A very low-calorie ketogenic diet (VLCKD) is characterized by low daily caloric intake (less than 800 kcal/day), low carbohydrate intake (<50 g/day) and normoproteic (1–1.5 g of protein/kg of ideal body weight) contents. It induces a significant weight loss and an improvement in lipid parameters, blood pressure, glycaemic indices and insulin sensitivity in patients with obesity and type 2 diabetes mellitus. Cushing’s syndrome (CS) is characterized by an endogenous or exogenous excess of glucocorticoids and shows many comorbidities including cardiovascular disease, obesity, type 2 diabetes mellitus and lipid disorders. The aim of this speculative review is to provide an overview on nutrition in hypercortisolism and analyse the potential use of a VLCKD for the treatment of CS comorbidities, analysing the molecular mechanisms of ketogenesis.

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