Maciej Gasior, Michael A. Rogawski, and Adam L. Hartman
The ketogenic diet has been in clinical use for over 80 years, primarily for the symptomatic treatment of epilepsy. A recent clinical study has raised the possibility that exposure to the ketogenic diet may confer long-lasting therapeutic benefits for patients with epilepsy. Moreover, there is evidence from uncontrolled clinical trials and studies in animal models that the ketogenic diet can provide symptomatic and disease-modifying activity in a broad range of neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease, and may also be protective in traumatic brain injury and stroke. These observations are supported by studies in animal models and isolated cells that show that ketone bodies, especially β-hydroxybutyrate, confer neuroprotection against diverse types of cellular injury. This review summarizes the experimental, epidemiological and clinical evidence indicating that the ketogenic diet could have beneficial effects in a broad range of brain disorders characterized by the death of neurons. Although the mechanisms are not yet well defined, it is plausible that neuroprotection results from enhanced neuronal energy reserves, which improve the ability of neurons to resist metabolic challenges, and possibly through other actions including antioxidant and anti-inflammatory effects. As the underlying mechanisms become better understood, it will be possible to develop alternative strategies that produce similar or even improved therapeutic effects without the need for exposure to an unpalatable and unhealthy, high-fat diet.