11 thoughts on “MS is not a disease of the immune system”

1. Any updates on corroborating (or invalidating) research?

2. Henk, it's not original research. It's a survey of extant research and a reframing of the paradigm. All the research eviewed is fully cited (and, itself, already reviewed and–mostly–replicated).

   I believe Dr Corthals is spot on: MS is the result of faulty lipid metabolism. I believe that ten years from now, no one will doubt it. It just takes time to turn the ship…

3. RESUBMITTED QUESTION: 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 established on-going 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.” (http://www.jneurosci.org/content/28/50/13609.full)

   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.”(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671276/)

   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.” (http://www.ncbi.nlm.nih.gov/pubmed/20857509)

   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.” (http://www.ncbi.nlm.nih.gov/pubmed/21343408)

   Indeed, Dr. Corthals it is worrisome to have you fail to address any of the foregoing research while advocating that statins be used in the treatment of MS; both as a monotherapy and in combination with fibrates. Beyond detrimental effects on myelin, statin drugs have very well-documented, and well-publicized, myotoxic side-effects in the general population; ranging from transient muscle pain, to skeletal muscle damage, to full-blown rhabdomyolysis — whereby muscle breaks down and muscle cell contents enter the bloodstream, which can culminate in acute renal failure and death. Unfortunately, the myotoxic properties of statin drugs are exacerbated when statins are used in combination with fibrate drugs. Overall, rhabdomyolysis is found to occur THREE TIMES more often when a statin drug is used in combination with a fibrate drug, versus statin monotherapy. More alarmingly, it is found to occur TWELVE TIMES more often when a statin is combined with a particular fibrate called Gemfibrozil (Lopid). The distinct down-side of combining statins and fibrates was most vividly apparent when the combination of Cerivastatin and Gemfibrozil resulted in 52 deaths and led to the withdrawal of Cervistatin from the market in 2001. See: “Incidence of Hospitalized Rhabdomyolysis With Statin and Fibrate Use in an Insured US Population”, Amend et al, 10/12/2011, The Annals of Pharmacotherapy…(http://www.medscape.com/viewarticle/751026). These concerns are of the gravest importance to us and we trust that you will see fit to reply in full.

4. Nicola, I've tried posting a particular comment three times and it initially shows up as “published” — but, when I refresh, it's no longer there. Is it being auto-deleted or something? Thanks.

5. Dr. Corthals' “faulty lipid metabolism” hypothesis claims to provide a definitive explanation as to why women are more likely to develop MS. The takeaway message appears to be that, in women, “faulty lipid metabolism” more commonly leads to MS — and in men it more commonly leads to atherosclerosis. Which begs the question: if so, how so?

   Furthermore, in people over the age of 50, the primary-progressive MS subtype is more likely to appear in men than in women. How does Dr. Corthals' hypothesis account for this phenomenon? See: “Primary Progressive Multiple Sclerosis”, by Miller and Leary, Lancet Neurology, August 2009. (http://www.ncbi.nlm.nih.gov/pubmed/17884680)

6. Anon, I've just retrieved your long comment from the spam folder. I assume it got flagged as span due to the number of URLs cited.

7. Anon, you are talking to the air. This is my blog. Dr Corthals doesn't read it, generally. But if you take the time to read through comments on the main post on this topic (linked in the post above), you'll find that your statin question has been asked and answered: they can't be used in their current form and need to be administered on a case-by-case basis. (Plus if you actually read the full paper, you'll see why your questions don't really make sense in context.)

   Next time you drop by, it would be nice to know your name.

8. Hello Nicola,

   My name is JP. Thank you for the reply and for your thoughtful reposting of my comment and questions to Dr. Corthals. I'm sorry that you appear to feel I'm nattering on here. Regarding your suggestion that I read the full paper by Dr. Corthals and all the comments on the previous main post — I had already done so prior to posting any of my own comments on this blog last month. (I am an academic by profession. Ergo, I usually have a go at the homework before weighing in, which is not to claim full and total comprehension of the material.)

   Long story short, Dr. Corthals paper hypothesizes: “MS is a chronic metabolic disorder”, akin to atherosclerosis, arising from a “dysregulation of lipid homeostasis”; that is caused by: “A diet high in terrestrial animal fats and carbohydrates; rich in triglycerides; and low in polyunsaturated fatty acids; compounded by environmental factors such as a low availability of sunlight, and genetic factors linked to the PPAR regulatory functions in lipid homeostasis and the immune system”.

   Having thus concluded that MS is a form of lipid disorder, Dr. Corthals further concludes that it must be treated with the same lipid-lowering lowering medications that are used to treat lipid disorders associated with atherosclerosis, namely statin drugs and fibrate drugs. More specifically, Dr. Corthals boldly states that these drugs will provide a CURE for MS (never mind that nobody has ever claimed that they are even a cure for atherosclerosis).

   By way of supporting argument for the impending cure, Dr.Corthals makes fleeting mention of a handful of studies wherein statin and fibrates have shown “much promise” in the treatment of MS. Suffice to say, there is nothing remotely resembling a scientific consensus on the matter of using these drugs to treat MS. Yet, Dr. Corthals makes no mention whatsoever of of this fact; nor a vast body of research on statin and fibrate side-effects in the general population; let alone a more specific body of extant research that finds evidence of harm, or no benefit, when these drugs are studied for their effect on MS.

   When queried on this subject Dr. Corthals' deflects by restating what she wrote in the conclusion to her paper: “A cure for MS will not be achieved by taking one or the other [statins and fibrates], or both, in a symptom-by-symptom approach, but by modulating the effects of both medications in order to reestablish the homeostasis of the lipid metabolism…The new framework presented here makes a cure for MS closer than ever”.

   Well, as long as we're waiting for a futuristic statin-fibrate MS cure, might we not use some of the time to discuss the adverse effects these drugs are having in their present-day form? At the risk of belaboring the point, I've previously cited a substantive body of research which demonstrates that statins have a detrimental effect on myelin; and, in the general population, the foremost statin-induced side-effect is muscle toxicity – which is compounded when statins are combined with fibrates. Surely, this subject has critical relevance to an MS patient cohort, if for no other reason than that there must be numerous people with MS who are ALREADY taking statins, and fibrates, in their CURRENT form without being made aware of the pertinent hazards with respect to their particular health condition.

   Nicola, on the original post you expressed concern that people with MS might hear of Dr. Corthals' lipid hypothesis and mistakenly conclude that they should start “randomly taking fibrates and statins hoping for a miracle”. Suffice to say, I share that concern ten-fold; and I sincerely hope that Dr. Corthals will see fit to contribute something further to the discourse, if only to ensure that her paper isn't mistaken for a prescription. Thank you kindly for hosting this discussion.

9. JP, welcome. But I'm a bit puzzled about what you're trying to achieve. We've all acknowledge that statis and fibrates in their current form are not what people with MS need in the context of Dr Corthals' new framework. I'm at a loss as to how she could be more explicit.

   As for this blog being a forum for more general debate about MS and the caveats surrounding various medications, no, that's not its purpose. You'll find that mostly here we talk about other things.

   But if some readers take away from your commentary the fact that we should all be careful and read all the literature, and discuss same with our physicians, then I'm happy, and I thank you for it.

   I

10. Hi Nicola,

    JP here. I realize, as you've said, your blog is not usually “a forum for more general debate about MS and the caveats surrounding various medications”, etc. However, your blog has had several posts about Dr. Corthals' research and, in that context, the blog has, indeed, become a forum for an unrestricted spectrum of MS-related discussion; particularly on the blog post that was up from December 21-February 21. Have the terms of discourse changed since then; and are commenters no longer welcome to speak freely about these topics on this new post that features Dr. Corthals' research once again?

    Now, perhaps I need to be more direct, if my intent is not yet clear. Here goes. In your defense of Dr. Corthals, you keep restating Dr. Corthals has acknowledged that current statin and fibrate protocols are not ideal treatments for MS. However, Dr. Corthals paper offers absolutely no exposition on this point, nor is there any mention of anything detrimental about the use of these drugs to date. In fact, Dr. Corthals' paper presents nothing but favorable studies wherein statins and fibrates have shown “promise” in the treatment of MS. Evidently, this exclusive focus on promising outcomes is a necessary prelude to Dr. Corthals' conclusion that MS can be “cured” by transforming this current class of lipid-lowering drugs into “made-for-MS fibrates, supplemented by statins”. Frankly, this an outrageous claim, all the more so because it is decidedly NOT supported by the totality of the existing medical literature.

    I have criticized Dr. Corthals for her exclusion of contrary evidence, particularly her failure to discuss well-established research demonstrating that statins and fibrates are detrimental to myelin and skeletal muscle. I have spent my life in peer-reviewed academia and this is the kind of omission that tends to be viewed as cherry-picking the evidence; sloppy scholarship; and/or intellectual dishonesty. Many of these points were also posed to Dr. Corthals by other commenters on an MS blog forum in the UK. (See: http://www.mssociety.org.uk/node/630969)

    Nicola, you have said you are “at a loss as to how Dr. Corthals could be more explicit” in this matter. Here's how: Dr. Corthals can start by acknowledging that there is a body of contrary evidence on the subject which shows lack of benefit and evidence of harm; Dr. Corthals can include citations and links to this opposing research in future iterations of her paper, public presentations, internet forums, etc.

    Note: statin drugs have had black box warnings about myotoxicity for several years and, this month, the FDA has issued additional warnings about memory loss and increased risk of diabetes in statin users. Regarding MS specifically, here is a link to the Cochrane Collaboration Review of the medical literature to date, by Wang et al, December 7, 2011: “Statins for Multiple Sclerosis; Conclusions: There is no convincing evidence to support the use of either atorvastatin or simvastatin as an adjunctive therapy in MS.”. (http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008386.pub3/full). Best to all.

11. JP, your comments keep being held back by this blog's spam filter. If at any point you find that your comments are not appearing, please resubmit you comment without the links. Just FYI. (I don't always remember to check the spam folder.)

    I've heard what you've said. So has Dr Corthals, who responded briefly here. We are all, as far as I can tell, in agreement.

    However, this isn't an academic forum. While you are, of course, welcome to speak freely, I suspect you're not going to get the kind of rigorously cited discussion you might be looking for.

Comments are closed.