Home / Methylation Cycle Block Theory & Chronic Fatigue Syndrome

Methylation Cycle Block Theory & Chronic Fatigue Syndrome

I was reading on co-cure a post by dr Rich van Kronyenberg, who is active in the forums over there and sometimes answers CFS questions. Ive read alot of what he has written that is up on the net. He talks alot about Glutathione depletion and its relation to chronic fatigue syndome. Alot of the things he talks about i tend to agree with because of my personal experiences with chronic fatigue. I had really low glutathione levels and was able to boost them up to normal with the help of NAC and glutathione pushes. One of his recent posts talks about a new paper out of Dubbo, Australia. It talks about how certain people can have a genetic predisposition and additional stessor that lower glutathione levels and interfere with the methylation cycle. This is really interesting to me because i was researchng the methylation cycle and came across certain supplements that promote methylation. I have tried just about every supplement known to man and i came across a few things that consistantly help me. These supplements that ive been taking for a long time just happen to promote the methylation cycle and go along with this hypothesis. They are Choline, Betain (in digestive enzymes), and l-methionine. Here is a diagram that illustrates this cycle:

I also came across a few articles on how the methylation cycle can relate to nitric oxide production in chronic fatigue. Ive thought that i had low nitric oxide levels, because when i take supplements that boost nitric oxide levels (l-arginine, hormone relaxin, etc) i can feel almost normal, but after a few days of this i crash really hard and am worse of than before. I came across some articles that might explain why:

“The overexpression of CBS (enzyme that synthesises cysteine at expense of methionine) resulting in the trapping of folate and loss of adenosine from the SAM cycle as the cause of oxidative damage ”

“Overexpression of CBS may overproduce cysteine and collapse SAM cycle”
So im tring to understand all of this and its hard;). The first article talks about how the vitamin folate (which is part of the methylation cycle contributes to another enzyme, and with out this enzyme the body cannot keep up demand for more nitric oxide.
After reading all of this i decided that i need to take folic acid supplments. This maybe will kick start my bodys nitric oxide production and take care of a nitrate tolerance i could have which is keeping my body from producing it normally. Its a long shot that this will help or makes any sense at all. But its only folate supplements (which is a b-vitamin) and it wont hurt.

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12 Responses to “Methylation Cycle Block Theory & Chronic Fatigue Syndrome”

  1. z2rus says:

    I am struggling with CFS as long as I can remember.
    And CFS is only label for neuroimmune reaction can be due to anything from HIV and Lyme to leukodystrophies.
    But any reliable study cut off those with infections and other known maladies at least those on the surface.
    As to me I am sure that my case is congenital 100% sure, but what exactly who knows, I am in search and I am on my own.
    About methylation…
    Methionine is definetly my choice but follic acid worsen my condition.
    B6 and B12 doesn’t change anything but B3 (niacin) helps a lot. I know that that B3 is helpful in depleting methyl groups…

  2. I came across your site in a search for references to a related hypothesis which I call the “methionine bottleneck” as it applies to chronic hepatitis C. This refers to the number of endogenous antioxidants that require methionine for synthesis (glutathione, lipoic acid, co-Q10, carnitine, creatine, taurine, cysteine), so that a stressor like Hep C can cause depletion in a vicious cycle also affecting methylation.
    I have independently found l-methionine with selenium (for the glutathione enzymes) effective against the depression and fatigue and GI syndrome of Hep C. However, lipoic acid (in a product called Hep C Complete) had a more complete effect against myalgia and “fluey” feelings that had persisted despite the earlier treatment. I now take this product (600mg lipooic acid, 400 mcg Se, 900mg milk thistle daily) with 500 mg l-methionine, 6g vitamin C, 800 iu vitamin E and multivitamin/mineral with Bs, molybdenum, chromium, magnesium etc.
    I will send you a copy of my paper on the hypothesis if I can find your address.

  3. Maynard says:

    Just going to add, I’ve been taking folic acid and B12 for ages, but read about the methylation cycle and that you have to take them (and B6) in their active forms to get the cycle up and running again.

    I’ve been taking active B6 (Pyridoxyl-5-phosphate, 50mg) for a while anyway, added methylcobalamin (B12, 1mg) sublingual – no problems… Then yesterday, for the first time, I tried Folinic Acid, 400mcg (the active form of Folic Acid) for the first time, and 12 hours later I felt like I was coming down with flu.

    I’m going to lay off it for a few days; continue with general mitochondrial support (Ribose, Q10, Carnitine, B3, Magnesium – which has been fantastic so far) before going at it again… I’ve read this acute detox/immune reaction is a good sign – it means your immune system’s working again! So I’m really interested to see how it goes now.

  4. admin says:

    The most difficult thing about this is that everyone is different. If you feel good with some of the yasko supplements, then (if you can afford it) maybe try the yasko genetic test. That could send you in the right direction and let you know what you should take and you should avoid.
    Its really hard to interpret, so you have to do alot of reading for it to make sense.

  5. Maynard says:

    I’m not sure of the practicalities of getting the genetic test over here (in the UK)… it’s actually hard enough getting the supplements – can’t seem to find hydroxocobalamin in oral form anywhere; although methyl is supposed to be better, a little concerned about methylating mercury, (if that might be an issue)…

    Quick update anyway. I went off the Yasko supplements for a bit because I figured I needed to take care of digestive issues first; not wanting a double die-off what with taking Caprylic acid for Candida.

    Started the Yasko up again with the addition of the quarter pill Folapro (Folate), and wow, that seems to step things up another notch.

    If anything, it’s how bad they’re making me feel which is so encouraging… I’ve felt sort of pre-viral since going back with the additional Folate, which suggests to me my immune system is dealing with infections, (for a change)…

    I’ve figured the best way is to take it easy and slowly add and take away supplements, but I look back to a few months ago and there’s certain things I’m not getting so much now – despite feeling worse than usual. My fatigue’s always bad with the Yasko supp’s, but it’s of a tired, sluggish nature; relaxing fatigue really; certainly not the sick feeling, unpleasant fatigue I used to get quite frequently.

    Recovery time from stress/exercise seems to have improved too. Response to stress seems reduced too.

    Early days, but of all the treatments I’ve tried so far, this seems like it might be getting to the bottom of things… While the Sinatra Protocol supplements seem to be a great support package – seem to have more consistent days; less ups and downs…

  6. Maynard says:

    Just thought I’d update… I’ve still been finding the Methylation Block supplements, *only* when taken all together, produce a very strong detox-type reaction, (a heavy headed and tired feeling)… The more I push it, the fewer CFS symptoms I seem to experience, but the more viral-type symptoms I seem to get… Although they seem to go within a day or so of stopping the Folapro, (which definetly seems to be the keystone of the treatment).

    So now I’m actually moving over to Dr Pall’s protocol – listed here – as I’m convinced he’s cracked it; and adding the low dose Folapro and Folinic acid from Kronyenberg’s protocol every other day, or every three days, just to ease out the intensity of the early detox reaction.
    I think both protocols work on the same principles, only Kronyenberg’s seems to kick start the internal detox mechanisms aggressively, while Pall’s seems to be more about supporting them… Both down-regulate the NO/ONOO cycle… I think in both cases, as Dr Pall says, you can’t expect to make significant progress unless you tackle as many parts of the cycle as possible at once, as well as avoiding exposure to anything which might increase/sustain damage (emotional stress, excessive exercise, chemicals/toxins, etc.)…

    After 6 years of trying everything under the sun, I think these protocols which focus on strict pacing & avoidance of stressors, the NO/ONOO cycle and raising glutathione, will be refined and improved, and I wouldn’t be surprised if they become to chronic/multisystems illnesses what antibiotics are to chest infections… Feeling incredibly positive about these!

  7. acronym says:

    To the OP
    “feeling good when taking arginine then crash”…,
    There are a number of great studies going on now regarding CFS and the latent HHV-6 and 7 viruses. People have made almost complete recoveries after being sick for yrs, and there is suspicion that a significant subset of CFS suffers’s immunity is compromised because this virus. Arginine is used by herpes virus to reproduce, maybe the inital boost you get from arginine is as result of enhanced circulation as a result of increased nitric oxide, but then you get major activation of HHV.

  8. kourosh says:

    try methylated folate available by prescription, deplin instead of the folinic acid. Also the flu may actually be your “healing crisis” which is very common with glutathione infusions. Also try the alpha lipoic acid as a stimulant for the liver to make more glutathione.

  9. Norma says:

    I have Fibromyalgia ,perhapswith CFS. Like the commentators above, have tried everything under the sun and nothing has worked. My biggest problem: how do you know if the reaction is “good” (because it is taking toxins out) or something should avoid at all costs, in any protocol? Sick and tired of tkain too much stuff.Any response? Thank you.

  10. Clare says:

    Has anyone tried Transfer Factor or Metazyme?

    I’ve had a long battle with CFS. I was ill for probably all my life until I found a great doctor in NY. He diagnosed me as having HHV-6, Candida, CMV, Epstein-Barre and hypothyroidism and food allergies. I started with detoxing with UltraClear and then used Borage Oil, Cal/Mag, CoQ10, Armour thyroid, T-Cell formula, Vit C, Acidophilus, Chromium Picolinate. This was in 1993. I was also thereafter diagnosed 5 separate times with Lyme disease and treated with high dosages of antibiotics. I responded quickly, lost 30 lbs. and was fine for years. Recently I am quite ill again and can not figure out what triggered it. I had stopped taking all supplements a few years ago except for the thyroid. Now I’m gluten intolerant, have high blood pressure, high cholesterol, and I think I have candida again. I’ve gained 40 lbs. I tried the blood type diet which is really bad for someone who is not healthy. Now I realize I am still harboring all these viruses and am trying to get back on track.In 1993 there was no way to even know all this stuff! Thank goodness for the internet.

    I’ve tried allopathic doctors here in California, but none of them are CFS informed. Since I didn’t feel that badly, I skated along, but now that I’m sick I’m searching for a good doc. Too bad the tests are so expensive. I tried a naturpath but I think she’s not informed either. Why do lab tests have to be doctor ordered? If you’re willing to pay, I don’t see why patients can’t order them. Oh well.

    My latest blood work was rather useless. Only an IgE allergy test was performed, and I have delayed food allergies which requires an IgG test, but my insurance company doesn’t cover them. My metabolic panel turned out normal!!! But I had an EIS test done (an electro interstitial scan) and it completely disagreed with the lame blood tests. For example, the blood tests said my sodium and potassium were normal, but the EIS revealed that my sodium is high and my potassium is low. So make sure you get good testing done, not the average doctor’s tests.

    Does Dr. Yasko have tests other than the genetic one? I’m sure my insurance company wouldn’t pay for that.

  11. Debbie says:

    CLARE –
    There are lab tests, and for a lot less $$$ available from Direct Lab Services (, AND every month one or a couple of related tests are on sale. Once you pay for a test you get a requisition form which is good for 6 months. In a few cases, you cannot have blood taken for them in certain states – I had to leave NY and go to CT for my labwork.
    I LOVE these guys. They’ve been very helpful for me as I’ve researched and managed the care of my 25 year old daughter who has CFS & Fibromyalgia.
    - Debbie

  12. mark says:


    SOunds like we have the same response to the NO drugs like arginine, caffine, horny goat weed, etc…. where I feel good crash.

    However, what caught my attention was the b-vitamins. Have you had anymore luck with the B-12 etc?

    I had good luck with the NAC and alpha lipoic acid/l carnitine for ahwile. my sex drive improved, energy increased, mood improved. however, it came to an end with like buring, feet burning, bladder burning. SOund familiar to anyone else? Those symptoms are relieved by methyl b-12, by the way. SO I am trying to figure out why.


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