CFS: What Specific Benefits Have You Gotten From Methylation?

Discussion in 'Fibromyalgia Main Forum' started by Slayadragon, Jul 12, 2008.

  1. Slayadragon

    Slayadragon New Member

    Rich recently posted a thread listing all the people here who have tried some version of the Simplified Methylation Protocol, Amy Yasko's program, or something else related to supporting methylation/glutathione.

    I have yet to see a comprehensive post suggesting ways in which people believe they have benefited.

    I mention this because I was thinking briefly today about the things that the approach is supposed to do and whether it seems reasonable to think that it actually does them.

    My own thoughts are CERTAINLY not definitive, and I look forward to having Rich correct them or elaborate upon them.

    Still, I thought I'd list them here.

    1. Removal of heavy metals from the body

    Heavy metals certainly are shown to have a negative effect on the body. However, I'm of the impression that even people with no methylation problems tend to have a difficult time getting them out of their systems. Once in, they don't easily come out.

    Thus, even if we presuppose that CFS sufferers (and autism sufferers) have high levels of these substances in their bodies, it may be that the removal of them from the body may be slow going. I'm not saying that it is impossible to get any of it out, just that seeing big improvements from just doing this in any reasonable period of time (meaning, perhaps, our lifetimes) MAY be optimistic.

    I also have seen little evidence that CFS sufferers have been disproportionately exposed to these substances compared to the rest of the population. Certainly there are exceptions, such as Rich Carson (who was exposed heavily to mercury during a spill).

    I thus am not wholly convinced that addressing heavy metals is the mechanism by which methylation/glutathione utilization might help CFS sufferers. Certainly getting out even a little bit of any heavy metal theoretically should be a good thing. Suggesting that this is going to make a big enough difference to get really sick people well is another matter though.

    2. Removal of chemicals residues from the body

    I strongly believe (and this is just a belief!) that this is something that supporting methylation and thus utilization of gluathione can do.

    Many ordinary chemicals (such as prescription drug residues) seem to be removed efficiently by the systems of most people. These chemicals seem to go through the glutathione route, and so impaired methylation indeed might cause these chemicals to accumulate in the body. Supporting methylation/glutathione utilization seems that it might bring people with genetic problems related to it indeed does seem to have the potential of helping to get these chemicals out of the body.

    All of us have been exposed to chemicals of various sorts as we have gone through our ordinary lives in the 20th and 21st centuries. The idea that dysfunctional detoxification systems might lead to the storage of these chemicals in the fat cells and other places does not seem wholly unrealistic to me.

    However, I have yet to see any literature that states what happens when these chemical residues are not removed efficiently. It thus is difficult to predict what sorts of positive benefits might be felt by getting them out.

    Getting them out certainly seems better than not getting them out even if we don't know what the result will be, though.

    3. Removal of xenoestrogens such as DDT

    Like heavy metals, these appear to be removed to some extent through the methylation/glutathione channel. However, even normal people seem to have a very difficult time getting these chemicals out of the body.

    For instance, I recently read a very mainstream book on this topic, called "Our Stolen Future." It was reviewed by top experts in the field of environmental science and medicine, and features an introduction from Al Gore (from when he was vice president).

    The book suggests strongly that these chemicals follow the principle of "once in, little out." According to the authors, the only ways in which these chemicals are typically removed from the body to any significant extent is through pregnancy and lactation. (Bad news for baby, thus accounting for the name of the book.)

    This at first made me think that I should find a way to get the breast milk going. However, I have yet to see even a hint of evidence on this board (much less in any literature) that suggests that CFS sufferers have been disproportionately exposed to xenoestrogens such as pesticides. (I do wonder based on what I've seen here whether fibromyalgia sufferers might have higher-than-average exposures to these substances, but that is just speculation and in any case I am focusing only on CFS in this discussion.)

    It certainly is clear that xenoestrogenic compounds are dangerous. I've yet to be convinced that supporting methylation will help this though.

    4. Addressing viral problems

    It certainly is true that CFS suffers have a lot of viral problems. And it seems to be true that optimal function of the methylation/glutathione pathway theoretically might be useful in addressing this.

    I admit that I am unclear with regard to exactly how methylation/glutathione accomplishes this task. My impression thus far is that mercury and other heavy metals hang onto viruses, and that much of the theoretical reason that this approach might help to address viruses is due to the fact that it is designed to remove heavy metals.

    It this is the case, then the effectiveness of this approach is dependent on the extent to which it actually does remove heavy metals. As noted above, I am not wholly convinced based on theoretical reasoning that the amount of metals being removed is significant enough to make a difference.

    Indeed, Amy Yasko herself frequently uses antivirals such as Valtrex to supplement her program. Considering that she is pretty strongly opposed to the use of most drugs, this suggests to me that she is unconvinced that support of methylation/glutathione utilization is going to adequately address this problem in autism sufferers.

    To the extent that CFS sufferers have the same underlying problems as autism sufferers (which many studying methylation issues now believe), it is questionable whether methylation will resolve viral problems in the former population either.

    5. Addressing fat-soluble biotoxins such as those made by lyme or toxic mold

    Rich van K has stated a number of times that these biotoxins appear to be removed from the body through a channel other than the methylation/glutathione one.

    I personally think that it possible that the removal of other sorts of toxins (such as chemicals) from the body may reduce total toxic load and therefore allow the body to better tolerate reasonably heavy burdens of lyme or mold toxins.

    To the extent that these toxins are present to a significant extent and are not removed in some other manner though, they will continue to be a problem even if optimal methylation is achieved.

    6. Addressing bacterial or other pathogenic problems

    I've yet to see any claims that this is affected to any significant extent through optimal utilization of glutathione, which is the point of the addressing methylation problems.

    7. Increased physical energy through Krebs cycle production

    To the extent that glutathione is involved in this (and I believe that's the case) and is not being used for other things (which would be the case if it's not doing a whole lot with regard to detoxifying stuff or killing viruses), increasing energy in this manner might be accomplished.

    If this indeed is the case, then we should expect to see CFS sufferers who have optimally supported methylation have more energy.

    It also seems that they might need less of the Krebs cycle supports (such as CoQ10 or ribose) in order to maintain the same level of physical energy.

    Whether this will diminish the extent to which CFS sufferers experience post-exertional malaise is another matter though. This seems to be the result of low VEGF (vascular endothelial growth factor). People with this problem do not get enough oxygen in their tissues, thus making it difficult or impossible for them to exercise without feeling bad afterwards.

    A couple of explanations have been posited for why VEGF tends to be low in CFS patients.

    Dr. Montoya tested for this in his Valcyte study, suggesting that he believes that viruses are a cause. I don't know if his study showed that this was the case, but at least one study participant on this board (cat003) reported that she got huge gains in this area after taking the drug.

    Dr. Ritchie Shoemaker suggests that biotoxins (toxic mold or toxic lyme) are an underlying cause. He has yet to publish his research findings though, and it thus is difficult to evaluate his claims. (The fact that his claims have not been published yet does not mean that they are not valid, however. Getting papers published in mainstream journals requires huge amounts of money, which can be hard to get when treatments do not involve the use of expensive pharmaceuticals.)

    It is possible that "regular" chemicals also create problems with VEGF. If so, supporting methylation could have the potential of improving functionality in this area. I've yet to see any claims that chemical toxicity other than that of biotoxins is directly or indirectly responsible for this problem, but that does not mean that it's not the case.

    8. Modulation of "stress"

    I am uncertain of the mechanism by which proper glutathione utilization helps in this area, but I will tentatively accept the fact that it is true.

    If that is the case, it is possible that this would allow CFS sufferers to lead more normal lives. Stress is a given in the 21st century (and all previous centuries! people in the olden days were stressed too), and so the ability to tolerate it is important.

    However, it frequently has been reported that CFS sufferers who have managed to eliminate every tiny bit of stress (physical, mental, emotional) from their lives do not get significantly better. I thus question whether this effect will be a significant factor in allowing CFS sufferers to actually get better rather than just _feeling_ a bit better.

    Of course, feeling a bit better is a good thing in itself. Anticipating that this effect will allow us to get well is another issue.

    I wonder if modulation of "stress" might include the diminishment of hypersensitivity to stimuli that many of us experience. That would be a very welcome development for some of us even if it didn't lead to remission.

    9. Effects on hormone production or utilization

    This was not on Rich's original list of benefits of improved methylation, and I've yet to see a claim for it in Amy Yasko's writings either.

    However, Rich frequently has talked about the issue of how and why improved methylation contribute to improved hormone function.

    I am not clear at the moment about whether this effect is downstream of the ones mentioned above or if it is more direct.

    Certainly, improved hormone function would be a real plus for many of us. While supplemental hormones seem to be helpful for many with CFS, that is not an optimal way to address the issue.

    Supplying the body with the proper amount of hormones is a tricky business, since too much can be as bad as (or sometimes worse than) too little. Moreover, many or most hormones used by the body are not available in supplemental form.

    10. Optimal usage of dopamine

    I have on the coffee table in front of me a book called "Molecular Origins of Human Attention: The Dopamine-Folate Connection." It is written by Richard C. Deth (pronounced "Deeth"), a mainstream academic researcher at Northeastern University.

    I personally think that the idea that inadequate usage of dopamine is an issue for CFS sufferers is not without plausibility. Dopamine is strongly related to things like thinking (especially "executive function" and task-switching), physical movement (especially switching from one activity to another, such as chopping onions to moving them to a pan), and experience of a normal range of emotions. At least some CFS sufferers seem to have problems in these areas, with an undefined "lethargy" as a result.

    To the extent that proper utilization of glutathione or folate helps with dopamine issues, CFS sufferers may benefit from addressing these areas. I am uncertain of the mechanism by which this is purported to occur, however. Reading this book (reputed to be a challenging one) is on my "To Do" list for the weekend. Hopefully I can figure it out.

    11. Other benefits

    There may be other potential benefits of supplementing with activated folate/B12 or supporting methylation/glutathione utilization that are noted here.


    Anyway, this is what I see thus far.

    Obviously I may be missing something. However, based on this analysis, it seems that while supporting methylation/glutathione usage has the potential of giving CFS sufferers significant improvements, it may not be sufficient to resolve all the problems associated with the disease.

    The fact that many board members who have diligently pursued this route have reported substantial improvements but nothing close to remission has nothing to do with my theoretical analysis, but does seem to be consistent with its conclusions.


    Considering whether the theoretical speculation above is consistent with people's experiences would be interesting, I think.

    I thus encourage those who have been using this approach to rate how well they believe they have done in each of the following areas.

    1. Removal of heavy metals
    2. Removal of "regular" chemicals
    3. Removal of xenoestrogens
    4. Removal of biotoxins
    5. Addressing viral problems
    6. Addressing bacteria or other pathogens
    7. Increased physical energy and/or reduction of post-exertional malaise (including VEGF improvements if test scores are available)
    8. Modulation of "stress"
    9. Improvements in the area of hormones
    10. Improved apparent dopamine functionality
    11. Other areas of improvement

    I am going to write my own assessment in the next post on this thread.

    General comments on this analysis are, of course, extremely welcome!!!

    [This Message was Edited on 07/12/2008]
  2. Slayadragon

    Slayadragon New Member

    1. Removal of heavy metals

    I have no evidence that heavy metals are a bigger problem for me than for the average person.

    I don't know whether this approach has helped me in this area since I have not been doing urine or fecal metals testing.

    2. Removal of "regular" chemicals

    My belief is that the astoundingly large detox reactions that I got when I first started using these supports was due to this.

    I have used a good number of prescription pharmaceuticals (including anticonvulsants, antidepressants and tranquilizers) during the past 12 years.

    The detox reactions I got at the beginning of supporting methylation were extremely similar to the hangover that people get when consuming too many tranquilizers or alcohol all at once. The idea that these chemicals/toxins might have been responsible makes sense to me, though I have no proof of this.

    Although I try to avoid chemicals in general, exposure to them is something that cannot be avoided.

    These kinds of strong reactions to the methylation supplementation have diminished to nil since I began it a year ago. There may be some of them left that are slowly coming out. To the extent that I still am getting exposure (which I obviously am), discontinuing this support would be incredibly stupid.

    I am not certain of what benefits I have achieved as a result of expelling these chemicals. My body most certainly wanted them out to go into that high of overdrive though.

    I've gotten a whole lot better over the past year, but how much of this improvement should be attributed to the removal of this kind of chemical is unclear.

    Hopefully a controlled experiment will give us this information.

    3. Removal of xenoestrogens

    I have no information that my exposure to these has been greater than that of the average person.

    I also have no evidence that these were removed through methylation support, though they could have been.

    4. Removal of biotoxins

    If methylation did help in this area, it did not do so in a complete way.

    During the past six months, I have gotten very large detox reactions as a result of using other methods said to address mold and lyme toxins (such as cholestyramine).

    I have been getting no obvious reactions to methylation support during this time. If methylation indeed were addressing biotoxins, I would think that my experience would have shown it during this time.

    5. Addressing viral problems.

    I took an antiviral during the first half of 2007, stopping it at about the same time that I started the methylation.

    I have no idea whether improved methylation helped in this area because:

    * I've not had much viral testing since then
    * It is my impression that viral testing measures (such as IgG levels) are extremely inaccurate beyond telling people whether they've got a problem with addressing herpes viruses in general
    * Improvements could have been due to effects experienced as a result of the antiviral (possibly delayed)
    * Addressing biotoxins also might have led to elimination of viruses

    Again, I'm not a controlled subject here.

    It seems to me that the best way in which I will be able to tell whether I've improved in terms of viruses will be to resume an antiviral and see if I get the same horrific level of die-off (from just a small amount!) that I did last year.

    I'm reluctant to do this until I feel that I am further along in terms of my recovery from biotoxin exposure though.

    6. Addressing bacteria and other pathogens

    I have some kind of problem with bacteria....certainly with chlamydia pneumoniae, maybe with lyme.

    I've not tested (either with lab tests or antibiotics) recently to see if this has improved.

    Eventually I will do so. Even if gains are made though, they could have been due to addressing biotoxins.

    I do think that my candida problem has improved quite a lot. That could have been due to addressing biotoxins too though. My doctor's super-potent probiotic (18 strains, 50 billion units per capsule) does a really good job on candida anyway, and I'm still taking that as "insurance."

    7. Increased physical energy

    This is one benefit that I noted almost immediately upon using the methylation support. My ability to tolerate physical exercise (such as going for long walks or long leisurely swims) went up substantially.

    This has continued over time. My main problem now is the task-switching lethargy that keeps me from getting up and out of the house in order to do the exercise.

    I do not exercise beyond what feels comfortable to me. Pushing myself to, say, go to an aerobics class likely would result in a crash for me. I thus avoid such things.

    Probably that means that my VEGF levels are still problematic. I'm going to be getting a blood test (part of Dr. Shoemaker's panel) that gives info on this next week, and so the results will be interesting.

    8. Modulation of "stress"

    I'm not convinced that I'm better at handling stress than I used to be.

    My irritability level seems to have decreased over the last several months, though it often re-emerges with a vengeance when I get an extended mold "hit." That makes me think that my newfound calm may be more related to addressing mold than to any other issue.

    My aversion to stimuli has gone down substantially. I think this was a lyme problem though, since it became extremely acute when I took even the slightest amount of antibiotics like doxycycline.

    That gives me a little hope that perhaps addressing biotoxins has boosted my immune system enough to address lyme to at least some extent on its own. This will become clearer when I eventually experiment once again with antibiotics.

    9. Improvements of hormones

    I've not been able to reduce the amount of thyroid hormone that I need.

    Testosterone and estrogen levels still seem to be on the low side, though moving into perimenopause (I'm 43) likely is related to that.

    I haven't gotten a panel related to adrenal hormones recently, but it seems like that may be improving.

    I've not gotten a urinary human growth hormone test recently, but feel this is still an issue for me. (My IGF-1 came up normal last week, but it's never been abnormal. Apparently low urinary hGH with normal IGF-1 is frequent in CFS patients.)

    10. Improved dopamine functionality

    This has not improved at all as a result of the methylation. It gets worse when I am actively detoxing mold toxins (e.g. through the use of cholestyramine), which makes me suspect that the biotoxins may be at the root of the problem.

    The only thing I've found so far that helps is Vitamin C in IV form. It seems to me like this is a result of its doing a "power wash" of the dopamine receptors. (Perhaps I will understand this better after reading Dick Deth's book.)

    I consider this to be my biggest problem at present. Perhaps if I manage to remove more mold poison, it will get better. Otherwise I will need to turn to other ways to address cognitive functioning (such as killing lyme).

    11. Other areas of improvement

    I used to have a small amount of trigger point pain, but this went away entirely while I was on the antiviral (ane before I started the methylation support). It is conceivable that the methylation support kept it from coming back though.

    I got a huge number of immediate and dramatic improvements within several weeks after moving out of my home (contaminated with toxic mold) and engaging in some treatments for biotoxins. Would the improvements have been as dramatic if I'd not been doing the methylation support for six months? Or if I'd not taken that antiviral? I have no idea.

    From a purely emotional/intuitive level, it seems to me that the methylation support will have contributed significantly to whatever level of recovery/remission I ultimately accomplish. I cannot deny the fact that it removed something bad from my body when I first started using it, and that seems that it can only be a positive thing. Improvements in physical energy also are very welcome.

    My own experiences seem consistent with the theory that improved methylation/glutathione utilization can be quite helpful for CFS sufferers but is not the answer in itself.

    Nothing else seems to be the answer in itself either.

    Maybe addressing as many factors as we can find will bring us to an answer though. I've yet to find anyone who's approached the problem in this way (at least insofar as including methylation and some of the other newer treatments), and so the jury still seems to me to be 100% out in terms of whether it will work.
  3. Slayadragon

    Slayadragon New Member

    What kind of depressive episodes did you used to get? Sort of overwhelmed/weepy (which would be serotonin)? Slowed down and not enjoying things (which would be more like dopamine)? Or something else?
  4. simonedb

    simonedb Member

    what did you mean about reacting to the vegetable juice and chelation?
  5. marti_zavala

    marti_zavala Member

    I am kind of brain fogged today so I will wait until I can think to respond in full as your requested.

    But I did want to say that some of the benefits that you listed are intended to occur at or after Step 3. Removal of heavy metals, chemical detoxification, etc.

    I don't believe that anyone has been on the protocol long enough to reach Step 3. (Assuming 2-3 years to be get to step 3, the longest person on this protocol is still just short of 2 years - I may be wrong but I am also on the Yasko board and I think one person may be right under 2 years).

    Second, the protocol is still experimental and Yasko is not finished identifying SNP's so this must be kept at the forefront. It is quite possible that she has not identified a SNP that could be the dam-breaker for us or for the autistic community. She has, though, identified a number of SNP's that could be real issues for us and with Rich's help, we have two protocols to delve into this experiemental treatment, the simplified and the full protocols. Remember, one half of this protocol has been done for years without a lot of progress - glutathione deficiency so perhaps methylation is the other piece of the puzzle. There could be more pieces that have not been identified yet.

    Thirdly, on a more personal note - I have been helped tremendously just by getting OFF supplements that don't fall in line with the methylation theory. I was at pre-Step 1 for a long time and feel better than I have in years - and I was on glutathione injections for 2 years.

    I am now at Step 1 (barely).

    Another thought - the protocol also assumes that you restrict your diet in a particular way and limit your supplements. I don't believe that many of us are really willing to get off all supplements and follow the protocol to the letter. The dietary restrictions are very difficult to follow for our population because we are too ill to cook from scratch. The autistic children have it easier in this regard because, hopefully, their parents are energetic enough to cook properly and the kids have no choice. Although school functions are a problem so they get off the diet too sometimes.

    Any, it is an interesting and valid post, just wanted to point out some caveats as we are evaluating this protocol.

  6. deliarose

    deliarose New Member

    Interesting questions. I guess what we need is some good data on the people following this approach. I kind of regret that I haven't done more extensive testing.

    I guess Rich is seeing some of the data from the patients who are working with that Missouri doc.

    On a concrete note, I can say that I am 17 months into this and my Krebs cycle is still very messed up.. per my test results. Based on what Rich said, it is still very impaired by glutathione depletion.

    To my mind, that supports what Marti said about it taking a long time and making any judgements premature. But it also begs the question, are there any adjunct therapies that could help?

    Oddly enof, even though my Krebs cycle is messed up, I feel quite good physically. Energy doesn't seem to be a problem, although I'm not pushing it by trying to do aerobic exercise.

    I think dopamine is my big issue right now. I can't retain information. Frustrating.

  7. tansy

    tansy New Member

    Hi Delia

    Have you tried l theanine? I've found it helped create feelings of calm whilst making my feel more mentally and cognitively alert. Others have reported it helping with sleep. There's some info on it at

    tc, Tansy
    [This Message was Edited on 07/12/2008]
  8. simonedb

    simonedb Member

    do you have a link to somewhere that goes over the dietary and supplement restrictions? do you mind saying what are some of the supps you feel better off without?
  9. Slayadragon

    Slayadragon New Member

    Let me add here a couple of comments that Rich van K has made on methylation and two important hormones, MSH and human Growth Hormone.

    MSH is especially intriguing to me, since Dr. Shoemaker insists that those patients' whose MSH levels do not come up to normal levels tend not to get well from biotoxin illness (lyme, mold, dinoflagellates).

    Forebearance also pointed out that MSH seems to be related to healing the gut. This has the potential of resolving allergy symptoms, such as those associated with gluten.

    If this indeed is the case (and Rich states that this is as of yet theoretical), that could be really important.

    I'm going to have my MSH levels (as well as the other measures that Dr. Shoemaker recommends) this week. Regardless of how they come up, continuing to support this function with methylation seems to be good enough reason to think this approach is important in itself.


    To Forebearance re: MSH 06/29/08 07:50 PM

    Hi, Forebearance.

    Fascinating! I, too, wish you had before and after measurements of MSH, but just for the heck of it, I'm going to suppose that the methylation cycle block treatment did in fact raise your MSH to normal.

    Now, I must warn you that Dr. Shoemaker currently is not buying the following explanation, but I'm hopeful that that will change if we can ever get enough data to check it out!

    Yes, you guessed it! Glutathione! The answer to every question! Well, almost. Once in a while I invoke the methylation deficit or the folate problem, just to keep people guessing! (;-)

    Here's the story: MSH is made from part of the molecule called POMC (proopiomelanocortin), which is formed in the pituitary. Other parts of this same molecule are used to form ACTH (which signals the adrenals to secrete cortisol) and an endorphin (which makes us feel better).

    If the cells in the pituitary that make POMC are low in glutathione, they will not be able to make as much POMC as normal, and they will not be able to route it to the so-called regulated secretory pathway.

    The reason is that there is normally a hook on the POMC molecule that contains four cysteine residues that have to be connected together properly to form the hook, which is used to route the molecule to the right pathway. If there isn't enough glutathione present when amino acids are strung together to make the protein, this hook will not be formed properly, because the cysteines will bind together with each other too soon, forming cystine molecules with the wrong partners, and this will mess up the process. A lot of the bogus molecules will be sent to the recycling bin (the proteosome), and others will be routed to the unregulated secretory pathway.

    Well, that's the hypothesis. It would really be cool to be able to test it, but as you noted, we don't have a before and after, and of course one case sure won't convince my friend Dr. Shoemaker. I'm sure of that!

    Thanks for posting this.



    to slayadragon re: hGH 06/29/08 10:10 PM

    Hi, Lisa.

    Same problem. The human growth hormone molecule has two cystine disulfide bridges in it. If those are not formed properly, the molecule won't do its job properly. Glutathione depletion is the problem here, too.

    By the way, this same argument holds for antidiuretic hormone, oxytoxin, ACTH, and perforin in NK cells. It may apply to some other secretory proteins in CFS also, but I haven't checked them all out.

    The reason I'm fond of this part of the hypothesis is that it can explain the oddball collection of several symptoms and several corresponding known biochemical abnormalities in CFS.

    By the way, Dr. Cheney tried supplementing hGH in some of his patients a few years ago, and it started out looking good for some of them, and then they really crashed. He doesn't advocate that anymore, as far as I know.