The Vanderbilt Protocol for Multiple Sclerosis

The antibiotic approach to MS therapy was developed at Vanderbilt by Drs. Stratton and Mitchell. They have patented multiple versions of their protocol, most recently in 2005. (Since patents are publicly available and the “Description of the Invention” is often an excellent overview of the science, we’ve put links to patents at the end of this post.)

Since we have some readers with MS, including Alexander, I thought I would post a summary of the Vanderbilt protocol. This was written by Dr. Stratton in 2009:

Treatment Protocol for Chronic Infections Caused by C. pneumoniae

As far as the Cpn Antimicrobial Regimen is concerned, my thoughts (as of 2009) are as follows:

First, as a general rule, the sicker a patient is, the slower they should go. This is why our early protocol started out with only one antibiotic and one dose, and then gradually adding the next dose/antibiotic as the reactions to each dose/antibiotic became apparent. These reactions appear to be caused by destruction of Chlamydia organisms as well as by the death of some of the infected host cells. Even destruction of elementary bodies by reducing agents such as N-acetyl-cysteine (NAC) can cause these reactions as chlamydial major outer membrane protein (MOMP) is released. MOMP is known to interact with Toll-like receptors (TLRs) and can thus induce the production of cytokines. Moreover, chlamydial cell wall contains LPS, which also interacts with TLRs and induces the production of cytokines. The reaction to anti-chlamydial therapy is sometimes referred to as “die-off” as presumable both chlamydial organisms and host cells are dying. These reactions can be delayed by days to weeks and may include “flu-like symptoms”, arthralgias and myalgias, “hangover-like symptoms (“brain-fog”, nausea, malaise), gastroenteritis (including diarrhea), and (rarely) fever. These reactions are akin to the “leprosy reaction” well described with the therapy of leprosy. The use of prednisone (10-20 mg per day) and/or pentoxifylline (Trental, 400 mg bid or tid), as done for the leprosy reaction, may be beneficial.

I think that all patients should start with supplements/vitamins before they start any antibiotics. Baseline lab studies, including CBC and liver function studies, should be done and these parameters followed every 3-4 months, more frequently (i.e., monthly) for sicker patients. As C. pneumoniae can infect white blood cells and liver cells, potential death of these cells should be monitored in sicker patients. Our initial protocol recommended this. I would add NAC to the supplements. We used amoxicillin, which is degraded in the body to penicillamine (a reducing agent) in our regimen as an anti-elementary body agent, but NAC seems to work equally well and may offer additional benefits in boosting the immune system as well as protecting the liver. As far as supplements/vitamins are concerned, I think Professor David Wheldon’s supplement/vitamin suggestions are very complete and should be the benchmark. Once antibiotics are ready to be started, I would start with a macrolide. We have used Azithromycin because it is easy to give and has become somewhat cheaper since it went off patent. Clarithromycin (500 mg twice a day) or Roxithromycin (300 mg once a day) can be used instead of Azithromycin. I would still give just one 250 mg azithromycin tablet and then wait two weeks to see if there is any reaction to it. Then I would give two tablets, one on Monday and one on Wednesday. Once again I would wait two weeks. I’d continue in this way, adding each dose until the patient was taking 250 mg of azithromycin MWF. If the patient has severe reactions (meaning they can’t work – most people are trying to work and take care of a family while they are on this therapy), I’d slow down the process. After the azithromycin, I’d add doxycycline – again doing this very slowly. Once the patient was taking both azithromycin (250 mg MWF) and doxycycline (100 mg twice a day), I’d start the metronidazole pulses – again, doing these slowly and working up to a once a month pulse of 7 days of metronidazole (500 mg twice a day). Once the patient could do the monthly pulse of metronidazole, I’d add rifampin (300 mg twice a day). Once this was tolerated, I would increase the metronidazole pulse to 14 days, doing so slowly. Eventually, the patient should be able to tolerate metronidazole (500 mg twice a day) on a daily basis. Once a patient could do this regimen without any reactions, I would continue it for at least a year and probably three years for MS patients. It might take a year or two (or longer) to get to the point where there is no reaction to the daily metronidazole, depending on the chlamydial load, followed by 1-3 years of therapy. This might be a 5-year program, but should allow the patient to continue to work with minimal disruption. Patients should also be gradually improving during this time. The sicker the patient is, the longer the therapy is going to be. There is no shortcut. Younger patients who have not been sick as long tend to respond more quickly. ?

With MS patients, due to the possible CNS damage that might occur by going slowly, I would move more quickly unless there were major reactions. This means compressing what might have taken a year into several months. 

The reactions patients have are varied – some are severe enough that they stop the antibiotics. That, of course, defeats the purpose of the therapy. It is very tricky and each patient has to learn his own limitations. When we started our protocol, we were thinking of a hotline to answer questions that are now easily and better answered via the internet (http://Cpnhelp.org). Finally, I don’t think this is the only regimen that will work nor do I think it will work better or faster. It is just what I do in 2009 when treating a patient.

I’ve been informed that the late stages of the protocol have been further refined in 2010. Now, once die-off reactions to the metronidazole subside, Dr. Stratton tries rifabutin or rifampin.

I would agree with Dr. Stratton that nutritional supplements should begin 3-4 months before antibiotics, but would add that our diet should be adopted 3-4 months before antibiotics begin. This is necessary to improve immune response and healing capacity; and to avoid unnecessary cell death and die-off toxicity when antibiotics begin. The eleven ways to enhance immunity, discussed in Step Four of the book, should be routinely practiced.

Simply introducing diet and nutrition alone can lead to significant die-off effects. This shows that the adoption of diet and nutritional supplements is therapeutic in its own right.

On a bad diet, antibiotics are dangerous, as they risk gut dysbiosis and introduction of new co-infections.

Like Dr. Stratton, I think being active at http://cpnhelp.org is essential for anyone on this protocol. Many people at cpnhelp.org have used this protocol, often for years, and their experience can be very helpful.

As Dr. Stratton notes, it takes years to cure MS. It is necessary to be patient and to balance speed of killing pathogens against allowing the body time to recover from die-off effects – toxic bacterial proteins and human cell death. Remember, “the dose makes the poison” – doubling the rate of pathogen killing may quadruple the toxicity effects, so the optimum course is not the one with highest rate of pathogen killing. Every patient has to progress at his own pace. Go as fast as you can but no faster.

There are steps that can be taken to reduce die-off toxicity, such as drinking lots of water and eating salt to help urine excretion, and taking “moppers” such as charcoal, bentonite clay, cholestyramine, or chlorella to help assure that toxins released from the liver through the bile are excreted in feces, not re-absorbed.

Conclusion

MS recovery is not impossible; indeed, many have recovered on this protocol. However, it is long and arduous. Optimizing diet will shorten time to recovery, but it will still take years. 

MS is not the only disease that may be caused by C. pneumoniae. Alzheimer’s dementia, atherosclerosis, stroke, rheumatoid arthritis, and rosacea are all associated with C. pneumoniae infections and may be treatable by Dr. Stratton’s protocol.

Links

“Multiple Sclerosis:  A Curable Infectious Disease?”, July 7, 2010, https://perfecthealthdiet.com/?p=157.

“Is Multiple Sclerosis an Autoimmune Disease?”, July 5, 2010, https://perfecthealthdiet.com/?p=151.

“Eleven Steps for Overcoming Alzheimer’s and Other Chronic Infectious Diseases,” July 1, 2010, https://perfecthealthdiet.com/?p=134.

A list of the Vanderbilt patents.

The 2005 patent, ID 7,094,397.

Leave a comment ?

31 Comments.

  1. This may have already been answered in another post but I was wondering if there was any way for healthy people to get tested for a C. pneumoniae infection?

  2. Hi woly,

    There are antibody tests but they’re not very reliable. Many false negatives. You can maintain an intracellular infection and yet be antibody-free.

    Also everyone gets infected with C. pneumoniae sooner or later, antibody positivity rates are around 70% among adults, and you can have C. pneumoniae seropositivity without obvious disease. It’s a very subtle pathogen until it spreads and becomes abundant.

    People who develop antibodies often lose seropositivity unless a persistent infection develops or they get re-infected.

    So if you have clear symptoms of a chronic bacterial infection, antibody levels may help diagnose the species, but you wouldn’t start treating an occult infection if there were no disease symptoms just based on antibody tests.

    There are also PCR-based tests which are more reliable, but I don’t know that they are in clinical use yet. C pn infects macrophages so a PCR measurement of white blood cells would be a good test.

    As a practical matter, the best test is reaction to antibiotics. If you take doxycycline and have a strong reaction, you have some kind of bacterial infection.

  3. You mention doxycycline (which I believe is what Wheldon uses/used as well), but Stratton suggests a macrolide. Is there consensus as to which is better diagnostically? I imagine that the symptoms would be the same as they are cause by bacterial die-off. But I’m wondering which is more predictive of infection. Interesting stuff, this stuff.

  4. Hi Poisonguy,

    Both end up with a doxycycline-macrolide combination as the second stuff, so the choice is over which to start with.

    There’s not much evidence to go on. Dr. Stratton has the most experience, so perhaps we should go with his choice.

    I’m not sure which is better for diagnostic value. I would think both would work.

  5. I just hope the reaction for most people is almost immediate. If one had to wait two weeks, likelihood is that something else is responsible for these vague symptoms, not bacterial die-off.

    • In my experience, certain effects were immediate, for instance cognitive and mood improvements, others were delayed a week or two. White blood cell die-off seemed to peak after a week or so.

  6. Hi Paul,

    Been away for a bit and catching up – love this post.

    Question: How would one go about observing/testing white blood-cell die off while on antibiotics, as you appear to have been able to do. Were you doing a frequent blood test, or is your conclusion drawn from monitoring some (set of) symptom(s)?

  7. Hi Sammy,

    It’s easy, a CBC test counts white blood cells.

    I would recommend doing a CBC just before and a week into antibiotics, as a diagnostic check for C. pneumoniae.

    My doctor and I weren’t as prepared, so I didn’t do one until two weeks after starting and it showed low counts, well below my previous physical, but probably not as low as they would have been a week earlier. I had a big fungal infection flare-up that peaked a week after starting antibiotics, I believe due to a heavy white blood cell die-off that was starting to get repaired at 2 weeks.

  8. Hi.
    There are 3 of us in my family with Neuro problems: One with a sudden onset of a heartbeat/rushing sound in the left ear and constant episodes of head-rushes and losing balance; after multiple scans, the only positive result is the EEG with increased brainwave activity on the left side of brain. The neurologists have no idea what it is, offered seizure meds, although they said the activity is not quite seizure level. She refused meds and had been on the ketogenic diet with improvement as long as she stays on the diet.
    The second of us has slow onset of difficulty with word recall, random memory loss both short and long-term, just really not herself/something is really wrong. The neuro work-ups are inconclusive so far.
    and the third of us has a parkinson’s like tremor, including head-bobble, but it is not parkinsons, and does not seem to get worse. Also, improving with ketogenic diet.

    SO, my question to you is: would you be willing to post your story? Detailed information on how you found your way through your symptoms and treatment? Even your thought-processes and theories that evolved. I know it would be invaluable and at very least inspirational to many of us.
    And it may give us clues to further our recoveries.

    Thank you for putting so much information up for all to read and for the references, too!

  9. Hi kriss,

    Yes, I’ll certainly tell my story in upcoming posts.

    I’ll tell some in the zero-carb series, and then more in a later series on bacterial infections of the brain.

    It’s great that your family has discovered the ketogenic diet! That’s an important step in all neurological conditions.

  10. Thanks for the explanation, Paul.

    “I would recommend doing a CBC just before and a week into antibiotics, as a diagnostic check for C. pneumoniae.”

    At the risk of sounding obtuse, I just want to be sure that I understand: Are you saying that a reduction in WBC count at 1 week into antibiotic treatment would indicate the presence of a C. Pneumoniae infection? (Due to the host WBCells being killed off along with the C. Pneumoniae bacteria?)

    Also, I’m wondering: Would you say that an already low WBC count (3.5, Reference Range 4.0-10.0 giga/L) – prior to a positive diagnosis and antibiotic treatment – indicates anything in relation to this? Or suggests keeping an eye out for anything other than what you’ve discussed above?

  11. Yes … Normally white blood cells die after ~45 days and are replaced … This kills any bacteria infecting the white blood cells, and assures a continuous flow of (presumably uninfected) new white blood cells from the marrow … C. pneumoniae has evolved ways to suppress apoptosis (cell death) in white blood cells, helping it maintain infections … so C. pneumoniae infected white blood cells live a very long time. But antibiotics inhibit the apoptosis suppression, causing infected white blood cells to die off suddenly.

    An already low WBC count suggests an infection or other condition in the bone marrow. Your doctor should look into that if it is persistent.

    Here’s the Mayo Clinic list of causes of low WBC counts:

    http://www.mayoclinic.com/health/low-white-blood-cell-count/MY00162/DSECTION=causes

    A low white blood cell count usually is caused by one of the following:

    Viral infections that temporarily disrupt bone marrow function
    Congenital disorders characterized by diminished bone marrow function
    Cancer or other diseases that damage bone marrow
    Autoimmune disorders that destroy white blood cells or bone marrow cells
    Overwhelming infections that use up white blood cells faster than they can be produced
    Drugs that destroy white blood cells or damage bone marrow

  12. That’s great information, Paul – thank you very much.

  13. Regarding C. pneumoniae (CPn)- I think it’s fascinating that this organism is being associated with a number of chronic diseases including RA, interstitial cystitis, alznheimer’s MS, and others although, like many breakthroughs, it may take years to be accepted by mainstream medicine.

    My question: Since I have read in the Perfect Health Diet book that by a certain age, CPn can be found in a fairly large percentage of the population (varies by country), does this necessarily mean it will eventually progress to one of these chronic ailments? Or could it safely lie dormant in some individuals and never cause problems, requiring some co-factor to cause it to progress to a disease state (e.g. inflamation at the site where the disease eventually develops?) I seem to have read something about this from Dr. Stratton, although I also seem to remember him saying CPn in the body is never a good thing to have.

    Other thoughts?
    Len

  14. Hi Len,

    Well, everyone gets C pn, but it takes decades to progress to disease. On a bad diet it takes 20 years and on a good diet it takes 100. You want to be the one in whom it takes 100.

    All of these pathogens partially disable the immune system, and the more infections you get the faster they all progress. So they are all co-factors for each other. Bad diet is a co-factor, it feeds the bacteria and suppresses immune defenses.

    It’s never a good infection to have, but you can minimize the damage. If you die of old age at 110 before it causes problems, that’s not so bad.

  15. Hi Paul

    I have Rosacea with permanently red nose and generally red and inflammed eyelids. I noticed in PHD that you mentioned sufferning from Rosacea. Can you elaborate your symptoms and then what you do to manage/treat it, as the conventional wisdom is that there is no cure.

  16. Hi Carroll,

    You can see what I looked like in 2009 on our “About Us” page, here: http://perfecthealthdiet.com/?page_id=2. I would say it has been improving for about 3 years, but so gradually that I can’t finger any particular thing as being particularly helpful.

    My belief is that it results from some combination of chronic infections of the gut, oral cavity and blood vessels and/or nerves of the face. Chronic infections are notoriously difficult to eradicate, though they can be reversed with good diet, nutrition, fasting, and antibiotics.

    I don’t really have symptoms any more, just mild redness that sometimes is hardly noticeable. I don’t do anything special any more for it, just eat our diet and nutrition. My hope is it will continue to fade.

    I’ll try to do some posts on rosacea at some point. The literature isn’t very helpful on this illness, it’s amazing how little headway researchers have made.

  17. Just wanted to add that c. pneumoniae probably plays a role in Chronic Fatigue Syndrome (CFS/ME).

    Jose Montoya from Stanford is mainly into the CFS-Herpes (mainly HHV-6) connection, but he “features” Charles Stratton on the Standford site on CFS:
    http://chronicfatigue.stanford.edu/infections/chlamydia-experts.html

    John Chia has done some considerable work on the role of enteroviruses (in the gut) in CFS and he has one paper showing that in a very small subset of CFS patients, c. pneumoniae alone can cause Chronic Fatigue.

    I currently see MS and CFS as “endpoints” in a wider spectrum of disease, caused by several factors: Several pathogens, environment/diet and of course genes.

  18. And regarding CFS I forgot to mention Anthony Komaroff from Havard, Nancy Klimas from University of Miami, Judy Mikovits from the WPI, and, and, and, …

  19. Thanks, Tony. I’m so glad more researchers are getting on to this track, it’s the right one!

  20. Carroll and Paul,

    I have struggled with Rosacea for many years and while I believe fixing the gut and having the best diet possible is the best path to take, I found a product that really helped me: http://www.rosacea-ltd.com/. When I copied the list of ingredients and showed them to my naturopath and my allopatic dermatologist, they both agreed that it seemed to be a very good choice. The dermatologist said she was happy to know of something she could recommend to her pregnant patients.
    Hope this is helpful.

  21. Hi Paul,

    I have been following a diet pretty close to yours for almost 10 years, but in the past 6 months after discovering the paleo blogs and your blog, much more recently, I have been fine-tuning and seem to be getting better every day. I have rheumatoid arthritis, which is well controlled with a fairly low weekly dose of methotrexate. Of course, I would like to get off this medication and since my gut has improved so tremendously, I now feel it may be possible for me to try the antibiotic treatment in the near future.

    I just finished my first read-through of your book and was horrified to see what you say about folic acid supplements because I have taken 1 mg daily for about 7 years to counteract the folate depletion that occurs when I take the methotrexate. My rheumatologist said, a couple years ago, that I could stop taking it, but I was afraid of losing my hair. What is your take? Perhaps choline supplements would be beneficial? Hopefully, since I have been following a diet similar to Perfect Health for so many years, I am not doomed! 🙂

    • Take Biotin. I lost my hair at one point – I think? from antibiotics – started 10,000 biotin a day and hair grew back after many trips to dermatologist/hair people. Now I take 3-4 a day and all good so far….

  22. Hi Cathryn,

    Congrats on managing your arthritis! Hopefully you can cure it soon.

    Yes, I would take choline, B6, B12, and seek foods rich in natural folate; this should be enough for folate status, but 400 mcg folic acid from a multi is probably an OK addition. I wouldn’t supplement 1 mg.

    Best, Paul

  23. Hi Paul,

    I have MS, and this theory that a major factor is a pathogen certainly has merit. I know for a fact in 1995 I had walking pneumonia, although I can’t say for sure whether C. pneumoniae was the infecting strain, although sounds like a majority of the population has been exposed regardless. I’m nervous about the long-term use of antibiotics. Do you have any opinions on the use of essential oils, like origanum, and/or high-dose monolaurin, or colloidal silver, as alternatives to antibiotics?

  24. Hi Sean,

    I think when you have overt disease such as MS, the benefits from antibiotics are highly likely to outweigh the harms.

    Essential oils are mainly valuable in the gut or the skin. MS is probably due to co-infection with Epstein-Barr virus and a bacterial partner like C. pneumoniae, both of which establish chronic internal infections and are largely out of reach of the essential oils. If you have signs of gut dysbiosis, they’d be more likely to help that.

    Monolaurin has reportedly had a systemic anti-viral activity in some people, so that may help, but the evidence seems anecdotal.

    Colloidal silver – I personally would be nervous about putting metals in my body. I would take antibiotics long before I would take colloidal silver. But I haven’t explored the literature on silver, so I could be mistaken.

  25. Thanks for your input, Paul.

  26. the CPN link to MS had some air time on Australian TV yesterday
    http://www.abc.net.au/catalyst/stories/3572695.htm

  27. hi 🙂

    is it possible that the hematocrit levels drop very low when the die off or herx r 2 big/strong?

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