Abstract: 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/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. 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. 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.

Plain-language summary: After a wide search, we identified 13 randomised studies that included 85 participants with McArdle disease. This is an update of a review first published in 2004. We found no new trials at this update. The review found no benefit compared with placebo with the following treatments: D-ribose, glucagon, verapamil, vitamin B6, oral branched chain amino acids, dantrolene sodium, high-dose creatine and ramipril. Low dose creatine and ramipril produced minimal benefit for patients who also have the D/D angiotensin converting enzyme (ACE) phenotype. Taking low dose creatine supplements had a minor benefit in improving exercise tolerance in a small number of people with the condition. Taking a sugary drink before planned strenuous exercise can improve performance but this treatment is not practical for day-to-day living. A diet rich in carbohydrate may be superior to a diet rich in protein. Adverse effects were reported in four studies. Oral ribose caused symptoms suggestive of a low blood sugar including light-headedness, hunger and diarrhoea. One study of branched chain amino acids resulted in a deterioration in participants. Dantrolene was reported to cause a number of side-effects including tiredness, sleepiness, dizziness and muscle weakness. Low dose creatine (60 mg/kg/day) did not cause any side-effects but high-dose creatine (150 mg/kg/day) worsened the symptoms of muscle pain. The quality of these studies was low due to the small number of participants; the largest number in one trial was 19 and one trial had only one participant. The evidence is current to August 2014.