Until recently, multiple sclerosis has been viewed as an entirely inflammatory disease without acknowledgment of the significant neurodegenerative component responsible for disease progression and disability.
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, Neurodegeneration is thought to underlie the pathogenesis of progressive MS. 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. 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 .
Current treatment options in MS affect immune function and relapse rate with little effect on disease progression. They are sometimes accompanied with significant side effects including lymphopenia, multifocal leukoencephalopathy, and malignancy . Consequently, it may be more favourable for some patients to pursue a relatively risk-free dietary approach that has the potential to reduce disease progression without affecting immune response.
In conclusion, the ketogenic diet deserves further investigation for the purposes of treating progressive MS for which there currently exists no treatment.
Department of Neuro-Ophthalmology, The National Hospital for Neurology and Neurosurgery, London