. 2005 Sep;37(9):1525-9.Links
Effects of creatine supplementation on body composition and renal function in rats.
Ferreira LG, De Toledo Bergamaschi C, Lazaretti-Castro M, Heilberg IP.
Nephrology Division, Universidade Federal de São Paulo, Brazil.
BACKGROUND: The aim of the present study was to evaluate the long-term effects of oral creatine supplementation on renal function and body composition (fat and lean mass) in an experimental model. METHODS: Male Wistar rats were supplemented with creatine (2 g.kg(-1) of food) for 10 wk in combination with treadmill exercise, 12 m.min(-1), 1 h.d(-1) (CREAT + EX, N = 12) or not (CREAT, N = 10), and compared with exercised animals without creatine supplementation (EX, N = 7) and CONTROL animals, N = 7. Body composition and bone mineral density (BMD) were determined by dual x-ray absorptiometry and glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by inulin and paraaminohippurate clearance, respectively. RESULTS: At the end of the study (post), CREAT+EX presented higher lean mass and lower fat mass than CREAT, EX or CONTROL (349.7 +/- 19.7 vs 313.3 +/- 20.3, 311.9 +/- 30.8, 312.4 +/- 21.0 g and 5.7 +/- 2.3 vs 10.0 +/- 3.3, 9.8 +/- 1.5, 10.0 +/- 3.5%, P < 0.05, respectively). Post lean/fat mass ratio was higher than baseline only in CREAT + EX (18.9 +/- 7.2 vs 8.6 +/- 1.8, P < 0.05). Post BMD was significantly higher than baseline in all groups. GFR and RPF were lower in CREAT versus CONTROL (0.5 +/- 0.1 vs 1.0 +/- 0.1 and 1.5 +/- 0.2 vs 2.4 +/- 0.5 mL.min(-1), P < 0.05, respectively). CONCLUSION: Creatine supplement in combination with exercise increased the proportion of lean mass more than EX or CREAT alone. The use of creatine alone induced an important and significant reduction of both RPF and GFR.

Mol Cell Biochem. 2003 Feb;244(1-2):95-104.Links
Long-term creatine supplementation does not significantly affect clinical markers of health in athletes.
Kreider RB, Melton C, Rasmussen CJ, Greenwood M, Lancaster S, Cantler EC, Milnor P, Almada AL.
Exercise and Sport Nutrition Laboratory, Department of Human Movement Sciences and Education, The University of Memphis, Memphis, TN, USA. Richard_Kreider@baylor.edu
Creatine has been reported to be an effective ergogenic aid for athletes. However, concerns have been raised regarding the long-term safety of creatine supplementation. This study examined the effects of long-term creatine supplementation on a 69-item panel of serum, whole blood, and urinary markers of clinical health status in athletes. Over a 21-month period, 98 Division IA college football players were administered in an open label manner creatine or non-creatine containing supplements following training sessions. Subjects who ingested creatine were administered 15.75 g/day of creatine monohydrate for 5 days and an average of 5 g/day thereafter in 5-10 g/day doses. Fasting blood and 24-h urine samples were collected at 0, 1, 1.5, 4, 6, 10, 12, 17, and 21 months of training. A comprehensive quantitative clinical chemistry panel was determined on serum and whole blood samples (metabolic markers, muscle and liver enzymes, electrolytes, lipid profiles, hematological markers, and lymphocytes). In addition, urine samples were quantitatively and qualitative analyzed to assess clinical status and renal function. At the end of the study, subjects were categorized into groups that did not take creatine (n = 44) and subjects who took creatine for 0-6 months (mean 4.4 +/- 1.8 months, n = 12), 7-12 months (mean 9.3 +/- 2.0 months, n = 25), and 12-21 months (mean 19.3 +/- 2.4 months, n = 17). Baseline and the subjects' final blood and urine samples were analyzed by MANOVA and 2 x 2 repeated measures ANOVA univariate tests. MANOVA revealed no significant differences (p = 0.51) among groups in the 54-item panel of quantitative blood and urine markers assessed. Univariate analysis revealed no clinically significant interactions among groups in markers of clinical status. In addition, no apparent differences were observed among groups in the 15-item panel of qualitative urine markers. Results indicate that long-term creatine supplementation (up to 21-months) does not appear to adversely effect markers of health status in athletes undergoing intense training in comparison to athletes who do not take creatine.
(qui’ vedo gia’ Master che si fa un drink alla creatina doppie per festeggiare)
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Int J Sport Nutr Exerc Metab. 2000 Sep;10(3):245-59. Links
Use of creatine and other supplements by members of civilian and military health clubs: a cross-sectional survey.
Sheppard HL, Raichada SM, Kouri KM, Stenson-Bar-Maor L, Branch JD.
College of Health Sciences, School of Community Health Professions and Physical Therapy, Old Dominion University, Norfolk, VA 23529-0196, USA.
A survey was used to collect anonymous cross-sectional data on demographics, exercise habits, and use of creatine and other supplements by exercisers in civilian (C) and military (M) health clubs. M (n = 133) reported more aerobic training and less use of creatine and protein supplements than C (n = 96, p <.05). Supplement users (SU, n = 194) and nonusers (SNU, n = 35) engaged in similar frequency and duration of aerobic exercise, as well as number of resistance exercise repetitions, but SU completed more sets for each resistance exercise (x- +/- SE, 5 +/- 1) than SNU (3 +/- 1, p < or =.05). Significant (p < or =.05) associations were observed between SU and resistance training goal of strength (as opposed to endurance), as well as greater frequency of resistance training. Male gender, resistance training goal of strength, lower frequency and duration of aerobic training, and use of protein, b-hydroxy-b-methyl butyrate, and androstenedione/dehydroepiandrosterone supplements were all associated with creatine use (p <.05). For creatine users, the dose and length of creatine supplementation was 12.2 +/- 2.7 g.day-1 for 40 +/- 5 weeks. Popular magazines were the primary source of information on creatine (69%) compared to physicians (14%) or dietitians (10%, p < or =.0001). This study underscores two potential public health concerns: (a) reliance on popular media rather than allied-health professionals for information on creatine, and (b) use of creatine, a popular supplement with unknown long-term effects, in combination with other anabolic supplements of questionable efficacy and/or safety.
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AIAIAIAIIIIII…. Lo studio e’ del 2006, quindi recente …

J Ren Nutr. 2006 Oct;16(4):341-5.Links
Acute renal failure in a young weight lifter taking multiple food supplements, including creatine monohydrate.
Thorsteinsdottir B, Grande JP, Garovic VD.
Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55902, USA.
We report a case of a healthy 24-year-old man who presented with acute renal failure and proteinuria while taking creatine and multiple other supplements for bodybuilding purposes. A renal biopsy showed acute interstitial nephritis. The patient recovered completely after he stopped taking the supplements. Creatine is a performance-enhancing substance that has gained widespread popularity among professional as well as amateur athletes. It is legal and considered relatively safe. Recently there have been case reports of renal dysfunction, including acute interstitial nephritis, associated with its use. Further studies are needed to evaluate the safety of creatine supplementation. It may be prudent to include a warning of this possible side effect in the product insert.

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Curr Sports Med Rep. 2002 Apr;1(2):103-6. Links
Effects of creatine use on the athlete's kidney.
Farquhar WB, Zambraski EJ.
HRCA Research and Training Institute, Harvard Division on Aging, 1200 Centre Street, Boston, MA 02131, USA. farquhar@mail.hrca.harvard.edu
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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Pharmacotherapy. 2005 May;25(5):762-4. Links
Lone atrial fibrillation associated with creatine monohydrate supplementation.
Kammer RT.
Department of Pharmacy, Moses H. Cone Memorial Hospital, Greensboro, NC 27401, USA.
Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.
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Sports Med. 2000 Sep;30(3):155-70. Links
Adverse effects of creatine supplementation: fact or fiction?
Poortmans JR, Francaux M.
Physiological Chemistry, Higher Institute of Physical Education and Readaptation, Free University of Brussels, Bruxelles, Belgium. jrpoortm@ulb.ac.be
The consumption of oral creatine monohydrate has become increasingly common among professional and amateur athletes. Despite numerous publications on the ergogenic effects of this naturally occurring substance, there is little information on the possible adverse effects of this supplement. The objectives of this review are to identify the scientific facts and contrast them with reports in the news media, which have repeatedly emphasised the health risks of creatine supplementation and do not hesitate to draw broad conclusions from individual case reports. Exogenous creatine supplements are often consumed by athletes in amounts of up to 20 g/day for a few days, followed by 1 to 10 g/day for weeks, months and even years. Usually, consumers do not report any adverse effects, but body mass increases. There are few reports that creatine supplementation has protective effects in heart, muscle and neurological diseases. Gastrointestinal disturbances and muscle cramps have been reported occasionally in healthy individuals, but the effects are anecdotal. Liver and kidney dysfunction have also been suggested on the basis of small changes in markers of organ function and of occasional case reports, but well controlled studies on the adverse effects of exogenous creatine supplementation are almost nonexistent. We have investigated liver changes during medium term (4 weeks) creatine supplementation in young athletes. None showed any evidence of dysfunction on the basis of serum enzymes and urea production. Short term (5 days), medium term (9 weeks) and long term (up to 5 years) oral creatine supplementation has been studied in small cohorts of athletes whose kidney function was monitored by clearance methods and urine protein excretion rate. We did not find any adverse effects on renal function. The present review is not intended to reach conclusions on the effect of creatine supplementation on sport performance, but we believe that there is no evidence for deleterious effects in healthy individuals. Nevertheless, idiosyncratic effects may occur when large amounts of an exogenous substance containing an amino group are consumed, with the consequent increased load on the liver and kidneys. Regular monitoring is compulsory to avoid any abnormal reactions during oral creatine supplementation.
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A proposito di questo abstract, in specie la parte evidenziata, mi permetto diricordare che anche l’associazione tra abuso di steroidi anabolizzanti e problemi cardiaci e’ dello stesso tipo … anedoctal, only case reports, etc etc etc …

J Sports Med Phys Fitness. 2004 Dec;44(4):411-6. Links
Is the use of oral creatine supplementation safe?
Bizzarini E, De Angelis L.
School of Sports Medicine, University of Trieste, Trieste, Italy.
This review focuses on the potential side effects caused by oral creatine supplementation on gastrointestinal, cardiovascular, musculoskeletal, renal and liver functions. No strong evidence linking creatine supplementation to deterioration of these functions has been found. In fact, most reports on side effects, such as muscle cramping, gastrointestinal symptoms, changes in renal and hepatic laboratory values, remain anecdotal because the case studies do not represent well-controlled trials, so no causal relationship between creatine supplementation and these side-effects has yet been established. The only documented side effect is an increase in body mass. Furthermore, a possibly unexpected outcome related to creatine monohydrate ingestion is the amount of contaminants present that may be generated during the industrial production. Recently, controlled studies made to integrate the existing knowledge based on anecdotal reports on the side effects of creatine have indicated that, in healthy subjects, oral supplementation with creatine, even with long-term dosage, may be considered an effective and safe ergogenic aid. However, athletes should be educated as to proper dosing or to take creatine under medical supervision.
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J Sports Med Phys Fitness. 2001 Mar;41(1):1-10. Links
Creatine as nutritional supplementation and medicinal product.
Benzi G, Ceci A.
Department of Physiological-Pharmacological Sciences, Faculty of Science, University of Pavia, Italy.
Because of assumed ergogenic effects, the creatine administration has become popular practice among subjects participating in different sports. Appropriate creatine monohydrate dosage may be considered a medicinal product since, in accordance with the Council Directive 65/65/EEC, any substance which may be administered with a view to restoring, correcting or modifying physiological functions in humans beings is considered a medicinal product. Thus, quality, efficacy and safety must characterise the substance. In addition, the European Court of Justice has held that a product which is recommended or described as having preventive or curative properties is a medicinal product even if it is generally considered as a foodstuff and even if it has no known therapeutic effect in the present state of scientific knowledge. In biochemical terms, creatine administration increases creatine and phosphocreatine muscle concentration, allowing for an accelerated rate of ATP synthesis. In thermodynamics terms, creatine stimulates the creatine-creatine kinase-phosphocreatine circuit, which is related to the mitochondrial function as a highly organised system for the control of the subcellular adenylate pool. In pharmacokinetics terms, creatine entry into skeletal muscle is initially dependent on the extracellular concentration, but the creatine transport is subsequently downregulated. In pharmacodynamics terms, the creatine enhances the possibility to maintain power output during brief periods of high-intensity exercises. In spite of uncontrolled daily dosage and long-term administration, no researches on creatine monohydrate safety in humans were set up by standardised protocols of clinical pharmacology and toxicology, as currently occurs in phases I and II for products for human use. More or less documented side effects induced by creatine monohydrate are weight gain; influence on insulin production; feedback inhibition of endogenous creatine synthesis; long-term damages on renal function. A major point that related to the quality of creatine monohydrate products is the amount of creatine ingested in relation to the amount of contaminants present. During the industrial production of creatine monohydrate from sarcosine and cyanamide, variable amounts of contaminants (dicyandiamide, dihydrotriazines, creatinine, ions) are generated and, thus, their tolerable concentrations (ppm) must be defined and made consumers known. Furthermore, because sarcosine could originate from bovine tissues, the risk of contamination with prion of bovine spongiform encephalopathy (BSE or mad-cow disease) can t be excluded. Thus, French authorities forbade the sale of products containing creatine. Creatine, as other nutritional factors, can be used either at supplementary or therapeutic levels as a function of the dose. Supplementary doses of nutritional factors usually are of the order of the daily turnover, while therapeutic ones are three or more times higher. In a subject of 70 kg with a total creatine pool of 120 g, the daily turnover is approximately of 2 g. Thus, in healthy subjects nourished with fat-rich, carbohydrate, protein-poor diet and participating in a daily recreational sport, the oral creatine monohydrate supplementation should be of the order of the daily turnover, i.e., less than 2.5-3 g per day, bringing the gastrointestinal absorption to account. In healthy athletes submitted daily to high-intensity strength or sprint training, the maximal oral creatine monohydrate supplementation should be of the order of two times the daily turnover, i.e., less than 5-6 g per day for less than two weeks, and the creatine monohydrate supplementation should be taken under appropriate medical supervision. The oral administration of more that 6 g per day of creatine monohydrate should be considered as a therapeutic intervention and should be prescribed by physicians only in the cases of suspected or proven deficiency, or in conditions of severe stress and/or injury. The incorporation of creatine into the medicinal product class is supported also by the use in pathological conditions, e.g., some mitochondrial cytopathies, the guanidinoacetate methyltransferase deficiency, etc.

[Eagle]

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Int J Sports Med. 2005 May;26(4):307-13.Links
Few adverse effects of long-term creatine supplementation in a placebo-controlled trial.
Groeneveld GJ, Beijer C, Veldink JH, Kalmijn S, Wokke JH, van den Berg LH.
Department of Neurology, University Medical Centre Utrecht, The Netherlands.
Although oral creatine supplementation is very popular among athletes, no prospective placebo-controlled studies on the adverse effects of long-term supplementation have yet been conducted. We performed a double-blind, placebo-controlled trial of creatine monohydrate in patients with the neurodegenerative disease amyotrophic lateral sclerosis, because of the neuroprotective effects it was shown to have in animal experiments. The purpose of this paper is to compare the adverse effects, and to describe the effects on indirect markers of renal function of long-term creatine supplementation. 175 subjects (age = 57.7 +/- 11.1 y) were randomly assigned to receive creatine monohydrate 10 g daily or placebo during an average period of 310 days. After one month, two months and from then on every fourth month, adverse effects were scored using dichotomous questionnaires, plasma urea concentrations were measured, and urinary creatine and albumin concentrations were determined. No significant differences in the occurrence at any time of adverse effects due to creatine supplementation were found (23 % nausea in the creatine group, vs. 24 % in the placebo group, 19 % gastro-intestinal discomfort in the creatine group, vs. 18 % in the placebo group, 35 % diarrhoea in the creatine group, vs. 24 % in the placebo group). After two months of treatment, oedematous limbs were seen more often in subjects using creatine, probably due to water retention. Severe diarrhoea (n = 2) and severe nausea (n = 1) caused 3 subjects in the creatine group to stop intake of creatine, after which these adverse effects subsided. Long-term supplementation of creatine did not lead to an increase of plasma urea levels (5.69 +/- 1.47 before treatment vs. 5.26 +/- 1.44 at the end of treatment) or to a higher prevalence of micro-albuminuria (5.4 % before treatment vs. 1.8 % at the end of treatment).
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Spinal Cord. 2006 May;44(5):275-9.Links
Influence of creatine supplementation on 800 m wheelchair performance: a pilot study.
Perret C, Mueller G, Knecht H.
Institute for Clinical Research, Swiss Paraplegic Centre, Nottwil, Switzerland.
STUDY DESIGN: Double-blind, placebo-controlled, randomly assigned, crossover. OBJECTIVE: To assess the influence of a short-term oral creatine supplementation on 800 m wheelchair performance. SETTING: Swiss Paraplegic Centre, Nottwil, Switzerland. SUBJECTS: In total, six (four male, two female subjects) competitive wheelchair athletes participated in the study. Their age was 33.0+/-9.1 years, height 171.5+/-7.7 cm and weight 63.1+/-6.2 kg. Average weekly training volume was 10.0+/-3.7 h. All of them have been engaged in regular training for over 10.5+/-7.2 years. METHODS: During the two treatment periods, subjects ingested 4 x 5 g of creatine monohydrate or placebo (maltodextrin) daily during 6 days in a randomised order. A washout period of 4 weeks lay in-between the two supplementation periods. Before and after each treatment period athletes performed an all-out 800 m wheelchair test on a training roller. Time to complete 800 m, rate of perceived exertion (RPE), lactate concentrations and heart rate were measured. Before each test, body weight was determined. RESULTS: Times to complete 800 m before and after creatine supplementation (102.8+/-13.9 versus 100.5+/-11.3 s) compared to before and after placebo supplementation (101.6+/-15.6 versus 99.5+/-13.8 s) were not significantly different. Moreover, for all other parameters measured, no significant differences between creatine and placebo supplementation were found. CONCLUSION: A short-term oral creatine supplementation compared to placebo seems not to enhance performance over 800 m in trained, spinal cord-injured, wheelchair athletes. Spinal Cord (2006) 44, 275-279. doi:10.1038/sj.sc.3101840; published online 20 September 2005.
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Arch Phys Med Rehabil. 2002 Jan;83(1):19-23.Links
Oral creatine supplementation enhances upper extremity work capacity in persons with cervical-level spinal cord injury.
Jacobs PL, Mahoney ET, Cohn KA, Sheradsky LF, Green BA.
Department of Neurological Surgery, University of Miami School of Medicine, Miami, FL 33136, USA.
OBJECTIVE: To examine the effects of short-term creatine monohydrate supplementation on the upper extremity work capacity of persons with cervical-level spinal cord injury (SCI). DESIGN: Randomized, double-blind, placebo-controlled, crossover design study. Consists of 2 treatment phases lasting for 7 days, separated by a 21-day washout period. SETTING: University research laboratory trial. PARTICIPANTS: Sixteen men with complete cervical-level SCI (C5-7). INTERVENTION: Subjects were randomly assigned to 1 of 2 groups and received either 20g/d of creatine monohydrate supplement powder or placebo maltodextrin powder for the first treatment phase; the treatment was reversed in the second phase. Incremental peak arm ergometry tests, using 2-minute work stages and 1-minute recovery periods, were performed immediately before and after each treatment phase (total of 4 assessments). The initial stage was performed unloaded, with power output progressively increased 10 watts/stage until subjects had achieved volitional exhaustion. MAIN OUTCOME MEASURES: Peak power output, time to fatigue, heart rate, and metabolic measurements, including oxygen uptake (VO2), minute ventilation, tidal volume (VT), and respiration frequency. RESULTS: Significantly greater values of VO2, VCO2, and VT at peak effort after creatine supplementation (P <.001). CONCLUSIONS: Creatine supplementation enhances the exercise capacity in persons with complete cervical-level SCI and may promote greater exercise training benefits. Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation
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J Spinal Cord Med. 2005;28(3):208-13. Links
Creatine supplementation for weak muscles in persons with chronic tetraplegia: a randomized double-blind placebo-controlled crossover trial.
Kendall RW, Jacquemin G, Frost R, Burns SP.
Division of Physical Medicine and Rehabilitation, University of Utah, Salt Lake City, Utah, USA.
BACKGROUND AND OBJECTIVES: Creatine supplementation improves muscle strength in some patient populations with neurologic disorders. The purpose of this study was to determine whether creatine supplementation improves muscle strength and endurance in weak upper limb muscles in persons with tetraplegia, and whether it improves function. METHODS: Outpatients with tetraplegia and mild wrist extensor weakness were randomized to receive either creatine or placebo in a double-blind crossover design. During creatine supplementation, participants were loaded with 10 g orally twice per day for 6 days, then maintained on 5 g daily until undergoing testing. Main outcome measures, performed at baseline, after placebo, and after creatine supplementation, included maximal voluntary wrist extensor isometric contraction strength (MVC), endurance times for 5 submaximal wrist extensor contractions, and the Grasp and Release Test for hand function. RESULTS: Eight individuals (7 men, 1 woman) with tetraplegia met inclusion criteria and completed all study phases. The mean age of participants was 48 years, and 7 of 8 had C6 motor level injuries. There were no significant differences in MVC, endurance times, or hand function for creatine vs placebo. CONCLUSION: Creatine does not improve MVC and endurance of weak wrist extensors and does not improve hand function in individuals with tetraplegia.
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Muscle Nerve. 2004 Jan;29(1):51-8.Links
Creatine monohydrate supplementation does not increase muscle strength, lean body mass, or muscle phosphocreatine in patients with myotonic dystrophy type 1.
Tarnopolsky M, Mahoney D, Thompson T, Naylor H, Doherty TJ.
Department of Medicine (Neurology and Rehabilitation), McMaster University, Hamilton, Canada. tarnopol@mcmaster.ca
Creatine monohydrate (CrM) supplementation may increase strength in some types of muscular dystrophy. A recent study in myotonic muscular dystrophy type 1 (DM1) did not find a significant treatment effect, but measurements of muscle phosphocreatine (PCr) were not performed. We completed a randomized, double-blind, cross-over trial using 34 genetically confirmed adult DM1 patients without significant cognitive impairment. Participants received CrM (5 g, approximately 0.074 g/kg daily) and a placebo for each 4-month phase with a 6-week wash-out. Spirometry, manual muscle testing, quantitative isometric strength testing of handgrip, foot dorsiflexion, and knee extension, handgrip and foot dorsiflexion endurance, functional tasks, activity of daily living scales, body composition (total, bone, and fat-free mass), serum creatine kinase activity, serum creatinine concentration and clearance, and liver function tests were completed before and after each intervention, and muscle PCr/beta-adenosine triphosphate (ATP) ratios of the forearm flexor muscles were completed at the end of each phase. CrM supplementation did not increase any of the outcome measurements except for plasma creatinine concentration (but not creatinine clearance). Thus, CrM supplementation at 5 g daily does not have any effects on muscle strength, body composition, or activities of daily living in patients with DM1, perhaps because of a failure of the supplementation to increase muscle PCr/beta-ATP content.
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Arch Phys Med Rehabil. 2005 Jul;86(7):1293-8.Links
Creatine monohydrate supplementation does not improve functional recovery after total knee arthroplasty.
Roy BD, de Beer J, Harvey D, Tarnopolsky MA.
Faculty of Applied Health Sciences, Brock University, St. Catharines, ON, Canada.
OBJECTIVE: To determine if creatine monohydrate supplementation can improve body composition and enhance recovery after total knee arthroplasty (TKA). DESIGN: Randomized trial in which creatine monohydrate or placebo was administered. SETTING: Public primary care facility. PARTICIPANTS: Thirty-seven adults (17 men, 20 women) with osteoarthritis undergoing TKA. Intervention Subjects received creatine monohydrate (10 g/d x 10 d presurgery to 5 g/d x 30 d postsurgery) or placebo. MAIN OUTCOME MEASURES: Body composition (dual-energy x-ray absorptiometry scanning), muscle metabolite concentrations (adenosine triphosphate, phosphocreatine, creatine, total creatine [phosphocreatine + creatine]), muscle histomorphometery, quadriceps, ankle dorsiflexion and handgrip strength, and functional capacity. All measurements were completed preoperatively (-7 d) and 30 days postoperatively, except for that of muscle metabolites. Muscle metabolite samples were collected during surgery (0 d) and at 30 days. RESULTS: A significant decrease in quadriceps and ankle dorsiflexion strength was observed at 30 days postoperatively (P < .01). There were no significant effects of creatine monohydrate supplementation on any of the measured outcome variables. CONCLUSIONS: Creatine monohydrate supplementation did not improve body composition or muscle strength when given before surgery, nor did it enhance recovery after TKA.
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Neurology. 2004 May 25;62(10):1771-7.Links
Creatine monohydrate enhances strength and body composition in Duchenne muscular dystrophy.
Tarnopolsky MA, Mahoney DJ, Vajsar J, Rodriguez C, Doherty TJ, Roy BD, Biggar D.
Department of Medicine, McMaster University, Hamilton, Ontario, Canada. tarnopol@mcmaster.ca
OBJECTIVE: To determine whether creatine monohydrate (CrM) supplementation increases strength and fat-free mass (FFM) in boys with Duchenne muscular dystrophy (DD). METHODS: Thirty boys with DD (50% were taking corticosteroids) completed a double-blind, randomized, cross-over trial with 4 months of CrM (about 0.10 g/kg/day), 6-week wash-out, and 4 months of placebo. Measurements were completed of pulmonary function, compound manual muscle and handgrip strength, functional tasks, activity of daily living, body composition, serum creatine kinase and gamma-glutamyl transferase activity and creatinine, urinary markers of myofibrillar protein breakdown (3-methylhistidine), DNA oxidative stress (8-hydroxy-2-deoxyguanosine [8-OH-2-dG]), and bone degradation (N-telopeptides). RESULTS: During the CrM treatment phase, there was an increase in handgrip strength in the dominant hand and FFM (p < 0.05), with a trend toward a loss of global muscle strength (p = 0.056) only for the placebo phase, with no improvements in functional tasks or activities of daily living. Corticosteroid use, but not CrM treatment, was associated with a lower 8-OH-2-dG/creatinine (p < 0.05), and CrM treatment was associated with a reduction in N-telopeptides (p < 0.05). CONCLUSIONS: Four months of CrM supplementation led to increases in FFM and handgrip strength in the dominant hand and a reduction in a marker of bone breakdown and was well tolerated in children with DD.
* * *
Muscle Nerve. 2003 May;27(5):604-10.Links
Beneficial effects of creatine supplementation in dystrophic patients.
Louis M, Lebacq J, Poortmans JR, Belpaire-Dethiou MC, Devogelaer JP, Van Hecke P, Goubel F, Francaux M.
Institut d'Education Physique et de Réadaptation, Université Catholique de Louvain, 1 Place Pierre de Coubertin, B-1348 Louvain-la-Neuve, Belgium.
The effect of creatine (Cr) supplementation on muscle function and body composition of 12 boys with Duchenne muscular dystrophy and three with Becker dystrophy was evaluated by a randomized double-blind cross-over study (3 g Cr or maltodextrin daily for 3 months, with wash-out period of 2 months). After placebo, no change was observed in maximal voluntary contraction (MVC) and resistance to fatigue, whereas total joint stiffness (TJS) was increased by approximately 25% (P < 0.05). The patients receiving Cr did not show any change in TJS, improved MVC by 15% (P = 0.02), and almost doubled their resistance to fatigue (P < 0.001). In patients still independent of a wheelchair (n = 5), bone mineral density increased by 3% (P < 0.05), and urinary excretion of collagen type I cross-linking N-telopeptide declined to about one third (P < 0.001) after Cr. No adverse effect was observed. Thus, Cr may provide some symptomatic benefit in these patients.
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[Eagle]

J Neurol. 2002 Dec;249(12):1717-22.Links
Creatine monohydrate in myotonic dystrophy: a double-blind, placebo-controlled clinical study.
Walter MC, Reilich P, Lochmüller H, Kohnen R, Schlotter B, Hautmann H, Dunkl E, Pongratz D, Müller-Felber W.
Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University, Ziemssenstr. 1a, 80336 Munich, Germany. Maggie.Walter@lrz.uni-muenchen.de
We assessed safety and efficacy of creatine monohydrate (Cr) in myotonic dystrophy (DM1) in a double-blind, cross-over trial. Thirty-four patients with defined DM1 were randomized to receive Cr and placebo for eight weeks (10.6 g day 1-10, 5.3 g day 11-56) in one of 2 treatment sequences. There was no significant improvement using manual and quantitative muscle strength, daily-life activities, and patients' own global assessment comparing verum with placebo administration. Cr supplementation was well tolerated without clinically relevant side effects, but did not result in significant improvement of muscle strength or daily-life activities.
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Neurology. 2000 Dec 12;55(11):1748-51.Links
A placebo-controlled crossover trial of creatine in mitochondrial diseases.
Klopstock T, Querner V, Schmidt F, Gekeler F, Walter M, Hartard M, Henning M, Gasser T, Pongratz D, Straube A, Dieterich M, Müller-Felber W.
Department of Neurology, Ludwig-Maximilians-Universität München, Germany. klopstock@brain.nefo.med.uni-muenchen.de
To test the efficacy and safety of creatine (Cr) monohydrate in mitochondrial diseases, 16 patients with chronic progressive external ophthalmoplegia or mitochondrial myopathy were randomized in a crossover design to receive double-blind placebo or 20 g Cr/day for 4 weeks. Cr was well tolerated, but there were no significant effects with regard to exercise performance, eye movements, or activities of daily life. The power of this pilot study was limited and future multicenter trials are needed.
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Neurology. 2000 May 9;54(9):1848-50.Links
Creatine monohydrate in muscular dystrophies: A double-blind, placebo-controlled clinical study.
Walter MC, Lochmüller H, Reilich P, Klopstock T, Huber R, Hartard M, Hennig M, Pongratz D, Müller-Felber W.
Friedrich-Baur-Institute, Ludwig-Maximilians-University of Munich, Germany. Maggie.Walter@lrz.uni-muenchen.de
The authors assessed the safety and efficacy of creatine monohydrate (Cr) in various types of muscular dystrophies in a double-blind, crossover trial. Thirty-six patients (12 patients with facioscapulohumeral dystrophy, 10 patients with Becker dystrophy, 8 patients with Duchenne dystrophy, and 6 patients with sarcoglycan-deficient limb girdle muscular dystrophy) were randomized to receive Cr or placebo for 8 weeks. There was mild but significant improvement in muscle strength and daily-life activities by Medical Research Council scales and the Neuromuscular Symptom Score. Cr was well tolerated throughout the study period.
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Neurology. 2003 Feb 11;60(3):500-2.Links
Creatine monohydrate in DM2/PROMM: a double-blind placebo-controlled clinical study. Proximal myotonic myopathy.
Schneider-Gold C, Beck M, Wessig C, George A, Kele H, Reiners K, Toyka KV.
Department of Neurology, University of Würzburg, Germany. chris.schneider@mail.uni-wuerzburg.de
The efficacy and safety of creatine monohydrate (Cr) in patients with myotonic dystrophy type 2/proximal myotonic myopathy were studied in a small placebo-controlled double-blind trial. Twenty patients received either Cr or placebo for 3 months. After 3 months, there were no significant differences of muscle strength as assessed by hand-held dynamometry, testing of maximum grip strength, Medical Research Council scoring, and the Neuromuscular Symptom Score between the two groups. Some measures indicated trends toward mild improvement with Cr. Myalgia improved in two patients.
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Ann Neurol. 2003 Apr;53(4):437-45.Links
A randomized sequential trial of creatine in amyotrophic lateral sclerosis.
Groeneveld GJ, Veldink JH, van der Tweel I, Kalmijn S, Beijer C, de Visser M, Wokke JH, Franssen H, van den Berg LH.
Department of Neurology, University Medical Center Utrecht, The Netherlands.
Amyotrophic lateral sclerosis (ALS) is a fatal disease with no cure. In a transgenic mouse model of ALS, creatine monohydrate showed a promising increase in survival. We performed a double-blind, placebo-controlled, sequential clinical trial to assess the effect of creatine monohydrate on survival and disease progression in patients with ALS. Between June 2000 and December 2001, 175 patients with probable, probable-laboratory supported, or definite ALS were randomly assigned to receive either creatine monohydrate or placebo 10 gm daily. A sequential trial design was used with death, persistent assisted ventilation, or tracheostomy as primary end points. Secondary outcome measurements were rate of decline of isometric arm muscle strength, forced vital capacity, functional status, and quality of life. The trial was stopped when the null hypothesis of indifference was accepted. Creatine did not affect survival (cumulative survival probability of 0.70 in the creatine group vs 0.68 in the placebo group at 12 months, and 0.52 in the creatine group vs 0.47 in the placebo group at 16 months), or the rate of decline of functional measurements. Creatine intake did not cause important adverse reactions. This placebo-controlled trial did not find evidence of a beneficial effect of creatine monohydrate on survival or disease progression in patients with ALS.
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[Black87]

ne ho letti sei e dicono tutti che l'uso a lungo termine e non ciclizzato fa male, e che soggetti con insufficienza renale non dovrebbero usarla perchè non riuscirebbero a "pulire" la creatinina... i restanti 300 che dicono in breve?

[bloodz]

ne ho letti sei e dicono tutti che l'uso a lungo termine e non ciclizzato fa male, e che soggetti con insufficienza renale non dovrebbero usarla perchè non riuscirebbero a "pulire" la creatinina... i restanti 300 che dicono in breve?

un'altro dice che la concentrazione di creatinina nel sangue non differisce se presa per 2 mesi invece che 12...un altro sui ratti che pure dandogli la terra da mangiare aumentavano il 200% di massa magra e diminuivano la grassa del 1132123 % ..naturalmente tutto ciò mentre il loro sistema immunitario si rinforzava, il rischio dei tumori s'è abbassato al 99,9% ecc ecc.

[DANIELS]

tanti spunti interessanti...
eagle sei il massimo

[The Trainer]

La creatina (dal greco kreas = carne) o metil-glico-ciamina è un componente del metabolismo intermedio che viene formata nel fegato in quantità quasi costante, secondo una reazione che coinvolge gli aminoacidi glicina, arginina e metionina, e che viene depositata per circa il 95% nei muscoli.

Notazioni storiche su creatina e creatinina
Gia nel 1832 il francese Chevreul aveva riferito della scoperta di un nuovo costituente organico della carne a cui diede il nome di creatina. Tuttavia, a causa di difficoltà concernenti i metodi di ottenimento della creatina stessa, solo nel 1847 Lieberg fu in grado di confermare che la creatina era un normale costituente della carne. In aggiunta, Lieberg osservò che la carne di volpi selvatiche conteneva una quantità di creatina dieci volte superiore alla concentrazione presente in quella di volpi tenute in cattività, ipotizzando che l’attività motoria comportasse un incremento della concentrazione muscolare di creatina.

Nello stesso periodo Heintz e Pettenkofer evidenziarono nelle urine una sostanza che poi Lieberg confermò essere la creatinina. Sulla base dell’osservazione che l’escrezione urinaria della creatinina era correlata all’entità della massa muscolare, fu ipotizzato che la creatinina tosse un diretto prodotto di metabolizzazione dalla creatina localizzata nei muscoli. I primi studi sugli effetti dell’assunzione di supplementi di creatina risalgono ai primi anni di questo secolo, utilizzando la sostanza allora estratta dalla carne o dalle urine. Fu notato che non tutta la creatina somministrata all’animale o all’uomo era rintracciabile nelle urine, suggerendo che parte della creatina potesse essere trattenuta nell’organismo a scopi plastici od energetici. Studi condotti da Folin e Denis nel 1912 e nel 1914 dimostrarono che il contenuto muscolare di creatina poteva essere incrementato fino al 70% dall’assunzione di supplementi dietetici di creatina. Nel 1923 Hahn e Meyer stimarono che, per un uomo di 70 Kg, il contenuto totale di creatina fosse di circa 140 g – valore simile a quello tutt’oggi considerato come attendibile e pari a 2 g/kg di peso corporeo.

La scoperta della creatina fosforilata: la fosfocreatina

Fiske e Subbarow nel 1927 misero in evidenza la presenza nel muscolo di un composto organico della creatina: la fosfocreatina o creatina fosfato. Gli stessi autori osservarono, in studi condotti sull’animale, che i livelli di fosfocreatina diminuivano durante la stimolazione elettrica del muscolo per poi aumentare nuovamente durante la fase di riposo. Le loro ricerche e quelle di Lundsgaard sulla creatina nella sua forma libera e fosforilata costituirono le basi per la comprensione del metabolismo intermedio della muscolatura scheletrica (Balsom et al. 1994). Gli studi circa il ruolo della creatina nel metabolismo muscolare hanno avuto un particolare impulso in campo umano dopo l’introduzione della tecnica bioptica mediante il prelievo di frammenti muscolari, utilizzando uno speciale ago (Bergstrom 1962). Tale metodologia di indagine è stata utilizzata per la prima volta nel 1967 nello studio dell’utilizzo e della risintesi dell’ATP e della fosfocreatina (Hulman et al. 1967). Un’altra metodica utilizzata nello studio del metabolismo della creatina è la risonanza magnetica nucLeare che non richiede interventi cruenti e consente eventuali indagini comparative sullo stesso soggetto (Kreis et al. 1997).

La sintesi, la degradazione intraorganica e l’eliminazione della creatina

Come indicato nello schema iniziale, la sintesi della creatina avviene a partire dagli aminoacidi glicina e arginina, con il contributo della S-adenosil-metionina e mediante la catalisi operata da alcuni enzimi (amidinotransferasi, metiltransferasi) localizzati a livello epatica, pancreatico e renale. Nel sangue, la normale concentrazione plasmatica della creatina è compresa fra le 50 e le 100 mmol/litro. Circa il 95% del contenuto totale di creatina dell’organismo umano è localizzato a livello dei muscoli scheletrici (Balsom et al. 1994) dove viene incorporata con un meccanismo sodio-dipendente (Fitch, Shields 1966; Fitch 1968; Loike et al. 1968). Per quanto riguarda la metabolizzazione della creatina, in assenza di una sua supplementazione, la molecola viene convertita irreversibilmente e non-enzimaticamente in creatinina e, quindi, escreta nelle urine. In tal caso, il turnover di trasformazione della creatina in creatinina è dell’1.6 % al giorno (Hoberman et al. 1948). Per un uomo di 70 kg, con un contenuto totale di creatina pari a 120 g, circa 2 grammi/die di creatina vengono metabolizzati in creatinina. La creatina così biometabolizzata viene rimpiazzata tramite sia la sintesi endogena (a partite da arginina e glicina) che l’apporto esogeno di tipo alimentare. Si stima che l’apporto alimentare medio di creatina per una dieta mista sia di circa 1 g/die. Un eccesso di apporto alimentare potrebbe, almeno in parte, influenzare la sintesi della creatina con un meccanismo a feedback che tenderebbe a deprimere la sintesi endogena (Walker 1960). La creatina di origine alimentare è contenuta principalmente nella carne, mentre solo tracce sono presenti in alcuni vegetali. Nel caso di una dieta priva di creatina, come avviene ad esempio nei vegetariani, il fabbisogno giornaliero è coperto dalla sola sintesi endogena. In tal caso, l’eliminazione urinaria della creatinina risulta molto limitata (Delanghe et al. 1989). Per ciò che concerne l’eliminazione della creatina introdotta con gli alimenti o la supplementazione, i dati presenti in letteratura sono discordanti. E’ stato osservato un aumento dell’escrezione urinaria di creatinina a seguito dell’assunzione di 20 g di creatina/die per cinque giorni. La sospensione dell’assunzione dei supplementi di creatina era poi seguita dal rapido ritorno alla norma dei valori di creatininuria (Hultman et al. 1996). Questa osservazione contrasta, tuttavia, con quanto osservato da vari altri Autori che rilevano come l’aumento della escrezione urinaria di creatinina sia lieve od anche nullo in caso di incrementata assunzione orale di creatina (Sipila et al. 1981; Earnest et al. 1995; Chanutin 1996; Poortmans et al. 1997).

Il ruolo biofisiologico della creatina a livello muscolare

L’energia utilizzata dal muscolo scheletrico per la sua contrazione deriva dall’idrolisi dell‘adenosina trifosfato (ATP) ad adenosina difosfato (ADP). La normale funzionalità dei muscoli richiede poi che l’ATP sia continuamente risintetizzato, a partire da suoi prodotti di trasformazione. Durante l'attività motoria di intensità massimale e di breve durata, la disponbilità dinamica di ATP è ottenuta quasi esclusivamente a mezzo del processo anaerobico alattacido che si realizza mediante la defosforilazione della fosfocreatina, con i conseguente passaggio dell'ADP allo stato di ATP, atto a liberare energia per la contrazione muscolare, mediante la seguente reazione reversibile pH-dipendente:

creatina chinasi

fosfocreatina + ADP <--> creatina + ATP -----> contrazione muscolare

per cui la creatina viene poi rifosforilata durante il periodo di riposo.

In considerazione dell’attività di detto circuito creatina/creatina chinasi/fosfocreatina, nel muscolo la concentrazione di fosfocreatina rappresenta un pool di riserva energetica rapidamente utilizzabile per il ripristino del contenuto di ATP. Inoltre, il circuito creatina/creatina chinasi/fostocreatina è connesso con i processi di trasduzione di energia dei mitocondri (Bessman, Geiger 1981; Wallimann et al. 1992). Questo comporta che a riposo la trasduzione aerobica mitocondriale può essere la fonte energetica per la fosforilazione della creatina supplementata in eccesso rispetto ala normale assunzione esogena od alla sintesi endogena. Durante l’attività muscolare intensa e di breve durata, il decremento della forza sviluppata può essere messo in relazione al depauperamento delle riserve muscolari di fosfocreatina, con conseguente rallentamento della velocità di rigenerazione dell’ATP (Katz et al. 1986; Hitchcock 1989). In tale situazione, l'affaticamento muscolare può essere messo in relazione con una riduzione della produzione di ATP prevalentemente nelle fibre muscolari di tipo Il (fast-twitch fibres), nelle quali le riserve di fosfocreatina vengono rapidamente utilizzate e deplete (Soderlund et al. 1992).

La supplementazione orale di creatina e il metabolismo muscolare

L’interesse per l'influenza dei supplementi dietetici di creatina sulle differenti prestazioni sportive risulta relativamente recente: tuttavia, a tale proposito numerosi lavori sperimentali sono presenti in letteratura (Balsom et al. 1993a, b; Casey et al. 1996; Cooke et al. 1995; Earnest et al. 1995; Febbraio et al. 1995; Greenhaff et al. 1993a; Kreider et al. 1998; Vandenberghe et al. 1997), basati sulle preliminari osservazioni che il contenuto muscolare di creatina può essere aumentato a mezzo della sua somministrazione esogena (Harris et al. 1992). L’ingestione di 5 g di creatina provoca un incremento dei livelli plasmatici di creatina fino a 500 µmol/litro, ad un'ora dalla somministrazione. A seguito dell’assunzione di 20-30 g/die di creatina, il contenuto muscolare di creatina totale può aumentare del 17% e, parallelamente, il contenuto di creatina fosfato risulta incrementato del 7.6% (Harris et al., 1992). Supplementazioni di creatina a dosaggi di 2 g/die per sei settimane non sembrano modificare il contenuto muscolare di creatina, il rapporto creatina/colina ed il consumo di ossigeno, sia a riposo che dopo opportuno allenamento (Thompson et al., 1996). Tuttavia, l’assunzione di 2 g/die di creatina sarebbero sufficienti per mantenere i massimi livelli di creatina muscolare raggiunti dopo l’assunzione di dosi di attacco di 20 g/die per sei giorni o, alternativamente, di 3 g/giorno per quattro settimane (Hultman et al. 1996). L’incremento del contenuto muscolare di creatina determinato dall’assunzione di supplementi dietetici è, tuttavia, soggetto ad una notevole variabilità interindividuale )Hultman et al. 1996). In particolare, il 30% della popolazione generale è caratterizzato da un regime dietetico e da un metabolismo intermedio tali per cui l’assunzione di supplementi dietetici non modifica significativamente le concentrazioni muscolari di creatina poiché queste sono vicine al livello fisiologico ottimale o massimale (Sipila et al., 1981). Numerosi studi hanno valutato gli effetti della supplementazione orale di creatina sulla rigenerazione dell’ATP e della forma fosforilata della creatina a livello muscolare (Febbraio et al. 1995; Casey et al. 1996; Greenhaff et al. 1993a; Balsom et al. 1994; Vandenberghe et al. 1996). Queste ricerche indicano che supplementi di creatina a dosaggi elevati non alterano i livelIi di ATP a riposo (Casey et al. 1996), ma la incrementata concentrazione di fosfocreatina conseguente alla assunzione di creatina permette di mantenere alte e in evoluzione dinamica le concentrazioni di ATP durante uno sforzo di elevata intensità e di breve durata (Casey et al. 1996; Greenhaff et al. 1993b; Balsom et al. 1995; Vandenberghe et al. 1996; Williams, Branch 1998). Ciò dipende dal fatto che iI circuito creatina/creatina chinasi/fosfocreatina è connesso con la funzionalità mitocondriale e rappresenta un ben organizzato sistema sia di tamponamento di energia che di trasferimento di energia per attuare il controllo del pooI degli adenilati (ATP/ADP/AMP) e, quindi, consentire un efficiente utilizzo di energia in senso termodinamico (Wallimann et al. 1992; Bessman, Geiger 1981). In relazione alle necessità metaboliche, predomina una di queste funzioni del circuito creatina/creatina chinasi/fosfocreatina: nelle fibre di tipo Il la funzione di “tamponamento di energia” è prevalente su quella di “trasferimento di energia”. Pertanto, a riposo la trasduzione aerobica mitocondriale può essere la fonte energetica per “tamponare” la fosforilazione della creatina supplementata, con conseguente incremento della disponibilità di fosfocreatina da utilizzare durante I'attività muscolare anaerobica.

La supplementazione orale di creatina e le prestazioni sportive

La creatina in dosaggi elevati (10-40 g/die) può determinare un incremento nell’attività contrattile e, quindi, motoria, opponendosi al decremento del rifornimento energetico in corrispondenza di attività ad alta intensità anaerobica (Clarkson 1996; Mujika, Padilla 1997). Per tali ragioni, la supplementazione della creatina è diventata una pratica ricorrente fra gli atleti professionisti, dilettanti ed amatori, ma, ciononostante, il CIO non ha introdotto la creatina e la fosfocreatina nelle Classi di sostanze proibite. Pur con la riserva della grande variabilità dei protocolli sperimentali messi in atto, si riscontra una notevole discordanza per quanto riguarda la possibilità di migliorare effettivamente la prestazione degli atleti mediante la supplementazione di creatina. Infatti, sono descritti effetti nulli nelle prestazioni di potenza e di sprint oppure nelle brevi ripetizioni ad alta intensità nel nuoto (Mujika et al. 1996; Burke et al. 1996), nell’atletica leggera (Javierre et al. 1997; Terrillion et al. 1997; Redondo et al. 1996) e nelle prove al cicloergometro (Cooke, Barnes 1997; Odland et al. 1997). Anche le prestazioni di endurance nel nuoto non sembrano essere positivamente modificate (Thompson et al. 1996). Di contrapposto alle osservazioni su citate, altri riscontri evidenziano effetti positivi nelle prestazioni di sprint o nelle prestazioni intermittenti ad alta intensità di giocatori di football (Kreider et al. 1998), di nuotatori juniores (Grindstaff et al. 1997), di sprinter e saltatori (Bosco et al. 1997) e di giovani ed attivi soggetti volontari (Schneider et al. 1997; Prevost et al. 1997; Volek et al. 1997). Vengono inoltre descritti effetti positivi anche nelle prestazioni di fondo in giovani volontarie non-allenate (Vandenberghe et al. 1997). Queste contrapposte osservazioni sulle modificazioni indotte dalla supplementazione di creatina nelle prestazioni sportive non devono stupire in quanto analoghe contraddittorie risposte si rilevano dall’esame della letteratura relativa alle variazioni delle performance indotte dall’assunzione di potenti farmaci dopanti, quali sono gli steroidi anabolizzanti (Benzi, 1993).

Effetti collaterali e tossici della supplementazione orale di creatina

Eventuali comparse di crampi muscolari, intolleranza al caldo, edemi, tensione muscolare, diarrea o addirittura di morti a seguito dell’assunzione di supplementi dietetici di creatina sono segnalate in alcune dichiarazioni e/o riportate nei mass media, ma non compaiono nelle pubblicazioni scientifiche. Si tratta di osservazioni non controllate per le quali non sono disponibili delle notizie valide sul piano tecnico, clinico e scientifico (Clark 1998). Tuttavia, negli Usa la Food and Drug Administration ha prudenzialmente consigliato consumatori di consultare i medici prima di iniziare un’assunzione di creatina, specie se per lunghi periodi di tempo. In carenza di studi nell’uomo relativi agli eventuali effetti tossici determinati dall’assunzione cronica di creatina, si rileva che l’assunzione acuta o sub-acuta di creatina sembra essere ben tollerata e nel complesso priva di effetti nocivi (Clark 1998; Mujika et al. 1996; Bosco et al. 1997; Kreider et al. 1998; Oopik et al. 1998; Maughan 1995). L’aumento del peso corporeo è segnalato come effetto collaterale in ricerche su soggetti utilizzatori di alti dosaggi di creatina (fino a 25 g/die) per periodi di tempo inferiori alle due settimane (Balsom et al. 1994). Questo effetto collaterale è riportato anche in uno studio clinico condotto su soggetti patologici ai quali sono stati somministrati 1.5 g/die di creatina per un periodo di circa un anno (Sipila et al. 1981). Per ciò che concerne una eventuale tossicità della creatina a livello del fegato, non risultano riportate nella letteratura scientifica delle alterazioni negli indici di funzionalità epatica a seguito dell’assunzione di supplementi dietetici di tale sostanza (Kreider et al. 1998; Earnest et al. 1996). Un possibile effetto nefrotossico della creatina con proteinuria è stato segnalato (Prichard, Kaira 1998) in un soggetto affetto da glomerulosclerosi segmentale e, per tale motivo, in terapia da cinque anni con ciclosporina. Lo stesso paziente aveva già mostrato in passato fluttuazioni della proteinuria per cui risulta molto discutibile la correlazione fra l’assunzione di creatina ed il danno renale (Greenhaff 1998). Inoltre, a seguito di differenti osservazioni cliniche, vari Autori concludono che i supplementi orali di creatina assunti per brevi periodi di tempo non hanno effetti nefrotossici (Earnest et al. 1996; Poortmans et al. 1997; Poortmans, Francaux, 1998).

Conclusioni

La sintesi della creatina avviene a partire dagli aminoacidi glicina e arginina, con il contributo della S-adenosil-metionina e mediante la catalisi operata da alcuni enzimi (amidinotransferasi, metiltransferasi) localizzati a livello epatico, pancreatico e renale. Dopo essere stata fosforilata a fosfocreatina, la molecola viene convertita irreversibilmente e non-enzimaticamente in creatinina e, quindi, escreta nelle urine. In tal caso, il turnover di trasformazione della creatina in creatinina è di circa l'1.6% al giorno. La creatina di origine alimentare è contenuta principalmente nella carne, mentre solo tracce sono presenti in alcuni vegetali. Nel caso di una dieta priva di creatina, come avviene ad esempio nei soggetti vegetariani, il fabbisogno giornaliero è coperto dalla sola sintesi endogena e l’eliminazione urinaria della creatinina risulta molto limitata. I supplementi di creatina non alterano i livelli di ATP a riposo, ma l’incrementata concentrazione di fosfocreatina conseguente alla assunzione di creatina permette di mantenere alte e in evoluzione dinamica le concentrazioni di ATP durante uno sforzo di elevata intensità e di breve durata. La fosfocreatina rappresenta, infatti, un pool di riserva energetica rapidamente utilizzabile per il ripristino del contenuto muscolare di ATP. Inoltre, il circuito creatina/creatina chinasi/fosfocreatina è correlato alla funzionalità mitocondriale come un ben organizzato sistema sia di tamponamento di energia che di trasferimento di energia per attuare il controllo del pool degli adenilati (ATP/ADP/AMP) e, quindi, consentire un efficiente utilizzo dI energia in senso termodinamico. Pertanto la trasduzione aerobica mitocondriale a riposo può essere la fonte energetica per tamponare la fosforilazione della creatina supplementata, con conseguente incremento della disponibilità di fosfocreatina da utilizzare durante l‘attività muscolare anaerobica. Durante l’attività muscolare molto intensa e di breve durata il decremento della forza sviluppata può essere messo in relazione a depauperamento delle riserve di fosfocreatina e l’affaticamento muscolare può essere correlato ad una riduzione della produzione di ATP prevalentemente nelle fibre muscolari di tipo Il (fast-twitch fibres), nelle quali le riserve di fosfocreatina vengono rapidamente utilizzate e deplete. Per tali ragioni, la supplementazione della creatina è diventata una pratica ricorrente fra gli atleti professionisti, dilettanti ed amatori, ma il CIO non ha introdotto la creatina nelle Classi di sostanze proibite. Le caratteristiche della creatina indicano che la sua supplementazione negli atleti potrebbe configurarsi come doping in quanto modifica il biochimismo e la bioenergetica muscolare e può, nel contempo, avere effetti anche positivi sulle prestazioni atletiche, soprattutto anaerobiche. In tal caso sia la creatina che a fosfocreatina devono essere inserite in una apposita e nuova Classe di sostanze proibite che potrebbe intitolarsi "Sostanze ad azione metabolica muscolare".

Considerando che solo l’inserimento nella lista uffIciale del CIO consente alle Autorità sportive di definire come doping la somministrazione o l’assunzione d sostanze attive, una tale iniziativa presuppone che il Coni presenti per la creatina e la fosfocreatina una documentata istanza alla Commissione Medica del CIO cui compete ogni decisione in merito alla definizione delle liste delle classi di sostanze proibite.

L’assunzione acuta o sub-acuta di creatina sembra essere ben tollerata e priva di effetti nocivi. In alcune ricerche l’aumento del peso corporeo è segnalato come effetto collaterale, mentre non risultano riportati nella letteratura scientifica dati significativi circa una eventuale epatotossicità e/o nefrotossicità. Tuttavia risultano indispensabili approfonditi studi nell’uomo relativi sia alla valutazione di eventuali fenomeni a feedback nella sintesi endogena di creatina, sia relativi agli eventuali effetti collaterali e/o tossici determinati dall’assunzione cronica di creatina.

[corlis1]

troppi pareri discordi , sinceramente i benefici li ho visti solo da cicli lunghi , il resto e' molto relativo

[sgksgk]

Molto interessante.
Buono Eagle.