Multiple acyl-coA dehydrogenase deficiency (MADD) is a rare inherited metabolic condition that reduces the body's ability to break down fats and proteins to produce adenosine triphosphate (ATP; i.e., energy).[1] MADD is caused by mutations in genes involved in mitochondrial electron transfer, which is crucial for energy production.[1] Without appropriate treatment, MADD can cause metabolic acidosis, hypoglycemia (low blood sugar), skeletal abnormalities, myopathy (muscle weakness), fatigue, poor exercise capacity, hepatomegaly (liver enlargement), and cardiomyopathy (heart defects), and it can be fatal.[1]
Standard treatment includes supplementation with riboflavin (vitamin B2) and L-carntine, a high-carbohydrate diet, and the avoidance of fasting.[1] However, a retrospective cohort study of 23 people with MADD found that supplementation with D,L-3-hydroxybutyrate improved cardiomyopathy, liver symptoms, muscle symptoms, and respiratory failure in some of the participants.[2] While this sounds promising, high-quality randomized controlled trials are needed to adequately determine the efficacy of exogenous ketones in the treatment of MADD.