Depot-glucagon in the treatment of McArdle's disease. A double blind, placebo controlled, crossover trial of D-ribose in McArdle's disease. Effect of high-dose creatine therapy on symptoms of exercise intolerance in McArdle disease: double-blind, placebo-controlled crossover study. Creatine therapy in myophosphorylase deficiency (McArdle disease): a placebo-controlled crossover trial. Carbohydrate- and protein-rich diets in McArdle disease: effects on exercise capacity. Oral branched-chain amino acids do not improve exercise capacity in McArdle disease. The effect of oral sucrose on exercise tolerance in patients with McArdle's disease. Chronic therapy for McArdle disease: the randomized trial with ACE inhibitor. Effect of oral sucrose shortly before exercise on work capacity in McArdle disease. Are high-protein diets effective in McArdle's disease?
Glucagon has been reported to improve exercise tolerance in some patients with myophosphorylase deficiency (McArdle's disease) but a placebo effect was not excluded in previous trials. A single-blind controlled trial of glucagon in a patient with myophosphorylase deficiency is described. Although an improved exercise endurance of the forearm muscles was demonstrated with both short-acting and depot-glucagon, this was not statistically significant when compared with placebo or no treatment. To determine whether seven days oral D-ribose would improve exercise tolerance in a group of 5 patients with McArdle's disease, we performed a double blind placebo controlled crossover trial. Subjects performed weekly treadmill exercise tests with expired gas analysis until their times were reproducible. They then received 60 g D-ribose daily or placebo for seven days. Exercise testing was repeated on completion of this period. A seven day washout period then followed. Subjects then performed a new baseline exercise test prior to starting the other solution. Again after seven days the exercise test was repeated. There was no significant difference between pre-treatment exercise tests for peak oxygen consumption or level of leg fatigue. Patients did not like taking the ribose and D-Ribose does not appear to be of benefit to patients with McArdle's disease. In a recent study, we showed that administration of low-dose creatine (Cr) (60 mg/kg daily) improved work capacity in patients with McArdle disease.
                To assess the efficacy of high-dose Cr therapy in McArdle disease.
                Randomized, double-blind, placebo-controlled crossover study.
                Nineteen patients with McArdle disease.
                Treatment with Cr, 150 mg/kg daily. Each treatment phase with Cr or placebo lasted 5 weeks.
                The patient's daily rating of symptoms of exercise intolerance. At the end of each treatment phase, serum creatine and serum creatine kinase levels, phosphorus 31 magnetic resonance spectroscopy, and surface electromyograms were assessed.
                Clinical end points revealed increases in the intensity of exercise-induced pain in working muscles (mean treatment-induced difference [d], 0.30 in log(score); 95% confidence interval [CI], 0.05-0.55; P =.02), the limitation of daily activities (d, 0.59; 95% CI, 0.22-0.97;P =.005), and body mass index (d, 0.33 kg/m2, 95% CI, 0.10-0.56 kg/m2; P =.008) with Cr use. Surface electromyograms revealed a smaller increase in the electromyographic amplitude over time during muscle contraction with Cr use (d, -13.52%/min; 95% CI, -23.71%/min to -3.34%/min; P =.01). There were no significant changes in phosphorus 31 magnetic resonance spectroscopy variables.
                Administration of high-dose Cr worsened the main clinical symptoms of exercise intolerance in McArdle disease. These neurologic adverse effects represent a major dose-limiting factor in Cr therapy for McArdle disease. Taken together with results of a previous study, the indication for symptomatic therapy with Cr needs to be clarified. An effective Cr dosage without adverse effects may be between 60 and 150 mg/kg daily. To determine whether treatment with creatine can improve exercise intolerance in myophosphorylase deficiency (McArdle disease).
                Double-blind, placebo-controlled crossover study with oral creatine monohydrate supplementation.
                Nine patients with biochemically and genetically proven McArdle disease were treated.
                Five days of daily high-dose creatine intake (150 mg/kg body weight) were followed by daily low-dose creatine intake (60 mg/kg). Each treatment phase with creatine or placebo lasted 5 weeks.
                The effect of treatment was estimated at the end of each treatment phase by recording clinical scores, ergometer exercise test results, phosphorus 31 nuclear magnetic resonance spectroscopy, and surface electromyography.
                Of 9 patients, 5 reported improvement of muscle complaints with creatine. Force-time integrals (P =.03) and depletion of phosphocreatine (P =.04) increased significantly during ischemic exercise with creatine. Phosphocreatine depletion also increased significantly during aerobic exercise (P =.006). The decrease of median frequency in surface electromyograms during contraction was significantly larger (P =.03) with creatine.
                This is the first controlled study indicating that creatine supplementation improves skeletal muscle function in McArdle disease. Two single case studies suggest that a protein-rich diet may be beneficial for patients with McArdle disease, based on improvements in either endurance or muscle energetics, as assessed by phosphorous MR spectroscopy. In healthy subjects, proteins contribute very little to energy metabolism during exercise, which questions the effect of protein in McArdle disease.
                In a crossover, open design, we studied seven patients with McArdle disease, who were randomised to follow either a carbohydrate- or protein-rich diet for 3 days before testing. Calorific intake on each diet was identical, and was adjusted to the subject's weight, age and sex. After each diet, exercise tolerance and maximal work capacity were tested on a bicycle ergometer, using a constant workload for 15 minutes followed by an incremental workload to exhaustion.
                During the constant workload, heart rate and perceived exertion were consistently lower (p<0.0005) on the carbohydrate- versus protein-rich diet. Patients also had a 25% improvement in maximal oxidative work capacity on the carbohydrate versus the protein diet.
                This study shows that patients with McArdle disease can improve their maximal work capacity and exercise tolerance to submaximal workloads by maintaining a diet high in carbohydrate instead of protein. The carbohydrate diet not only improves tolerance to everyday activities, but will probably also help to prevent exercise-induced episodes of muscle injury in McArdle disease. To determine whether oral branched-chain amino acids (BCAAs) improve exercise capacity, six fasting patients with McArdle's disease were given a solution of BCAA (77 mg/kg) or a control noncaloric beverage 30 minutes before exercise. The BCAA meal tripled plasma BCAA levels, increased BCAA catabolism as indicated by greater exercise increases in plasma glutamine and alanine, but lowered mean peak free fatty acid levels and reduced exercise capacity in five of six patients. Lower work capacity may be attributed to a net reduction in muscle fuel availability after BCAA administration. Energy metabolism in muscles relies predominantly on the breakdown of glycogen early in exercise. In patients with McArdle's disease, blocked glycogenolysis in muscles results in low exercise tolerance and can lead to muscle injury, particularly in the first minutes of exercise. We hypothesized that ingesting sucrose before exercise would increase the availability of glucose and would therefore improve exercise tolerance in patients with McArdle's disease.
                In a single-blind, randomized, placebo-controlled crossover study, 12 patients with McArdle's disease drank 660 ml of a beverage that had been sweetened with artificial sweeteners (placebo) or with 75 g of sucrose after an overnight fast. Thirty to 40 minutes later, the patients rode a stationary bicycle at a constant workload for 15 minutes while the heart rate, level of perceived exertion, and venous blood glucose levels were monitored.
                Supplemental sucrose increased the mean plasma glucose level by more than 36 mg per deciliter (2.0 mmol per liter) and resulted in a marked improvement in exercise tolerance in all patients. The mean (+/-SE) heart rate dropped by a maximum of 34+/-3 beats per minute (P<0.001), and the level of perceived exertion fell dramatically when the patients ingested glucose as compared with when they received the placebo.
                This study suggests that the ingestion of sucrose before exercise can markedly improve exercise tolerance in patients with McArdle's disease. The treatment takes effect during the time when muscle injury commonly develops in these patients. In addition to increasing the patients' exercise capacity and sense of well-being, the treatment may protect against exercise-induced rhabdomyolysis.
                Copyright 2003 Massachusetts Medical Society nan Oral sucrose (75 g) ingested 40 minutes before exercise improves exercise tolerance in McArdle disease.
                To determine whether a lower dose of sucrose administered closer in time to exercise could have a similar beneficial effect on exercise capacity in patients with McArdle disease.
                Placebo-controlled crossover.
                Neuromuscular Research Unit at the Department of Neurology, Rigshospitalet, Copenhagen, Denmark.
                Six patients with biochemically and genetically diagnosed McArdle disease.
                On separate days, the patients were tested after ingestion of either 75 g of sucrose or a placebo 40 minutes before exercise, or 37 g of sucrose or a placebo 5 minutes before exercise. Patients were blinded to test substances.
                Treatment effectiveness was assessed by monitoring heart rate and perceived exertion during exercise.
                Both sucrose treatments dramatically improved exercise tolerance, compared with the placebo. The low-dose, 5-minute sucrose trial had a more sustained effect on exercise capacity than the 40-minute trial. The more sustained effect was probably related to more continuous glucose uptake from the intestine and correspondingly higher circulating glucose levels later during exercise.
                This study shows that 37 g of sucrose ingested shortly before exercise has a marked and prolonged effect on exercise tolerance in patients with McArdle disease. This treatment is more convenient for the patients and saves more calories than the currently recommended sucrose treatment. nan