Providing alternative fuel for the brain in anorexia nervosa: a review of the literature on ketones and their effects on metabolism and the brain

Recent genetic findings have highlighted the importance of metabolic factors in contributing to risk for anorexia nervosa. The treatment of anorexia nervosa, however, has largely not yet attempted to modulate metabolic pathways, given that knowledge and understanding of potential metabolic targets and treatment goals remain limited. In search of potential metabolic mechanisms at play in psychiatric disorders, we look at the brain and beyond, focusing on ketones, related molecules, and nutritional therapies, e.g. the ketogenic diet, highlighting their brain and behavioural effects. The aim of this review is therefore to summarize knowledge on the physiology of ketones and related molecules, as well as evidence on their role on energy balance, brain, and behaviour. We then review the role ketones might have on the pathophysiology of anorexia nervosa, and how the intake of exogenous ketones and ketone precursors might impact on brain and behaviour in anorexia nervosa. We conclude with an hypothesised model explaining the potential role of ketones in the pathophysiology of anorexia nervosa and propose that exogenous ketones and ketone precursors could be an alternative source of brain energy in this illness and deserve further investigation.