ResearchSpeak & BrainHealth: New Year's resolutions and ketosis

Could intermittent ketosis be a treatment for progressive MS? #ResearchSpeak #BrainHealth #MSBlog #MSResearch

"The Evening Standard ran an article last night on Boris Johnson, our flamboyant London Mayor, and his commitment to a carbohydrate-free diet in January to help raise money for a charity and to improve his health."



"Low-carb diets have been the rage for several decades in various different guises. You may have heard of the Atkins Diet (high-protein low-carb), Dukan Diet (French version of the Atkins diet) and more recently the Banting Diet (high-fat, high-protein, low-carb) and the paleo diet (high-fat, high-protein, low-processed carb). How do they work? They starve the body of sugars and change your metabolism by switching off, or lowering, your circulating levels of insulin. Too much insulin is bad for you and drives the so called metabolic syndrome (truncal obesity, fatty liver, insulin resistance, high cholesterol, hypertension, increased cancer risk, etc.). Interestingly these diets cause you to become ketotic; your body starts making ketones to feed your brain. Ketones may have several benefits to health, including brain health. There is emerging evidence that they may actually reduce your appetite and ketones may be neuroprotective. There is some evidence that ketogenic diets can improve mitochondrial function (see hypothesis paper below). Neurologists have also known for decades that some forms of epilepsy are ketone responsive and we treat patients with specific epilepsy syndromes using ketogenic diets. The metabolic changes that underlie ketosis include the rapid mobilisation of fats from adipose tissue, which is why these diets are so effective at causing rapid weight loss. Interestingly, the so called 5:2 diet (another UK fad) in which you fast for 2 days of the week may also work via intermittent ketosis."

"How is this all relevant to MS? There is some evidence that ketosis may be neuroprotective in an animal model of MS and the hypothesis paper below makes the case for ketogenic diets as a potential treatment of progressive MS. Interesting? I think so, which is why we are in the process of reviewing the literature on the topic to see if we can study the underlying biology."

"At a personal level I am almost tempted to give intermittent ketosis a try to see how it makes me feel; losing weight and getting fit is part of my Brain Health drive. How is your Brain Health initiative going? From an evolutionary perspective intermittent ketosis was probably the norm for our ancestors; i.e. intermittent feasts and famines. Therefore it is likely that our bodies evolved with intermittent ketosis. The change in our dietary habits, in particular high-carbohydrate diets, is one of the reasons underlying the global obesity and diabetes epidemic. May be we should all be thinking about how we cut down on eating processed carbohydrates?"

"Will it be easy going onto an intermittent ketosis diet? Definitely not. I am acutely aware from my time as a neurology trainee that the hardest thing for patients with epilepsy to do was to stick to their ketogenic diets. I suspect in the long term dietary manipulation is not the way to go, but as with all things biological we may be able to drug the biology; I am sure Pharma are on the case already. If any funders are reading this post can I suggest you host a meeting on the topic and may be put out a funding call to research intermittent ketosis as a potential treatment for progressive MS. I know there is an unmet need; not a week goes by without one of my patients asking me about one of these diets. With no evidence all I can say is I don't know."



Storoni & Plant. The Therapeutic Potential of the Ketogenic Diet in Treating Progressive Multiple Sclerosis. Multiple Sclerosis International. Volume 2015 (2015), Article ID 681289, 9 pages.

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. 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.

Kim et al. Inflammation-mediated memory dysfunction and effects of a ketogenic diet in a murine model of multiple sclerosis. PLoS One. 2012;7(5):e35476. doi: 10.1371/journal.pone.0035476.

A prominent clinical symptom in multiple sclerosis (MS), a progressive disorder of the central nervous system (CNS) due to heightened neuro-inflammation, is learning and memory dysfunction. Here, we investigated the effects of a ketogenic diet (KD) on memory impairment and CNS-inflammation in a murine model of experimental autoimmune encephalomyelitis (EAE), using electrophysiological, behavioral, biochemical and in vivo imaging approaches. Behavioral spatial learning deficits were associated with motor disability in EAE mice, and were observed concurrently with brain inflammation. The KD improved motor disability in the EAE model, as well as CA1 hippocampal synaptic plasticity (long-term potentiation) and spatial learning and memory (assessed with the Morris Water Maze). Moreover, hippocampal atrophy and periventricular lesions in EAE mice were reversed in KD-treated EAE mice. Finally, we found that the increased expression of inflammatory cytokines and chemokines, as well as the production of reactive oxygen species (ROS), in our EAE model were both suppressed by the KD. Collectively, our findings indicate that brain inflammation in EAE mice is associated with impaired spatial learning and memory function, and that KD treatment can exert protective effects, likely via attenuation of the robust immune response and increased oxidative stress seen in these animals.


Disclaimer: I am not promoting anyone of these diets as a treatment for MS; the concepts behind these diets are in relation to general health and their potential to improve brain health.

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