Wednesday, December 21, 2011

Huge news: multiple sclerosis is a metabolic disorder

** For those coming to this post from Facebook, please see my most recent thoughts **

***The paper is now published. Read it here.***

In the latest issue of the Quarterly Review of Biology (Vol 86 Number 4, December 2011), in a paper titled "Multiple Sclerosis is Not a Disease of the Immune System," Dr Angelique Corthals argues that multiple sclerosis (MS) isn't a disease of the immune system: it is caused by faulty lipid metabolism.

The very basic précis of the paper: looking at MS as a metabolic disorder helps to explains many puzzling aspects of the disease. MS cases are on the rise as a direct consequence of a high-sugar, high-animal-fat diet. MS is similar in many ways to atherosclerosis.

This is huge. It is not an incremental improvement of what's known about MS, it's a paradigm shift. It will change the way MS is understood, researched, and treated.

Full disclosure: Angelique is a good friend of mine. I've seen every draft of this paper. It is not original research. It's an overview of what is known to be known. It takes what has been researched, reviewed and replicated and reassembles it into something utterly new: a jigsaw puzzle in which, for the first time, all the pieces fit. There are no pieces left out, none hammered in with brute force. It's brilliant. It's elegant, clean, and makes complete and utter sense.

At some point soon I'll write about how this makes me feel. But today I want to give you the gist of the paper without editorialising. (All mistakes are mine; nifty illustration and direct quotes are from Angelique.)

The medical profession has believed for a long time that MS is a disease in which the body’s own immune defenses attack nerve tissue in the central nervous system. [For an overview of changing medical wisdom, see The Incredible Journey, courtesy Rocky Mountain MS Center.] The disease's main characteristic is inflammation, then scarring, of tissue called myelin which insulates the brain and spinal cord. Over time this scarring can lead to profound neuron damage.
Researchers have thought that the fault lies with a runaway immune system, but no one's been been able to explain what triggers the onset of the disease. They've linked genes, diet, pathogens, and vitamin D deficiency to MS, but evidence for these risk factors is oddly inconsistent and often contradictory. This frustrates researchers in their search for effective treatment.

"Each time a genetic risk factor shows a significant increase in MS in one population, it's been found to be unimportant in another. Pathogens like Epstein-Barr virus have been implicated, but that doesn’t explain why genetically similar populations with similar pathogen loads have drastically different rates of disease. The search for MS triggers in the context of autoimmunity simply hasn’t led to any unifying conclusions about the etiology of the disease."

Understanding MS as metabolic in origin rather than autoimmune begins to bring the disease and its causes into focus. "The new approach explains both the recent rise in incidence and all pathological, genetic, and environmental aspects of the disease."

In other words, this new understanding of MS will finally make it possible to find effective treatmentincluding preventative treatment.


The etiology of MS (click to enlarge)

Corthals believes that the primary cause of MS can be traced to transcription factors in cell nuclei that control the uptake, breakdown, and release of lipids (fats and similar compounds) throughout the body. When the lipid-metabolizing function of these receptors, known as peroxisome proliferator-activated receptors (PPARs), is disrupted, it can cause the accumulation of toxic lipids known as oxidized LDL, which form plaques on the affected tissues. The accumulation of plaque triggers an immune reaction, in part also regulated by the PPARs. With a failed inflammation control and the accumulation of oxLDL, the immune response runs amok and the toxic plaques leads to scarring of the tissue. The mechanism is essentially the same as atherosclerosis, in which PPARs' failure in heart cells leads to inflammation and an immune response in coronary arteries. "When lipid metabolism fails in the arteries, you get atherosclerosis. When it happens in the central nervous system, you get MS."

There are several risk factors for reduced PPAR function, including:
  • a diet high in saturated fats and carbohydrates
  • genetic predisposition
  • environmental factors (such as poor exposure to sunlight or sources of vitamin D)
If the PPARs and the disruption of lipid homeostasis are the culprit in MS, it would explain why statin drugs, which are used to treat high cholesterol, have shown promise as an MS treatment. It would also explain why cases of the disease have been on the rise in recent decades. "In general people are increasing their intake of sugars and animal fats, which often leads to high LDL cholesterol. So we would expect to see higher rates of disease related to lipid metabolism—like heart disease and, in this case, MS."

It also sheds light on the vitamin D link. Vitamin D helps to lower LDL cholesterol, so it makes sense that vitamin D deficiency increases the likelihood of the disease—especially in the context of a high-fat/high-carbohydrates diet.
The lipid hypothesis also explains the inconsistent evidence for MS triggers. In many cases, Corthals says, having just one of the risk factors for reduced PPAR function isn’t enough to trigger a collapse of lipid metabolism. But more than one risk factor could cause problems. For example, a genetically weakened PPAR system on its own might not cause disease, but combining that with a poor diet can. Under these conditions, the body is "primed" for the onset of the disease, which is then triggered either by a pathogen (it can be any) or trauma, or even stress.

Finally, the lipid hypothesis also explains why MS is more prevalent in women.

"Men and women metabolize fats differently. In men, PPAR problems are more likely to occur in vascular tissue, which is why atherosclerosis is more prevalent in men. But because of the way women metabolize fat differently in relation to their reproductive role, their lipid metabolism is more likely to affect the production of myelin and the central nervous system, leading to the neurological equivalent of atherosclerosis. MS is more prevalent in women, just as atherosclerosis is more prevalent in men—but this framework excludes neither sex from developing the other disease."

Much more research is necessary to fully understand the role of PPARs in MS, but Corthals hopes that this new understanding of the disease could eventually lead to new treatments and prevention measures: "This new framework makes a cure for MS closer than ever."

And that, dear reader, is the magic word: cure. For the first time, ever, I think there might one day be one. Even better, we might be able to prevent MS.

If you have questions—and I'm sure many of you do—please drop a comment here. Angelique has promised to answer as many as she can. I will, too. But please note: neither of us will give specific medical direction or advice. For one thing, I'm seriously not qualified. For another, there is no substitute for talking in person to your healthcare professional. I'm happy to share my opinion—I'm opinionated; it's my blog—but do not construe this as medical advice. Angelique will discuss her understanding of MS in general, particularly as it relates to this new paradigm. But she will not tell you what you should do. There will be no exceptions.

ETA: QRB is not yet live (sigh), so I've reverted the link to the forthcoming page. I'll update when this changes.

ETA2: This an emotional topic. I will be moderating comments here carefully. Please remember that neither Angelique nor I am making money from this. This blog post is a service. Don't even think of getting impolite or I'll delete your comment. Let's all play nicely.

ETA3: QRB informs us there's been a delay and the paper will go live on Friday. But I have a copy of the final document, the PDF that will be downloadable free in a couple of days. It's 25 pages of double-columned, densely argued fabulousness, with 9 pages of double-columned bibliography. It is solid. For those who know their PPARs from their peroxisomes and can't wait until Friday, email me.

ETA4: Comments on this post are now closed.

ETA5: But comments are open on my most recent post on the topic.



  1. is CCSVI helpful for MS

  2. CCSVI only "treats" (I use the term loosely) one aspect of multiple sclerosis, which is restenosis (or narrowing of the blood vessels). Therefore, since MS itself is not treated, the chances of relapse and failure of the procedure in the long term are very high. The problem with CCSVI is that it is fairly unregulated, and there has been no serious clinical trials. There are, to date, no reliable statistics on the benefits or potential harm of the procedure in the long term. More worrying is that the MD who first came up with the procedure, Dr. Zamboni, is now cautioning against it, worried about the procedure's lack of regulation around the world.

  3. Loosely---and I stress that term---this upends the traditional approach, making MS more a symptom than a primary cause. This would make it a consequence of factors to date unacknowledged as primary. The relationship between all these various factors---diet, D3 deficiency, even geography (it always puzzled me how an autoimmune disease could be tied to life above the 36th parallel)---is reversed. At least, that's my take-away from all this.

  4. Here is a link from the latest ECTRIMS meetings (one of the largest MS research annual meetings) from a panel discussion where Dr. Zamboni and independent MDs caution that "CCSVI treatment outside of a proper trial is not recommended":

  5. Mark, I am not sure what you mean by reverse. But yes, all of the factors you quote are crucial to "priming" the body for MS, along with a genetic factor (though the disease an be developed without it) which predisposes populations living above the 36th parallel to develop the disease (and potentially pass the genetic factor on to their offsprings).

  6. "Reversed" in the sense that their significance must now be placed front and center rather than sidelined as "merely" exacerbating factors, with no clear explanatory etiology.

  7. Wow! This is just fantastic news. Also: meta data, utterly, utterly fascinating as a process of research.

    [And on my side of the illness things celiac has been reclassified as an auto-immune disease and suddenly all my "complaints" are being grouped together and ameliorative treatment offered.]

  8. Mark, oh yes, absolutely.

    Farah, thank you. The process of meta data is really complex (my office looks like John Nash's), because it requires to approach different fields at once. My biggest hope, apart from sending MS into the history books, is to make people think outside the box. To start a new dialog.

  9. This is beautifully elegant and I hope it pans out. When you say cure, do you think there's a potential to reverse damage, or would it just prevent further damage (and, of course, prevent the beginning of damage if caught early)?

  10. This makes sense to me, based on my experience with my dad. And it explains why the immuno-suprressing drugs he's taking post-bone marrow transplant haven't "helped" his MS the way the doctors thought it would.

  11. Farah, yes, it's brilliant. In every sense of the word. I saw that about celiac. Also good news, yes?

  12. Elaine, yes, I think the new paradigm opens the door to potential cures that would reverse the damage by first preventing further damage and then by "encouraging" (through boosting the synthesis of specific proteins by the PPARs) the neuronal cells called oligodendrocytes to repair the myelin. I also hope that it may help prevent the disease to arise in at-risk populations. Obviously, more applied work is to be done to achieve these goals. But at least, I am hoping that the new paradigm I am proposing will act as a road map.

  13. Jennifer, I've done many of the immuno-modulatory and immuno-suppressive therapies for MS. They didn't work for me. And the side-effects were terrible. I stopped even considering that kind of treatment many years ago. I haven't regretted it.

  14. This is total crap. "Dr Angelique Corthals" is anthropologist (biological/biomedical and forensic).

    Her "theory" is very old and naive (animal fats cause MS ) . Actually many vegetarians get MS, some of them are on "this is ms" forum, and their condition improved when they reintroduced animal food in their diet. Swank diet is bs too, 99% who tried it saw no improvement, and that's the big truth everyone is scared to say publicly.

    There's nothing easier than to stop consuming animal fats. You can eat ton of pasta and bread, margarine (hydrogenated vegetable oil), soy, vegetable protein etc. but will that cure your MS ? I don't think so.

    I'm sorry but this kind of crap really pisses me off.

  15. Anonymous, actually, I am not saying that diet only can cure MS or even prevent it. There are still the other environmental and genetic factors to contend with. Furthermore, the point of the article is to illuminate another potential area of research that has been neglected and is becoming more and more the focus of the scientific community.
    And there lies the point of science: if you think it is crap (we've all been there), prove it by experimentations, publish it, and I'll happily applaud you for it.

  16. Anon, I hear your frustration. I'm sorry you feel pissed off. But part of the seventy pages of the paper are twenty pages of reference to research that backs up this new perspective. Dr. Corthals is eminently qualified. Her research program at John Jay uses proteomics, DNA-based ecology and epidemiology to model the environmental and genetic risks of diseases.

  17. This is fabulous work. I remember when the change in thinking about atherosclerosis filtered down to my level (when I was writing training doc for pharma sales reps) and how it changed how we could write about it. Although I no longer do that medical writing as my fulltime job, I hope to see/hear about a similar trickle-down in paradigm shift in the next few years, because, above all else, this *makes so much sense*.

    (And, of course, the paradigm shift should make big pharma sit up and wag its many tails, since it brings in SO many more druggable target possibilities.)

    Have you started writing the grant for a collaborative project with a sequencing center that can start plowing through MS/MS-related subjects, looking for key variations that might be more likely to be related to this causative POV?

  18. This is absolutely amazing - More than one thread of research is often VITAL to discovering cures! Meta-research never gets the praise its due - you can discover some amazing things with that approach!

    I hope someone gets this info to Jerry Lewis, he's worked SO hard to eradicate this disease for SO long.

  19. Jude, oh, I'd love to hear about your experience writing for big Pharma. That's a whole world of its own. And yes, there are many MANY drug possibilities here.
    About the grant, yes, I have written AND submitted a grant to the NIH about exactly what you are describing. I should hear in late January, beginning February. I am hoping that the powers that'd be at NIH will see the article (though you never know which way it could influence the outcome), which, of course, was only submitted at the time I submitted my grant to the NIH.

  20. twilight, Jerry Lewis raises funds for muscular dystrophy. But it would still be cool to get the info into his hands. I want it into everyone's hands.

  21. Oh, excellent! Best of luck with the grant process!

    Writing for big pharma WAS a really fascinating experience, especially hearing about some of the backstage magic used in and around clinical trials and the analysis thereof. I still do some occasional freelancing, but I no longer talk to the clients, which suits me *just fine*. :)

  22. Jerry Lewis is no longer associated with MDA, and they do work on diseases other than muscular dystrophy, though I don't see MS listed. (They work on ALS, for example.)

    My god, if the condition could be reversed! Wow!

  23. Elaine, wow doesn't begin to cover it :)

  24. Angelique, Nicola: consumption of saturated fat is not, after all correlated with heart disease. See Siri-Tarino 2009 “Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease” among others. I think the whole terrestrial animal/saturated fat/LDL/atherosclerosis hypothesis needs to be revisited with an open mind that much of the beliefs of the last few decades rest on slim and inconsistent evidence. A promising improvement is to distinguish between dense and fluffy LDL ("pattern A" and "pattern B").

    You are apparently already familiar with the process of revisiting established beliefs and finding them wanting. :-)

    I'd be happy to chat more with you about this. I'm no expert, but I'm sufficiently interested that I've accumulated a collection of relevant papers that I would be happy to share. I'm attempting to write a book.

  25. My concern is presenting this as a "new" paradigm may lead to this paper as being seen outside of the current discourse thereby making it "irrelevant." My hope is that it can be reviewed in a manner that would allow it to decenter the current discourse. I appreciate the energy that went into this project and hope people can see the value of this approach.

  26. Might this help explain why the seemingly different medications like interferons and glatiramer acetate both can slow/stop the progression of the disease? Although I have never had a neurologist sucessfully explain to me why (and in more detail than generalizations) what any of the medications do, it seems that they both would have something to do with the metabolizaiton process that both lipids and proteins are involved in.

  27. Twilight2000: thank you so much. Yes, I am looking in a lot of private foundations to get funding for the next steps (they are many!).

    Jude: thank you so much!


    Zooko, yes, I am familiar with that side of the literature and think it is amazing research too! In the new paradigm, I make sure to emphasize that it is not only the diet that is at the root of MS, and certainly not just dietary fats. In fact, the lipid metabolism encompasses many different dietary macromolecules, and some carbohydrates are just as much to blame. But of course, there are the other elements to take into account, such as the geography, the exposure to UV, etc. It is the combination of these elements which starts deregulating the transcription factors, the PPARs, which are at the regulatory junction between the lipid metabolism and immune system. You're writing a book?! Brilliant, I'd love to talk more about this.

  28. payshunzb: interesting point. What I want most is to facilitate engagement with this idea. Any suggestions about the best way to do that?

  29. Oops. Elaine, I don't know why my comment was erase. I was just replying that it is my dearest wish. And I am going to work at it... by doing what every scientist does: trying to prove myself wrong! ;)

  30. Christopher, I'm not the expert, but an updated Cochrane review (2010) concluded "Treatment with glatiramer acetate (Copaxone ®) of patients with Relapsing-Remitting (RRMS) and with Progressive Multiple Sclerosis (PMS) seems to have few beneficial effects in RRMS, while the drug is not effective in PMS patients." This reflects my personal experience with the drug.

    I'll let Angelique address the rest in context of her paper.

  31. Christopher said, "Although I have never had a neurologist successfully explain to me why (and in more detail than generalizations) what any of the medications do..."

    Me: That's because they don't know. The key lesson I learned working for big pharma: they don't actually know HOW most of their drugs work. They have *theories* that may or may not be correct. This is especially true for drugs that act on neurologic disorders (ranging from MS to migraines to seizures to schizophrenia), and demonstrated by the fact that FDA will very often not let them put their theories in their package inserts. Neuro drugs often have "The mechanism of action of [X drug] is not known," in the label, followed by some variation of, "But we think it *might* be this."

  32. Nicola, thank you for your comment. My personal experience with the drug has been different. Since I have been on Copaxone, the active lesions I've had for years have gone away, and my symptoms have greatly been reduced (even during my flair-ups). Conflicting experiences like this, along with the statistics in improvement in symptoms while using a placebo, are baffling. I have been doing other complimentary health "things" that I'm sure have had a positive effect as well.

    I'm excited to read the paper.

    Thank you again.

  33. Payshunzb: you've got a great point. Any input would be awesome.

    Christopher: interferons (depending on the type) act on the inflammation pathways of immune system cells (i.e. the different way cells respond to inflammation). For example, interferon alpha will prevent the activation of a toxic inflammatory pathway called the growth factor. Glatiramer acetate works in a very similar way, to help the expression of the antiinflammatory agents (cytokines), and prevent the expression of growth factor. Do not hesitate to let me know if you need more info.

  34. This is fascinating. "When lipid metabolism fails in the arteries, you get atherosclerosis. When it happens in the central nervous system, you get MS." In my research, I have been thinking that MS & diseases like RA & Lupus are related - and NOT auto-immune.

    For a long time I have wanted to try grape seed extract for many reasons. One of its many benefits is lowering LDL. "When the lipid-metabolizing function... is disrupted, it can cause the accumulation of toxic lipids known as oxidized LDL, which form plaques on the affected tissues."

    "If the PPARs and the disruption of lipid homeostasis are the culprit in MS, it would explain why statin drugs, which are used to treat high cholesterol, have shown promise as an MS treatment. "

    Statin drugs are killers, so any natural substances that lower LDL are the way to go. One is grape seed extract; another is high-dose niacin; yet another is high-dose vitamin D3 which, in so MANY chronic diseases (and cancer), is shown to be deficient. In concert, I think they show great promise - along with ridding the diet of LDL-raising foods, of course.

    If anyone here is familiar with, you may want to do some searches on related problems such as athersclerosis or systemic sclerosis. GreenMedInfo is a compilation/organization of studies.

    Still reading the précis, but wanted to comment on this part. Thank you!

  35. "Finally, the lipid hypothesis also explains why MS is more prevalent in women."

    If MS is indeed related to other so-called auto-immune diseases (like RA & Lupus), it may also explain why those too are more prevalent in women.

    REALLY looking forward to reading the paper!

  36. @Zooko. Agreed! I believe the "saturated fat is bad" assumption began with a study on coconut oil - which was hydrogenated!!!

    In fact, coconut oil (virgin & extra virgin) & coconut milk are an absolutely integral part of my healing diet. Grass-fed organic butter and grass-fed organic raw cheese as well.

    There are good saturated fats and there are bad saturated fats.

    @Anon... I appreciate your skepticism, but I encourage you to do a lot more research and in much greater detail. The animal fat replacements you mention are all extremely damaging as well (especially soy), and remember vegetarians continue to consume animal fats via dairy.

  37. ristpastels, thank you! One thing I very much insist on in the paper is that treatment will most likely come from a modulation of several existing drugs (and of course, adjusting one's diet does not hurt). I can send you the article by email, if you'd like.

  38. romance, I think Copaxone works for some people in concert with other adjustments, e.g. diet. If it's working for you, that's fantastic.

  39. I am definitely looking forward to reading this paper!

    I apologise if this is a dumb question; I don't know much about MS. Are there any animal models of the disease, or mouse knockouts that mimic the disease?

  40. FranW, there are mouse models but they're unsatisfactory. Researchers are constantly trying to improve them.

  41. Romancc, yes, it is brilliant that Copaxone has been working for you!! Let me know if you want the paper by email.

    FranW, I can send you the paper via email too, if you'd like. As Nicola said, model organisms are not great, and can provide confounding results (false positive or false negative). The animal model that has been and is still being used are the EAE mouse (experimental autoimmune encephalomyelitis). But it is not a perfect model, and there has been a lot of drawbacks.

  42. @ristpastels: done! The article is in your inbox. :)

  43. Thanks for the info!

    Yes, I can see that the EAE mouse model would be not be a very good model for MS if, as hypothesised, MS is not an autoimmune disease. Antigenic myelin protein + CFA + PT will, like the more recent spontaneous mouse models described in the second link, induce T-lymphocyte- and/or B-lymphocyte-driven demyelination. The pathology might be similar to MS but not the mechanism.

    Hmm. And a quick search turns up a recent paper describing how PGC1α KO mice have deficient postnatal myelination and myelin basic protein (J Neurosci. 2011 Jun 29;31(26):9544-53).

    Yes, I'd love to read your review, please!

  44. @Angelique... Thank you! I look forward to reading it!

  45. @ristpastels, my pleasure. I look forward to your comments.

  46. Anyone interested in fats/lipids in the diet... this is a good layman's explanation re diet & fats' role in inflammation:

  47. Holy crap, it's too big for my stapler! :-D

  48. ristpastels, thanks for that link. Now that you have the paper would you like me to delete the comment with your address to avoid spambots?

  49. Thanks so much Nicola and Angelique.

    This is really fascinating and important.

    My first signs of a flare of what led to an MS diagnosis came two years after entering a new relationship with a great cook that led to a (very tasty) change in my diet that involved significantly higher levels of animal fats and dairy products, after many years of a mostly vegetarian and low-fat diet.

    I have wondered if this was a trigger that took previous disposition and/or exposure to something else to that next level, as I'd had vaguer health troubles about a decade before that then subsided that could have been pre-MS or small flares.

    I went on the Swank Diet and did not have a repeat flare until I added more fat back as I was trying to get pregnant. I then had a small flare, and then a big flare post-partum (which is common, and I'm wondering if there is something to consider that supports or critiques your theory about the high prevalance of post-partum flares?)

    However, I have now been re-diagnosed as having neuromyelitis optica (NMO) spectrum disorder, having had another flare (4 months after ending a year of tysabri infusions, and just 2 weeks after a very encouraging MRI with no active lesions and reduced scarring).

    I was always considered "atypical": I have never had significant brain involvement from the MS, do not have oglioclonal bands in spinal fluid, and have had multiple flares involving transverse myelitis (longer stretches of inflammation than generally seen in MS, stretching over 3 vertibrae). Like 20-30% of people now being diagnoses with this, I do not test positive on the NMO antibody test.

    Would your theory also apply to NMO?

    I would love a copy of your paper: jdavids13 (at) gmail dot com

  50. JD, I'm sending you the paper.

    I'll let Angelique answer your question.

  51. @Nicola... Yes, please! Thank you!

    @JD... please be aware that fat is not fat is not fat. Some are awesome, some are very damaging. Even animal fats can be good but only if unadulterated and fed on their natural diet. See my link above re Inflammation. My best to you in finding healing solutions.

  52. JD, thank you for your comment, which is fascinating. I am sorry to hear about the NMO diagnosis and flares. Yes, I do believe that the same or a very similar (just specific to its location in the body) mechanism is involved in NMO.
    While it makes sense that a diet that poor in saturated fats is potentially problematic (as you have experience) several other factors, from a lack of vit D and/or genetic predisposition, may also be at play. Interestingly, most aquaporins (of which A4 is the protein supposedly involved in NMO) are regulated by the transcription factors that are at the root of MS, and that I studied in detail in the paper, the PPARs. I have quite a bit of literature on the regulation of these in relation to NMO, diabetes, obesity etc. I would be happy to share these article with you, if you'd like. Two articles that comes to my mind above all are: "PPAR-γ,Microglial Cells, and Ocular Inflammation: New Venues for Potential Therapeutic Approaches" by Malchiodi-Albedi et al. published in 2008 in the journal of PPAR Research ( and "Effects of chronic treatment with statins and fenofibrate on rat skeletal muscle: a biochemical, histological and electrophysiological study" by Pierno et al. published in 2006 in the British Journal of Pharmacology. Though the later is about skeletal muscle, it involves the regulation of aquaporin 4 by the administration of statins and fibrates (aka PPAR agonists).
    I'd be happy to answer further in an email, if you wish to go into more details.

  53. Nicola, I'd love to see the paper violentbloom (at) gmail Thanks for posting all this great info. My friend has MS and has been in decline for years. (openID doesn't seem to be working for me...)

  54. @ristpastels - I agree with you and have generally been trying to have mostly grass-fed meat for a while now, though I must admit it doesn't happen all the time. I am also gluten-free and cow-dairy-free but eat goat milk, butter and cheeses, and use coconut oil, fish oil, etc.

  55. JD, I had written a very long reply back to you, and for some reason it does not appear. So here it is again: I am very sorry to hear about your NMO diagnosis and flares. Yes, I do believe that NMO follows the same, or at least a very similar, mechanism as MS. Whether it is or not a form of MS is still a matter of debate. I personally think it is .
    What's most interesting is that some of the aquaporins (of which A4 is linked to NMO) are regulated by the very same transcription factors I am describing in details as part of the etiology of MS, the PPARs (peroxisome proliferator activated receptors). Aquaporins are also implicated - surprise surprise - in hyperlypidemia, diabetes, obesity and many other metabolic disorders. I recall quite a bit of literature on both ocular inflammation and how some fibrates and statins regulated aquaporin 4. The two articles that come to mind are: PPAR-gamma, microglial cells, and ocular inflammation: new venues for potential therapeutic approaches by Malchiodi-Albedi et al. 2008 in the Journal of PPAR Research; Enhancement of the aquaporin adipose gene expression by a peroxisome proliferator-activated receptor by Kishida et al. 2002 in the Journal of Biological Chemistry; and A futile metabolic cycle activated in adipocytes by antidiabetic agents by Guan et al. 2002 in Nature. I have a ton of literature on the subject, and I'd be very happy to share it with you, and if you'd like, answer your question in more detail by email.

  56. @JD... good for you!!! Remember to be kind and forgiving with yourself, as it is never easy to change one's diet. Just keep doing your best. If you can, try to avoid animal protein completely unless it is pasture-fed/grass-fed.

    It has taken me a long time to change my diet but it is finally evolving with success. I have created lot of recipes that can make you forget about meat. :-)

    @all above... has anyone tried high dose grape seed extract (for instance, 300mg/day)? If so, what are your results to date?

  57. Nicola and Angelique.....I don't know the words to use that mean more than THANK YOU. If I did, I would say them to you. Wherever this all leads, it is bound to do something positive in the MS world and beyond....I am very eager to read your paper. I'm not a scientist but I am VERY interested. I have been diagnosed with MS since 1977. I am 72 years old now, and would love to see a CURE for this disease before I make my transition. I was diagnosed after a very traumatic episode in my personal life. Also, I was sexually abused in childhood. I am female and for most of my life my diet has not been good. I have always wondered about my absorption of nutrients. I have been taking 10,000 units of D-3 daily for a few years, and it took quite some time for me to ever even get to low "normal" readings. I have never taken any of the "MS" "old" neurologist was skeptical and I followed his advice. This probably sounds like an uneducated question, but I'm going to ask it...when you get to be 72 you don't worry about looking foolish! Is there any sort of test one can take to get an idea of one's lipid metabolism? Thank you and God bless you. I'm grateful. Corky

  58. @Angelique, thanks so much for this very thorough and very quick reply! Yes, I'd appreciate that additional literature - I've started an NMO journal club and have already shared your article with them and this would be very helpful. jdavids 13 at gmail.

    @ristpastels, thanks so much for the encouragement - and I'd love to see your recipes! My new year's resolution is to eat closer to the Dr. Wahl's diet, are you familiar with it? Seems like it's similar to what you are practicing.

  59. Dear Corky, thank you so much for your encouragements. I do hope this article will make the research community think outside the box, or at least outside its comfort zone for a little while. I will be delighted to send you the article. My email address is aspcorthals (at) gmail (dot) com. If you send me an email, I'll reply to it with the article. And your question is not at all foolish. There are lipid panel tests, but usually levels of oxLDLs (oxidized LDL) are not tested. So you must specifically ask for it. The absorption of nutrient is another big topic. Top research is being done right now on gut bacteria and their role in the absorption of nutrient (specifically lipids) and MS. Specific profile of gut flora seem to increase the likelihood of autoimmune disease, because essential nutrients cannot be absorbed properly and put to use in the metabolic cycles. Please do email me, and I'll send you the article.

  60. JD, an NMO journal club is great! I will compile the citations and PDFs, and send all that to you tomorrow (it's just about midnight in NYC...).

  61. Corky, it's my pleasure. I think we're so lucky be right here right now, with all this amazing research of the last ten years to build upon. So lucky to have people like Angelique to put it all together. So lucky to have a community like this to help push the news out into the world.

  62. If the discussion is focused on the way the past research is framed, then the discussion must remain within the current discourse. (sorry for the late response)

  63. The UK MS Society has not referenced this paper or made comment in relation to it. Given that it is in a respected journal and I am a little surprised by that and have asked them, via the website and directly by email if they have comment to make. I have yet to read the paper so wont comment until I have, but given that the collected symptoms that are said to be MS have always been bedfellows somewhat forced into a clumsy and clunky diagnosis the precis you post here is very intriguing and on the face of it (for a non-scientist, person who has the clumsy symptoms) intriguing.
    I will re-post here any response I get from the UK MS Society.

  64. @JD... I have a very busy week trying to meet a 12/28 deadline but if you email me ( I will respond when I have time with a few recipes you may find useful. I am not familiar with Dr. Wahl's diet, will look into it. Thank you. As an artist, my income is extremely limited. I cannot afford many vitamins or supplements, and I unfortunately depend on food stamps. So I have learned to get most of the vitamins, minerals & nutrients I need from food - which the standard American diet does not provide. It's tricky. I do this on about $6.50/day. Others with better resources can do even more.

  65. If this is true, carbs, not the animal fat are the problem, IMO.

    We have AGEs from carbs that induce ROS damage on LDL. Vitamin D3 is IN animal fat, so high fat should help, as long as there is no carbs around. Furthermore dietary cholesterol doesn't influence much blood cholesterol. Lack of vitamin C due to inborn error of metabolism might be responsible for oxLDL. High fat diets promote C deficiency but its reversible with supplementation. Carbs on the other hand, attenuate vitamin C absorption, it is much less reversible with supplementation due to competitive receptors. Lack of C promotes inflammation that also leads to oxLDL.

    Animal fats can't be the problem because we use those on ketogenic diet which improves ALS, MS (related: and various neurological diseases. Combination of carbs and animal fats, on the other hand, can.

  66. @ Lel, there is a quick explanation for why the paper has not reached MS societies yet (but is on its way there!): it was under strict embargo until last week. It only started getting disseminated earlier this week. In any case, the paper is on its way to your inbox. Thanks for reaching out to the UK MS society!

    @majkinetor: yes, absolutely, carbs are also part of the problem, as you explain. I have described that particular mechanism as well in the paper. Again, it's also not just diet on its own, but a combination of factors which prime the body for the disease. I'd be happy to send yo the paper, if you wish. Would love to have your feedback.

  67. @Angelique, please do.

    E: miodrag.milic at

  68. @ majiknetor: done! Looking forward to your comments.

  69. This is great news, and makes an awful lot of sense from my point of view. Thank you very much for the research, Angelique, and for posting about it, Nicola. I hope this leads to a cure, or even just better treatment (though the current one isn't all that bad). I really want my legs back the way they were.

  70. Karen, the way I see it, some of our MS might be reversible. But it won't be easy. It'll require work and time. But, wow, just the possibility...

  71. This might support the work of Dr. Terry Wahls, who has managed to reverse the effects of her MS syptoms through diet and exercise and is studying the method in other subjects.

  72. Very interesting. I wonder how much of this applies to myalgic encephalomyelitis (chronic fatigue syndrome)? There are similarities, though in my case I've been vegan most of my life and my LDL is ridiculously low. I do get deficient in vitamin D, though, so there may be a connection. I look forward to hearing more about this!

  73. @ Karen: thank you. I do hope MS research will get a bit of boost with this new framework

    @Anon: possibly. Of course, with all research and trial, results will need to be closely analyzed and solid evidence will need to support the findings to see whether there really is something to it or not. But yes, it is my dearest hope that the paper will give a framework from which to work from.

  74. @ Classical Bookworm. That is a tough question, and I have not really looked into CFS. But I would not be surprised if there were a link, indeed. Email and I'll send you the paper right away.

  75. @ristpastels "Even animal fats can be good but only if unadulterated and fed on their natural diet."

    That's an interesting hypothesis, but it doesn't seem to fit with the epidiomological data. New Zealand is listed as having the highest worldwide prevalence of MS ( and pretty much all NZ beef and lamb is grass-fed; all the dairy products also come from grass-fed cows.

  76. Anon @2:06, I watched Wahls' TED talk. I'll want to watch it again and ponder it but, yes, I think the two approaches have some overlap.

    Classical, my first diagnosis was ME (in the UK, in 1989). I moved to this country, my dit changed (from vegetarian to omnivorous)--and I had a lot of stress (immigration, etc.). I got diagnosed with MS in 1993. Angelique will correct me if I'm wrong, but this vicious cycle isn't just about just LDL numbers. It's about the combination/ratio of many varieties of lipids, and carbohydrates, and stress (trauma, pathogens, etc.) as well as D3.

  77. Nicola, another interesting paper is:

    The correlation between prevalance of MS and geographical latitude (Figure 3) is amazing.

  78. FranW, "The correlation between prevalence of MS and geographical latitude is amazing." Not if you read Angelique's paper. Then it makes perfect sense :)

  79. Wow.

    I don't have MS, nor do I know anyone who does. I'm just a curious guy. I love it when something like this comes about.

    I was diagnosed in 1991 with Wilson's Disease, but this year the diagnosis was, um, unconfirmed, so to speak. In the intervening 20 years I did become familiar with the Wilson's community, and with the dynamics of groups of folks with a chronic and debilitating condition. So I love it when something new like this is uncovered.


  80. I hope Angelique will contact the researchers of the International Society of Neurovascular Disease with her paper.

    Dr. John Cooke is the endothelial researcher from Stanford University I contacted in '08 regarding endothelial dysfunction and MS. My theory was based on cardiovascular research into nitric oxide. He will be making a presentation at the ISNVD meeting in February regarding his research, as well as Dr. Michael Dake, the physician who treated my husband for malformed jugular veins, and dozens of researchers looking at MS as related to the vascular system.

    There is a connection to all of this. Whether we look at NO, C-reactive protein, or lipid metabolism, it is still about the blood and vasculature. It is heartening to see the EAE model of MS falling away. Here is the program I created for my husband-

  81. Tim, I hope that whatever your condition is, it's under control. And, yes, I love when this kind of thing comes together.

    Joan, thanks for the link. I'll check it out.

  82. This is huge news, not just for me (undiagnosed) but for my entire family - mother, aunt, cousin and I all have something that has been tentatively diagnosed in 3 out of 4 as secondary progressive multiple sclerosis.

    It makes sense - I moved to Chicago in 2009, where my diet changed radically (very vegetarian with low amounts of animal fats) to a very... gastronomically-rich diet. My cholesterol jumped, my exposure to sunlight dropped, and after a particularly stressful trip to Texas with a nasty encounter with bedbugs in 2010, I started having fasticulations, pain, and vision issues.

    This gives me hope - I have three daughters, my cousin has two, and that's five little girls I want to spare this.

    Thank you. Thank you, thank you, thank you.

  83. g.rowan, I wish all of you well. I hope to talk early next year about what I'll be doing to help myself in light of this paper. I couldn't presume to suggest anyone else make the same choices, but I'll be contemplating diet, exercise, and supplementation.

    I do think we can reverse some of this.

  84. Hi Nicola and Angelique. I am part of a health discussion group on Facebook and we caught wind of your paper yesterday. Would it be possible for you to send me a copy as well,if it's not too much trouble. A few of our members are keen to read more as they live with MS, and a few more have other autoimmune issues that may relate. Thank you so much for this work!


  85. Well,I suppose I should give my email! Sorry, :)

  86. Hi Angelique,

    This is great news. Would it be possible to send me the paper as well?
    Thank you so much.

  87. Meredith, it's our pleasure. The paper is on the way.

    Uli, it is, isn't it? I've sent you a copy of the paper.

  88. Hi Nicola and Angelique. This is Christopher. Could you please send a copy of the paper to "romancc112(at)" Thank you so much.

  89. Aha! found comments section after writing an email to you personally. To resummarize briefly, I have been on Swank diet for over a quarter century and it's a MUST for me to control my neurological problems, which occur if off the diet. I also MUST have enough magnesium, D3, calcium, E, and B1 to stop spasm and jerkiness. I have two other major diseases, Porphyria (error of metabolism) and Polycythemia Vera (proliferation of white cells and red cells). I have been on a balanced good carb and protein diet, with low saturated fat, for many years. I am sure I have a lipid disorder but no one has followed up. I avoid most sugar. I think this vindicates Dr. Swank's work, even though he himself thought MS was an autoimmune disease wherein the body got overactivated in the presence of fat, and then attacked myelin. I was his patient, although he was not my first diagnosing doctor. My porphyria became a more dominant dx,
    but I still follow the Swank diet.

    Mariel, Seattle native, New Mexico exile.

  90. Christopher, done.

    Mariel, yes, I think Swank was on the right track. Now we have the science to prove it. Sceptics like me need a framework to bolster our will power--but I'm delighted that you found a way to make it work. I'll send you a copy of the paper; perhaps your doctors will find some useful clues.

  91. Dear Nicola and Angelique,thank you very much! In "my" facebook group whose members are MS patients something was posted which seems like similar research
    If it is possible to send me papers,on webadresa(at)yahoo(dot )cом many,i'm very interested to read it... I hope and belive that Angelique is on the right way. Thank you.
    Best Regards

  92. Irena, done. The paper's on its way.

    Yes, that paper (Serum Lipid Profiles Are Associated With Disability and MRI Outcomes in Multiple Sclerosis, Bianca Weinstock-Guttman; Robert Zivadinov; Naeem Mahfooz; Ellen Carl; Allison Drake; Jaclyn Schneider; Barbara Teter; Sara Hussein; Bijal Mehta; Marc Weiskopf; Jacqueline Durfee; Niels Bergsland; Murali Ramanathan | J Neuroinflammation. 2011;8(127) ) looks extremely interesting. Thank you.

  93. Everyone, I'm going offline for a couple of days. We'll pick this up when I get back.

  94. My mom has MS (1995) but many doctors doubt her diagnosis, because in addition to hand numbness, and confirmed lesions on MRI,predominantly in the spinal cord, but no other symptoms. She has been lying in bed for the last two years because of the severe pain and cramps in the stomach (appearing every few hours,and every time she gets up) All gastroenterological analysis we have done have not revealed the cause. She has a deficit of iron,vitamin D and the last doctor told us that it could be a rare disease of metabolism .She hasn't celiac disease. I think she has to do analyse on Porphyria, but I don't know much about it. Every advice is welcome. l would be greatful if Mariel would give me opinion .Thank you.
    @Nicola Griffith Thank you for the document!:)

  95. Hi Nicola and Angelique,

    Fascinated to read your meta-analysis, especially after all the hype about CCSVI. I was diagnosed 19 years ago with MS, doing *fairly* well, on Copaxone, Vitamin D3 and Low-dose Naltrexone, but would like to see whether I can get rid of it altogether.
    Could you send me your full paper, please?
    Many thanks,

  96. @ Classical: sorry for the delay in answering, as I was traveling (currently in Belgium for the Holidays - with a severe jetlag!). You're absolutely correct: it's not just about LDL levels (in fact, those can be very variable and elusive when tested outside of relapse or acute events), but a combination of factors such as carbs, lack of VD3 etc. And of course, for some MS patients, genetics also play a great role.

    @g.rowan: I very much hope this new framework will move research and treatment forward so that MS can be a thing of the past.

    @Joan: Actually, I have found a connection between restenosis, levels of NO and explain it in the context of my new hypothesis.

    @Tim, Mariel, Uli, Irina, Meredith, Christopher and Lesley: the paper is on its way (either via me or via Nicola). We very much look forward to your feedback/comments/critique/questions. :)

    @Irena, thanks so much for the link! Yes, it was amazing to see this new study come to light as my paper was being in press. It offers further empirical evidence for the framework I just hypothesized. I actually contacted the SUNY Buffalo team.

    In the meantime, I wish you all a very Happy Holiday Season!

  97. Hi Angelique Corthals, I am so pleased that you have spent the time on this subject. I have been researching the jigsaw MS and find that you have come to a similar understanding as I have been. The variances in people with MS in itself is the key to not hanging ones hat on any theory. There has always had to be an underlying 'reason' that had to be explained and studies begun. I have placed Nicola's blog address on many FB sites with the hope of stirring some positive action. Thankyou.
    Can I please have a copy of you paper,

  98. Nigel: Thanks for reposting the link. The paper is on its way.

  99. Has anyone considered if the processes detailed in this review paper may also be applicable in other situations such as Type 1 diabetes and Alzheimer's?

  100. Ted: yes, very much so. I do believe a lot of autoimmune disease may follow a similar pattern (because they share similar symptoms/processes). However, I only concentrated my research on MS, so it would be too early for me to equate Type 1 diabetes and Alzheimer's to MS in the framework I am currently proposing without further research. (But I have a hunch that it will be done soon!). Also, there are many teams currently working on the roles of PPARs in diabetes and Alzheimers, and they are very much going in the direction of lipid metabolism as well.

  101. I would like a copy of the paper too, please.

  102. Just saw this on FB may be of interest!

    We view the etiology of MS as being a wound
    in the CNS which leads to a compromise of the
    cerebral microcirculation and an ischemic hypoxia of the associated tissues. The wound results
    from damage done to susceptible arteriolar walls
    by shear and pressure trauma, the subsequent activation of arachidonate and polyenoic fatty acid
    metabolism, stimulation of endothelial cells to
    become phagocytic with these processes producing PRROS, which in conjunction with endothelial cells undergoing mitosis, cause disruption of
    capillaries-including the normally impermeable
    blood-brain barrier: there is subsequent edema
    formation, capillary and venule constriction resulting in an exacerbation of an ischemic hypoxia,
    followed by a secondary damaging process related
    to the immune system

  103. Nicola--I truly hope you contact the researchers at the ISNVD with your Nigel (above) links a paper I posted yesterday from the 1990s on the Facebook page I admin, CCSVI in Multiple Sclerosis. There has been over a century of research into the connection of MS to bloodflow...from Rindfleisch, Fog, Putnam, Swank, James.

    Dr. Zamboni found intraluminal truncular venous malformations, which change hemodynamics--just as they do in Budd-Chiari disease. NO and endothelial dysfunction could create restenosis, but so could a return of an intraluminal flap or inability to repair a malformed valve. If you believe you have an answer as to restenosis that may not have been considered-it would be wonderful to get your input to the doctors.

  104. excuse me...above addressed to Angelique.--Joan

  105. I would like a copy of your paper as well. Thank you

  106. Nigel, Joan, I'll let Anqelique respond to your suggestions. But thanks for the links.

    Anon@5:50, it's on it's way.

  107. @Nigel and Joan. Thank you very much for your comments. I am going to reply to both, as your questions have some overlap. Nigel, I have no doubt that a wound is part of the mechanism of MS. But I do not believe that it is the etiology of the disease. What causes the wound in the first IS more likely to be the etiology. As we know from many cases of MS, the disease can be triggered by any number of events, ranging from trauma to bacterial, viral or even parasitic infections. And this is where the wound to the BBB (blood brain barrier) is a result, rather than a cause, of MS: under hyperlipidemic conditions, platelet-expressed CD36, a scavenger receptor, sense oxidative stress and modulate platelet reactivity, leading to vascular atrophy and thrombosis (which also explains - in part - the narrowing of blood vessels). By increasing platelet aggregation, CD36 alters the structure and permeability of the BBB, increasing the adherence of platelets to microvascular beds and activating the neurotoxic cytokines. Furthermore, under hyperlipidemic condition and dysregulation of the lipid homeostasis, the expression of the central lipid/immune system node PPARβ/δ in the brain, which regulates the integrity of the BBB by controlling the VAP-1 adhesion molecules, as well as enhance angiogenesis and vascular repair, collapses. The deficient expression of PPARβ/δ, induced by elevated levels of free fatty acids and oxLDL in the serum, results in impaired vascular repair, diminished vascular flow, a reduced hyperplastic development of the microvasculature, and dysregulation of the VAP-1 adhesion molecules, inducing more rolling monocytes to enter the layers of the endothelium, which will eventually choke on excess oxLDL, not go through apoptosis (ie. those now toxic, oxLDL loaded monocytes-become-macrophage do not die) and accumulate as cytotoxic plaques on the CNS, causing lesions and inflammation.
    So Nigel, yes, there is a wound, but I really don't belief it is the origin, but a mechanism, part of the process of MS. But I do not believe it is part of the etiology.
    In terms of restenosis, a deficient PPARβ/δ accelerate the expression of endothelin-1 (ET-1), a potent vasoconstrictor and regulator of vascular smooth muscle cells (VSMC) proliferation, and stops the synthesis of the main vasorelaxant, nitric oxide (NO), which leads to severe restenosis, by constriction of the vessel and unchecked accumulation of smooth muscle cells.

    Joan, what CCSVI does, is that it alleviates (for some), the symptoms of restenosis, but does not treat the cause of the restenosis. And I am afraid that many patients, sooner or later, will have relapses, since the root of the problem has not been taken care of. And those relapses may be worse than the original condition, because of the trauma of surgery. Now I know that many people would happily go through the CCSVI treatment to have, if only for the amount of time it will last, the alleviation of those symptoms. I absolutely respect that.
    I just find it extremely dangerous how quickly the procedure spread around the world, without clinical trials or solid scientific data to back up its benefits or show its potential harm in the long term. I can completely understand the reservation that even Dr. Zamboni himself has about the procedure now (

    I hope I answered your comments/questions, and that I have not been too technical. Don't hesitate to let me know. :)

  108. @ Joan and anyone interested in CCSVI: I think I found a good metaphor which reflects my views on CCSVI. Imagine your body is a diesel car. You put in it regular gas (cheaper, more conveniently available). Eventually, your engine's tubes get clogged, because it is the wrong fuel. To remedy that, you replace the tubes, but your engine is still a diesel, and you are still putting regular gas in. Eventually, the new tubes will get clogged again, and what's worse, smaller, irreplaceable, parts of the engine will break down because the source of the problem has not been addressed.
    Of course there are limits to this metaphor. But this is pretty much my view on the problem: you cannot mechanically fix a problem that is not mechanical in origin. Any fix like that is temporary. Though I perfectly understand and respect that a temporary fix is, for some, a real source of hope and strength.

  109. Regarding CCSVI, my own views on CCSVI are public: I wouldn't do it until/unless I get the disease itself under control. But everyone's disease is different. Everyone gets to make their own choices. People have their own lives and own reasons.

  110. If I can clear up the terminology, Angelique, there is some confusion on your part. "CCSVI" is a medical condition, documented by Dr. Paolo Zamboni--chronic cerebrospinal venous insufficiency. The treatment is called venoplasty--or angioplasty on the veins.

    CCSVI IS mechanical. It is caused by truncular venous malformations found in the jugular veins of pwMS. Dr. Fox of the Cleveland Clinic found malformed valves in jugular veins of pwMS upon autopsy. To put it in layman's terms and use your analogy, it is a broken valve, just like a broken valve in an engine.

    Please read Dr. B.B. Lee's explanation on congenital truncular venous malformations. They are formed in the womb.

    The fix is not temporary. My husband received stents at Stanford University, and has not restenosed in almost 3 years. His gray matter atrophy has reversed, his cerebral hypoperfusion is gone. He has had no relapses, no MS progression. It's not about's about the physical reality of a congenital malformation being repaired.

    Blood matters. The vasculature matters. The two work together and are inextricably linked. I encourage you, once again, to read the research and work with the team of the ISNVD. The doctors from Stanford will be presenting their research on the endothelium and MS, and their animals model of CCSVI in Orlando in February. I encourage you to join us there. best, Joan

  111. Joan, yes, I did mean CCSVI treatment. I am very happy for the success of the treatment in your husband, and hope that he will enjoy a relapse-free life. I want to reiterate that, though I am skeptical, I respect patients choosing to undergo the treatment and applaud their success, when warranted.
    As a scientist, however, I must keep on questioning results in terms of statistics. And so far, there are none to be had. I, like many others (I am expecting Dr. Z included) expect those impatiently. I also understand very well that for many, waiting is not an option.
    And yes, if possible (heavy teaching load next semester!), it would be lovely to attend the ISNVD conference.

  112. Hi, Nicola asked me to write my questions and dr Corthals answers here on the blog so others may get benefits as well and this is a good idea, here they are:

    drAC: To answer your questions:

    tomke: Is there any method of analyze to check whether my lipid metabolism
    is dysregulated? so I can go and verify?eg oxLDL?

    drAC: Yes, indeed, there is a method. Regular tests usually do not detect the finer kinks of the lipids, such as oxLDL levels, or VLDLs. These tests have to be done in specialized lab. You can ask your GP (personal physician) to point you to such a lab in Poland. There should be a dozen at least able to perform that test.
    There has been an interesting comment on a french blog addressing that question in response to my article (if you use Google Chrome, you can have the page translated):
    (look at the last comment on the page)

    tomke: For instance, I did a blood analyse and results showed that I have a
    big amount of cholesterol, especially LDL:

    Cholesterol 242mg/dl
    LDL 171mg/dl

    drAC: Yes, so that's already showing a trend towards too much LDL, which then increases the possibility of turning into oxLDL and lead to further exacerbation of your symptoms. Have you discussed the possibility of lowering your cholesterol with your doctor/ personal physician?

    tomke: and what is more interesting, I do have also very little D vitamin,
    below the theshold.
    In my case its 24 (range 30 - 80).

    However, not all MS patients are in the same situation, many of them
    have cholesterol and vitamin D in normal, how can it be explained?
    Does it have any meaning those levels of cholesterol?

    drAC: Low levels of vitamin D are common in patients with MS. The levels are particularly low when the cycle of MS is close to or after a relapse. During remission, patients may experience normal levels of vitamin D (but usually not without some supplementation).
    Also, levels of vitamin D depends from populations to populations (in some populations, the levels of VD3 may be normal), and from the type of MS you may have.

    tomke: I've taken Copaxone (since not long time) but Im interested how does
    it work according to your theory?

    drAC: It acts on your immune systems cells, and prevents the Th1 to become inflammatory by shifting them into the less anti-inflammatory Th2 cells.
    It fits in my framework by performing the role that a functional PPAR alpha has: to activate the IL-4 Interleukin-4 which stimulates the differentiation of naive helper T cells into Th2 (CD4) cells. If your PPAR alpha is deficient, due to a dysregulation of lipids, than your Th2 cells are differentiate into Th1, toxic cells. So, in effect, copaxone replaces that one disabled function of the PPAR alpha.

    tomke: What are next steps, how can we (patients) follow-up events going on
    in this subject?

    Can we - patients help you somehow in the research?

    drAC: I am going to write a biweekly lab blog, which will keep up with research in my lab, and will post any news or link of interests.
    And you are very much helping with your comments and your experiences. I have been applying for a grant at the NIH on the etiology of MS and address my initial findings indeed, and should this be successful, I will interview both MS patients and controls. I will let you know the status of the grant as soon as I know. You can also stay tuned to my lab news at this page:

  113. Tomke, Angelique, thank you so much for sharing all that information.

  114. Nicola.... been reading and reading. This is so wonderful and exciting. Could you please send me the paper also? I have two Neuro's that I want to share it with. I am so anxious to hear about your 48 hour (so far) regime. Can hardly wait the few more days. Jeannie (having trouble posting this so trying the anon for my name)

  115. this is so interesting! Before my diagnosis I had a change from a healthy outdoor lifestyle to an indoor poor diet life. Since my diagnosis 5 years ago I have been following Swank without an exacerbation. Please send me a copy of your article.

  116. I'm both fascinated and excited by this news. I'll certainly keep an eye on this useful blog. Thanks to both of you!

  117. Hello and thank you for this wonderful research!
    There are many in the MS world who have successfully reversed their condition and gone from being bedridden or in wheelchairs to walking and running normally again by going on specific diets (no gluten, no sugar, no alcohol, little-no grains/ starches and eating lean meats, low sugar fruits, nuts and seeds and lots of vegetables) along with taking specific supplements and exercising.
    How could diet/ supplements/ exercise impact 'faulty lipid metabolism'? Do you think that those who have successfully reversed their MS (through diet/ exercise/ supplement/ stress management) did it by unintentionally fixing the problem you are proposing? Can PPAR dysfunction be remedied with lifestyle changes?
    Thank you and best of luck with your future endeavors!

  118. Hi Nicola

    You might like to look at the work of Ray Peat, who has long been arguing nutrition as key to many things, including MS:

    best wishes

    some old thoughts of mine:

  119. K-Man, I believe Dr Corthals (the real authority) is currently travelling so might not be able to respond for a day or two. My non-expert opinion is that, yes, dietary (and other changes) can improve PPAR function which leads to an unravelling of the vicious cycle of MS.

    Dennis, thanks for that. I'm encountering many such stories now...

  120. I would like a copy of the paper too, please.

    Thanks, Vladan

  121. I was DX with MS in 2000. I have tried everything under the sun. Copaxone, Avonex, LDN, Hookworms, Best Bet diet, you name it I have tried it. Do you know what has worked wonders! more than wonders is Cholestyramine (CSM). I quadruple the dose. It flushes all the junk out of my gallbladder and liver. I have no idea how it works. I just stumbled on it. I do it every 3 months. Havent had a flare forever since doing it. Your Liver and Gallbladder have alot to do with your cholesterol and LDL right? Anyway, for those of you that have tried everything like me. Try Cholestyramine. Its super cheap and generic. Airon

  122. Airon, I'm really glad you've found something that works.

  123. I hope you also look at the role Estrogen plays with LDL particle size. It may explain issues related to menopausal cycles and abatement with birth control pill use.

  124. Hello,
    I love the way everyone ignores the "high carbohydrate, High Sugar intake" portion of her hypothesis and immediately focus on fat Intake.


  125. Beth, people hear 'lipid' and jump to conclusions. But I think the carbs are very, very important.

  126. Thank you for this information. My history: 35 yrs ago EBV DX, then Probable MS, then ME (CFS). Currently have chronic symptoms of CFS and very high LDL (even though on a very low fat diet)and severe PLMD. Take Estrace. Am 65 yrs. old

    Research sounds related to my condition and would very much appreciate a copy of the research paper. Thank you.

  127. QUESTION for Dr. Corthals: if diet is responsible for disrupting lipid homeostatis, why would you look to drugs (statins and fibrates) to address the symptoms? Wouldn't it be preferable to change the diet and thereby remedy the actual CAUSE of the problem?

  128. Anonymous: the lack of lipid homeostasis can be genetic (compounded by environmental factors - just like hyperlipidemia), and in that case, diet alone will not be sufficient. LDL-lowering drugs and PPAR agonists (fibrates) may be necessary. But neither statins or fibrates as they are currently on the market would help in their current state. It would have to be a very carefully controlled, individually tailored the patient use of made-for-MS fibrates, if necessary supplemented by statins.

    1. Dr. Corthals, how does your promotion of statin drugs in the treatment of MS square with research showing that statins are detrimental to myelin? Consider the following few examples from a much broader body of research:

      1) Negative Impact of Statins on Oligodendrocytes and Myelin Formation In Vitro and In Vivo, by Steve Klopfleisch et al, The Journal of Neuroscience, December 10, 2008. ABSTRACT EXCERPT: "In this context, our study indicates that statins should be used carefully since long-term application may negatively influence the intrinsic remyelinating capacity, not only in MS patients, but also in other demyelinating diseases of the CNS." (

      2) Statin Therapy Inhibits Remyelination in the Central Nervous System, by Veronique E. Miron et al, American Journal of Pathology, May 2009. ABSTRACT EXCERPT: "Our findings suggest that simvastatin inhibits central nervous system remyelination by blocking progenitor differentiation, indicating the need to monitor effects of systemic immunotherapies that can access the central nervous system on brain tissue-repair processes."(

      3) Simvastatin Interferes with Process Outgrowth and Branching of Oligodendrocytes, by Smolders, J Neurosci Res., Nov 15, 2010. ( ABSTRACT EXCERPT: "We conclude that simvastatin treatment has detrimental effects on OLG process outgrowth, the prior step in (re)myelination, thereby mortgaging long-term healing of MS lesions."

      4) Cholesterol: A Novel Regulatory Role in Myelin Formation [of the CNS and PNS], by Saher G et al, Neuroscientist, February 2011. ABSTRACT EXCERPT: "The function of myelin for rapid saltatory nerve conduction is dependent on its unique composition, highly enriched in glycosphingolipids and cholesterol. Cholesterol emerged as the only integral myelin component that is essential and rate limiting for the development of myelin in the Central Nervous System and Peripheral Nervous System. Experiments with conditional mouse mutants that lack cholesterol biosynthesis in oligodendrocytes revealed that only minimal changes of the CNS myelin lipid composition are tolerated. In Schwann cells of the PNS, protein trafficking and myelin compaction depend on cholesterol." (

      Do you address the foregoing research in your paper? What are the implications for your proposed use of statins in treating MS?

  129. Anon, Angelique, I really hope the pharmaceutical industry is paying attention. Similarly, I hope that people with MS don't start just randomly taking fibrates and statins hoping for a miracle.

    1. Nicola, your concern is certainly not unwarranted.

  130. so is there a cure for MS

  131. So there ain't no cure for MS

  132. Ever since I was diagnosed I started taking 4000iu vitamin D daily and changed my diet to include less carbs and fat and more lean protein such as tuna, lost about 60lb. That was 3 years ago. Now I am reading this article and so far it all makes sense. I doubt these changes I have made will correct the problem but at least I am convinced it should not make it worse. The only puzzling part is none of my relatives even distant ones have MS and their diet consists of similar food and quantity. Only difference being I moved to a colder country when I was 15 and got diagnosed when I was 29.

  133. Anon, colder generally means farther from the equator which means less sunlight. This, of course, means less production of vit D. That's the difference--or at least part of it.

  134. Nicola, even before I was 15 I was not much of an outdoor person so I know vitamin D definitely plays a role in it. Also up until I was diagnosed me and my family were a big fan of carbs. Maybe its a cultural thing but we ate a lot of white bread,rice and pasta and cheese.

  135. Anon, well, if you're genetically predisposed to MS then, yep, that diet wouldn't be good.

  136. Hi, I have a diagnosis of ME but have been mostly well for past 10 years or so. I am really interested in this research. Could I have a copy of the paper please? kazolis[at]f2s[dot]com

    1. Hi Kath, I believe the article is highly problematic in that it summarily promotes pharmaceutical intervention via lipid-lowering medications, including statin drugs.

      I am still awaiting the author's response to my preceding comment on the matter. I cited examples from an ongoing body of research indicating statins are detrimental to myelin -- which is of special concern in this context since, as we know, MS is a demyelinating disease.

      That being said, you can download a FREE COPY of the article at this link...

  137. Hello-
    But crucially what 'carbs' are you talking about?
    And what saturated 'animal fats' This is so non specific as to be fairly meaningless. Almost every vege/fruit has some carbohydrate.
    There is a world of difference between say KFC deep fried battery chicken in rancid veg oil-and say grass fed anything, oily fish, free range poultry etc - There is a world of difference between white 'bread'and sugar and say a baked yam -all carbs. Its very dangerous being inacurate and vague about definitions,you must be as specific as possible or it breeds paranoia, dangerous confusion and misunderstandings about diet.
    Plus the American diet appears to be the most grotesque, unnatural and bizarre on the planet-It barely registers as nourishment.

  138. Why do you talk about CCSVI as if it was a blocked artery, dependent on diet?

    As I understand it,
    its a damaged vein either in utero or possibly through subsequent trauma