This shows you the differences between two versions of the page.
Both sides previous revisionPrevious revisionNext revision | Previous revisionNext revisionBoth sides next revision | ||
home:publications:marshall_chlamydia1_2009 [04.30.2009] – drtrevormarshall | home:publications:marshall_chlamydia1_2009 [01.03.2012] – external edit 127.0.0.1 | ||
---|---|---|---|
Line 1: | Line 1: | ||
+ | |||
+ | ~~NOTOC~~ | ||
+ | ====== Presentation - The Marshall Protocol in a Clinical Environment - Observations from the Initial Cohort ====== | ||
+ | |||
+ | {{ vimeo> | ||
+ | |||
+ | **Type:** Conference presentation\\ | ||
+ | **Presenter: | ||
+ | **Conference: | ||
+ | **Location: | ||
+ | **Date: | ||
+ | **See also:** [[http:// | ||
+ | ===== Transcript ===== | ||
+ | |||
+ | |||
+ | |||
+ | |||
+ | Dr. Radek Klubal: I would like to welcome back Dr. Marshall. He is mostly known according Marshall Protocol and he promised to comment the situation and to say his real view on the problem. So please, you can start. | ||
+ | |||
+ | |||
+ | ====Slide #1==== | ||
+ | |||
+ | |||
+ | Thank you very much. I'm going to quickly run through the Marshall Protocol. It's just an overview. What I first want to point out is something that was said by the FDA, the U.S. Food and Drug Administration Commissioner when he was talking to the U.S. Congress in 2006. And he said that new scientific discoveries are generating an emerging science of safety. This new science combines an understanding of disease and its origins at the molecular level (including adverse events) with new methods of signal detection, data mining and analysis. In other words, what the FDA Commissioner has been pushing towards is an understanding of the disease and the exact way the drugs work. That is really what we have been doing with the Marshall Protocol. | ||
+ | |||
+ | |||
+ | ====Slide #2==== | ||
+ | |||
+ | |||
+ | So, I'll start off saying what the Marshall Protocol is not. Firstly, it's not a method of using antibiotics to treat disease. That's first and foremost. The MP is a method of arresting and reversing the method whereby the persistent Th1 Metagenomic Microbiota - in other words the biofilm of bugs - overcomes the innate immune system in order to cause the chronic disease. The MP allows the patient’s own bodies to attack the pathogens and at a controlled rate, to reverse the ravages of the disease process. Especially with the most seriously ill patients, the MP is not a therapy where a physician can prescribe drugs and the patient will heal. There needs to be a partnership between the physician and the patient, where a significant responsibility towards cure lies in a patient’s own self education, understanding what is happening in their bodies as they heal and persistence. It is tough. | ||
+ | |||
+ | ====Slide #3==== | ||
+ | |||
+ | Now the documents describing in the actual protocol are available online here at this URL. And this presentation is going to be very quick and concentrate on those aspects of recovery which are most helpful to physicians who are seeking to understand the six stages of disease and recovery. And you can find those six stages in graphical form at that URL. As I said, a copy of these slides is available if you give us your email address afterwards. | ||
+ | |||
+ | ====Slide #4==== | ||
+ | |||
+ | Again, this is a picture of the cytoplasmic inclusions and these are some longer type of bacterial inclusions as well, inside the cell. | ||
+ | |||
+ | ====Slide #5==== | ||
+ | |||
+ | So we all know that antibiotics work really well This is a picture from the Max Planck Institute. And it shows part of the bacterial ribosome which turns RNA into proteins. And you have various antibiotics, | ||
+ | |||
+ | ====Slide #6==== | ||
+ | |||
+ | And here are some other pictures. We know that the rate of bacterial death is controlled by inhibiting proteins synthesis in the bacterial ribosome. We have to use sub-inhibitory, | ||
+ | |||
+ | ====Slide #7==== | ||
+ | |||
+ | **In chronically ill patients, people who are really ill, antibiotics alone will not kill the persistent pathogens.** If you get the disease early enough, then the patients will respond to the antibiotic reasonably well. But as the bacteria slowly overcome the patients immune system and shut down the patient’s own immune response, you get down to the point where the antibiotics just do not work anymore //in vivo//. | ||
+ | |||
+ | Remember that most antibiotics are actually tested outside the body, in the lab. When they are operating inside the body it’s a totally different environment. All three major antibiotics that we use, well actually minocycline and clindamycin and an antibiotic targeted against Tuberculosis: | ||
+ | |||
+ | Two things are disabling the innate immune system. One is the bacteria themselves. The bacteria are in a number of different ways overcoming the innate immune system and slowly shutting it down, thus allowing the bacteria to persist within the phagocytes. And then the other thing is exogenous Vitamin D. Because all we’re doing when we give Vitamin D supplements to a patient is actually making it easier for the bacteria to shut down the innate immune system. | ||
+ | |||
+ | ====Slide #8==== | ||
+ | |||
+ | This graph I showed in my first presentation – I won’t go over it again. To point out here is the PXR making the key enzymes CYP27A1 and here another key enzyme CYP24A1, CYP24A1 and CYP3A4 actually. And the PXR nuclear receptor is targeted by rifampin, minocycline and clindamycin. **So they have effects beyond the effect they have in the Petri dish.** | ||
+ | |||
+ | ====Slide #9==== | ||
+ | |||
+ | So the first thing about the Marshall Protocol is in order for the innate immune system to be given its best chance at restarting, all Vitamin D must be removed from the diet. The 25-hydroxyvitamin D, which is what you’ll measure in the blood when your Vitamin D that you get back from labs, should be less than about 30nmolar per liter, about 30nanomolar, | ||
+ | |||
+ | ====Slide #10==== | ||
+ | |||
+ | Well, we can use a drug to help the VDR restart. It’s a drug called Olmesartan, which was developed for high blood pressure. It’s a mild hypertensive agent. Here you can see the amount of blood pressure reduction in healthy patients. It’s not very much, about 12mm of mercury and occurs at very, very low doses of Benicar. The blood pressure effect is not really dose-related, | ||
+ | |||
+ | ====Slide #11==== | ||
+ | |||
+ | But this particular drug is what is called an agonist, it switches on the VDR, the Vitamin D Receptor which is at the heart of the immune system. So when Olmesartan is put inside the VDR it switches it on. Tt forms hydrogen bonds with the same amino acids essentially as 1, | ||
+ | |||
+ | So it’s a different way of turning on the Vitamin D receptor and it avoids the flow-on effects to the other nuclear receptors that the Vitamin D metabolites have. | ||
+ | |||
+ | ====Slide #12==== | ||
+ | |||
+ | This is another image of how the VDR works. I’m going to skip this one because we’re short on time. | ||
+ | |||
+ | ====Slide #13==== | ||
+ | |||
+ | And if you remember, this is the picture we show the emulation of the behavior of the human Vitamin D Receptor with Olmesartan sitting stably in the binding pocket and keeping the helices in the correct location. Keeping the molecule in the correct shape so it can transcribe the genes that the VDR has to transcribe, including the body’s immune defenses: cathelicidin, | ||
+ | |||
+ | ====Slide #14==== | ||
+ | |||
+ | Here we have the rat VDR. It looks essentially the same but there are some very significant differences. This particular element, the tetrazole, is just not behaving properly. It sits in a totally different orientation from where it is in //Homo Sapiens//. It is wandering around quite a lot, the forces are very weak on it. So there’s a difference. A rat is different from a human being. | ||
+ | |||
+ | ====Slide #15==== | ||
+ | |||
+ | So, once we switched on the immune system, of course then everything is plain sailing from that point, right? You have got your immune system working again? Well there’s a problem. When the immune system kicks back in and it recognizes the bacteria, the persistent bacteria, which are in the body and which are causing the problem, then it goes after those bacteria. And you get an effect called immunopathology. The immune system, as it attacks the intracellular bacteria, then some of the cells that those bacteria are in will undergo apoptosis and some will disintegrate. | ||
+ | |||
+ | In other words, you’ll loose cells. **The loss of cells and the resulting cytokine storm has to be controlled or otherwise it can be life threatening.** | ||
+ | |||
+ | ====Slide #16==== | ||
+ | |||
+ | The damage is called immunopathology and it means the damage to other parts of the body caused when the immune system is actually doing its job. | ||
+ | |||
+ | People who are seriously ill and carrying a heavy bacterial load need to spread the therapy over many years if the immunopathology is to be kept at a tolerable level. | ||
+ | |||
+ | The symptoms of immunopathology are very similar to the disease symptoms themselves. | ||
+ | |||
+ | ====Slide #17==== | ||
+ | |||
+ | Now, Olmesartan alone can induce immunopathology in patients carrying a heavy bacterial load, with a heavily compromised innate immune system. When you commence the basic dose of the Olmesartan, which is 40mg every 6 hours, which is for recovery from immune disease, then those people who are healthy - feel fine. The drug does nothing if the immune system is already working. Then helping the immune system work a little better does not make any difference. In healthy people it has no effect. The blood pressure is a little depressed as we saw in the other graph. About 10 percent of the patients, the most seriously ill, experience very bad immunopathology just from their VDR activation. About 70 percent really has no significant benefit or degradation at that point and about 30 percent experience improvement. Especially from fibromyalgia and spinal pain and migraines. | ||
+ | ** | ||
+ | But: a physician must be very, very careful.** When you get the VDR back in control the effects on the adrenal axis and the thyroid axis will disappear. And we found that in some patients the need for thyroid hormone supplementation can disappear in just the first week, and certainly within the first few months. So with people who are on thyroid medications you need to be very, very, careful and monitor the TSH, and other parameters, very carefully. | ||
+ | |||
+ | ====Slide # 18==== | ||
+ | |||
+ | There are very profound changes that are going on when the VDR is working again. This is the graph that we gave at the Autoimmunity Congress in Portugal, and it’s basically showing the symptom level, basically the amount of discomfort as a function of time from one day to 250 days on the MP. | ||
+ | |||
+ | Because the immune system in most patients will not actively attack the pathogens in that 70 percent of cases. In those cases people use the antibiotics to help the immune system recognize the pathogens, weaken the pathogens a little, and get things going. | ||
+ | |||
+ | We start off with minocycline. Initially a dose of 25mg every 48 hours, increasing to 100mg every 48 hours. Then when the patients have got comfortable with that level, they add a second antibiotic (which is usually azithromycin) and this starts at 1/10th of a tablet. One tenth of a 250mg tablet! This is very difficult for physicians. Physicians are used to giving four or five 250mg tablets to handle simple disease. **But if you give that to a patient who is taking Benicar, and who has the chronic inflammatory disease, you’ll find him in the cardiac ward very quickly.** You’ve got to be very, very careful with the antibiotics. You start them at a tenth of a tablet. Then gradually work up over a period of about a year to around a half of a tablet every 10 days. Every ten days! And that’s the maximum rate! So you can see that here the symptoms fluctuate on a 48 hour basis. Then when you increase the dosing, the symptoms increase again. And here the symptoms really jump up when you add the tiny fraction of azithromycin. And then over that 10 days cycle, you see the 10 days cycles of the azithromycin, | ||
+ | |||
+ | ====Slide #19==== | ||
+ | |||
+ | Phase 1 which is minocycline alone, typically lasts about three months. Here we have periods ranging from 0 days to 450 days with the average being somewhere around 120 and the most frequent period around 90 days, about three months. | ||
+ | |||
+ | So people can build up their dosage from 25 to 50, to 75, to 100mg over about three months. And by that time the patient has got fairly familiar with dealing with their immunopathology. | ||
+ | |||
+ | Phase 2, two antibiotics, | ||
+ | |||
+ | ====Slide #20==== | ||
+ | |||
+ | When you activate the VDR it has profound effects on the kidneys and cardiac function of the individual. That’s because the VDR activation turns on the renin subsystem, the VDR actually transcribes //(actually transrepresses)// | ||
+ | |||
+ | ====Slide #21==== | ||
+ | |||
+ | The Olmesartan gives protection of the kidneys despite the surge in metabolites. We see GFRs as low as 23 is not unusual (normal GFR is around 60). Creatinine as high as around 2.2 (normal max. 1.2). And a Blood Urea Nitrogen as high as 38 (typically 7-25) and all of those without any adverse events. The blood work values typically return to normal over a period of about 1-6 months. The mitigation measures are increasing the fluid intake and increasing the Olmesartan to 40mg every 4 hours. I stress that **// - increase// | ||
+ | |||
+ | ====Slide #22==== | ||
+ | |||
+ | Cardio-protection, | ||
+ | |||
+ | Bradycardia, | ||
+ | |||
+ | ====Slide #23==== | ||
+ | |||
+ | So, for immunopathology we’ve seen 10bpm bradycardia, | ||
+ | |||
+ | Patient education: it’s very important for the physician, to let the patient know what is happening and to maintain very close contact with the patient. Now, with our Internet outreach we have tried to take some of that load off the physician’s shoulders but we can’t do it all. | ||
+ | |||
+ | Chronic pathogens are very nasty indeed, they must be respected. They must be killed slowly and steadily. And therapy must be guided be an understanding of the disease model. You have got to understand what you are doing. It’s not just good enough to take an antibiotic and see what happens. Once you have activated the innate immune system again everything happens very quickly. | ||
+ | |||
+ | ====Slide #24==== | ||
+ | |||
+ | This is a graph that we gave of a sampling from our cohort. Our currently reporting cohort is around 600. Many of them have been members of the cohort for three or more years. This was a sampling from them with a whole lot of different disease diagnoses. You’ll be able to read these on the printouts. Rheumatoid Arthritis, Hashimoto’s Thyroiditis, | ||
+ | |||
+ | Fibromyalgia is even more effective. We have got 70 patients reporting in this particular group and Chronic Fatigue Syndrome / Myalgic Encephalomyelitis: | ||
+ | |||
+ | We find that 81 percent of the cohort who started out experienced reduced disease and symptoms between 18 and 23 months, depending on how sick they were when they started out. | ||
+ | |||
+ | So that is my quick summary of the Marshall Protocol. Thank you. | ||
+ | |||
+ | ==== Questions ==== | ||
+ | |||
+ | Dr. Radek Klubal: Thank you very much. It’s very good to open the field. My question is: is there any animal model in that we can see the same effect, because if you have rats, mice with certain genetic predisposition like rheumatic arthritis or something. If you keep them under sterile condition they won’t develop the disease and if you keep them under normal conditions they develop the disease. So that would be probably a good model to test how that antibiotics would.. | ||
+ | |||
+ | Dr. Marshall: Well, but Professor Bach, who invented the hygiene hypothesis, er, //derived// the hygiene hypothesis, I spoke to him quote recently in Portugal and they found that in fact if they injected their NOD mice with some bacterial proteins, very close to birth, that they didn’t develop the Diabetes. So there are a lot of questions about exactly how the NOD mice work at this point. So I don’t really want to go into that one. But look, if I was trying to find an animal model which was similar to humans I would go that animal’s genome and I would find out what transcribes cathelicidin what transcribes beta-defensins, | ||
+ | |||
+ | Dr. Radek Klubal: What about the dosage of the medication because I think every human is elementary different.. | ||
+ | |||
+ | Dr. Marshall: Well, there are different types of medication used for medicine... There is medication which is dose-specific, | ||
+ | |||
+ | This new class of drugs, the receptor blockers, is very safe. They are not dose dependent. Their effects are not dose dependent. We have identified three effects of Benicar: at very low dose, it affects the angiotensin 2 receptor. Slightly higher dose, it affects the VDR, and at very high dose it gives palliation and protection due to probably the opioid delta, and maybe some other receptors that we haven’t fully isolated yet. But you’ve got discrete steps of activity in the dosing regime. It is not a continuum and once somebody’s got to taking the Olmesartan once every three or four hours there is no benefit from giving a higher dose than that, they get no benefit. | ||
+ | |||
+ | Dr. Radek Klubal: Is there any race difference. Like black people, white people..? | ||
+ | |||
+ | Dr. Marshall: We haven’t seen any. We’ve a pretty diverse group from all over the world actually. And we haven’t seen any real differences, | ||
+ | |||
+ | Dr. Radek Klubal: Thank you. | ||
+ | |||
+ | Questioner (Czech MP-doctor): I have just a question to the pulsed dosing of the antibiotics, | ||
+ | |||
+ | Dr. Marshall: Well, the reason it happens is because what the Benicar does is turn on the immune system. So when you weaken the bacteria a little bit by the azithromycin or a little bit of minocycline, | ||
+ | |||
+ | **You are not trying to directly kill the pathogens with the antibiotics with the Marshall Protocol.** You are just trying to weaken them. Like I said: one antibiotic molecule lodged in one ribosome disables, partly disables, one bacterium. | ||
+ | |||
+ | Questioner (Czech MP-doctor): I forgot to tell that this reaction came at the end of this ten day period. | ||
+ | |||
+ | Dr. Marshall: Azithromycin has got a half life in cells of 45 days. So it stays around an awful long time which is a real problem when people take too much, because they are stuck with too much for a month. We are starting to move now towards using clindamycin instead of azithromycin. Clindamycin is a 48 hour dosing just the same as Minocycline. But clindamycin goes after the neurological symptoms very quickly. The problem is that it enhances suicidal ideation, depression, OCD. All of the neurological sequeli are enhanced when you use clindamycin in Phase 2. And that’s why we have avoided it until recently because in an environment where the physician is not in too close a contact with patient, and we are at great distance because of the Internet, it is very hard to support people that have suicidal ideation. We had a grand-mal seizure from a patient in Canada who took a 250mg azithromycin in the start of Phase 2. So it is a real problem that the patients become very sensitive to the antibiotics when you turn on the VDR again. It’s a real problem. | ||
+ | |||
+ | Questioner (Czech MP-doctor): Thanks for your answer. | ||
+ | |||
+ | Dr. Radek Klubal: What happens after you stop? | ||
+ | |||
+ | Dr. Marshall: Well the problem with stopping, it’s a very difficult job to stop. Because when you turn on the immune system it keeps running. Even if you cut the Benicar off, the immune system will keep running for usually for weeks, a couple of weeks. And during that time the body, or the organs, are no longer being protected by the reno-protection, | ||
+ | |||
+ | Dr. Radek Klubal: What happens to your saliva after you are on such a dose of… | ||
+ | |||
+ | Dr. Marshall: We haven’t done any full genome studies.. | ||
+ | |||
+ | Dr. Radek Klubal: Because I would like to see it after one year of such small amounts of antibiotics. | ||
+ | |||
+ | Dr. Marshall: Well, the study with West China Hospital will be doing that. They’ve got all of the latest sequencing equipment, the pyro equipment. And I’m sure they’ll be keeping a close eye on that. We signed a collaborative deal with West China Hospital back in December and we’re just cementing all of the studies now for this year. And they would be doing things very thoroughly because they’re a Cochrane Collaboration Unit. | ||
+ | |||
+ | Questioner (Martin78): One of the basic parts of the treatment is avoiding Vitamin D. That’s maybe the part of the points that most people find most controversial. At least when I’m discussing it with others. What do you have to say to researchers that are claiming that taking Vitamin D actually transcribes or increases cathelicidin or other AMP’s and that they have studies showing that Vitamin D is good for the immune system. | ||
+ | |||
+ | Dr. Marshall: Well, but they **// | ||
+ | |||
+ | I chaired a session at the International Congress on Autoimmunity in Portugal last September, some of those presentations are online on Vimeo, and you can watch them and find out all about Vitamin-D-related issues. And as I said there is a paper which has just been published in Autoimmunity Reviews and that’s available online and there is a paper which is in press at the moment at the New York Academy of Sciences asking and answering that same question: ‘how could so many people have made such a big error?’ | ||
+ | |||
+ | Questioner: Dr. Marshall mentioned that it should be a long time even a life long treatment, so what about that long time that was mentioned..(???? | ||
+ | |||
+ | Dr. Marshall: Well, “life long”, I mean it’s been a life time building up to this point. You are born with microbiota, you are born with one. It usually does not give you disease until you reach middle age or, hopefully, old age. But you are born with a microbiota. So, you’ve been working up to this stage for quite a long time. Many patients are triggered, “pushed over the edge” if you like, by an acute infection. In many diseases this happens. In MS it’s reported, certainly in CFS it’s reported very commonly. So, it’s been a lifetime getting here - but it doesn’t take a lifetime to get out of there. Recovery times vary by the patients, and the ones that we have contact with on the Internet, those that we’re observing, are probably the sickest of the patients that are out there. Absolutely desperate by the time they try something as ' | ||
+ | |||
+ | So, we find that typically after about 18 months the patients see the light at the end of the tunnel. They can sense that they’re improving a little bit. We get them to write down logs, frequent logs. There’s some forms which they can download and that allows them to keep track of what it used to be like so they can look back in 12 months and say: yes, this has improved, you know. About 18 months they see improvement. They’re going to be photosensitive for about two to three years, gradually getting less photosensitive as the time goes by. And then once they get to about the two to three year mark, they’re able to start integrating again with their community, with their family, with jobs, that sort of things. So, that’s the time frame. Now, the problem is that we have a total time of observation of only about six and a half years at this point from when we started. So I can’t extrapolate beyond six and a half years - but we have a lot of people who have gotten to the four or five year mark that are back at work, studying again. | ||
+ | |||
+ | Questioner: This treatment with Benicar, will this also cover viral problems? | ||
+ | |||
+ | Dr. Marshall: We have seen viruses disappear because when the immune system is activated again it will go after all the pathogens It will go after funguses, after viruses and of course the bacteria. You are not weakening the viruses in the same way as you are the bacteria with the antibiotics. But we’ve had viruses disappear - disappear as the patients recover. And even simple things like warts disappear, for example, as people recover. That’s routine. | ||
+ | |||
+ | |||
+ | |||
+ | |||
+ | |||
+ | |||
+ | |||
+ | |||
+ | |||
+ | |||
+ | |||
+ | {{tag> |