Neuroprotective and Disease-Modifying Effects of the Ketogenic Diet

The ketogenic diet is a high-fat content diet in which carbohydrates are nearly eliminated so that the body has minimal dietary sources of glucose. After depleting carbs consumed in food, the body metabolizes body fat, converting it to glucose — which is the true fuel of the body and especially the brain. However the metabolized fat also produces ketones, which are the most efficient fuel for the body and brain. The ketogenic diet has been in clinical use for over 80 years, primarily for the symptomatic treatment of epilepsy.

Quoting from the abstract of this study: “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. “The ketogenic diet is an established and effective nonpharmacological treatment for epilepsy (Vining et al., 1998; Stafstrom, 2004; Sinha and Kossoff, 2005).” Although the diet is useful in people of all ages, clinical experience suggests that it may be more valuable in children, if only because adults have greater difficulty adhering to it. Importantly, the diet is often effective in pharmacoresistant forms of common epilepsies as well as in the difficult to treat catastrophic epilepsy syndromes of infancy and early childhood such as West Syndrome, Lennox–Gastaut Syndrome, and Dravet Syndrome (Crumrine, 2002; Trevathan, 2002; Caraballo et al., 2005).” Recently, there has been interest in the potential of the ketogenic diet in the treatment of neurological disorders other than epilepsy, including Alzheimer’s disease and Parkinson’s disease.” Studies in these neurodegenerative disorders have led to the hypothesis that the ketogenic diet may not only provide symptomatic benefit, but could have beneficial disease-modifying activity applicable to a broad range of brain disorders characterized by the death of neurons.”

Keywords: Alzheimer’s disease, cellular energetics, epilepsy, ketone bodies, ketogenic diet, mitochondria, neuroprotection, Parkinson’s disease, stroke, traumatic brain injury