Journal of Nutritional Therapeutics, 2015, 4, 137-142 137 E-ISSN: 1929-5634/15 © 2015 Lifescience Global Safety and Efficacy of Long-Term Use of Extended Release Cornstarch Therapy for Glycogen Storage Disease Types 0, III, VI, and IX Katalin M. Ross, Laurie M. Brown, Michelle M. Corrado, Tayoot Chengsupanimit, Latravia M. Curry, Iris A. Ferrecchia, Laura Y. Porras, Justin T. Mathew, Monika Dambska and David A. Weinstein * Glycogen Storage Disease Program, Division of Pediatric Endocrinology, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA Abstract: Background: Impaired glycogen release with fasting results in hypoglycemia in the glycogen storage diseases. A waxy-maize extended release cornstarch was introduced in the United States in 2012 to maintain glucose concentrations during the overnight period, but no studies have assessed the long-term safety and efficacy of this product in the ketotic forms of GSD. Objective: To assess long-term safety and efficacy of modified cornstarch in patients with ketotic forms of GSD. Design: An open label overnight trial of extended release cornstarch was performed. Subjects who had a successful trial (defined as optimal metabolic control lasting 2 or more hours more than with traditional cornstarch) were given the option of continuing into the long-term observational phase. Participants were assessed biochemically at baseline and after 12 months. Results: A total of 16 subjects participated in the open label trial. Efficacy was demonstrated in 100% of the subjects with GSD 0, III, VI, and IX. Of the patients who entered the longitudinal phase, long-term data are available for all subjects. The mean duration of overnight fasting on traditional cornstarch prior to the study for the cohort was 4.9 hours and 9.6 hours on the extended release cornstarch (P < 0.001). All laboratory markers of metabolic control have remained stable in the chronically treated patients. Conclusion: Extended release cornstarch dramatically prolongs the overnight fast duration, maximizes safety from hypoglycemic events, reduces the possibility of sleep deprivation, and improves the quality of life of patients by eliminating the need to awaken without fail for middle of the night therapy without sacrificing metabolic control. Keywords: Glycogen storage disease, uncooked cornstarch, extended release cornstarch, ketotic hypoglycemia. INTRODUCTION The ketotic forms of hepatic glycogen storage diseases are rare, inherited, metabolic disorders characterized by the abnormal storage (GSD 0) or release (GSD III, VI, and IX) of glycogen [1]. Hypoglycemia results from the inability of glycogen to breakdown while fasting. Since gluconeogenesis is intact, however, the extent of hypoglycemia is milder than is seen in type I GSD. Moreover, the patient can be asymptomatic due to the ketone body formation, which the brain can use as a source of energy, but chronic ketosis can result in long-term complications including poor growth, osteoporosis, and hepatic transaminase elevation [2, 3]. Maintaining normal blood glucose concentration is the main goal of treatment for all hepatic forms of GSD. In 1982, uncooked cornstarch therapy was introduced *Address correspondence to this author at the P.O. Box 100296, Gainesville, FL 32610-0296, USA; Tel: (352) 273-5823; Fax: (352) 294-8113; E-mail: weinsda@peds.ufl.edu as an alternative to continuous feeds to prevent hypoglycemia in GSD [4], and it has remained the standard therapy in North America. While some patients with the ketotic forms of GSD can tolerate an overnight fast with cornstarch therapy, many patients require therapy during the hours of sleep to prevent hypoglycemia and ketosis. We previously described the efficacy of an extended release cornstarch therapy for maintaining glucose concentrations during the overnight period in GSD Ia and Ib [5]. In 2009, the extended release waxy-maize cornstarch Glycosade ® (Vitaflo International Ltd, Liverpool, United Kingdom) was approved in Europe for treatment of GSD, and it was released as a medical food in the United States in 2012. This waxy-maize product has been available to patients for several years, but the only publication on the long-term safety and efficacy of the therapy was limited to GSD I [6]. This paper describes our long-term, overnight experience with the extended release cornstarch in a cohort of patients with GSD types 0, III, VI and IX.