Tuesday, 5 January 2016

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.


  1. Hi Prof G.

    I did the Swank diet for a while and in as far as my MS goes it was a REAL significant difference. My attention span was tighter and more focal. I had much more energy .vs. bout's of MS fatigue. My cognition improved via that tighter attention span. Short term memory was better. It was a huge difference.

    The problem is no matter what I tried I could not maintain weight. In one month I dropped 32 lbs. for example. So I basically modified it and now short of the holidays when I slam a some pounds on I keep it stable. But some of the positive impacts I had with Swank have I believe not been as profound. I am still experimenting. Every person being different hard to pin things down. I take Tecfidera, LDN, Baclofen, Vitamin D, A womens multi-vitamin. LDN ramps me up so I cant sleep.

    Due to that I was put on Serzone which MESSED ME UP. Came off that and a different mental wellness professional put me on a very low dose of Seroquel in which now I sleep well.

    Finding the "sweet spot" in nutrition is really elusive and atop that its really hard to measure smaller gains. Swank was like, BAM, "Wow! What a difference in how I feel!". I did a detox before starting Swank. That "night" .vs. "day" difference when having to change or alter dietary protocol makes it difficult to measure loss or gain. The dramatic is easily noticed.

    My fiance' Rick on and off as time allows is trying to figure out a protocol by which we can measure the losses and/or gains in a granular fashion using software he's coding along with paper materials to record data for input.

    We are also doing some multi-processing attempts at therapy. Not multi-tasking. You know the difference so need not explain that.

    I can say that it also appears to have some real cognitive positive impacts. He multi-processes naturally now. Back in the 80's he and a bunch of game coders trained just to see if they became more productive producing better code in less time .vs. staying up for 16+ hour programming sessions. It worked.

    For me, I feel the transition strongly at times and not sure if its my MS or just age + my ways seems to tune it off again. He continues to work on it with me and believes its a bit of both. Overcoming the MS "shorts" as he deems them he believes takes more focus. In other words instead of it being trained on that it need be more routine.

    I can say that when its apparently working the difference from my normal MS status towards multi-processing is just enormous. He thinks as well that via software the ability can be far far more rapidly engaged in the CNS. He's just not quite sure where to start.

    1. Thanks this is an example where you feel good, but how do we measure this experience because there will be people who do not find benefit and this is the inherent problem with many so called alternative therapies. There is not real data collected with sufficent number of people doing the same and therefore the experience is nothing but anecdote, which does little to really inform but maybe sells a book.

    2. Part of the problem with some of the various non-mainstream dietary approaches to MS is that for followers of some of the “programs” every improvement in any symptom or overall wellbeing is attributed to the diet, and any large or small setbacks (including relapses) are frequently cited as being caused by a failure to adhere 100% to whatever program is being followed. Overall, most of the alternative dietary programs are indeed generally better for you that than the average Western diet full of highly processed foods and calorie laden takeaways and I am sure that some of the improvements that people get when adopting one of these programs should be attributed to the overall improvement in what they eat, with much better intakes of fruit and vegies and a focus on unprocessed foods.

      Especially with the approaches which either ban or severely restrict meat intake (such as Swank and the Jelinek OMS program), there are frequently people complaining about losing too much weight. The advice offered to them is almost always to eat more carbohydrates such as bread and pasta!

      However, there is also unfortunately a somewhat cultish feel emanating from many of the followers, and in some instances a blaming culture where people who do confess to having a relapse or worsening of symptoms are told that it has happened because they were not following XYZ Program 100%. Alternatively they are advised that it would be so much worse if they were not following XYZ Program. What is clear is that almost without exception these followers are blind to any recognition that some improvements and setbacks may in fact just be the natural and unpredictable course that MS follows.

      This is not to completely discount the benefits and improvements that some people do experience when the adopt one of these approaches, but it is the unremitting conviction that whatever program an individual is following will produce the same results for everyone which I find hard to swallow. It is almost a religious battlefield, just about which foods you eat (or don’t eat) instead of which God you may (or may not) believe in.

      PS – for MS Unites – have you done any research on magnesium? I did, and I found some interesting research out there – and it was not all in the hippy dippy camps either.

    3. Spot on the money all the way down the line. This is also why IMHO people need document their MS. Thus they can or a professional can see if patterns are occurring. If a person is actually improving or declining. Sure, a Neuro takes notes in the office into a computer. But how many people for the 15 minutes or 30 minutes they get can cover or perhaps even remember what need be purveyed of the 6 months prior?

      I think there should be standardized forms that people can duplicate and just record matters onto. The digital revolution is now engaging this, "Use your smart device" and actually these devices are not too smart, highly insecure and all might be lost if it falls into the soup bowl.

      Digital health may have its place but right now the industry is running at it like hungry wild dogs after chicken legs. When in fact the care systems are so convoluted and dysfunctional themselves lets just add another layer atop it. The consumer goes, "Oh how cool" not realizing they again just have been duped.

      All of these varied areas revolve around the same basic attributes that cause problems. Right in the center of it is money. As we swing outward we see the effects of that and somewhere in the tornado are patients, caregivers and clinicians.

      We are not speaking of common colds. With chronic disorders managing them means knowing whats happening preferably daily and educating patients proper. MS is not a new disease yet no standardization exists in management that the patients can aspire to try and work towards. Instead, its take some pills, a shot or infusion.

      The rest is "eat right" without any form of standards as to what that means. Exercise, again, without any protocols thereof, and use your parasympathetic nervous system which most people have never heard of.

    4. Dietary interventions have not been effective in the
      treatment of multiple sclerosis (MS). Here, we show
      that periodic 3-day cycles of a fasting mimicking
      diet (FMD) are effective in ameliorating demyelination
      and symptoms in a murine experimental autoimmune
      encephalomyelitis (EAE) model. The FMD
      reduced clinical severity in all mice and completely
      reversed symptoms in 20% of animals. These
      improvements were associated with increased
      corticosterone levels and regulatory T (Treg) cell
      numbers and reduced levels of pro-inflammatory
      cytokines, TH1 and TH17 cells, and antigen-presenting
      cells (APCs). Moreover, the FMD promoted
      oligodendrocyte precursor cell regeneration and
      remyelination in axons in both EAE and cuprizone
      MS models, supporting its effects on both suppression
      of autoimmunity and remyelination. We
      also report preliminary data suggesting that an
      FMD or a chronic ketogenic diet are safe, feasible,
      and potentially effective in the treatment of relapsing-
      remitting multiple sclerosis (RRMS) patients

  2. Exactly. Thus the question becomes one of how can gain / loss be measured in a granular long term data set towards each individual.

    Just as some people wont have a positive impact on say the Swank diet they may not on Tecfidera either.

    The measurement mechanism for DMT's is activity on an MRI yet all of that is in question as to whether an MRI can adequately measure if a DMT is actually staving off activity .vs. staving off significant activity.

    Just as the alternative therapies mechanisms differ and in large part relatively unknown towards MS this also stands true for the DMT's which state they either "believe the mechanism is this" or "how it works is unknown presently".

    The facts however are they do appear to work for some patients and not for others just as is the case with the more anecdotal alternate therapies.

    Yet, more is known about dietary and exercise in the human body than and DMT towards same. Perhaps this is due to brain and sensory/control systems science being more recent and the technology to really probe and understand it still in infancy.

    I agree there are many books out there that people with MS turn to in an attempt to improve quality of life. This shows the desperation involved with the disorder.

    Thus the fairly age old question that still exists does come to bare. Why are none of these diets actually studied in real clinical trials to get some concrete results.

    Why is there no granular protocol by which true disability measurement in MS is measured when assessments do exist for cognition, memory, ambulatory, motor skills etc. exist but are not melted into MS assessment. Instead its EDSS, a summary result based on none of the use of the above noted data sets.

    Yet when my fiance's father years back had stroke that was moderately disabling all these were applied.

    Would said data result in more effective therapies, treatments and outcomes? Apparently in stroke it does. MS however is not stroke. MS is progressive and thus such assessments would need be engaged as an ongoing protocol and the data extracted per individual resulting in a personalized wellness protocol and regiment. Thats complex. That costs time. Time is money.

  3. Interesting to consider. The evidence base on this sort of stuff is really poor though, and it makes it very hard to navigate.

    When I was first diagnosed I asked my neuro about diet and she said that saturated fat was something that I should look to minimise, not specifically for MS but also in general. Is this something to consider as well as carb minimisation and/or fasting? There's a lot of talk about red meat being minimised as well, but I don't know if this is simply to do with saturated fat?

    The other big question I have is regarding exercise. I remain physically fit and active, if am doing exercise does this change the equation re: ketosis?

  4. My concern is that the licencing system for drug's is so corrupt that it now counts as organised crime (Ref 2014 BMA book of the year ''Deadly Medicines and Organised Crime'') This means to the laymen that there is no reliable evidence based medical system. I agree there are many problems assessing any therapy mainstream licenced or alternative, however we have to do the best to assess available evidence, in the form it is available to us. I put evidence of people dealing with MS personally high on the list and if that person also happens to be a doctor so much the better. Diets now fit into that category along with things like LDN treatment of CCSVI and many others. If the medical profession wishes to retain the public’s confidence then they must develop a method of assessing evidence independent from an increasingly corrupt non evidence based system. If we concentrate purely on the licenced drugs for MS then a very low percentage of people in the UK have access to them anyway. Realistically these people do nothing and take a chance or try something ‘’alternate’’.
    David Taylor

  5. Dr Wahls is conducting a clinical trial on her ketogenic paleo diet (see https://clinicaltrials.gov/ct2/show/NCT01915433). The estimated study completion date has passed, hopefully she’ll publish results soon.

  6. Prof G,

    You wrote:

    If you tried this, how would you go about achieving the intermittent ketosis? Would you use the fasting approach? If so, how often? Or would you use one of the diets you mentioned? (If so, which one?)


  7. yes neurons die with ms but let's move on to how to make best of what remains. Functional neurology aims to do just that http://functionalforum.com/january-2016-functional-forum/
    PS, I believe ketosis does help: to become fat adapted is brilliant - the brain can make glucose from fat rather than relying on a steady flow of carbs for its fuel.
    When you starve it of carbs over about a couple of weeks 4+ hours between meals becomes everyday.
    Reducing postprandial inflammatory response can only be a good thing?

      Your breath will smell terrible though.
      "Reducing postprandial inflammatory response can only be a good thing?"
      Now lets not stray into quackery here.

    2. "the brain can make glucose from fat "
      What? THis is wrong the brain does not do any thing its the liver and the kidney that do glucose but from the muscle tisssue gluconeogenesis

  8. I wonder if the people who avoid carbs feel better just because they are consuming less processed foods. I wonder if you eat better carbs, like give up boxed cereal in favor of oatmeal, if that would make the same difference.

    How about switching from white bread to whole grain bread from a bakery that uses basic simple ingredients?

    1. I gave up the boxes and now make my own. Oatbran is easier on the stomach than wheatbran. Advice from my neuro dietician.

    2. Oats contain a good amount of biotin apparently and if there are any benefits to having biotin for MS...

  9. I was under the impression pubmed was a reasonably reliable source of information? I saw a huge referenced list on there of useful compounds in vegetables... cruciferous veg, garlic etc. You know what? Halitosis is the least of my issues when optimal functioning of a failing brain is on the cards.
    if my walking improves I'll cope with bad breath and do my best not to breathe on those around me!
    sweet potato and occasional brown rice I guess are my main sources of carbs, Anonymous?
    Whole grain or white bread will turn to glucose and enter the bloodstream at almost exactly the same speed, have the same effect on your blood sugar and the resulting swing in insulin is still going to be tough on the brain... type III diabetes/alzheimers?

    1. Whole grains add bulk to your diet and don't get absorbed by your body. They help your bowels move smoothly, which I believe promotes good gut bacteria. There has been a lot of speculation about MS and gut bacteria, and if they are related.

    2. Some of it depends on whether you have joined the current fad for avoiding gluten - even if you do not have medically diagnosed irritable bowel or genuine celiac disease. A nice big serving of broccoli will give you just as much fibre as whole grains, and there is some good research out there showing that it is fibre which generates positive effects on the gut biome, so whether the fibre comes from whole grains or elsewhere is not the point. I agree wholeheartedly though that whole grain is better than processed, which then comes back to the core message of avoiding processed foods as much as possible.

    3. I agree that you should eat fibrous fruits and veggies. They are soluble fibers and good for your heart health and sugar. Fiber from grains is insoluble and better for your bowels. Constipation is a symptom of MS and I believe that high fiber diet should be suggested by neuros. I am kinda disappointed on how little emphasis is placed on it.

  10. Well I am a former athlete and still practicing intense physical activity. So lindam athletes well with ketogenic diets. The great thing is that there is no way to keep a ketogenic diet for the rest of your life, every day, even for an athlete, former athlete or amateur sports practitioner. They are too restrictive, an hour you will get bored. Many practitioners of my friends bodybuilding, for example, has the "waste time", which can not eat all and then returned to cetogenia. The Yale University published a study last year on the anti-inflammatory of ketogenic diets action. I even before having the outbreak that made me discover MS stake practicing cetogenia ... Nowadays it is to keep me as healthy as possible I asked my nutritionist who passed me a diet based on the Mediterranean diet. The most interesting will look at bio-physiological mechanism behind these diets, how they would promote an anti inflammatory and neuroprotective effect? And I know that they act on improving mitochondrial function because they do not test in a study supplementation of Coenzyme Q10 or LN-Acetyl-Cysteine ​​(the latter neuroprotective)? ... I can say so "anecdotal" that as I am still training weight creatine supplementation every day where training (4x to 6x week) play away fatigue and strength improves absurdly. It would be "placebo" effect? I do not know, but I know it is the same problem with diets depends on the individual variability ...

    1. Dear Cinara,

      If you training that often, you are still an athlete! Could you put together a training regiment for a certain mouse doctor; we need him to remain healthy. :)

    2. Hahahahaha Aidan it would be cool :D

  11. Do we have any numbers for people like drug users, that would follow a ketosis diet because of their drug use, getting MS?

  12. Isn't low carb bad for kidneys? If so, not good for people with persistent UTIs and how about constipation. I thought carbs help combat fatigue. Shouldn't we just follow a balanced, low fat, varied diet without cutting out food groups other than processed food?

  13. This post is rather startling. I have heard of Ketones only as something to avoid in diabetes

    1. As we demonstrated, survival during prolonged starvation
      depends upon the ability of the body to spare the
      oxidation of vital proteins in the liver, muscle, heart, kidney,
      etc. Of special importance in this regard is the metabolic
      role of ketone bodies. Because of their association
      with diabetes, ketone bodies were long held to reflect a
      disease state; our research totally changed this view.

      Fatty acids themselves
      are not metabolized by the brain, so that ketone
      bodies (which do cross the blood-brain barrier) are the fuel
      of choice during starvation. Finally, it is interesting to note
      the changes in blood ketone body concentrations during
      starvation. The magnitude of their changes is among the
      greatest that occur in biological systems. Starvation
      causes an exponential rise in acetoacetate and -hydroxybutyrate
      (Fig. 3). These fuels plateau after about 18 days of
      total starvation. During prolonged starvation, the concentrations
      of acetoacetate plus -hydroxybutyrate increase
      from barely detectable levels immediately after a meal
      containing carbohydrate to 6–8 mM. The concentration of
      acetone slowly drifts upward to about 1–2 mM. The fall in
      blood glucose reaches a nadir after 3 days of starvation
      and is paralleled by a decrease in serum insulin.
      Our work on ketone body metabolism by the human
      brain demonstrated how human beings survive and maintain
      mental function during physiologic hypoglycemia and
      hyperketonemia of prolonged starvation. Ketone body
      consumption by the brain has an essential role in preserving

      Ketone Bodies as a Fuel for the Brain during Starvation

      Vol. 33, No. 4, pp. 246–251, 2005

  14. I think there are enough papers on gluten's negative effect on the body from cardiologists, gastro-enterologists and neurologists now that it can't really be called a fad.
    I stopped gluten over 10 years ago as I found it messed with my brain but we’re all different.
    If your body/digestion is working perfectly then having it chipped away on a daily basis is not a problem but if things are less than optimal try changing bits of the diet? http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210916/table/nutrients-06-04273-t003/

    Do we need to define 'low carb' before labeling it as bad for kidney function?

    Did anyone see the BBCs Doctor in the House at the end of last year which showed a gp reversing the onset of type II amongst families he was staying with by adjusting diet and lifestyle?

    Whilst cures aren’t forthcoming shall we try and make life a little bit better where we can?

    1. This is Anon of 6th Jan 1.06pm
      My reference to a the gluten avoidance "fad" is because there are an awful lot of people going gluten free without any sound justification, such as medically diagnosed conditions including celiac disease. I totally agree that there is a significant amount of research around on gluten, covering a wide range of viewpoints and perspectives, some based on sound scientific research and some not. There is also an increasing amount of research indicating that some of the sensitivity problems with foods that contain gluten is not actually a sensitivity to gluten itself, but other substances in the same foodstuff.

      My reference to "fad" is aimed at those who jump on the bandwagon, based on an unsupported/ unsubstantiated belief that if no gluten is good for people with a genuine problem then no gluten is better for everyone. I know a couple of people with celiac disease, and the struggles they have with genuine problems that gluten can cause them. However, the bandwagon jumpers are a marketing executive's dream - flog it hard and watch the profits soar on high margin products.

    2. I am gluten free and I eat 'by default gluten free food'. I eat fish, meat and vegetables mainly, brown rice, sweet pots etc. I do eat oats which are generally gluten free but the milling process if in the same factory as other grains may get cross contamination.

      I don't buy much of the 'gluten free range' at supermarkets. I bake my own quick and cheap gluten free foods. My point is there is no real need to buy into the high price 'gluten free supermarket ranges', unless you have no time or not able to cook.

      There's a programme recently been on TV about Victorian bakers, they said that bread back then had a lower gluten level.

  15. I feel for everyone trying to find the 'right' diet for MS. Before addressing that notion though, it worth remembering that the population at large is eating a pretty dreadful diet right now. You can see that in any public place, fast food outlets, supermarkets and, unfortunately at school.

    Im a doctor with MS and Ive been interested in diet for years. However my focus has been attempting to improve some very bad dietary habits, rather than aiming for excellence.

    With MS, its even more important to eat a good diet, and I cant help but feel the guiding notion for me is 'low calorie - high nutrition'.

    The bulk of my diet is fresh salad and veggies in large quantities, and avoiding the starch ones too. Lots of leaf , raw beetroot, herbs, celery and celeriac (as many different rest ingredients as possible) )in salad with omega 3 rich salad dressings, accompanied by bean burgers, I do eat eggs, but my chicken are well fed. Im lucky to be in the position of being a smallholder, but with MS, why not make sure the quality of the food we eat is absolutely excellent, and in as large quantities as we need to maintain weight. I avoid starchy staples such as potatoes, rice, and wheat so I can eat more of the high nutrition stuff.

    Further, more exercise means more food intake and more good food will therefore provide even more vitamins, minerals, antioxidants and god knows what else!

    I don't bother with cereals much either - they would just mean eating less greens to meet my daily requirements.

    Before waiting for the magic bullet of the therapeutic diet which may never arrive, get added sugar, processed foods, low quality meat and dairy (which the vast majority are) and just eat down to earth, simple, good food. I feel so much better for it, and I hope you will too.

    1. Re: "Dr Colin Bannon ...."

      All very sensible, the problem is that you have to battle against the marketing might of the food industry and the fact that processed foods are relatively cheap. An uphill battle, but worth fighting for.

    2. It's a shame the hospital vending machines are full of sugary snacks and drinks.

