Neuroprotective and disease-modifying effects of the ketogenic diet
The publisher's final edited version of this article is available at Behav Pharmacol
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Abstract
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.
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