Nutritional Studies Evaluating Ketogenic Diets as a Treatment for Obesity and Obesity-Associated Morbidities: Underlying Mechanisms and Potential for Clinical Implementation

Background: The ketogenic diet (KD), characterized by high-fat content, virtually no carbohydrates, and adequate protein intake, induces a metabolic state resembling fasting, as the absence of carbohydrates forces the body to rely on the energetic supply from hepatically produced ketone bodies using free fatty acids as substrate. While the KD is clinically used in pharmacologically refractory epilepsy and specific genetic conditions such as GLUT1 deficiency, recent research suggests that, due to its “fasting mimicking” properties, the KD may also beneficially affect obesity and obesity-associated metabolic diseases. Results: Here, we present a narrative review discussing completed and ongoing nutritional studies in human volunteers specifically addressing the potential of the ketogenic diet as an anti-obesity approach and, from a larger perspective, as an intervention to ameliorate the metabolic state in conditions such as type 1 and 2 diabetes and polycystic ovary syndrome (PCOS). Published studies as well as ongoing clinical trials will be discussed. Efficacy and safety considerations will be discussed, as well as the potential physiological mechanisms mediating the effects of the KD in humans in the context of the (i) energy balance model (EBM) and (ii) carbohydrate–insulin model (CIM) of body weight control. Conclusion: Ketogenic diets may be beneficial to attenuate obesity and improve obesity-related metabolic disease, and here, we try, based on current evidence, to define the boundaries of the KD’s nutritional and clinical usefulness.