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Thoughts on the methylation treatment for CFS

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by richvank, Jul 14, 2010.

  1. richvank

    richvank Senior Member

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    Hi, all.

    Here's a repost of something I just posted to the Yahoo CFS_Yasko group, and which may be of interest to people here, also:


    I want to express some thoughts on the methylation treatment for what they are worth, and would welcome your opinions and experiences related to these comments.

    First, as many of you know, back in 1999 I first became aware of glutathione depletion in CFS from talks given by Dr. Cheney. I did quite a bit of studying to see what glutathione was all about, and I convinced myself that many or most of the aspects of CFS could be explained by glutathione depletion.

    Over the next five years or so, I encouraged people who had CFS to try to raise their glutathione levels in various ways. Many of them reported that this was beneficial to them, though if they stopped boosting glutathione, their situation relapsed to what it was before. So it was only a temporary fix. And there were others who were made worse temporarily by boosting glutathione, and could not tolerate it.

    I became convinced by the fall of 2004 that there must be a vicious circle mechanism that was holding down glutathione, but I didn't know what it was.

    Then in December of 2004, S. Jill James et al. published an autism research paper in which they found that glutathione was also depleted in autism, and that this depletion was linked to a dysfunction in the methylation cycle, which is located upstream in the sulfur metabolism from glutathione synthesis. In addition, they found that treating to lift the methylation cycle partial block also caused glutathione to come up automatically.

    I realized at that point that the same thing must be going on in CFS.
    So I began encouraging people with CFS to do treatments to lift a partial methylation cycle block. Over the course of the next few years, we accumulated evidence that this mechanism is in fact present in most people with CFS, and that these types of treatments were significantly helpful to about two thirds of the PWCs who tried them.
    A small number of people have reported to be essentially completely recovered as a result of this treatment. However, most have experienced significant benefit, but are not completely recovered, and some have been doing these types of treatments for over three years now.

    About a third of the people have reported either that they could not tolerate the treatments, or that they have not experienced any benefit from them.

    Among those who have not been able to tolerate the treatments, it appears that excitotoxicity has been one of the main problems. This leads to insomnia, anxiety, hypersensitivity of the senses, and a constantly "wired" feeling.

    In recent months I have been trying to understand how to improve this situation, and I want to share some more thoughts on that.

    First, for the people who can tolerate the treatments but do not experience benefits from them, I suspect that the likely causes are that the methylation cycle and related pathways do not have all the nutrients they need to come back up to normal operation. These include amino acids (especially methionine, serine, glycine, glutamine, and cysteine), vitamins (especially the other B vitamins and vitamin C), and certain minerals (especially zinc, copper, magnesium, manganese, selenium and molybdenum). These deficiencies could be at least partly caused by dysfunction of the digestive system, and I think that there is a lot of potential in working to fix the gut problems. I think the biofilm treatments and Dr. de Meirleir's most recent gut work are things we should pay attention to here. I think the KPU or HPU that Dr. Klinghardt has emphasized comes in here, too, in some cases, depleting zinc, B6 and other nutrients.

    For people who experience severe excitotoxicity and thus cannot tolerate the treatments, I suspect that this is caused by a temporary further depletion of glutathione as more of the homocysteine is converted back to methionine, and less is available for making cysteine and glutathione.

    I recently read Dr. Amy's article on excitotoxicity in the publications section of her website. She has some interesting ideas there, and I think that her discussion of the metabolism of glutamate in the brain shows where the main cause of excitotoxicity on this type of treatment lies. Normally, glutamate is secreted by neurons into their synapse with other neurons, serving as an excitatory neurotransmitter. The astrocytes are then supposed to import the glutamate, convert it to glutamine, and send it back to the neurons to be converted to glutamate and to be used again as a neurotransmitter. But this importation and conversion requires energy in the form of ATP, and I think that's where the problem arises. If glutathione becomes more depleted, the mitochondria of the astrocytes will be less able to produce ATP at normal rates, because of the oxidative stress that will arise, partially blocking the Krebs cycle and the respiratory chain. So I think there is a good basis for suspecting that the temporary glutathione depletion that occurs when this treatment is used is what is responsible for the rise in excitotoxicity.

    If this is true, then it would seem that boosting glutathione while doing the methylation cycle treatments would help this situation. There are lots of ways to try to do this. I know that some people have been nebulizing glutathione, and some have been using liposomal forms of glutathione. There are other ways as well. For people who can tolerate glutathione boosting, this may help to calm the excitotoxicity when doing methylation cycle treatments.

    For people who have experienced some benefits, but have then plateaued and have not had much improvement for a long time, I suspect that the problem is that there are factors that are preventing glutathione from coming up, or are preventing the methylation cycle from coming up, or both. So far, the people in this situation who have repeated the methylation pathways panel offered by Health Diagnostics and Research Institute (formerly Vitamin Diagnostics) have reported that their results on this panel have still not normalized. That's why I suspect that something is preventing recovery of this part of the metabolism in these people.

    So what is it? I think the major suspects are things known to deplete glutathione. These include mold toxins, Borrelia bacteria (Lyme disease), and heavy metals, such as mercury. We don't know yet about how important XMRV is in CFS, but this may also be a possibility.

    If these factors are indeed holding down glutathione, then I suspect that they will need to be dealt with directly before the methylation cycle treatments will be successful in restoring the methylation cycle and the folate and glutathione levels.

    I have just heard from Lisa (slayadragon) that when she and another person have dealt with other issues, including mold toxins, they have then found that the methylation treatments have been much more effective in helping them to detox. Again, I think this suggests that other impediments to raising glutathione may need to be dealt with first.

    Along this same line, the women who were treated in the study that Dr. Neil Nathan and I carried out had already been treated for a variety of other issues before starting the methylation treatments. These issues included mold illness, Lyme disease, and heavy metal toxicity.

    In addition, the people who have reported essentially complete recovery from these treatments have also reported that they did a number of other treatments beforehand, some of them being antiviral treatments.

    So I think there are bits and pieces of evidence that support this line of thinking.

    One other thing that occurs to me is that this may be a major difference between CFS in adults and autism in children. The children with autism are of course much younger, in general. This being the case, they have had much less time to accumulate toxins and infections than have the adults. They also don't have amalgam fillings in their baby teeth. The really young ones have probably not had as much possible exposure to tick bites as the adults. The point is that the adults (especially those who have been ill with CFS for many years) may have many more impediments to the success of these treatments than the young children with autism, and they may need more additional treatments to address them specifically.

    I would be interested in your thoughts about these things. Does this seem to make sense in the light of your experiences?

    Best regards,

    Rich
  2. Tal

    Tal

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    The quote above really stands out to me, as I feel it's important to look at the big picture while doing a B12 treatment. For some people extra benefit could come from something as simple as drinking more water, or trying another supplement regardless of whether or not it helps the B12s to work better, as the problem may be larger than simply a B12 deficiency.

    Normally now I would be deep into my allergy season (grass pollen), but I have had little to no allergies right now. This clearly isn't from the B12 which I have only recently started, but because of other supplements that I've been taking for months beforehand.

    Though I do seem to respond to B12 treatment, I also noticed that I dont seem to be suffering as much as many others have. Now perhaps thats because I didnt buy a 5 star brand of B12, or for some other reason... regardless, I decided to continue on with it and to try other brands, which I probably wouldnt be doing if I did suffer as much as some others.
  3. BEG

    BEG Senior Member

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    Rich,

    Thanks for posting. How does one begin a treatment such as this?
  4. richvank

    richvank Senior Member

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    Hi, BEG.

    My position is that a person needs to be under the care of a licensed physician when doing treatment for the methylation cycle. Though rare, there have been some adverse effects reported, and it's important that they be recognized and properly dealt with promptly.

    I recommend that a person run the methylation pathways panel offered by the Health Diagnostics and Research Institute in New Jersey before starting the treatment, to find out whether they have a partial methylation cycle block and glutathione depletion, and to get baseline values for comparison later, to gauge the progress of the treatment. The treatment may require some months, and it's difficult to judge progress from symptoms alone, because detox and die-off of pathogens can produce symptoms. This panel requires an order from a physician or chiropracter, and costs $300 plus the cost of shipping the blood samples to the lab.
    The lab's phone number is (732) 721-1234.

    The most recent version of the protocol that I have suggested can be found at www.cfsresearch.org by clicking on CFS/M.E. and then on my name. The protocol is the last item on my list of papers there. The supplements in the protocol are available without a prescription, and the cost of treatment works out to less than $3 per day.

    Best regards,

    Rich
  5. Tal

    Tal

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    So $300.00, then $90.00 a month? Now if someone is already taking supplements to address their CFS by means other than B12 (since CFS could be do to many factors), couldn’t they simply add Methylcobalamin, Adenosylcobalamin, and Metafolin to their list, and do it in a moderate way as not to overdrive the methylation cycle? And ask questions here while picking and choosing (like between folinic acid and methylfolate) to find what works best for them?

    I could be wrong as I have just found this site, and still learning whatever I can about all of this. I just can't help but show my skepticism even when I have no idea what I'm talking about :)
  6. richvank

    richvank Senior Member

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    Hi, Tal.

    I'm glad you found this site. Welcome!

    Yes, a person can certainly decide to do whatever they choose.

    If you are suggesting avoiding getting the methylation pathways panel and just adding some supplements to a person's current regimen to see what happens, sure, a person can do that.

    If you are asking whether I think that's a good idea, that's another matter! :)-)

    I think it's wise to diagnose before treating, so that you are not just groping in the dark or wasting your money. The methylation panel will tell you whether this treatment is likely to help you. In fact, I'm coming to the point of view that this panel is about the best biomarker panel for CFS in general, because the methylation partial block appears to be at the heart of the pathophysiology of this disorder. Also, I've heard from several people who went ahead with the treatment without testing, and have later regretted it, because they had no baseline data with which to compare over time to see how the treatment was doing. This is not an overnight treatment. It takes at least several months, and maybe longer if a person has a lot of toxins stored up in their body. So it's very helpful to be able to repeat the panel and do a comparison to see where you are.

    With regard to the choice of B12 supplements, I favor starting with hydroxocobalamin. Many people make good progress with that, and there are fewer issues to be concerned about than with methylcobalamin (shelf life, possible reaction with inorganic mercury to make methylmercury, overdriving the methylation cycle). If hydroxocobalamin doesn't do the job, one can switch to methylcobalamin later on. With regard to the folates, I favor taking both folinic acid and 5-methyl tetrahydrofolate, because they have different roles, and all of the roles should be covered until the folate metabolism is back up to normal, in my opinion.

    I hope this is helpful.

    Best regards,

    Rich
  7. JAH

    JAH Senior Member

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    Hi Rich,

    I appreciate your thoughtful posts on this treatment-- I have had cfs for 23 years and have never known about it. (I honestly thought I had tried everything!) I have 2 questions: do you have any opinion on the hydroxocobalamin being sold by prohealth? And 2: have you ever heard of itching as a side effect of starting b12. I have been very itchy since taking it, and it could be totally unrelated, (I'm a very allergic person) but has been roughly coincident with starting hydroxo.

    thank you,

    JAH
  8. richvank

    richvank Senior Member

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    Hi, JAH.

    It's not too surprising that you hadn't heard about the methylation treatment. The simplified approach wasn't suggested until early 2007, and it's been kind of slow going to get the mainstream physicians interested. There are a few alternative and complementary docs who are using it fairly routinely now.

    I don't have an opinion on the hydroxocobalamin sold by ProHealth. I don't think I've heard from anyone who has reported that they have used it. The hydroxocobalamin in the protocol I've suggested is Perque sublingual hydroxocobalamin.

    I have heard that some people can develop a rash from taking B12, but I don't know if it's the B12 itself or an additive in the supplements.
    There is no known actual toxicity to cobalamin itself. Taking high dosages of cyanocobalamin can cause problems, because of the cyanide.

    You're welcome.

    Best regards,

    Rich
  9. BEG

    BEG Senior Member

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    YIKES. I've been doing B12 injections for approx. 5 years. I've used a compounding pharmacy, and the ingredient is cyanocobalamin (I just called them.) I thought the injections were helpful, but I began to get migraines the day after, so I use it less often. Prescription calls for every other day @ 1 CC of 3000MCG/ML.

    Would you have an opinion on this, Rich?
  10. richvank

    richvank Senior Member

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    Hi, BEG.

    The human body has four ways of detoxing cyanide. These are reactions with thiosulfate, pyruvate, alpha ketoglutarate, and hydroxocobalamin. If these are not exhausted, the cyanide can be dealt with. However, some people have a rare hereditary disease called Leber's optic neuropathy, and they are more sensitive to cyanide. I have consulted on one CFS case in which the person was taking several forms of B12, including several milligrams per day of cyanocobalamin. In this case, all the detox pathways for cyanide were exhausted, and he suffered from cyanide toxicity. His condition was worsening. I advised his doctor (this was in another country) to give him hydroxocobalamin and oxygen by mask. The hydroxocobalamin will pick up the cyanide, and the oxygen will help to push it off the cytochrome enzymes, where it binds in the site where oxygen belongs. This pulled him out of it.

    I can't give you individual treatment advice unless a physician is involved to review my suggestions. However, in general, when dosages get into the milligram range (thousands of micrograms) such as you mentioned, I think it is advisable to use another form of B12 than cyanocobalamin. If you prefer injections, I believe that hydroxocobalamin can be injected. The DAN! doctors do subcutaneous injection of methylcobalamin. The protocol I've suggested uses sublingual hydroxocobalamin.

    Best regards,

    Rich
  11. xchocoholic

    xchocoholic Senior Member

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    Rich,

    Do we have to use this lab ? It looks like Genova has a similar test and I know my doctor uses Genova ... X
  12. citybug

    citybug Senior Member

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    Hi Rich,
    I've been wanting to ask you about that. That's the simplified protocol.
    What about the people whose atp cycle is completely flat? Can you do a more comprehensive list of everything needed around the "clock"? With pall and cheney and inflammation, and antioxidants oxidising, is there any way to balance antioxidants?
    i'm just not making enough atp to run anything.
    Has anyone successfully detoxed the diamine hair coloring in mitos? how?
    Has anyone managed the methylation protocol while doing electro-dermal testing for what supplements they tolerate? (I was told to stop most, but was taking bs, and methylb12 and in the hyper phase till migraines and crash. still have mercury fillings (with lead higher heavy metal).
    I tried some cider vinegar and tooth broke immediately, kind of scared now.
    Thanks,
    Kathy
  13. caledonia

    caledonia

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    I"ve been working with my naturopath on this. With electrodermal testing, I tested good for Folapro and methylcobalamin.

    I have also been using self muscle testing to determine the amounts, because the electrodermal doesn't do that, and I often need a fraction of a normal dose. I used to use trial and error to determine amounts, but this is faster and generally accurate.

    I had already tested for and chelated out metals before starting the methylation supps. I had also done a number of other things such as thyroid support, getting the gut working properly, etc. I also tried and failed at adrenal support for several years, but have just recently found something that works and I can tolerate. It's given me a nice boost.

    The methylation protocol has nearly cured my MCS and given me some additional energy. I'm looking forward to seeing if I can continue gaining energy from it over time, as things detox out. I'm still having detox symptoms.

    So I agree, it may be a multi step approach to get a complete remission.
  14. richvank

    richvank Senior Member

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    Hi, xchoc.

    Genova offers a red blood cell total glutathione test. This is less sensitive a measure of tissue glutathione status than the plasma glutathione test offered by Health Diagnostics. As far as I know, Genova does not offer measurement of the other metabolites on the Health Diagnostics methylation pathways panel. SAMe and SAH are particularly important for evaluating the status of the methylation cycle, and the folate forms are very helpful, also. Genova's Metabolic Analysis Profile (their urine organic acids test) includes methylmalonic acid and formiminoglutamic acid. If both these are high, it's a pretty good indirect indication of a partial methylation cycle block. There are also a couple of indirect ways of evaluating the glutathione status on this profile (pyroglutamic acid and ratio of citric acid to later Krebs metabolites). I really prefer the Health Diagnostics methylation pathways panel because of the direct information it gives about the real parameters of interest, but I find that having results of the Genova MAP profile is very helpful as confirmatory data, as well as giving information about several other aspects of the overall metabolism. When I consult on cases, I often ask for both, if they have not already been run.

    Best regards,

    Rich
  15. richvank

    richvank Senior Member

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    Hi, Kathy.

    I presume what you are referring to is urine organic acids test results that show low values for all the Krebs cycle metabolites. Is that right?

    This is caused by a failure of the normal anaplerosis ("filling up") process that keeps the Krebs metabolites up. In CFS, this is usually caused by major depletion of the amino acids levels, since they are what normally perform anaplerosis. In CFS, some people go very low in amino acids. This is usually caused by two things: the condition of the gut may be such that protein is not properly digested and amino acids absorbed. Also, because the Krebs cycle is often blocked at aconitase (because of glutathione depletion and the consequent rise in oxidizing free radicals, which inactivate aconitase), it is not able to burn carbs and fats normally, and thus resorts to burning amino acids for fuel, as occurs in starvation conditions. This lowers the amino acids levels.

    The amino acids levels can be meausured in either the blood or the urine. There are conventional medical lab tests that doctors can order (even in New York state!) to evaluate these levels. I actually prefer the Doctor's Data Lab tests, which can be obtained without a doctor's order from www.directlabs.com but I don't know if they are able to serve New York state, because they have their own lab certification requirements.

    If the gut is not in condition to bring in amino acids very well, and the person is too weak to undergo treatment to restore gut function, then the amino acids may need to be given intravenously, such as by installation of a picc line. When the amino acids levels have been restored to normal, and levels of the vitamins and minerals are also in their normal ranges, which may also require IV supplementation if the gut will not take them in well enough, treatment of the methylation cycle can be undertaken. If antioxidant levels are low, these can also be supplemented, and this should be done taking into account the antioxidant network. That is, they should be brought up together.

    I don't recall if I've read any reports of successful detox of the diamine chemical. I know that Dr. Myhill has recommended FIR sauna treatments for that.

    I think you already received a response to your question about electrodermal testing. I don't have anything to add to that.

    The presence of high levels of heavy metals can prevent success of methylation cycle treatment, because they block certain enzymes in this part of the metabolism. Heavy metal detox may need to be done before this treatment will be successful.

    I'm sorry about your tooth breaking. Do you mean that the cider vinegar attacked it? I know that lemon juice can do that. It's important to use a drinking straw and to flush the mouth after drinking highly acid liquids.

    I hope this is helpful.

    Best regards,

    Rich
  16. richvank

    richvank Senior Member

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    Hi, Caledonia.

    Thanks for the update and information. I'm glad this protocol is helping you.

    Best regards,

    Rich
  17. biophile

    biophile Places I'd rather be.

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    What would a bad reaction to SAMe indicate?
  18. richvank

    richvank Senior Member

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    Hi, biophile.

    You didn't mention what your reaction consisted of. I would be interested to know that.

    It would indicate that there is a problem in the sulfur metabolism. I think there are a couple of possibilities:

    1. Perhaps there is a partial block in the methylation cycle, so that the additional SAMe is converted to SAH, then to homocysteine, and then, instead of being recycled to methionine, it goes down the transsulfuration pathway and is converted to cysteine. If cysteine goes too high, it can cause problems due to auto-oxidation. Or there could be excessive conversion to either sulfite or hydrogen sulfide. These can both produce symptoms if they rise high enough. Excessive sulfite can sometimes be helped by taking molybdenum, which forms a cofactor for sulfite oxidase. If there is a genetic polymorphism in the CBS enzyme, which many PWCs have, that will cause an even greater flow down the transsulfuration pathway.

    The methylation pathways panel offered by the Health Diagnostics and Research Institute in New Jersey will tell whether there is a partial methylation cycle block. Amy Yasko offers a nutrigenomic panel that includes the CBS polymorphisms.

    2. There may be excessive sulfate reducing bacteria in the gut. The extra sulfur from the SAMe may go through the sulfur pathway to become sulfate, but then these bacteria may convert it to hydrogen sulfide, which produces a lot of problems if in excess. Dr. Kenny de Meirleir's lab in Belgium offers a urine test for hydrogen sulfide, to see if this is a problem, and quite a few are positive on this test. He treats by determining what bacteria are present in the gut, and using specific antibiotics, not broad-spectrum antibiotics, to knock them out, and then replace with probiotics.

    I hope this is helpful.

    Best regards,

    Rich
  19. xchocoholic

    xchocoholic Senior Member

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    Thanks ... I have some new words to learn ... lol ... Due to the expense, I'm going to see if I can get the Genova test for now. I have a history of kidney stones so I think my insurance will pay for urine testing. I'm going to print this off and ask my doc about this when I see her on Wednesday. My orthostatic intolerance has been so bad in the last couple of months that I think she'll be happy to order this for me. She's really been trying to nail this down for me. TC ... X
  20. dannybex

    dannybex Senior Member

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    Hi Kathy,

    I'm certainly no doctor, but have read in many places that one should not attempt to chelate (or detox) mercury until three months after the fillings have been removed.

    d.

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