Glycogenesis

Use of ketogenic diet in "muscle" glycogenosis

Glycogenolysis (GSD) types III, V and VII share a common clinical picture consisting of progressive exercise intolerance, muscle pain and cramps with deterioration of muscle structure that increasingly loses its functional capacity. Underlying this muscle damage is the fact that the enzyme defect in these diseases prevents the proper utilization of carbohydrates to produce energy because the normal activity of glycogenolysis (GSD III and GSD V) or glycolysis (GSD VII) is blocked. In these diseases, however, neoglucogenesis, that is, the ability to produce sugar from other substrates such as protein and fat, is intact.

In addition to muscle, there are also other organs affected, differing according to the type of GSD. In some cases, the damage is due to glycogen accumulation, in others simply due to energy deficiency. While in GSD V only skeletal muscles are involved, in GSD III the liver and/or heart are also affected (there is also a small percentage of patients who have only hepatic involvement), in GSD VII a picture of hemolytic anemia is also observed.

The current recommended treatment for GSD III consists of frequent high-protein meals (protein, through neoglucogenesis, can produce glucose), with raw cornstarch supplementation to avoid hypoglycemia. The diet proposed in GSD type V is rich in carbohydrates to promote hepatic glycogenolysis, which is intact in this disease, and small amounts of sugar-sweetened beverages are recommended before exercise to ensure circulating glucose that can be used by muscle.

Despite currently proposed treatments, clinical observation of patients shows progressive deterioration with increasing age. In the scientific literature, since the 1970s, there are some reports of GSD V patients who had important clinical (improved exercise tolerance) and biochemical (very significant reduction in CPKs) improvements following treatment with hyperlipid/ketogenic diet. Even more reports concern GSD III, where important improvement in cardiomyopathy and exercise tolerance was observed, along with a very marked reduction in muscle biochemical parameters.

The most striking finding, from the point of view of management of the GSD III patient treated with a hyperlipid/ketogenic diet, is that he or she can discontinue the night meal and progressively reduce and then discontinue the raw cornmeal because blood sugar is kept constant even during an 8- to 10-hour overnight fast. Recently, there have been published reviews commenting on the possibility that excess sugar may be harmful in muscle glycogenosis and suggesting that patients should be considered to be treated with high protein and fat and reduce sugars, especially simple sugars, as much as possible.

Although the reports in the literature always concern one or more case reports, reevaluating them all together, these cases constitute good evidence for the effectiveness of the hyperlipid/ketogenic diet in muscle glycogenosis. The aim of the diet is to make sure that the patient always has ketones available, as an alternative energy source to glucose. In this sense, synthetic ketone bodies have been given to patients, but this is a treatment that cannot be continued for a long time because synthetic ketone bodies have very poor palatability.

The ketogenic diet could also be prepared with only natural foods, choosing them from those with a low glycemic index. This, however, would impose major dietary restrictions that would make it difficult to maintain such a diet in the long run. It is necessary, therefore, that patients with muscle glycogenosis, who have to follow the diet for life, should have the most varied choice of ketogenic foods available to them that would enable them to have a sufficiently varied diet that could then be maintained for a long time without difficulty.

The preparations in the trade for the ketogenic diet are therefore indispensable to maintain a palatable diet for a long time and to prevent the patient from abandoning the treatment. I conclude by mentioning that the ketogenic diet should always be supplemented with vitamins and minerals and should be followed closely by an experienced physician and dietitian. The patient on the ketogenic diet should have his or her blood tests checked about every 3 months, and if developmental age, his or her weight and height should be checked at each visit (in fact, cases have been reported in which growth has stunted after starting the ketogenic diet).