Methylation and Glutathione papers posted

Discussion in 'Fibromyalgia Main Forum' started by richvank, Jun 5, 2009.

  1. richvank

    richvank New Member

    Hi, all.

    Cort Johnson has kindly posted a collection of my papers on methylation and glutathione in CFS spanning the past five years on his website:

    If anyone is looking for information about these topics, I would suggest going there.

    Best regards,

  2. Dlebbole

    Dlebbole New Member

    I am still plugging away....I always read your posts and and a year ago I bought a medical biochemistry book and I find your ideas very interesting. Can you address this issue: in some of the genomics papers I've read, the MTHFR gene doesn't seem to be important.....could methylation problems be an "epigenetic problem?"
    [This Message was Edited on 06/05/2009]
  3. FM58

    FM58 New Member

    Thanks Rich. It's wonderful to have all your papers in one place.

    I am quite interested in trying this approach. However, I can not take a multi-vitamin - it's on the IC "no-no list". I don't dare risk taking something that will flare my bladder.

    I do take supplements & vitamins separately. I have not tried the Methylation yet. Can I attempt the protocol and just skip the multi-vitamin?

  4. mbofov

    mbofov Active Member

    and thanks to Cort Johnson, too. A couple of weeks ago I was looking for one of your papers on-line and an old link I had no longer worked. So this is a very good resource -

  5. richvank

    richvank New Member

    Hi, Dlebbole.

    I'm glad to hear that you're digging into this stuff!

    As you probably know, there are two SNPs commonly found in MTHFR. The C677T SNP is in the catalytic domain of the enzyme, and affects the binding of FAD. Having this SNP slows the production of 5-methyl THF.

    The other one, the A1298C one, is in the SAMe regulatory domain of the molecule. Normally, SAMe downregulates this enzyme in order to control the overall coordination of the folate metabolism with the methylation cycle.

    From what I've seen, the first one is not more prevalent in PWCs than in the general population, so I don't think it contributes to causing CFS. However, it looks as though the second one is more prevalent in CFS, so it probably contributes to causing the onset of CFS in some PWCs.

    This is based on the small amount of data I have. As far as I know, there is one published paper about MTHFR in CFS, by Harmon et al. I don't have a copy of it. Do you? The UCSF medical library, which I use, doesn't have the journal in which it was published.

    I don't know about the epigenetics of MTHFR, but it may be a possibility.

    Even though the first MTHFR SNP is apparently not more prevalent in CFS, I think it will still cause the production of 5-methyl THF to be slower, and this form of folate is needed as a reactant by methionine synthase. It is therefore a little puzzling that it doesn't seem to be causal in CFS. Perhaps the reason is that it would tend to counter the effect of the methyl trap. According to the methyl trap, when methionine synthase slows down, 5-methyl THF builds up, because it's production is essentially irreversible. Because it does not have a glutamate tail, it leaks out of the cells into the blood, and over time, this depletes the other forms of folate in the cells, such as those responsible for helping to make RNA and DNA. So the first MTHFR SNP would perhaps limit this loss, and that would be a benefit in the methyl trap situation.

    I don't know what the effect of the second SNP is on the SAMe regulation of MTHFR. That is, I don't know if it would increase or decrease the production rate of 5 methyl THF.

    Best regards,

  6. richvank

    richvank New Member

    Hi, FM58.

    I can't give individual treatment advice unless a licensed physician is involved, to review my suggestions. However, I can tell you that some people have proceeded without the multi, or have taken another multi that does not contain substances to which they are sensitive. It's difficult to predict how that will work out in a given case, because everyone's nutritional status is different.

    The purpose of the multi is partly to cover any nutritional deficiencies that might be present, but it also contains some specific supports for the sulfur metabolism as well as nucleotides, which are particularly helpful in the treatment. Here is the composition of the multi:

    Amount per serving: Vitamin A (as palmitate)5000 IU,Vitamin C (ascorbic acid)500 mg,Vitamin D (as cholecaliciferol)400 IU,Vitamin E (as d-alpha tocopheryl succinate)400 IU,Vitamin K (as phytonadione)40 mcg,Vitamin B-1 (as benfotiamine)25 mg,Vitamin B-2 (as riboflavin)12.5 mg,Niacin (as niacinamide)37.5 mg,Vitamin B-6 (as pyridoxal-5-phosphate)12.5 mg,Folic Acid100 mcg,Vitamin B-12 (cyanocobalamin B12)250 mcg,Biotin150 mcg,Pantothenic Acid (as d-calcium pantothenate)50 mg,Calcium (as calcium d-glucarate)25 mg,Magnesium (as citrate, oxide)100 mg,Zinc (as monomethionine)5 mg,Selenium (as L-selenomethionine)100 mcg,Manganese (as arginate)1 mg,Chromium (as polynicotinate)100 mcg,Molybdenum (as amino acid chelate)75 mcg,Potassium (as citrate)5 mg,Broccoli florets powder160 mg,Citrus bioflavonoids50 mg,Choline (as bitartrate)25 mg,Inositol25 mg,PABA (para-amino benzoic acid)5 mg,Garlic (Allium sativum) bulb powder200 mg,L-methionine150 mg,Milk thistle (Silybum marianum) seed extract100 mg,N-acetyl-cysteine75 mg,Pine (Pinus maritimus) bark extract25 mg,Taurine250 mg,Turmeric (Curcuma longa) root extract50 mg,Intrinsic Factor5 mg,Trimethylglycine (TMG)50 mg, Free Form Nucleotide Complex100 mg,Boron1 mg,L-Carnitine (Tartrate)100 mg.

  7. richvank

    richvank New Member

    Hi znewby.

    I generally suggest starting with the multi and the phos. serine complex, because they support the basic metabolism and help to correct any deficiencies that might be present in the essential nutrients.

    Then I generally suggest that people start a few days later with the folate-containing supplements, at the suggested dosages, and then add the hydroxocobalamin a few days later. If the detox symptoms become intolerable, it's O.K. to stop all the supplements to calm them down, and then proceed. People seem to need different dosages, and have to experiment a little to see what works for them. I do not recommend going higher than the recommended dosages for the folate-containing supplements, at least until a person has been on the treatment for a while, because some people have experienced detox symptoms that have momentum, and do not stop right away when they stop the supplements, if the dosage has been high.

    As always, I want to state my position that it's necessary for a person to be monitored by a physician while on this treatment, even though it consists only of food supplements, because it can have profound effects, especially in people who have some other conditions along with CFS, and a few people have had some serious adverse effects, as I have written.

    Best regards,

  8. frickly

    frickly New Member


    Thanks for posting this as I have been reading as fast as I can. I have spent dozens of hours researching this subject and beleive I am on the right track and recovering. During my research I discovered the connection between autism and CFS. My son has aspergers, adhd, ocd and now tourettes. I have him with a DAN! doctor now and am very excited about the possibility of improving his life as well. We are both on many of the same supplements. I am glad I found this board as it seems that many people on this forum are determined to get better just as I am. Thanks for your work in this area. I hope more doctors will follow as I am sure you are moving in the right direction.

    Take care,
  9. Dlebbole

    Dlebbole New Member

    Hi FM58. I tried the multi just once, but it did bother my IC symptoms. Good luck.
  10. Dlebbole

    Dlebbole New Member

    Thanks for the extremely cool biochemical information!! I can see why you love this stuff!

    I only have access to the Journal of CFS back to 2007. Do you know the date of Harmon's article? Frustrating since there are articles in 2006 I would really like to get, but haven't been able to.
  11. ChuckNBerkeley

    ChuckNBerkeley New Member

    I too wondered if; "could methylation problems be an "epigenetic problem?""

    The current issue of Scientific American has an article describing non-SNP problems that cause or increase the likelyhood disease. RNA-related. I could just barely follow it.

  12. FM58

    FM58 New Member

    Thanks so much everone for all this valuable information!

    Rich, I appreciate the breakdown of the multi, I will probably skip that. I also appreciate the info given in how to start the protocol; what to take first, the advice to go slowly.

    Dlebbole, thanks for your experience with the multi & your IC. Now I definetely will skip it!

    Znewby, best of luck starting the protocol. Please keep us posted.

    Frickly, the more research I have been doing - I too am seeing the ME/CFS & autism connection. I used to work with autistic children- it was my passion! If you told me this 7 years ago, I would have thought you were nuts. Oh my goodness, I even have a much better respect & understanding of the biomedical approach to the ASD -even being away from the field.

    Now to read ALL of Rich's articles and send a thank you to Cort. I'm going to order the supplements I need to start & I will keep you posted. I am really excited about starting this protocol
  13. frickly

    frickly New Member

    I am sure you can imagine the reaction I get when I tell people that I beleive my CFS and my sons autism is related. I already know that I cannot discuss this with his pediatrician. She'll just think I'm a hypochondriac who wants my children to be as sick as me. I'm glad your exited about this protocal, I'm excited for you. I hope the best for you and a recovery.
  14. richvank

    richvank New Member

    Hi, Caledonia.

    One important thing to keep in mind in trying to sort out what causes what is the principle that "Association does not prove causation." Many people with CFS have this SNP, but about the same proportion of people who do not have CFS also have it. If it were a strong factor in causation, I would expect this SNP to be found significantly more often in people with CFS.

    It seems to be true that there is not just one SNP or one mutation that is responsible for a person being vulnerable to developing CFS, but a collection of them, and this collection is not the same for each person with CFS. This is being found to be true in quite a few other disorders, also.

    If a person has CFS, I do think that having MTHFR C677T will influence their folate metabolism, and will influence their response to treatment, but I don't think the evidence is there to say that it contributes to causation.

    I'm glad to hear that you are planning to get the Vitamin Diagnostics panel. I have found that to be very helpful in indicating where the issues are in a particular case. Some people have a particular issue with low folate, some with low B12, and some with both.

    Best regards,


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