Diet change in the management of metabolic encephalomyopathies.

Abstract

Dietary treatment of mitochondrial disease caused by oxidative metabolic defects has traditionally been limited to the use of ketogenic diets for the treatment of pyruvate dehydrogenase (PDH) deficiency. However, defects in mitochondrial function resulting in a failure of oxidative metabolism can result in a block in the utilization of various food substrates and dietary manipulation might be beneficial. Certain predictions might be made based on the site of particular enzymatic blocks. Some disorders primarily block a particular substrate pathway, such as PDH deficiency which predominantly affects the utilization of carbohydrates and acyl-CoA dehydrogenase deficiencies which predominantly affect fat metabolism. Defects of the terminal electron transport chain, ubiquinone to cytochrome oxidase (COX), affect the ‘final common pathway’ for energy production and might be expected to impair the utilization of all food substrates. In complex I deficiency utilization of carbohydrates which generate NADH, might be expected to be impaired. The β-oxidation of fats produces NADH, ETFred and acetyl-CoA. Reducing equivalents derived from β-oxidation enter the electron transport chain at both site 1 (complex I) and site 2 (ubiquinone). Electron transport defects involving complex I may theoretically benefit from the use of high fat diets as reducing equivalents from ETFred can be introduced through the ETF/ubiquinone pathway from the metabolism of fatty acids. In patients whose lactic acid production is increased by carbohydrate intake, fructose, which is rapidly metabolized to pyruvate, might be less well tolerated than glucose as a food source.