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.