AbstractUntil recently, multiple sclerosis has been viewed as an entirely inflammatory disease without acknowledgment of the significant neurodegenerative component responsible for disease progression and disability. This perspective is being challenged by observations of a dissociation between inflammation and neurodegeneration where the neurodegenerative component may play a more significant role in disease progression. In this review, we explore the relationship between mitochondrial dysfunction and neurodegeneration in multiple sclerosis. We review evidence that the ketogenic diet can improve mitochondrial function and discuss the potential of the ketogenic diet in treating progressive multiple sclerosis for which no treatment currently exists.
The ketogenic diet has the potential to treat the neurodegenerative component of progressive MS on the basis of the following observations obtained from in vitro and in vivo studies,(1)Neurodegeneration is thought to underlie the pathogenesis of progressive MS.(2)Mitochondrial dysfunction may result in reduced ATP availability. This may promote axonal atrophy, leading to degeneration. There is evidence of mitochondrial dysfunction within “normal appearing” grey matter and mitochondrial function appears to correlate with axonal survival.(3)According to in vitro and animal studies, the ketogenic diet increases ATP production, promotes mitochondrial biogenesis, and bypasses dysfunctional steps within the mitochondrial bioenergetic process, increases antioxidant levels and reduces oxidative damage. Since an increase in ATP and overall improvement in mitochondrial functioning correlates with axonal survival, the ketogenic diet may offer a therapeutic benefit for the neurodegenerative component of MS.These premises are largely theoretical with regard to the contextual application of the ketogenic diet in MS as there is no data currently available on the ketogenic diet from human studies on MS. Animal models of EAE do not accurately represent the underlying pathogenesis of MS, since neurodegeneration does not play a significant role in EAE. Mitochondria-targeting agents, ketones, and the ketogenic diet have however shown positive results in several models of neurodegeneration, and given the complete absence of available treatment for progressive MS, the relatively safe option of a ketogenic diet deserves further investigation in the context of progressive MS.
Despite its high fat component, the ketogenic diet is safe and even beneficial for cardiometabolic risk factors . It has been in continuous use for almost a century for the treatment of epilepsy and has shown good tolerability, even in children . Current ketogenic diet protocols involve a range of options, which encourages patient compliance. Where compliance may pose a challenge, mimicry of various components of the ketogenic pathway through the use of ketone analogues may offer a palatable therapeutic option .
Supplementation with ketones to induce ketosis has also shown an acceptable safety and tolerability profile .
Mithu Storoni and Gordon T. Plant, “The Therapeutic Potential of the Ketogenic Diet in Treating Progressive Multiple Sclerosis,” Multiple Sclerosis International, vol. 2015, Article ID 681289, 9 pages, 2015. doi:10.1155/2015/681289
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Kevin W. Grego
Just a guy who wants to help make the world a healthier, happier place by spreading the word about the amazing benefits of the ketogenic diet and RapidKetosis.