Acute ketone supplementation in the absence of muscle glycogen utilization: Insights from McArdle disease.

BACKGROUND & AIMS: Ketone supplementation is gaining popularity. Yet, its effects on exercise performance when muscle glycogen cannot be used remain to be determined. McArdle disease can provide insight into this question, as these patients are unable to obtain energy from muscle glycogen, presenting a severely impaired physical capacity. We therefore aimed to assess the effects of acute ketone supplementation in the absence of muscle glycogen utilization (McArdle disease). METHODS: In a randomized cross-over design, patients with an inherited block in muscle glycogen breakdown (i.e., McArdle disease, n = 8) and healthy controls (n = 7) underwent a submaximal (constant-load) test that was followed by a maximal ramp test, after the ingestion of a placebo or an exogenous ketone ester supplement (30 g of D-beta hydroxybutyrate/D 1,3 butanediol monoester). Patients were also assessed after carbohydrate (75 g) ingestion, which is currently considered best clinical practice in McArdle disease. RESULTS: Ketone supplementation induced ketosis in all participants (blood [ketones] = 3.7 ± 0.9 mM) and modified some gas-exchange responses (notably increasing respiratory exchange ratio, especially in patients). Patients showed an impaired exercise capacity (-65 % peak power output (PPO) compared to controls, p < 0.001) and ketone supplementation resulted in a further impairment (-11.6 % vs. placebo, p = 0.001), with no effects in controls (p = 0.268). In patients, carbohydrate supplementation resulted in a higher PPO compared to ketones (+21.5 %, p = 0.001) and a similar response was observed vs. placebo (+12.6 %, p = 0.057). CONCLUSIONS: In individuals who cannot utilize muscle glycogen but have a preserved ability to oxidize blood-borne glucose and fat (McArdle disease), acute ketone supplementation impairs exercise capacity, whereas carbohydrate ingestion exerts the opposite, beneficial effect.

Repeated oral sucrose dosing after the second wind is unnecessary in patients with McArdle disease: Results from a randomized, placebo-controlled, double-blind, cross-over study.

It is well-established that oral sucrose ingested shortly before exercise improves early exercise tolerance in individuals with McArdle disease. This is by supplying blood-borne glucose for muscle metabolism to compensate for the blocked glycogenolysis. The present study investigated if individuals with McArdle disease could benefit further from repeated sucrose ingestion during prolonged exercise. In this double-blind, placebo-controlled, cross-over study, the participants were randomized to ingest either sucrose or placebo first and subsequently the opposite on two separate days. The participants ingested the drink 10 min before and thrice (after 10, 25, and 40 min) during a 60-min submaximal exercise test on a cycle ergometer. The primary outcome was exercise capacity as indicated by heart rate (HR) and perceived exertion (PE) responses to exercise. Secondary outcomes included changes in blood metabolites, insulin and carbohydrate, and fatty acid oxidation rates during exercise. Nine participants with McArdle disease were included in the study. We confirmed improvement of exercise capacity with oral sucrose vs. placebo during early exercise (pre-second wind) indicated by lower peak HR and PE (p < 0.02). We found no further beneficial effect with repeated sucrose versus placebo ingestion during prolonged exercise, as indicated by no difference in HR or PE post-second wind (p > 0.05). Glucose, lactate, insulin, and carbohydrate oxidation rates increased, and fatty acid oxidation decreased with sucrose versus placebo (p ≤ 0.0002). We can conclude that repeated sucrose ingestion is not recommended during prolonged exercise. This finding can prevent excessive caloric intake and reduce the risk of obesity and insulin resistance.

No effect of oral ketone ester supplementation on exercise capacity in patients with McArdle disease and healthy controls: A randomized placebo-controlled cross-over study.

Patients with glycogen storage disease type V (GSDV), also known as McArdle disease, have blocked glycogen breakdown due to myophosphorylase deficiency, leading to exercise intolerance, muscle pain, and risk of muscle damage. Blood-derived ketone bodies (KBs) constitute an alternative energy source that could fuel the muscle independent of glycogenolysis. However, except for long-time fasting or ketogenic dieting, KBs are present in low quantities. This led us to explore the effects of a drink containing exogenously produced KBs in the form of D-ß-hydroxybutyrate esters (KE) on exercise capacity and metabolism in patients with GSDV. Eight GSDV patients and four healthy controls (HC) were included in this placebo-controlled, cross-over study where subjects were randomized to receive a KE drink with 395 mgKE/kg or placebo drink on two separate days 25 min before a submaximal cycle exercise test. The primary outcome was exercise capacity as indicated by heart rate response (HR) to exercise. Secondary outcomes included perceived exertion (PE) and measures of KB, carbohydrate, and fat metabolism during exercise. In GSDV, the KE drink vs. placebo increased plasma KBs and KB oxidation (p ≤ 0.0001) but did not improve exercise capacity as judged from HR (p = 0.120) and PE (p = 0.109). In addition, the KE drink lowered plasma glucose, free fatty acids, and lowered lipolytic rate and glucose rate of appearance compared with placebo. Similar results were found in the HC group. The present study indicates that an increase in KB oxidation by oral KE supplementation does not improve exercise capacity in GSDV possibly because of KB-induced inhibition of lipolysis and liver glucose output. Thus, oral KE supplementation alone cannot be recommended as a treatment option for patients with GSDV.

Exercise therapy for muscle and lower motor neuron diseases.

Muscle and lower motor neuron diseases share a common denominator of perturbed muscle function, most often related to wasting and weakness of muscles. This leads to a number of challenges, such as restricted mobility and respiratory difficulties. Currently there is no cure for these diseases. The purpose of this review is to present research that examines the effects of exercise in muscle and lower motor neuron diseases. Evidence indicates that moderate intensity aerobic- and strength exercise is advantageous for patients with muscle diseases, without causing harmful exercise-induced muscle damage. On the contrary, motor neuron diseases show a rather blunted response from exercise training. High-intensity training is a modality that seems safe and a promising exercise method, which may circumvent neural fatigue and provide effect to patients with motor neuron disease. Although we have come far in changing the view on exercise therapy in neuromuscular diseases to a positive one, much knowledge is still needed on what dose of time, intensity and duration should be implemented for different disease and how we should provide exercise therapy to very weak, non-ambulatory and wheelchair bound patients.

Missense mutations have unexpected consequences: The McArdle disease paradigm.

McArdle disease is a disorder of muscle glycogen metabolism caused by mutations in the PYGM gene, encoding for the muscle-specific isoform of glycogen phosphorylase (M-GP). The activity of this enzyme is completely lost in patients' muscle biopsies, when measured with a standard biochemical test which, does not allow to determine M-GP protein levels. We aimed to determine M-GP protein levels in the muscle of McArdle patients, by studying biopsies of 40 patients harboring a broad spectrum of PYGM mutations and 22 controls. Lack of M-GP protein was found in muscle in the vast majority (95%) of patients, irrespective of the PYGM genotype, including those carrying missense mutations, with few exceptions. M-GP protein biosynthesis is not being produced by PYGM mutations inducing premature termination codons (PTC), neither by most PYGM missense mutations. These findings explain the lack of PYGM genotype-phenotype correlation and have important implications for the design of molecular-based therapeutic approaches.

Exercise and Preexercise Nutrition as Treatment for McArdle Disease.

McArdle disease is due to an inborn defect in the muscle isoform of glycogen phosphorylase (or "myophosphorylase"), the enzyme that catalyzes the first step of glycogenolysis. This condition is still not fully understood, and although advances in research would help patients immeasurably, these would also enhance our understanding of exercise metabolism. It has been 10 yr since the first published report demonstrating the benefits of regular aerobic exercise for these patients. However, misconceptions remain and the value of exercise prescription for patients with McArdle disease is still overlooked. Here, we review the role of exercise in McArdle disease with the aim to better inform health-care professionals and thus better serve the interests of patients. Recommendations for regular exercise together with preexercise nutrition in children and adult patients are also provided along with examples of exercise practice and its benefits.

Pharmacological and nutritional treatment for McArdle disease (Glycogen Storage Disease type V).

Background McArdle disease (Glycogen Storage Disease type V) is caused by an absence of muscle phosphorylase leading to exercise intolerance,myoglobinuria rhabdomyolysis and acute renal failure. This is an update of a review first published in 2004.Objectives To review systematically the evidence from randomised controlled trials (RCTs) of pharmacological or nutritional treatments for improving exercise performance and quality of life in McArdle disease.Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE on 11 August 2014.Selection criteria We included RCTs (including cross-over studies) and quasi-RCTs. We included unblinded open trials and individual patient studies in the discussion. Interventions included any pharmacological agent or nutritional supplement. Primary outcome measures included any objective assessment of exercise endurance (for example aerobic capacity (VO2) max, walking speed, muscle force or power and fatigability). Secondary outcome measures included metabolic changes (such as reduced plasma creatine kinase and a reduction in the frequency of myoglobinuria), subjective measures (including quality of life scores and indices of disability) and serious adverse events.Data collection and analysis Three review authors checked the titles and abstracts identified by the search and reviewed the manuscripts. Two review authors independently assessed the risk of bias of relevant studies, with comments from a third author. Two authors extracted data onto a specially designed form.Main results We identified 31 studies, and 13 fulfilled the criteria for inclusion. We described trials that were not eligible for the review in the Discussion. The included studies involved a total of 85 participants, but the number in each individual trial was small; the largest treatment trial included 19 participants and the smallest study included only one participant. There was no benefit with: D-ribose,glucagon, verapamil, vitamin B6, branched chain amino acids, dantrolene sodium, and high-dose creatine. Minimal subjective benefit was found with low dose creatine and ramipril only for patients with a polymorphism known as the D/Dangiotens in converting enzyme(ACE) phenotype. A carbohydrate-rich diet resulted in better exercise performance compared with a protein-rich diet. Two studies of oral sucrose given at different times and in different amounts before exercise showed an improvement in exercise performance. Four studies reported adverse effects. Oral ribose caused diarrhoea and symptoms suggestive of hypoglycaemia including light-headedness and hunger. In one study, branched chain amino acids caused a deterioration of functional outcomes. Dantrolene was reported to cause a number of adverse effects including tiredness, somnolence, dizziness and muscle weakness. Low dose creatine (60 mg/kg/day) did not cause side-effects but high-dose creatine (150 mg/kg/day) worsened the symptoms of myalgia.Authors' conclusions Although there was low quality evidence of improvement in some parameters with creatine, oral sucrose, ramipril and a carbohydrate rich diet, none was sufficiently strong to indicate significant clinical benefit.

[A case of acute renal failure secondary to late-onset McArdle's disease]. / Un caso di insufficienza renale acuta secondaria a malattia di McArdle ad esordio tardivo.

INTRODUCTION: Mc Ardles disease, also known as Type V glycogen storage disease, is a rare deficiency of the enzyme glycogen phosphorylase in muscle cells, inherited as an autosomal recessive trait. In the absence of this enzyme, muscles cannot break down glycogen during exercise, so in patients affected by McArdles disease even moderate physical activity produces cramps, pain and fatigue. Anaerobic activity leads to severe fixed contractures and rhabdomyolisis with myoglobinuria and raised serum creatine-kinase, which, in turn, can lead to acute renal failure. Disease onset is usually in early childhood, although diagnosis is often not made until the second or third decade. CASE REPORT: We present the case of a 68-year-old man who presented to the Emergency Room with fatigue, vertigo, diarrhea and oliguria. The patient underwent five daily hemodialysis sessions, diuresis reappeared and there was progressive recovery of renal function. The patient described episodes of fatigue and muscular pain occurring since childhood: the positive personal history, together with persistently raised CPK levels in the absence of any infective or toxic cause of myositis, led us to suspect the presence of this rare metabolic disease, which was subsequently confirmed by muscle biopsy. CONCLUSION: To date, there is no specific treatment for type V glycogenosis, although a diet rich in protein and saccarose, vitamin B6 supplementation and creatine administration are generally recommended. Moderate physical activity can help manage symptoms by improving exercise tolerance and blood supply to the muscles, ensuring provision of glucose and free fatty acids for the muscle fibers.

Resistance (weight lifting) training in an adolescent with McArdle disease.

Owing to the risk of severe rhabdomyolysis, clinicians advise McArdle disease patients to refrain from strenuous exercise, particularly weight lifting. A 15-year-old male McArdle disease patient performed a 6-week, supervised, light- to moderate-intensity (~65-70% of one-repetition-maximum) resistance (weight lifting) training program (2 sessions/week). Training resulted in ~27% and ~6% increase in one-repetition-maximum bench press and multipower squat performance while inducing no myoglobinuria. The patient changed to a lower disease severity class, that is, he became virtually asymptomatic in terms of exercise limitations. The authors' preliminary data suggest that supervised, light to moderate resistance training is feasible in children with McArdle disease and has potential clinical benefits.

Confirmation of the efficacy of vitamin B6 supplementation for McArdle disease by follow-up muscle biopsy.

No effective treatment for McArdle disease exists.We report a Japanese patient with McArdle disease who was treated with vitamin B(6) supplementation (60-90 mg/day). After treatment, increased muscle phosphorylase activity was confirmed by follow-up muscle biopsy (3.8 times higher than pretreatment levels). Increased lactate levels were seen on the forearm exercise test, and regular work activities could be resumed. Vitamin B(6) supplementation can enhance residual phosphorylase activity and improve insufficient anaerobic glycolysis of skeletal muscle.

Pharmacological and nutritional treatment for McArdle disease (Glycogen Storage Disease type V).

BACKGROUND: McArdle disease (Glycogen Storage Disease type V) is caused by an absence of muscle phosphorylase leading to exercise intolerance, myoglobinuria rhabdomyolysis and acute renal failure. OBJECTIVES: To review systematically the evidence from randomized controlled trials of pharmacological or nutritional treatments for improving exercise performance and quality of life in McArdle disease. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Specialised Register (17 May 2010), the Cochrane Central Register of Controlled Trials (Issue 2, 2010 in The Cochrane Library), MEDLINE (January 1966 to May 2010) and EMBASE (January 1980 to May 2010) using the search terms 'McArdle disease', 'Glycogen Storage Disease type V' and 'muscle phosphorylase deficiency'. SELECTION CRITERIA: We included randomized controlled trials (including cross-over studies) and quasi-randomised trials. Unblinded open trials and individual patient studies were included in the discussion. Interventions included any pharmacological agent or nutritional supplement. Primary outcome measures included any objective assessment of exercise endurance (for example aerobic capacity (VO(2)) max, walking speed, muscle force or power and fatigability). Secondary outcome measures included metabolic changes (such as reduced plasma creatine kinase and a reduction in the frequency of myoglobinuria), subjective measures (including quality of life scores and indices of disability) and serious adverse events. DATA COLLECTION AND ANALYSIS: Three review authors checked the titles and abstracts identified by the search and reviewed the manuscripts. In the first review two authors (RQ and RB) independently assessed methodological quality of relevant studies and extracted data onto a specially designed form. In this update methodological quality of data was assessed by RQ and AM with comments from BS. MAIN RESULTS: We identified 31 studies,13 fulfilled the criteria for inclusion. Excluded trials are included in the Discussion. The largest treatment trial included 19 subjects. There was no benefit with: D-ribose, glucagon, verapamil, vitamin B(6), branched chain amino acids, dantrolene sodium, and high dose creatine. Minimal benefit was found with low dose creatine and ramipril only for patients with a polymorphism known as the D/D angiotensin converting enzyme (ACE) phenotype. A carbohydrate-rich diet resulted in better exercise performance compared with a protein-rich diet. Two studies of oral sucrose given at different times and in different amounts before exercise showed an improvement in exercise performance. AUTHORS' CONCLUSIONS: Although there was low quality evidence of improvement in some parameters with creatine, oral sucrose, ramipril and a carbohydrate rich diet, none was sufficiently strong to indicate significant clinical benefit.

Pharmacological and nutritional treatment for McArdle disease (Glycogen Storage Disease type V).

BACKGROUND: McArdle disease (Glycogen Storage Disease type V) is caused by the absence of the glycolytic enzyme, muscle phosphorylase. People present with exercise-induced pain, cramps, fatigue, and myoglobinuria, which can result in acute renal failure if it is severe. OBJECTIVES: To systematically review the evidence from randomised controlled trials of pharmacological or nutritional treatments in improving exercise performance and quality of life in McArdle disease. SEARCH STRATEGY: We updated the review by searching the Cochrane Neuromuscular Disease Group Trials Register (November 2007), MEDLINE (January 1966 to November 2007) and EMBASE (January 1980 to November 2007) using the search terms 'McArdle disease' and its synonym 'Glycogen Storage Disease type V'. SELECTION CRITERIA: We included randomised controlled trials (including crossover studies) and quasi-randomised trials. Open trials and individual patient studies with no participant or observer blinding were included in the discussion. Types of interventions included any pharmacological agent or micronutrient or macronutrient supplementation. Primary outcome measures included any objective assessment of exercise endurance (for example aerobic capacity (VO(2)) max, walking speed, muscle force or power and improvement in fatiguability). Secondary outcome measures included metabolic changes (such as reduced plasma creatine kinase activity and a reduction in the frequency of myoglobinuria), subjective measures (including quality of life scores and indices of disability) and serious adverse events. DATA COLLECTION AND ANALYSIS: Three review authors checked the titles and abstracts identified by the search and reviewed the manuscripts. Two review authors (RQ and RB) independently assessed methodological quality of the full text of potentially relevant studies and extracted data onto a specially designed form. MAIN RESULTS: We reviewed 24 studies. Twelve trials fulfilled the criteria for inclusion, with two being first identified in this update. The 12 excluded trials are included in the discussion. The largest treatment trial included 19 cases. The other trials included fewer than 12 cases. As there were only single trials for a given intervention we were unable to undertake a meta-analysis. AUTHORS' CONCLUSIONS: There is no evidence of significant benefit from any specific nutritional or pharmacological treatment in McArdle disease. In one small trial low dose creatine produced slight benefit but high dose creatine caused myalgia. Ingestion of oral sucrose immediately before exercise reduced perceived ratings of exertion and heart rate and improved exercise tolerance. This treatment will not influence sustained or unexpected exercise and may cause significant weight gain. A carbohydrate rich diet did benefit patients. Because of the rarity of McArdle disease, there is a need to develop international multicentre collaboration and standardised assessment protocols for future treatment trials.

Pharmacological and nutritional treatment trials in McArdle disease.

A systematic review of evidence for randomised controlled trials using pharmacologic and nutritional therapies in McArdle disease was undertaken. Primary outcome measures included any objective assessment of exercise endurance. Secondary outcome measures included changes in metabolic parameters, subjective measures such as quality of life scores and adverse outcomes. Ten randomised controlled trials were identified. Two trials low dose creatine (60 mg/kg/day) and oral sucrose 75 g prior to exercise demonstrated a positive effect.

Treatment of glycogenosys type V (McArdle disease) with creatine and ketogenic diet with clinical scores and with 31P-MRS on working leg muscle.

McArdle's disease is caused by genetic defects of the muscle-specific isozyme of glycogen phosphorylase, which block ATP formation from glycogen in skeletal muscle. Creatine supplementation and ketogenic diet have been tested as potential supplements for muscle energy metabolism which may improve muscle symptomatic. Outcome measures were clinical scores describing muscle symptomatic and parameters derived from 31P-MRS examinations on working muscle. In two placebo controlled cross-over studies low dose creatine showed beneficial effects on muscle symptoms and performance whereas high dose creatine distinctly worsened muscle symptomatic in patients. In both studies, however, the absence of an elevation in phosphocreatine indicated the absence of a creatine uptake by the muscle fibre. The effects of creatine on muscle symptomatic may be independent from energy metabolism in muscle. In a case study, ketogenic diet improved muscle symptomatic and performance. However, these effects again did not result in 31P-MRS visible changes in muscle energy metabolism.

Clinical use of creatine in neuromuscular and neurometabolic disorders.

Many of the neuromuscular (e.g., muscular dystrophy) and neurometabolic (e.g., mitochondrial cytopathies) disorders share similar final common pathways of cellular dysfunction that may be favorably influenced by creatine monohydrate (CrM) supplementation. Studies using the mdx model of Duchenne muscular dystrophy have found evidence of enhanced mitochondrial function, reduced intra-cellular calcium and improved performance with CrM supplementation. Clinical trials in patients with Duchenne and Becker's muscular dystrophy have shown improved function, fat-free mass, and some evidence of improved bone health with CrM supplementation. In contrast, the improvements in function in myotonic dystrophy and inherited neuropathies (e.g., Charcot-Marie-Tooth) have not been significant. Some studies in patients with mitochondrial cytopathies have shown improved muscle endurance and body composition, yet other studies did not find significant improvements in patients with mitochondrial cytopathy. Lower-dose CrM supplementation in patients with McArdle's disease (myophosphorylase deficiency) improved exercise capacity, yet higher doses actually showed some indication of worsened function. Based upon known cellular pathologies, there are potential benefits from CrM supplementation in patients with steroid myopathy, inflammatory myopathy, myoadenylate deaminase deficiency, and fatty acid oxidation defects. Larger randomized control trials (RCT) using homogeneous patient groups and objective and clinically relevant outcome variables are needed to determine whether creatine supplementation will be of therapeutic benefit to patients with neuromuscular or neurometabolic disorders. Given the relatively low prevalence of some of the neuromuscular and neurometabolic disorders, it will be necessary to use surrogate markers of potential clinical efficacy including markers of oxidative stress, cellular energy charge, and gene expression patterns.

Pharmacological and nutritional treatment for McArdle's disease (Glycogen Storage Disease type V).

BACKGROUND: McArdle's disease (Glycogen Storage Disease type V) is caused by the absence of the glycolytic enzyme, muscle phosphorylase. Patients present with exercise-induced pain, cramps, fatigue, myoglobinuria and acute renal failure, which can ensue if the myoglobinuria is severe. OBJECTIVES: To systematically review the evidence from randomised controlled trials of pharmacological or nutritional treatments in improving exercise performance and quality of life in McArdle's disease. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group register (searched December 2001 and updated in December 2003), MEDLINE (January 1966 to December 2003) and EMBASE (January 1980 to December 2003) using the search term 'McArdle's disease and it's synonym 'Glycogen Storage Disease type V'. SELECTION CRITERIA: We included randomised controlled trials (including crossover studies) and quasi-randomised trials. Open trials and individual patient studies with no patient or observer blinding were included in the discussion but not the review. Types of interventions included any pharmacological agent or micronutrient or macronutrient supplementation. Primary outcome measures included any objective assessment of exercise endurance (for example VO2 max, walking speed, muscle force/power and improvement in fatiguability). Secondary outcome measures included metabolic changes (such as reduced plasma creatine kinase activity and a reduction in the frequency of myoglobinuria); subjective measures (including quality of life scores and indices of disability); and serious adverse events. DATA COLLECTION AND ANALYSIS: Two reviewers checked the titles and abstracts identified by the search, independently assessed methodological quality of the full text of potentially relevant studies and extracted data onto a specially designed form. MAIN RESULTS: We reviewed 20 trials. Ten trials fulfilled the criteria for inclusion and ten trials were included in the discussion. The largest treatment trial included 19 cases, the other trials included fewer than 12 cases. As there were only single trials for a given intervention we were unable to undertake a meta-analysis. REVIEWERS' CONCLUSIONS: It is not yet possible to recommend any specific treatment for McArdle's disease. Low dose creatine supplementation was shown to demonstrate a statistically significant benefit, albeit modest, in ischaemic exercise in a small number of patients. Ingestion of oral sucrose immediately prior to exercise reduces perceived ratings of exertion and heart rate and improves exercise tolerance. This treatment will not influence sustained or unexpected exercise and may cause significant weight gain. Because of the rarity of McArdle's disease, there is a need to develop multicentre collaboration and standardised assessment protocols for future treatment trials.

Exercise to exhaustion in the second-wind phase of exercise in a case of McArdle's disease with and without creatine supplementation.

The cardio-pulmonary and biochemical changes observed in a case of McArdle's disease, exercising with increasing work rates to exhaustion in the "second-wind" phase of exercise are reported for the first time. A work rate of 275-325 watts was achieved. Venous blood lactate remained unchanged throughout. The plasma ammonium level reached a plateau of approximately 400 mmol/l at 100 watts. At a work rate of 150-175 watts the ratio of O2 consumption to CO2 production increased, the inverse of an anaerobic threshold. Maximal cardiopulmonary responses were achieved at 200 watts. During the final periods of exercise from 200 to 275/325 watts pulmonary ventilation did not significantly change but there was a decrease in the venous blood H+ concentration, and pO2 and in increase in the pCO2. Creatine supplementation at 25 g/day for five days did not improve exercise performance.

Effect of vitamin B6 supplementation in McArdle's disease: a strategic case study.

A patient-blind study into the effect of a 10-week cessation of long-term vitamin B6 supplementation on B6 status and performance in McArdle's disease is reported. Muscle performance was assessed both subjectively and objectively by an ischaemic fatiguing protocol of the adductor pollicis muscle. Nine weeks after withdrawal of supplementation, vitamin B6 status had changed from adequacy to inadequacy and the force loss during the ischaemic fatiguing protocol had increased at all frequencies studied. The patient reported decreased exercise tolerance after 7 weeks and by the tenth week was experiencing an increase in muscle cramps. Vitamin B6 status and muscle performance may be linked in McArdle's disease and there is potential for enhancement of performance by B6 supplementation.

[31P-mr spectroscopy of peripheral skeletal musculature under load: demonstration of normal energy metabolites compared with metabolic muscle diseases]. / 31P-MR-Spektroskopie der peripheren Skelettmuskulatur unter Belastung: Darstellung des normalen Energiestoffwechsels im Vergleich zu metabolischen Muskelerkrankungen.

PURPOSE: 31P-MR spectroscopy of skeletal muscle under exercise was used to obtain the range of normal variation and comparison was made for different neuromuscular diseases. METHODS: 41 examinations of 24 volunteers and 41 investigations in 35 patients were performed on 1.5 T MR systems (Gyroscan 515 und S15/ACSII, Philips). Localised 31P-MR spectra of the calf muscle were obtained in time series with a resolution of 12 s. RESULTS: Two types of muscle energy metabolism were identified from the pattern of spectroscopic time course in volunteers: While the first group was characterised by a remarkable decline to lower pH values during exercise, the second group showed only small pH shifts (minimum pH: 6.48 +/- 0.13 vs 6.87 +/- 0.07, p < 10(-6)) although comparable workload conditions were maintained. The pH-values correlated well with blood lactate analysis. Patients with metabolic disorders and chronic fatigue syndrome (CFS) showed decreased resting values of PCr/(PCr + Pi) and increased pH levels during exercise. PCr recovery was significantly delayed (0.31 vs 0.65 min-1, p < 0.00005) in metabolic muscle disorders but was normal in CFS patients. CONCLUSION: Findings in volunteers indicate utilisation of different metabolic pathways which seems to be related to the fibre type composition of muscle. Reduced resting levels for PCr/(PCr + Pi), altered pH time courses, and decreased PCr recovery seem to be helpful indicators for diagnosis of metabolic muscle disorders.