Methylation Protocol

Discussion in 'Fibromyalgia Main Forum' started by MicheleK, May 20, 2012.

  1. MicheleK

    MicheleK Member

    Is anyone else on the Methylation Protocol?

    Have any of you had the genetic testing done to see if you have a methylation problem? My test came back double positive. So I inherited the gene defect from both mother and father.

    I've only been on the protocol for a month and a half. So far haven't noticed any difference but my doctor said it may take up to a year to really notice an improvement in my symptoms.
  2. Mikie

    Mikie Moderator

    Hope RichVanK sees this. He's the father of the MP here. I found the protocol very helpful and still use the supps. I'm now on the peptide injections and don't know whether I will keep up the MP or not. Don't give up on the MP. It has helped others here. I do know that the dose is important but it's also important to start out slowly.

    Good luck.

    Love, Mikie
  3. richvank

    richvank New Member

    Hi, Michele.

    Here is something I posted to another ME/CFS internet board recently, giving my current perspective on the methylation protocol and the hypothesis behind it, for what it's worth. These are my opinions, based on the available evidence up to the time. It has been five years now since the methylation protocol has been out. A large number of people in several countries have used it, and many are currently using it, also.

    Hi, all.

    I've written the following in order to try to see the "big picture" concerning ME/CFS, in order to focus efforts going forward. These are my own views at present. I of course may be wrong, and I have probably left out some important things. I would appreciate comments. I have taken the liberty of using the royal "we." :)-)

    My goal with respect to ME/CFS is for everyone who has it to be able to completely recover as soon as possible. I realize that this is a difficult goal to attain, but I believe it’s the goal we need to have.

    So how do we work toward achieving this goal? I believe that we first have to develop an understanding of this disorder, and that this understanding will serve as the basis for developing effective treatment.

    What aspects to we need to understand? I would say that we need to understand the etiologies (root causes), the pathogenesis (development of the disease process), the fundamental pathophysiology (what’s the core mechanism of what’s wrong with the way the body is working in this disorder) as well as additional contributions to the pathophysiology due to features that accumulate during the illness after the initial onset, and the symptoms, explained on the basis of the pathophysiology.

    What do we need to treat? Based on experience up to now, I would say that we need to treat the fundamental pathophysiology, but we also need to treat the etiologies and the additional features that have accumulated. I have learned this the hard way.

    Again, based on experience up to now, I would say that the fundamental pathophysiology is the same in nearly all cases of ME/CFS, and it involves a chronic vicious circle mechanism that includes depletion of glutathione, a functional deficiency of vitamin B12, a partial block of methionine synthase (which links the methylation cycle with the folate metabolism), and loss of folates from the cells. Essentially everything else in ME/CFS (other than direct effects of pathogens or initial toxins) stems from this vicious circle. This is elaborated in the Swedish seminar here:$%7Bweburl%7D

    (Note that the slides are available by clicking on the blue print below the video.)

    I believe that the etiologies, on the other hand, differ from one case to another. For the sporadic cases of ME/CFS (as differentiated from the cluster or epidemic cases), there is an inherited genetic predisposition that is not yet well defined, but likely consists of a collection of polymorphisms, the specific ones again differing from one case to another.

    The coexistence of an inherited genetic predisposition and some combination of a variety of physical, chemical, biological and/or psychological/emotional stressors is the etiology of ME/CFS, in my opinion. This variety of stressors has in common the characteristic that they all place demands on glutathione, and if they are sufficiently severe and long lasting in a person who has the genetic predisposition, it appears that they will produce a large enough depletion of glutathione to set up the chronic vicious circle mechanism that I believe is the core of the pathophysiology of ME/CFS.

    What are the additional features that can accumulate during the illness? I believe that they are toxins and infections by various pathogens. They accumulate because two of the body’s major defense systems, i.e. the immune system and the detoxication system, are rendered dysfunctional by the chronic vicious circle mechanism in the pathophysiology of ME/CFS.

    Where are we now in terms of treatment of the aspects that must be treated to bring about recovery? I would say that we have a basic understanding of the methylation treatment necessary to overcome the partial methylation cycle block in the pathophysiology, and it has been possible to accomplish this in a majority of PWMEs who have used this treatment. The essential part of the treatment is a combination of a high-dosage of Vitamin B12 (of the order of 2 milligrams per day) given sublingually or by injection, and one or more active (chemically reduced) folates at approximately the RDA for folate (400 to 800 micrograms per day). These two support the methionine synthase reaction, which appears to be partially blocked in ME/CFS. Successful treatment usually also includes other supportive nutrients.

    However, there are still many who either experience no response from this treatment, or who experience such severe exacerbation of symptoms from it that they are not able to continue it. We need to identify the reasons for these in each case, and treat them effectively.

    In addition, we have found that in most cases, even though this treatment overcomes the vicious circle mechanism and usually brings significant symptomatic improvement, it is not the complete answer for producing total recovery. There are many who experience improvement in their methylation cycle, folates and glutathione from this treatment, based on repeated lab testing, but their ratio of reduced to oxidized glutathione does not return completely to normal, suggesting that oxidative stress continues to be present. I think this is due to the presence of the original etiologies and/or the additional features that have accumulated.

    With regard to treating the etiologies and the additional features that accumulate during the illness, I would say that we have had success in some cases, but in many other cases these have not been successfully identified or have not been successfully treated. More work is needed to identify them and to develop treatment for them.

    What are some possible reasons why a PWME would experience no response from the methylation treatment? One obvious possibility might be that the person does not have the vicious circle mechanism described above. Though this mechanism appears to be fundamental to the pathophysiology of ME/CFS, there may be some people who have similar symptoms but do not have this vicious circle. This is one of the main reasons it is helpful to run the Health Diagnostics methylation pathways panel (I refer here to the biochemical panel, not the genomic panel with a similar name.)

    I suspect that another possibility is deficiency in one or more of the essential nutrients for the methylation cycle and related pathways. There are several vitamins, minerals and essential amino acids needed to support this part of the metabolism, and many PWMEs have been found to be deficient in some of them. Those who have hemopyrrollactamuria (HPU) are a subset of this group. Again, testing is available to determine whether there are deficiencies. This includes direct determination of the levels of the nutrients in the blood, measurements of certain enzyme activities that are specific to particular nutrients, and inferring deficiencies from metabolic tests (such as urine organic acids and amino acids in the urine), hair mineral tests, and essential element tests in the urine. The interpretation of hair testing is not simple or straightforward and requires considerable understanding and experience. Testing for HPU is also available.

    Another possibility is high body burdens of one or more toxic metals, such as mercury, that are capable of blocking enzymes in this part of the metabolism. Testing is available to look for these in urine, blood, feces and hair, and chelation may be needed if the levels of the toxic metals are high.

    Now, what about those who find this treatment to be intolerable? There are several categories of this. One that is very common is an increase in excitotoxicity when the treatment is started. This involves symptoms such insomnia, anxiety, nervousness, a “wired” feeling and hypersensitivity of the senses. This is likely due to an initial further decrease in glutathione in the astrocyte cells of the brain, as a result of conversion of more of the homocysteine to methionine, so that less is available for supporting glutathione synthesis. Sometimes lowering the dosages at first, especially of Vitamin B12 and the folates, and increasing them slowly over time, is effective. There is also a variety of substances that may help to calm down the excitotoxicity, including GABA, theanine, magnesium, taurine, grape seed extract, pycnogenol, progesterone cream, and Valerian root.

    Another negative reaction, which is sometimes described as a “toxic” feeling, is probably due to mobilization of toxins by the improved sulfur metabolism, together with the time lag between mobilization and excretion. If the digestive system is not operating well, it may not be able to excrete toxins in the stool very well. If there is low stomach acid, intestinal bacterial dysbiosis, malabsorption, and/or leaky gut syndrome, these may need to be diagnosed with comprehensive stool testing and treated before the methylation protocol can be used. If there is at least one bowel movement per day, the use of various binders may help. These include activated charcoal or modified citrus pectin, which will help to usher toxins from the gut into the stools. Lemon juice (taking care to use a drinking straw and to flush the teeth with water afterward) can help to increase the excretion of some toxins into the urine.

    Another negative reaction can be caused by development of potassium deficiency. This occurs because as the folates rise in the cells, the cells are able to divide and reproduce more rapidly. Since potassium is the most abundant positive ion inside all cells, this produces a demand for potassium, which is generally low in PWMEs to start with. Symptoms associated with low potassium include heart palpitations and muscle spasms. The blood serum potassium level can be measured with a standard comprehensive blood metabolic panel. Supplementing with potassium supplements or foods high in potassium may help with this.

    Now, what about the etiologies and additional features that accumulate during the illness?
    There is a wide variety of possibilities. First, there is ongoing psychological or emotional stress. This may be difficult to avoid because of life circumstances, but it is important to lower this to achieve full recovery, because this will continue to place demands on the HPA axis to secrete cortisol and on the sympathetic nervous system to secrete norepinephrine and epinephrine, which will produce oxidative stress and hence, continuing demands on glutathione.

    Ongoing exposure to toxins and especially biotoxins (for those who are susceptible), must be eliminated, and as mentioned above, it may be necessary to do chelation or FIR sauna treatments to lower the levels of toxins.

    There is a variety of pathogens that can serve as etiologies or that can accumulate during the illness. Some of them have ways of hiding from the immune system and thus will need to be dealt with specifically and directly. These may include Lyme disease and its coinfections, intestinal bacterial dysbiosis (as mentioned above) and yeast infection, a variety of viral infections, including enteroviral infections (and possibly retroviral infections), intracellular bacterial infections including mycoplasma, chlamydia and rickettsia, infections involving root canals and cavitations where teeth have been removed, sinus infections, including fungal as well as MARCONS (multiple antibiotic resistant coagulase negative Staphyloccus). Dealing with these infections is perhaps the most difficult aspect of treating ME/CFS. Some PWMEs have histories of many infections during the early part of their lives, before the onset of ME/CFS, suggesting possible genetic deficiencies in their immune systems. Testing for some of them (such as Lyme disease and retroviruses) is not very clearcut at present. Treatments for some of them are not always very effective. This is an area that needs a lot more work.

    This is the status as I see it today. I would appreciate hearing your thoughts.

    Best regards,

  4. richvank

    richvank New Member

    Hi, Mikie.

    Just want to let you know that I am following your posts on the peptide treatment. I'm happy to hear of your progress, and hope it continues to full recovery.

    I would like to get a better understanding of this treatment and how it works. Do you know of good references that explain what it is all about? Or is it sort of proprietary?

    Best regards,

  5. Mikie

    Mikie Moderator

    Thanks for all this excellent info on the MP. It really helps each time you bring something new for our consideration. I'm not a scientist, like you, but I also inferred a long time ago that it is likely a combination of genetic abnormalities and stressors, such as exposure to toxins, trauma, infection, etc., which overload the system so that the body cannot recover. Many of us recovered from flares of our CFIDS several times before something pushed us over into this downward spiral.

    BTW, a friend has told me that there is a peptide serum for Lyme being tested. It seems they discovered that the bodies of Lyme patients lack the ability to react properly to the infection and it triggers an abnormal immune response. This is what happens when CFIDS is triggered full blown by mycoplasma infections. It isn't the infection; it's the immune response. Of course, an improper immune response is what can lead to autoimmune illnesses. I believe this is what caused my Sjogren's.

    Understanding the peptide theory is amazingly simple and yet, developing the exact synthetic peptide sequences in the lab was agonizingly slow. It is the synthesizing part which is kept secret. I had to sign a paper stating that I would never try to find out just what is in the serum itself. Oxford University, and the research lab, keep everything secret. Big Pharma is fast on the trail of finding sera of their own so it likely won't be long before they are in trials for lots of things.

    The theory is that ill people have abnormal peptide sequences in their bodies. The correct peptides are injected and attatch to cell receptors in the body. Over time, the body learns the correct peptide sequence and one will become well. It is thought that this situation is also genetic. I know that this is so simplistic as an explanation but I've not been able to find anything more online or in my doc's material, which is pretty brief. His slide presentation isn't any more informative. Anything more would get into the proprietary area.

    The belief among these docs, scientists and researchers is that the peptide theory can be applied to many illnesses and they are working toward peptide sequences for Alzheimers, Autism, Parkinson's and other conditions. The peptide serum I get is considered "old hat," according to my doc. It's effective but not as exciting as what's coming for other conditions.

    This last shot didn't seem to work but I had had a virus the week before and I had to postpone the shot a week. I've been having a Herx-like response and I now believe the shot worked but either that virus, or a chronic virus in my body, reactivted and my immune system's been busy killing off pathogens. This is similar to the Herx-like reaction some of us have had to the MP.

    I wish I could be more helpful. If I had a better understanding of the body and its systems, perhaps I could. If you were to write to Dr. Dakos, he might be able to give you more info without revealing what he cannot talk about, which is really only the formulae.

    I'll keep updating everyone as I go along. Regardless of not feeling well right now, overall, I'm soooooo much improved over where I was before I started the injections. To me, it's amazing that my arthritis in my hands and wrists if gone. No more pain, swelling nor tenderness. It went away completely with the first injection. The doc said it will not return and it hasn't.

    Again, Rich, thank you so very much for all you have done for us. You will never know how many lives you have touched.

    Love, Mikie
  6. mbofov

    mbofov Active Member

    I tried Rich's methylation protocol for some 3-1/2 years, off and on. Most of the time I was on it I had unpleasant side effects -fatigued and digestion screwed up - which could have been detoxing or might have been due to an induced folate deficiency from the original methylation protocol, which has since been revised.

    I believe Rich now recommends a trial of some 3 to 4 months, and if no positive results within that time, to investigate other things such as heavy metals.

    A little over a year ago I started a similar protocol devised by Freddd of the Phoenix Rising board, and had no detox or other negative symptoms, apart from a rather sudden increased need for potassium, which caused severe fatigue until the potassium deficiency was remedied. I can't tell you right now what exactly the differences are between Rich's protocol and Freddd's, but here's a link to Freddd's and you can compare them if you like:

    This post is from 2011, and there have been many posts since, but it will give you the basics. And if you try Freddd's protocol, I can't stress strongly enough the very real possibility of a sudden increased need for potassium, which he stresses. It made all the difference when I added it in.

    I found a noticeable increase in energy after starting Freddd's protocol. Unfortunately, it has not stopped my crashing (post-exertional malaise), so while I feel better on Fredd's protocol, I still have to ration my energy rather carefully or else I crash.

    I'm currently doing a mercury detox using dmsa under the supervision of my doctor. It's unpleasant but I have read of people (and Rich told me about at least one woman) who tried the methlation protocol, but were unable to overcome their PEM until they did a mercury detox.

    Doing a mercury detox is a whole other story and anyone considering it should do some careful research first. If you google Andrew Cutler, he's a good source for information, although my doctor does not follow his protocol to the letter, but it's a good starting point.

    So I think your doctor may be incorrect in thinking it could take a year to get results. I know Rich did a lengthy post above which gives several reasons why the methylation protocol does not work for everyone.

    I would see where you are after 3 or 4 months and then perhaps consider some of these other factors mentioned by Rich.

    Best wishes,

  7. Mikie

    Mikie Moderator

    I hope you get to see this as Rich has posted a lot of good info for you here. Please let us know that you got to see it.

    Love, Mikie
  8. MicheleK

    MicheleK Member

    Thank you Rich for giving all of us such in depth information on the subject of Methylation.

    When I first got my tests back and then did research on the subject, I was actually surprised how very important the processes are and how it affects RNA & DNA. I wondered if this was one of the reasons I became so ill with M.E & FM and if it is keeping me from getting enough healing to improve the percentage of activity I might attain.

    I plan to stay on the protocol. I do think things must be given a fair chance. I have friends who have been on it almost a year (from Metanex though), and they said after a few months they felt much better. We'll see what kind of results I get. But I do have a moderate severe case of M.E so I'm sure many systems are going haywire and need support.

    I did think I was deficient in zinc since I can no longer taste or smell, so I have added that to my supplement regimen.

    Thanks to all of you for your suggestions and helpful references. I appreciate your kind spirits.

  9. This is all especially interesting to me because I, too, have a double mutation of the MTHFR gene that Michele mentioned and I have heavy metal toxicity, esp mercury... I also have tried peptide injections, Mikie, but am not sure if they helped or not. I've been on the fence as to whether I should get my amalgam fillings removed because that would require a long trip (about 12 hours away) to get to a qualified dentist for safe removal.

    I'm concerned about how draining the trip and then dental work would be. I've called the office and it would require multiple visits as well. Can't afford more setbacks. I feel like I'm between a rock and a hard place. Any suggestions or thoughts on this? I know this would need to be handled before trying the Methylation Protocol, right? My CFS/ME has been in a severe flare for more than a year now, although I know much of that is due to extraordinary demands and stress starting in Feb. 2011 and lasting through June of this year. But I'm just not sure which direction to go in order for my health to improve. I still have my youngest at home who is only 11 years old and he needs a healthy mom! And when I tried chelation a couple years ago, my body crashed so badly the next day that I couldn't move and couldn't even speak. That was scary, to say the least....

    Rich, can you tell me your thoughts on foot detox? Could this help me at all? Just not sure if it's legitimate.

    Thanks for any thoughts or suggestions.

    [This Message was Edited on 08/07/2012]
  10. richvank

    richvank New Member

    Hi, Shelly.

    I don't know whether foot detox is valid or not. I have read posts from some people who report that it has helped them, but I don't know of any actual quantitative testing of this approach.

    You may be able to try the methylation treatment before removing your amalgams.
    Some people have been able to do that. It depends on whether the level of mercury in the body is so high that it blocks the enzymes in the methylation cycle. If not, it is possible to get the methylation cycle going better, and that will help the body to detox naturally. You might consider trying it.

    Best regards,


  11. Thanks so much, Rich, for the input! I will look into the treatment. Do I need to start on lower doses than suggested since my body tends to be hypersensitive? With school about to start back for my son, I wouldn't want to have a rougher time than I'm already having. I've heard from others that they had some rough symptoms while their body started the detoxing process.

    Thanks again,
  12. richvank

    richvank New Member

    Hi, Shelly.

    Yes, I do recommend starting at lower dosages, especially if you have a history of hypersensitivity. Some people start with "crumbs" of the folate supplements, for example, to see how they will respond.

    As always, I recommend working with a physician while on this type of treatment.

    Best regards,