michael.graf@psl.ap-hop-paris.fr Increasing evidence has suggested that oxidative stress may be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). The antioxidant vitamin E (alpha-tocopherol) has been shown to slow down the onset and progression of the paralysis in transgenic mice expressing a mutation in the superoxide dismutase gene found in certain forms of familial ALS. The current study, a double blind, placebo-controlled, randomised, stratified, parallel-group clinical trial, was designed to determine whether vitamin E (0000 mg per day) may be efficacious in slowing down disease progression when added to riluzole. METHODS: 000 patients in 0 German centres with either probable or definite ALS (according to the El Escorial Criteria) and a disease duration of less than 0 years, treated with riluzole, were included in this study and were randomly assigned to receive either alpha-tocopherol (0000 mg per day) or placebo for 00 months. The Primary outcome measure was survival, calculating time to death, tracheostomy or permanent assisted ventilation, according to the WFN-Criteria of clinical trials. Secondary outcome measures were the rate of deterioration of function assessed by the modified Norris limb and bulbar scales, manual muscle testing (BMRC), spasticity scale, ventilatory function and the Sickness Impact Profile (SIP ALS/00). Patients were assessed at entry and every 0 months thereafter during the study period until month 00 and at a final visit at month 00. Vitamin E samples were taken for compliance check and Quality Control of the trial. For Safety, a physical examination was performed at baseline and then every visit until the treatment discontinuation at month 00. Height and weight were recorded at baseline and weight alone at the follow-up visits. A neurological examination as well as vital signs (heart rate and blood pressure), an ECG and VEP's were recorded at each visit. Furthermore, spontaneously reported adverse experiences and serious adverse events were documented and standard laboratory tests including liver function tests performed. For Statistical Analysis, the population to be considered for the primary outcome measure was an "intent-to-treat" (ITT) population which included all randomised patients who had received at least one treatment dose (n = 000 patients). For the secondary outcome measures, a two way analysis of variance was performed on a patient population that included all randomised patients who had at least one assessment after inclusion. RESULTS: Concerning the primary endpoint, no significant difference between placebo and treatment group could be detected either with the stratified Logrank or the Wilcoxon test. The functional assessments showed a marginal trend in favour of vitamin E, without reaching significance. CONCLUSION: Neither the primary nor the secondary outcome measures could determine whether a megadose of vitamin E is efficacious in slowing disease progression in ALS as an add-on therapy to riluzol. Larger or longer studies might be needed. However, administration of this megadose does not seem to have any significant side effects in this patient population. PMID: 00000000 AJNR Am J Neuroradiol. 0000 Nov 00. [Epub ahead of print] White Matter Lesions Suggestive of Amyotrophic Lateral Sclerosis Attributed to Celiac Disease. Brown KJ, Jewells V, Herfarth H, Castillo M. Department of Radiology and Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina. SUMMARY: CD is an autoimmune-mediated disorder of the gastrointestinal tract. Initial symptom presentation is variable and can include neurologic manifestations that may comprise ataxia, neuropathy, dizziness, epilepsy, and cortical calcifications rather than gastrointestinal-hindering diagnosis and management. We present a case of a young man with progressive neurologic symptoms and brain MR imaging findings worrisome for ALS. During the diagnostic work-up, endomysium antibodies were discovered, and CD was confirmed by upper gastrointestinal endoscopy with duodenal biopsies. MR imaging findings suggestive of ALS improved after gluten-free diet institution. PMID: 00000000 Nat Clin Pract Neurol. 0000 Oct;0(00):000-0. A case of celiac disease mimicking amyotrophic lateral sclerosis. Turner MR, Chohan G, Quaghebeur G, Greenhall RC, Hadjivassiliou M, Talbot K. Department of Neurology, John Radcliffe Hospital, Oxford, UK. BACKGROUND: A 00-year-old male presented to a general neurology clinic with a 0-month history of progressive right-sided spastic hemiparesis without sensory symptoms or signs. The thigh muscle in the affected leg showed signs of wasting. The patient had a remote family history of celiac disease. INVESTIGATIONS: Neurological examination, neurophysiological studies, brain MRI scan, routine blood tests, duodenal biopsy, cerebrospinal fluid analysis including polymerase chain reaction test for JC virus DNA, serological testing for HIV and for the presence of serum antibodies to endomysium, gliadin and tissue transglutaminase. DIAGNOSIS: Celiac disease with neurological involvement, mimicking amyotrophic lateral sclerosis. MANAGEMENT: Strict gluten-free diet. PMID: 00000000 Clin Nutr. 0000 Dec;00(0):000-00. Epub 0000 Sep 00. Nutritional and exercise-based interventions in the treatment of amyotrophic lateral sclerosis. Patel BP, Hamadeh MJ. School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada M0J 0P0. BACKGROUND & AIMS: Disease pathogenesis in amyotrophic lateral sclerosis (ALS) involves a number of interconnected mechanisms all resulting in the rapid deterioration of motor neurons. The main mechanisms include enhanced free radical production, protein misfolding, aberrant protein aggregation, excitotoxicity, mitochondrial dysfunction, neuroinflammation and apoptosis. The aim of this review is to assess the efficacy of using nutrition- and exercise-related interventions to improve disease outcomes in ALS. METHODS: Studies involving nutrition or exercise in human and animal models of ALS were reviewed. RESULTS: Treatments conducted in animal models of ALS have not consistently translated into beneficial results in clinical trials due to poor design, lack of power and short study duration, as well as differences in the genetic backgrounds, treatment dosages and disease pathology between animals and humans. However, vitamin E, folic acid, alpha lipoic acid, lyophilized red wine, coenzyme Q00, epigallocatechin gallate, Ginkgo biloba, melatonin, Cu chelators, and regular low and moderate intensity exercise, as well as treatments with catalase and l-carnitine, hold promise to mitigating the effects of ALS, whereas caloric restriction, malnutrition and high-intensity exercise are contraindicated in this disease model. CONCLUSIONS: Improved nutritional status is of utmost importance in mitigating the detrimental effects of ALS. PMID: 00000000 CNS Drugs. 0000;00(00):000-00. The role of creatine in the management of amyotrophic lateral sclerosis and other neurodegenerative disorders. Ellis AC, Rosenfeld J. Carolinas Neuromuscular/ALS Center, Charlotte, North Carolina 00000, USA. amy.ellis@carolinahealthcare.org 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. PMID: 00000000 Amyotroph Lateral Scler. 0000 Oct;0(0):000-00. Creatine monohydrate in ALS: effects on strength, fatigue, respiratory status and ALSFRS. Rosenfeld J, King RM, Jackson CE, Bedlack RS, Barohn RJ, Dick A, Phillips LH, Chapin J, Gelinas DF, Lou JS. The Carolinas Neuromuscular/ALS Center, Charlotte North Carolina, Carolinas Medical Center, USA. Our objective was to determine the effect of creatine monohydrate on disease progression in patients with amyotrophic lateral sclerosis (ALS). One hundred and seven patients with the diagnosis of probable or definite ALS, of less than five years duration from symptom onset, were randomized to either treatment with daily creatine monohydrate (0 g/d) or placebo. In this multicenter, double-blinded study we followed changes in disease progression: using quantitative measures of strength via maximal isometric voluntary contraction, forced vital capacity, ALSFRS, quality of life, fatigue and survival. Patients were followed for nine months. The results showed that creatine monohydrate did not significantly improve motor, respiratory or functional capacity in this patient population. The drug was well tolerated and the study groups well balanced, especially considering the absence of forced vital capacity criteria for entrance into the study. There was a trend toward improved survival in patients taking daily creatine monohydrate and this was identical to the trend seen in another recently published report of creatine in ALS patients 0. In conclusion, creatine monohydrate (0 g/d) did not have an obvious benefit on the multiple markers of disease progression measured over nine months. We measured fatigue during isometric contraction and found no significant improvement despite anecdotal patient reports prior to and during the study. The trend toward improved survival was also found in another recently completed blinded trial using creatine monohydrate. Further investigation on the possible survival benefit of creatine in this patient population is ongoing. PMID: 00000000Dear Dr. Novella, How can you conclude a negative? First you "moderate" my response, then you ignore my plea that you contact the Seattle neurology department (which I am attempting to do on your behalf to see if they have unpublished data), and finally you conclude that I have nothing to offer when I'm only starting.  Please unmoderate my responses unless you have decided to moderate all blog responses. It made me very concerned that you had simply blocked my response and had no intention of engaging in a dialogue. After days of delay, I had given up on you. I just checked back for the first time today.  Before you read further, do you know that over half your patients are likely to be using alternative medicine? How open are you about that discussion?  Do you really expect me to produce high quality studies that you would even consider from the Naturopathic journals? The information we both can use is readily available on medline. But the question is whether or not ALS patients are currently receiving the following:  Megadoses of vitamin E- good safety profile and short term benefits, no long term benefits or long term side effect picture.  If you're doing all of the above, great, but if not, please tell me which ones aren't in current use. I have attached the creatine information. Surely you are supplying patients already?  J Neurol Sci. 0000 Oct 00;000(0-0):000-0. The use of alternative medicine by patients with amyotrophic lateral sclerosis. Wasner M, Klier H, Borasio GD. Department of Neurology and Interdisciplinary Palliative Care Unit, Ludwig Maximilians University, University Hospital, Grosshadern, D-00000, Munich, Germany. The use of complementary and alternative medicine (CAM) is increasing in all industrialised countries, especially in patients with chronic and incurable diseases. However, no data are available on the use of CAM by patients with amyotrophic lateral sclerosis (ALS). The German Association for Neuromuscular Diseases (DGM) mailed out a questionnaire on CAM to 000 ALS patients, 000 of whom completed and returned the survey (response rate 00%). The use of CAM was reported by 00 patients (00%). There were no significant demographic differences between users and nonusers. The patients used 00 different methods or substances; some tried up to 00 different treatments. The most widely used methods were: acupuncture (00%), homeopathy (00%), naturopathy (00%) and esoteric treatments (00%). The lower the patients' expectations from CAM, the better was the subjectively perceived effect. In most cases (00%), alternative treatments were performed by a physician. Patients spent on average 0000 (approximately US$0000) on CAM, generally without reimbursement. CAM is most often used in addition to conventional treatments and may be part of the patients' coping strategy. Open communication between patients and physicians is essential to warn the patients of medically or financially hazardous treatments. Future research should look at the possible palliative effects of CAM on symptom control and quality of life of patients and families. PMID: 00000000 J Herb Pharmacother. 0000;0(0):00-00. The use of herbal supplements and alternative therapies by patients with amyotrophic lateral sclerosis (ALS). Vardeny O, Bromberg MB. University of Winconsin-Madison School of Pharmacy, Madison, WI, USA. OBJECTIVES: Alternative medicine is widely used in all industrialized Western countries. However, there are no published data regarding the use of botanical or herbal supplements in Ayotrophic Lateral Sclerosis (ALS). Our goal was to survey patients with ALS in our clinic regarding their use of herbal supplements, vitamins, and other therapies or compounds. METHODS: Study subjects participated in the University of Utah Motor Neuron Disease Clinic. An anonymous questionnaire was mailed and designed to assess the following: disease duration and onset site, use of riluzole, alternative therapies (i.e., homeopathy, acupuncture), vitamins, herbal supplements, and other compounds, sources of information about herbal supplements or vitamins, estimated monthly expenditure on vitamins, herbal supplements, and other compounds, and expectations from herbal supplements/vitamins. RESULTS: Fifty-three subjects participated; mean age 00 years old (range 00-00 years), 00 females, 00 males. Symptom duration averaged 0-0 years (00 limb onset, 0 bulbar onset). Thirty-two percent took riluzole and 00% used herbal supplements, 00% took vitamins, and 00% used other compounds (prescription medications used for ALS, but not indicated for ALS). Fifteen percent used alternative therapies. Information about herbal medicines was obtained mostly via friends and relatives (n = 00), a physician (n = 00), and the Internet (n = 0). Our patients selected improvement of general well being and slowing of disease progression most often as reasons for using these therapies. CONCLUSIONS: Our study demonstrated that almost half of patients surveyed utilized herbals supplements, and two thirds of ALS study subjects took vitamins. Twenty-one percent used unproven prescription drugs, and 00% used other alternative therapies. PMID: 00000000 Amyotroph Lateral Scler Other Motor Neuron Disord. 0000 Mar;0(0):0-00. A double-blind, placebo-controlled randomized clinical trial of alpha-tocopherol (vitamin E) in the treatment of amyotrophic lateral sclerosis. ALS riluzole-tocopherol Study Group. Desnuelle C, Dib M, Garrel C, Favier A. Service Médecine Physique et de Réadaptation, Maladies Neuromusculaires, CHU de Nice Hĵpital, France. desnuelle.c@chu-nice.fr INTRODUCTION: Increasing evidence suggests that oxidative stress may be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). The antioxidant vitamin E (alpha-tocopherol) has been shown to slow down the onset and progression of paralysis in transgenic mice expressing a mutation in superoxide dismutase found in certain forms of familial ALS. The current study was designed to determine whether alpha-tocopherol (000 mg b.i.d.) may be efficacious in the treatment of ALS. METHODS: Two hundred and eighty-nine patients with ALS of less than 0 years duration, treated with riluzole, were enrolled in this study, and were randomly assigned to receive either alpha-tocopherol or placebo daily for one year. The primary outcome measure was the rate of deterioration of function assessed by the modified Norris limb scale. Patients were assessed at entry, and every 0 months thereafter during the study period. Survival was also recorded. Biochemical markers of oxidative stress were measured in a subset of patients on entry and after 0 months of treatment. RESULTS: After 00 months of treatment, alpha-tocopherol had no effect on the primary outcome measure. Survival was not influenced by treatment. Among secondary outcome measures, patients given alpha-tocopherol were less likely to progress from the milder state A to the more severe state B (P=0.000) of the ALS Health State scale. After 0 months treatment, analysis of oxidative stress markers showed an increase in glutathione peroxidase activity in plasma (P = 0.0000) and a decrease in plasma levels of thiobarbituric acid reactive species (P = 0.0000) in the group of patients given alpha-tocopherol in combination with riluzole. CONCLUSION: Although alpha-tocopherol did not appear to affect the survival and motor function in ALS, patients receiving riluzole plus alpha-tocopherol remained longer in the milder states of the ALS Health State scale and showed, after 0 months, changes in biochemical markers of oxidative stress. Further studies are required to confirm the greater sensitivity of the ALS Health State scale over other clinical endpoints. PMID: 00000000 J Neural Transm. 0000 May;000(0):000-00. Epub 0000 Oct 00. High dose vitamin E therapy in amyotrophic lateral sclerosis as add-on therapy to riluzole: results of a placebo-controlled double-blind study. Graf M, Ecker D, Horowski R, Kramer B, Riederer P, Gerlach M, Hager C, Ludolph AC, Becker G, Osterhage J, Jost WH, Schrank B, Stein C, Kostopulos P, Lubik S, Wekwerth K, Dengler R, Troeger M, Wuerz A, Hoge A, Schrader C, Schimke N, Krampfl K, Petri S, Zierz S, Eger K, Neudecker S, Traufeller K, Sievert M, Neundörfer B, Hecht M; German vitamin E/ALS Study Group.michael.graf@psl.ap-hop-paris.fr Increasing evidence has suggested that oxidative stress may be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). The antioxidant vitamin E (alpha-tocopherol) has been shown to slow down the onset and progression of the paralysis in transgenic mice expressing a mutation in the superoxide dismutase gene found in certain forms of familial ALS. The current study, a double blind, placebo-controlled, randomised, stratified, parallel-group clinical trial, was designed to determine whether vitamin E (0000 mg per day) may be efficacious in slowing down disease progression when added to riluzole. METHODS: 000 patients in 0 German centres with either probable or definite ALS (according to the El Escorial Criteria) and a disease duration of less than 0 years, treated with riluzole, were included in this study and were randomly assigned to receive either alpha-tocopherol (0000 mg per day) or placebo for 00 months. The Primary outcome measure was survival, calculating time to death, tracheostomy or permanent assisted ventilation, according to the WFN-Criteria of clinical trials. Secondary outcome measures were the rate of deterioration of function assessed by the modified Norris limb and bulbar scales, manual muscle testing (BMRC), spasticity scale, ventilatory function and the Sickness Impact Profile (SIP ALS/00). Patients were assessed at entry and every 0 months thereafter during the study period until month 00 and at a final visit at month 00. Vitamin E samples were taken for compliance check and Quality Control of the trial. For Safety, a physical examination was performed at baseline and then every visit until the treatment discontinuation at month 00. Height and weight were recorded at baseline and weight alone at the follow-up visits. A neurological examination as well as vital signs (heart rate and blood pressure), an ECG and VEP's were recorded at each visit. Furthermore, spontaneously reported adverse experiences and serious adverse events were documented and standard laboratory tests including liver function tests performed. For Statistical Analysis, the population to be considered for the primary outcome measure was an "intent-to-treat" (ITT) population which included all randomised patients who had received at least one treatment dose (n = 000 patients). For the secondary outcome measures, a two way analysis of variance was performed on a patient population that included all randomised patients who had at least one assessment after inclusion. RESULTS: Concerning the primary endpoint, no significant difference between placebo and treatment group could be detected either with the stratified Logrank or the Wilcoxon test. The functional assessments showed a marginal trend in favour of vitamin E, without reaching significance. CONCLUSION: Neither the primary nor the secondary outcome measures could determine whether a megadose of vitamin E is efficacious in slowing disease progression in ALS as an add-on therapy to riluzol. Larger or longer studies might be needed. However, administration of this megadose does not seem to have any significant side effects in this patient population. PMID: 00000000 AJNR Am J Neuroradiol. 0000 Nov 00. [Epub ahead of print] White Matter Lesions Suggestive of Amyotrophic Lateral Sclerosis Attributed to Celiac Disease. Brown KJ, Jewells V, Herfarth H, Castillo M. Department of Radiology and Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina. SUMMARY: CD is an autoimmune-mediated disorder of the gastrointestinal tract. Initial symptom presentation is variable and can include neurologic manifestations that may comprise ataxia, neuropathy, dizziness, epilepsy, and cortical calcifications rather than gastrointestinal-hindering diagnosis and management. We present a case of a young man with progressive neurologic symptoms and brain MR imaging findings worrisome for ALS. During the diagnostic work-up, endomysium antibodies were discovered, and CD was confirmed by upper gastrointestinal endoscopy with duodenal biopsies. MR imaging findings suggestive of ALS improved after gluten-free diet institution. PMID: 00000000 Nat Clin Pract Neurol. 0000 Oct;0(00):000-0. A case of celiac disease mimicking amyotrophic lateral sclerosis. Turner MR, Chohan G, Quaghebeur G, Greenhall RC, Hadjivassiliou M, Talbot K. Department of Neurology, John Radcliffe Hospital, Oxford, UK. BACKGROUND: A 00-year-old male presented to a general neurology clinic with a 0-month history of progressive right-sided spastic hemiparesis without sensory symptoms or signs. The thigh muscle in the affected leg showed signs of wasting. The patient had a remote family history of celiac disease. INVESTIGATIONS: Neurological examination, neurophysiological studies, brain MRI scan, routine blood tests, duodenal biopsy, cerebrospinal fluid analysis including polymerase chain reaction test for JC virus DNA, serological testing for HIV and for the presence of serum antibodies to endomysium, gliadin and tissue transglutaminase. DIAGNOSIS: Celiac disease with neurological involvement, mimicking amyotrophic lateral sclerosis. MANAGEMENT: Strict gluten-free diet. PMID: 00000000 Clin Nutr. 0000 Dec;00(0):000-00. Epub 0000 Sep 00.  Nutritional and exercise-based interventions in the treatment of amyotrophic lateral sclerosis. Patel BP, Hamadeh MJ. School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada M0J 0P0. BACKGROUND & AIMS: Disease pathogenesis in amyotrophic lateral sclerosis (ALS) involves a number of interconnected mechanisms all resulting in the rapid deterioration of motor neurons. The main mechanisms include enhanced free radical production, protein misfolding, aberrant protein aggregation, excitotoxicity, mitochondrial dysfunction, neuroinflammation and apoptosis. The aim of this review is to assess the efficacy of using nutrition- and exercise-related interventions to improve disease outcomes in ALS. METHODS: Studies involving nutrition or exercise in human and animal models of ALS were reviewed. RESULTS: Treatments conducted in animal models of ALS have not consistently translated into beneficial results in clinical trials due to poor design, lack of power and short study duration, as well as differences in the genetic backgrounds, treatment dosages and disease pathology between animals and humans. However, vitamin E, folic acid, alpha lipoic acid, lyophilized red wine, coenzyme Q00, epigallocatechin gallate, Ginkgo biloba, melatonin, Cu chelators, and regular low and moderate intensity exercise, as well as treatments with catalase and l-carnitine, hold promise to mitigating the effects of ALS, whereas caloric restriction, malnutrition and high-intensity exercise are contraindicated in this disease model. CONCLUSIONS: Improved nutritional status is of utmost importance in mitigating the detrimental effects of ALS. PMID: 00000000 CNS Drugs. 0000;00(00):000-00. The role of creatine in the management of amyotrophic lateral sclerosis and other neurodegenerative disorders. Ellis AC, Rosenfeld J. Carolinas Neuromuscular/ALS Center, Charlotte, North Carolina 00000, USA. amy.ellis@carolinahealthcare.org 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. PMID: 00000000 Amyotroph Lateral Scler. 0000 Oct;0(0):000-00. Creatine monohydrate in ALS: effects on strength, fatigue, respiratory status and ALSFRS. Rosenfeld J, King RM, Jackson CE, Bedlack RS, Barohn RJ, Dick A, Phillips LH, Chapin J, Gelinas DF, Lou JS. The Carolinas Neuromuscular/ALS Center, Charlotte North Carolina, Carolinas Medical Center, USA. Our objective was to determine the effect of creatine monohydrate on disease progression in patients with amyotrophic lateral sclerosis (ALS). One hundred and seven patients with the diagnosis of probable or definite ALS, of less than five years duration from symptom onset, were randomized to either treatment with daily creatine monohydrate (0 g/d) or placebo. In this multicenter, double-blinded study we followed changes in disease progression: using quantitative measures of strength via maximal isometric voluntary contraction, forced vital capacity, ALSFRS, quality of life, fatigue and survival. Patients were followed for nine months. The results showed that creatine monohydrate did not significantly improve motor, respiratory or functional capacity in this patient population. The drug was well tolerated and the study groups well balanced, especially considering the absence of forced vital capacity criteria for entrance into the study. There was a trend toward improved survival in patients taking daily creatine monohydrate and this was identical to the trend seen in another recently published report of creatine in ALS patients 0. In conclusion, creatine monohydrate (0 g/d) did not have an obvious benefit on the multiple markers of disease progression measured over nine months. We measured fatigue during isometric contraction and found no significant improvement despite anecdotal patient reports prior to and during the study. The trend toward improved survival was also found in another recently completed blinded trial using creatine monohydrate. Further investigation on the possible survival benefit of creatine in this patient population is ongoing. PMID: 00000000  ]]>By: Steven Novellahttp://theness.com/neurologicablog/index.php/homeopaths-on-the-run/comment-page-0/#comment-00000 Steven Novella