The body of scientific literature supporting low-carb and ketogenic diets for numerous health issues is undeniable. Carbohydrate restriction is a powerful dietary therapy for managing blood sugar and insulin in people with type 2 diabetes or metabolic syndrome, for improving the signs and symptoms of PCOS, and for non-alcoholic fatty liver disease NAFLD. An exciting new area for research into the potential therapeutic effects of ketogenic diets is glycogen storage diseases GSDs. There are numerous different types of GSDs, each one caused by abnormalities in a different enzyme or biochemical process. For example, GSD 0 involves deficiency of glycogen synthase, so these patients do not produce glycogen effectively. Most other GSDs have to do with breaking down, accessing, or using glycogen: GSD III is caused by reduced activity of a glycogen debranching enzyme; GSD IX involves deficiency of phosphorylase kinase, which plays a key regulatory role in the breakdown of glycogen. Research suggests that ketogenic diets may be helpful for various forms of GSD. Heterozygous individuals are asymptomatic. Because glycogen breakdown is impaired, local glucose supply to working muscles is limited, which then limits the availability of pyruvate that would have been produced via glycolysis. Limited supply of pyruvate then reduces oxidative phosphorylation and leads to an abnormally low amount of substrate for energy generation via the Krebs cycle. This explains the rapid muscle fatigue and exercise intolerance McArdle patients experience.
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