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System Reset? Study Suggests Pro-Inflammatory / Autoimmune Reset Occurred in Chronic Fatigue Syndrome (ME/CFS)

Epigenetics research holds the fascinating possibility of figuring out what shifted at the very beginning of chronic fatigue syndrome (ME/CFS).  For many with ME/CFS a sudden change occurred – some sort of biological reset quickly happened – which never relinquished itself.

epigenetic reset ME/CFS

Something triggered ME/CFS. Could it have been an epigenetic reset?

Finding out what “reset” occurred is what epigenetics is all about.  Epigenetics identifies changes in the expression of our genes that occur after we meetup with biological stressors such as pathogens, drug, toxin or even foods.

Most of our genes that produce proinflammatory cytokines, for instance, have a kind of a lock on them. Removing that lock leaves them free to express themselves and leaves us open to poor health.

Epigenetics explores how the biological challenges we encounter in life can remove those locks (or add to them) resulting in an entirely new genetic landscape – one that could perhaps cause something like ME/CFS.

Many people’s ME/CFS/FM starts with an infection, and viruses can exert major epigenetic changes to our genome.  Herpes simplex virus (the virus Dr. Pridgen is targeting in fibromyalgia) engineers changes to our genome which help the virus avoid destruction and enhance its replication. Those changes include a suppression of our immune system, which can result in an increased risk of cancer.

What goes around comes around, though.  Epigenetic News recently reported that an epigenetic modifying cancer drug was able to return the parts of the immune system that the  herpes simplex virus had disturbed to normal. The drug was able to effectively fill in the immune hole created by the herpes virus by boosting a number of immune factors (IFN-a, IL-8, IL-6, transcription factors, stress response factors). Mouse studies revealed that the drug also reduced reactivation of the virus.

That suggests that some similar drugs now in clinical trials could help in the fight against herpes and other viruses or could perhaps simply return to normal epigenetically modified genes that have suppressed immune functioning.

 “A new class of antivirals based on this study might be useful for patients who are resistant to existing antivirals like acyclovir and ganciclovir….. (or in) viral infections for which there aren’t pharmaceuticals to boost an individual’s immune response.” Dr Kristie

If epigenetics turns out to play the major role in ME/CFS that it does in cancer and other diseases, a cancer drug could someday be in store for ME/CFS treatment.

Epigenetics Study Highlights Immune Alterations in ME/CFS

The epigenetics story begins with gene transcription – the first step in the process of translating our genes into proteins.  Gene expression gets enabled by the removal of methyl groups that block transcription and/or by the addition of methyl groups that stop genes from being expressed.

Malay Trivedi and Lubov Nathanson at Dr. Klimas’s Institute of Neuroimmune Research at Nova Southeastern University recently published the most comprehensive study yet on epigenetics in chronic fatigue syndrome .

Just a few epigenetic studies have been done in ME/CFS and none like this one. For one, the group took advantage of a new breakthrough in genetic testing (an advanced Illumina array) to almost double the number of testing sites (from 450,000 to 850,000 sites). For another, the larger sample size (64 participants from two geographically distant locations) ensured a more comprehensive look at the epigenetic changes in ME/CFS. This allowed the group to produce what they called “consensus hypomethylated sites” they believe could be used in future studies.

The general findings of the study agreed with those from past ME/CFS epigenetic studies. Hypomethylation – the deletion of methyl groups, which make it easier for the genes to be expressed – was the theme, with 98% of differentially methylated sites in ME/CFS hypomethylated compared to controls. (Only 2% were hypermethylated compared to controls.)  The hypomethylation was most prominent in genes associated with immune cell regulation.

The high degree of hypomethylation was intriguing for several reasons. For one, Epstein-Barr Virus – presumably a common trigger in ME/CFS – overwhelmingly triggers hypomethylation and almost no hypermethylation of genes. Hypomethylation is also associated with pro-inflammatory gene expression in autoimmune diseases as well as in cancer promotion.

Multiple Sclerosis Breakthrough

A “global” hypomethylation, for instance, is also found in lupus and rheumatoid arthritis. The hypomethylation of a promoter gene for IL-6 in rheumatoid arthritis causes an overexpression of pro-inflammatory cytokines and other immune factors which ultimately results in joint damage.

Epigenetic changes to the HLA genes may have triggered MS. (HLA Gene Expression – by ZionLion77 –

The recently uncovered hypomethylation of an HLA gene in multiple sclerosis (MS) prompted researchers to state that epigenetic changes may even be “caus(ing) the disease”. That bold statement reflected the findings of a recent large study, which indicated that epigenetic changes were directly causing the largest risk factor found yet for MS.

That finding may have implications that go far beyond MS and could conceivably reach ME/CFS/FM.  Since the HLA region of the genome is associated with almost all autoimmune diseases, the authors believe their finding will impact other autoimmune diseases.

(Several years ago Ron Davis pegged the HLA region as a potential study area for ME/CFS. His Stanford Genome Lab has developed new methods of assessing this complex region of our genome, and he and Mike Snyder at Stanford are doing an intensive analysis of that HLA region in ME/CFS.)

Back to Chronic Fatigue Syndrome (ME/CFS)

The highest degree of hypomethylation in a genetic region in ME/CFS occurred in gene promoters associated with natural killer cell functioning, no less – the most consistent finding in ME/CFS.  That suggested that some sort of epigenetic reset – perhaps triggered by an infection – occurred in the NK cells of ME/CFS patients.

With regard to single genes, the authors highlighted the hypomethylation of genes associated with muscle hypotonia (low muscle tone) and cognitive impairment (MED13L), problems with protein synthesis (metabolism), and glucocorticoids (SGK3 gene – inflammation).

It was the immune genes, though, where the hypomethylation really came to the fore. Immune genes that regulate the adaptive immune response (T & B cells) and the production of immunoglobulins were hypomethylated. The authors asserted that those findings were in sync with reports of improvement from Rituximab.

Promoters (MMP14, MAP4K4, MAPK12 and CREB5), which may be activating tumor necrosis factor signaling pathways and thus contributing to the pro-inflammatory problems believed present in ME/CFS, were hypomethylated as well.

A gene (miRNA-148a) that impairs the innate immune response was also hypomethylated. Several of the hypomethylated genes were also found in prior ME/CFS studies.

Then there’s the IL21R gene. The hypomethylation of the IL21R gene promoter in ME/CFS could promote inflammation, autoimmunity, thyroid disease, intestinal inflammation, and others.  IL-21 also plays a critical role in triggering spontaneous experimental autoimmune encephalomyelitis – an animal model of brain inflammation.


IL-SR gene chronic fatigue syndrome

Unleashing the IL2R gene could contribute to inflammation (including neuroinflammation), thyroid disease and autoimmunity

Epigenetics is a relatively new science which is already proving to be a boon to the study of autoimmunity and cancer. Larger studies will be needed in ME/CFS for epigenetics to reach its potential, but the study from Dr. Klimas’s group suggested that, just as in some autoimmune diseases, enhanced hypomethylation may be increasing the expression of genes which promote inflammation and autoimmunity in ME/CFS.

The most encouraging thing about epigenetics is the possibility of reversing the epigenetic changes a pathogen, toxin or drug has caused. Much more study is needed to isolate any epigenetic culprits in ME/CFS, but epigenetic altering drugs are being developed for other diseases. One intriguing drug seeks to reverse the epigenetic changes caused by herpes simplex virus – thus returning the immune system to normal.  Another breakthrough suggests that epigenetic changes may be major drivers of multiple sclerosis.

This is clearly a field to keep an eye on.

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  • Robert Buelteman

    August 4, 2018 at 5:18 pm - Reply

    “One intriguing drug seeks to reverse the epigenetic changes caused by herpes simplex virus – thus returning the immune system to normal.” It happened to me after 6 months on Dr. Pridgen’s protocol. However, my wife has not experienced this, even after 17 months on the same protocol.

    • Cort Johnson

      August 4, 2018 at 5:51 pm - Reply

      Congratulations to you. Unfortunately I would be surprised if one treatment protocol worked for all. (What a nice surprise that would be, though. :)) I suppose it’s possible that if herpes simplex was the cause of your wife’s illness some epigenetic changes occurred to her that didn’t happen to you which have not been reversed. I’m sure there are many possibilities, though.

      • Robert Buelteman

        August 4, 2018 at 6:13 pm - Reply

        We are both Lyme survivors with different co-infections. We know several who have come out on tops as the result of Dr. Pridgen’s protocol, but you are right – many possibilities. After all, there is no control group for the diversity among human beings.

        • Cort Johnson

          August 4, 2018 at 6:21 pm - Reply

          I wish your wife had found her answer but it’s so good to hear that some people are really benefiting. I just saw Dr. Pridgen, really enjoyed meeting him and just started on the protocol today as a matter of fact (!). After almost 40 years of this my expectations are limited but who knows? It’s working for some people. 🙂

          • Grete Linerud

            August 5, 2018 at 9:00 am -

            Hi! I have an ambitious doctor, willing to try new approaches, where can I find details in Dr. Pridgens protocol?
            Thank you! And good luck Cort! Thanks for all your work!

          • Cort Johnson

            August 5, 2018 at 12:26 pm -

            Congrats on finding a doctor open to new ideas. Check out Health Rising’s resource center on Dr. Pridgen –

          • Karin

            August 5, 2018 at 7:21 pm -

            Thanks for the great article Cort. I have also just started Dr. Pridgen’s protocol (15 days in now). I’d like to know if there’s a group or forum of those who are on this protocol where we could share how things are going and compare with each other? If not, perhaps we should start one? I don’t have a FB account so can’t do it there.

          • PamC

            December 24, 2018 at 9:37 am -

            Cort I was just catching up with your very interesting articles and was wondering if you have benefitted for Dr Pridgen’s protocol which you had just started in August.

            Hope it has worked for you. I have autoimmune hashimotos and several genetic markers for other autoimmune illnesses as well as long standing ME hence my interest so I would love to know if you are one of the lucky ones for who it has worked.

      • Lauren Gordon

        August 6, 2018 at 3:59 am - Reply

        Hi Cort, huge good luck trying the Dr Pridgen protocol. I was searching through the links but cant find any recent info on his protocol? Could you point me in the right direction? Would love to consider it for my son (if I can find a dr out here who could/would do this with us).

    • Chris Pfeiffer

      August 4, 2018 at 6:37 pm - Reply

      So, is Dr Pridgen still seeing patients – did you find another doctor willing to prescribe for you. After 22 years of no pain with my CFS, my latest crash 4 weeks has opened the door to widespread excruciating pain. Can you tell me what dosages of the medication you were using?

      • Perrier

        August 4, 2018 at 8:23 pm - Reply

        Yes, I would also love to hear what you Cort are taking. What did the doctor say to you about your situation. Was he optimistic? Thanks

        • Cort Johnson

          August 4, 2018 at 10:16 pm - Reply

          Yes, he seemed pretty optimistic. I’m a fairly uncomplicated case. I’m being put on a pretty standard protocol – valtrex + celecoxib + tramadol for pain + a nasal spray for sinuses and that’s it I think. If the changes occur he thinks they’ll start in about 3 months when I start to walk or do some exercise and then don’t crash afterwards.

          • Issie

            August 5, 2018 at 2:26 am -

            What’s in the nasal spray?


          • Chris Pfeiffer

            August 5, 2018 at 1:08 pm -

            Hi Cort,

            Sorry to here you are dealing with more symptoms. What dosages of the medication is Pridgen using with you. I read the study bu did not see dosages, so if I am going to try and convince my doctors, that would be helpful.

          • Perrier

            August 5, 2018 at 7:36 pm -

            That is wonderful Cort. Thanks for all your hard work too. I have read Dr Skip’s materials, and I have trouble understanding how the drugs he uses would help with toxic feeling, sick feeling, weakness, PEM, and all the horrid CFS/ME symptoms.

            Were you tested Cort? Was the herpes virus found in you to warrant these drugs?

            And has Dr Skip been in touch with Dr Ron Davis.

            Folks are desperate for help because this illness is very disabling.

          • Robert Buelteman

            August 6, 2018 at 3:55 pm -

            Several questions above re: Dr. Pridgen’s protocol and my success with the treatment. His concept is to “silence” and neutralize the HSV1 infection of the vagus nerve. I am taking Celebrex, Duloxetine, Famcyclovir or Valcyclovir, Mometasone Furoate Monohydrate Nasal Spray, Ondansetron, Pantoprazole, Tramadol, and Trintillex. Dr. P will work with your doctor after initial consultation. He is a gem of a man! (When was the last time your doctor gave you his cell phone number?)

          • Tim

            August 6, 2018 at 6:17 pm -

            Robert, is there any way to test whether the vagus nerve is infected?

          • Robert Buelteman

            August 6, 2018 at 10:51 pm -

            I do not know, and i am not a doctor.

          • Denise

            August 13, 2018 at 5:43 am -

            I’m also looking for specific dosages, and asked Cort on his latest comment below near the bottom of the comments, since I’m reading this a whole week later 🙁 Several of us are asking for this. Does anyone know if Pridgen does Telemed appointments? Or know his contact info?

          • Karin

            August 13, 2018 at 7:07 am -

            Dr. Pridgen will share all the dosages with your doctor. He asks that your doctor get in touch and he is more than happy to instruct on dosages. His email (which he himself has put on other posts on this site, so I don’t think he will mind me putting it again here) is The website is
            Dr. Pridgen is a wonderful man, dedicated and truly wants to help.

    • Aidan

      August 5, 2018 at 3:06 pm - Reply

      How well are you now Brian & are you off all medications & fully exercising? Have you been tested for ALPHA GAL MEAT ALLERGY from Lyme History?

  • Pat S.

    August 4, 2018 at 5:55 pm - Reply

    Thank you Cort, and God bless Dr. Klimas and the INIIM team and all the others who keep plugging away to find a treatment for this disease.

    • Cort Johnson

      August 4, 2018 at 6:18 pm - Reply

      Indeed. I think we’re going to hear some really interesting stuff from her group. Dr. Klimas has contributed in more different ways to this illness than anyone I can think of.

  • Issie

    August 4, 2018 at 6:08 pm - Reply

    This is an interesting field. We may be predisposed to certain changes due to our inherited snps in our genes. But just because the snp is there, doesn’t mean that snp will get activated. It may be working just fine even though considered mutated. We have to be careful with what we do with the knowledge of those snps and look at the whole not just a snapshot of the whole. That being said… you have the 23&me related snp alleles to the one mentioned about brain and thyroid inflammation?


    • Cort Johnson

      August 4, 2018 at 6:25 pm - Reply

      The layer that epigenetics puts on our genome is fascinating indeed. Personally I don’t know if I carry SNP’s for that gene or the others. That’s an interesting question.

  • Tim

    August 4, 2018 at 6:31 pm - Reply

    So does this confirm why the Rich Van K/Amy Yasko methylation protocol is a good idea?

    • Cort Johnson

      August 4, 2018 at 7:37 pm - Reply

      I don’t know. As I remember Rich was very interested in glutathione and oxidative stress. The findings in this study suggesting that a kind of inflammatory state was unleashed would make sense with Rich’s ideas I think but this and other studies are much more targeted. They’re uncovering specific gene sites where the methyl groups attached to the gene promoters have been lost. That’s very different in the end because I think ultimately they could lead to much more targeted treatments.

      • dejurgen

        August 4, 2018 at 9:43 pm - Reply

        Hi Tim, Cort,

        May you or somebody else have a good link on Rich Van K’s idea’s on the combination methylation/oxidative stress/glutathione?
        I’ve been diving lately in poor glutathione recycling and next to impacting oxidative stress it seems to be directly and strongly downregulating both glycolysis and the Krebbs cycle, crippling ATP production. The proposed mechanism seems to be reïnforced by hot weather. Both effect us dearly.

        When searching for “hypomethylation” I looked into and clicked on the “” link just at the start of the article. Immediately this drew my attention: “While the methyl group is usually part of a larger molecule, it can be found on its own in any of three forms: anion, cation or radical.”

        If my chemistry intuition is wright, both methyl anions, cations and radicals are “perfect” targets for chemical reactions with ROS and hydrogen peroxide. That should “react away” a decent amount of methyl groups no longer available for methylation of DNA (or even “chipping them from methylated DNA”). That could be a powerful source of hypomethylation. And if overwhelmingly hypomethylated DNA would lead to more oxidative stress… …then we have a “nice” vicious circle. Especially so if some strong “hit” on our system temporarily depleted glutathione reserves and our ability to replenish them. A lack of glutathione would destroy the best key we have to unlock this vicious circle, and plenty of ROS would deplete glutathione creating another important part to close the vicious circle.

        Searching further on this suspicion I found “Methyl hydrogen peroxide (MHP) exhibits a tendency to form a stable dimer by hydrogen-bonding.” A stable chemical end product from the reaction between methyl anions, cations and radicals with hydrogen peroxide is but 1 way to react methyl groups away.

        On top of that, most diseases correlating to hypomethylation mentioned in the blog tend to be near the “high oxidative stress side”. And EBV infected cells are known to produce significantly higher amounts of oxidative stress compared to uninfected cells.

      • dejurgen

        August 4, 2018 at 9:52 pm - Reply

        (retry, probably blocked due to bad link)

        Hi Tim, Cort,

        May you or somebody else have a good link on Rich Van K’s idea’s on the combination methylation/oxidative stress/glutathione?
        I’ve been diving lately in poor glutathione recycling and next to impacting oxidative stress it seems to be directly and strongly downregulating both glycolysis and the Krebbs cycle, crippling ATP production. The proposed mechanism seems to be reïnforced by hot weather. Both effect us dearly.

        When searching for “hypomethylation” I looked into and clicked on the link just at the start of the article. Immediately this drew my attention: “While the methyl group is usually part of a larger molecule, it can be found on its own in any of three forms: anion, cation or radical.”

        If my chemistry intuition is wright, both methyl anions, cations and radicals are “perfect” targets for chemical reactions with ROS and hydrogen peroxide. That should “react away” a decent amount of methyl groups no longer available for methylation of DNA (or even “chipping them from methylated DNA”). That could be a powerful source of hypomethylation. And if overwhelmingly hypomethylated DNA would lead to more oxidative stress… …then we have a “nice” vicious circle. Especially so if some strong “hit” on our system temporarily depleted glutathione reserves and our ability to replenish them. A lack of glutathione would destroy the best key we have to unlock this vicious circle, and plenty of ROS would deplete glutathione creating another important part to close the vicious circle.

        Searching further on this suspicion I found “Methyl hydrogen peroxide (MHP) exhibits a tendency to form a stable dimer by hydrogen-bonding.” A stable chemical end product from the reaction between methyl anions, cations and radicals with hydrogen peroxide is but 1 way to react methyl groups away.

        On top of that, most diseases correlating to hypomethylation mentioned in the blog tend to be near the “high oxidative stress side”. And EBV infected cells are known to produce significantly higher amounts of oxidative stress compared to uninfected cells.

      • Tim

        August 4, 2018 at 10:26 pm - Reply

        Cort wrote, “As I remember Rich was very interested in glutathione and oxidative stress.” Yes, but Yasko was only interested in methylation.

      • dejurgen

        August 5, 2018 at 9:30 am - Reply

        I am currently looking into improving glutathione recycling. Glutathione can ideally be recycled many many times, so availability of reduced glutathione and the ratio reduced/oxidized glutathione can be both increased by glutathione supplementation, supporting glutathione and supporting the bodies own glutathione recycling speed.
        These options can support each other but I’ll try to separate things for better observation. I’ll compare supporting glutathione versus supporting recycling glutathione to not washing dishes but buying a new set of plates every two months versus buying only one set of plates every five years but washing dishes every day.
        I’ll learned a thing or two about the importance of vitamine B too. Thanks. Maybe there’s a gut connection here too: I may have inherited my mothers intollerance for vegetables containing sulfur, needed for methylation and glutathione production. Probably vit B absorbtion is affected by bacterial overgrowth as well.

      • dejurgen

        August 5, 2018 at 10:19 am - Reply

        I just come to think of it: main ketone bodies contain methyl groups. all three pictures on the right hand side have 1 or 2. And ketones are said to increase anti-oxidant production by altering gene expression.
        I don’t know how they get there methyl group (yet), but I guess it’s more by deconstructing fat molecules then by methylation. That opens several potential mechanisms.
        1) ketones are not cleanly/fully burned as full and produce “waste” ketone anions/cations/radicals which should help with DNA/RNA methylation and potentially with ROS removal
        2) by replacing acethyl groups with methyl groups; exchaging them with DNA/RNA again changing gene expression.
        See “Ketosis increases the activity of a family of transcriptional repressors known as sirtuins. Sirtuins are a class of histone deacetylases (HDACs), or proteins that remove acetyl groups from histones at specific genes to turn off gene expression.” and “A 2016 study by Heyward et al. found that mice that were chronically overfed had memory impairments and decreased hippocampal Sirt1.3 Decreased expression of several learning and memory genes, including Sirt1, was associated with an increase in DNA methylation.” The latter is a correlation; the methyl group on ketones might therefore be a driving mechanism just as well.

        If correct, it would split working diets into two distinct categories with few overlap: keto diet with methyl groups from ketones influencing gene expression on one hand and increased NADPH/glutathione recycling through the Penthose Phosphor Pathway as long as one lives on a low callory diet with relative flat blood glucose levels.

  • Issie

    August 4, 2018 at 7:40 pm - Reply

    I would actually look into Dr. Ben Lynch work. He has a new book out “Dirty Genes”.

  • Cort Johnson

    August 4, 2018 at 8:08 pm - Reply

    Maschelle left this comment on Health Rising. I thought I would pass it on

    “I haven’t heard much about this from anybody else, and my questions regarding it have not been answered in social media. But I presented with a positive ANA (Anti Nuclear Antibody) test result in the beginning stages of this disease. It was the beginning of the highly alarming things happening, like forgetting how to sign your name when you are checking into the doctor’s office. That’s so commonplace for me now that it doesn’t frighten me anymore. But having that kind of a test result combined with having such bizarre things happening to the way my systems worked might not be simply coincidental. And then it just went away, but the ME/CFS had become deeply entrenched and I was down to 17% of my normal level of function overnight.
    It happened the same way for my child.

    I can’t help but wonder if there IS an autoimmune connection here. I realize that even healthy people can have a positive ANA. But I was NOT healthy and I have not recovered, but instead have continued to decline over the past 12 years. And that’s in spite of my very best efforts of self-help, pacing my activities and cutting stressors (that were under my control) out of my life.

    There has to be a reason why the first place it seems the road to diagnosis begins with is a referral to a rheumatologist. Are other people having their blood test come back with positive ANA’s, which,when combined with presenting symptoms,sets off an autoimmune disease alert in the family practitioners’ brain?

    Yet, try as they might, rheumatologists are unable to find a Trace of any known autoimmune disease.

    And then came the neurologist and about a year later a Psyologist & an initial diagnosis of Somatoform Disorder AKA Conversion Disorder (more commonly known as “it’s all in their head”).”

    • Issie

      August 4, 2018 at 9:26 pm - Reply

      In response to this question, I’d highly suggest looking into Lyme and CIRS. Both can be present but hard to test for. Addressing those things have been a life changer for me. If the autoimmune system is compromised, you can get a negative Lyme test when it is positive. I’ve had several doctors tell me this. There still is not enough science to detect what all possibilities could be an issue. If it looks like a duck, quacks like a duck…….then why not treat it as such and see if things improve. So to answer question – yes – there can be markers positive at one time and not another — yet the problem can still be there. And it seems that autoimmune and inflammation are core issues.


  • Tamesin

    August 4, 2018 at 8:45 pm - Reply

    This is a reply to Maschelle –Yes, I have had a positive ANA since I was first tested in my teens (in my 50s now), but none of the other tests that confirm autoimmune disease have ever been positive. But I have been evaluated for Lupus and MS by any and every doctor I’ve been to (and that’s a lot). They all think I have some sort of autoimmune disorder, and they say, “But which one?” and I say, “One that hasn’t been defined yet,” or “Yes, ME/CFS.” Hard for them to get their heads around.

  • konijn

    August 4, 2018 at 9:30 pm - Reply

    Hi cort,

    thanks again for the hope you give me allthough it is so confusing. Everytime an other reson to be ill with a blog. And als, living in belgium, totaly out of my control to try anything.

    I had a question. do you know more about nancy klimas and her homeostasis trial she wanted to do on me/cfs patient?

    thank you!

  • OM

    August 4, 2018 at 9:35 pm - Reply

    The MTHFR defect causes a reduction in Glutathione which is the most important antioxidant in the body. In and of itself it could cause a lot of the problems of ME/CFS. Hope the med works for you Cort! Would love to hear more about it.

    • Cort Johnson

      August 4, 2018 at 9:42 pm - Reply

      Thanks! Me To 🙂

    • Wayne

      August 4, 2018 at 10:23 pm - Reply

      Hi OM. That’s interesting what you say about glutathione. I have had a liver function test and was found to be low in glutathionation. This could explain chemical sensitivities, metabolic “poisoning” (lactic acid not being detoxified sufficiently, lactic acid in the muscles (pain), etc. Should I be tested for the MTHFR defect then in your opinion? Is there any way to improve my health if a problem with the MTHFR gene is found? Please help!

      • Cort Johnson

        August 5, 2018 at 12:53 am - Reply

        Shungu has also multiple times validated low glutathione levels in the ventricles surrounding the brain in ME/CFS. He believes rampant oxidative stress is the key to the neuroinflammation in ME/CFS.

  • Troy

    August 4, 2018 at 10:10 pm - Reply

    “Reset” implies a return to the original/normal state (ie healthy) so I don’t think it’s a very good choice of word when describing a suddent change to a very much not normal not original sickness state.

  • Issie

    August 5, 2018 at 1:51 am - Reply

    I can’t help but think there is a connection to glutamate and that Channel. It’s a precursor to glutathione. I think there must be some sort of connection to a high sympathetic response. I keep trying to find how it all plays in. A fault either there or too low GABA. There is also a tie in with cysteine. Trying to figure out if the lows are a compensation or an end result. Are precursors up regulated to cause a downregulation? If so, WHY? With me, I paradox to anything that tries to go into GABA. Instead of it having a calm down affect – does opposite. I haven’t been able to take glutathione and may be connection to CBS mutation and issues in sulphur methylation pathways. The methylation systems are important, but taking a supplement may not swing things in right direction if it’s not addressed at proper breakdown point. As I’ve said before – just because there is a mutation on a snp – doesn’t mean that’s what needs to be addressed. That might not be the main issue. Correcting something else may complete the circle. The down regulation may be needed for other more complex issues.


    • Tamesin

      August 5, 2018 at 12:43 pm - Reply

      I have the same problems with trying to address low GABA as Issie. It stimulates my body, and creates restless legs, pain and spasming, etc. The doc who tried to treat me for it is also treating me for Methylation problems, and she is baffled by my reactions to things. She thinks the problem with contradictory reaction to meds to calm GABA is related to my high Glutamate levels. She thinks the things she’s using to try to increase GABA do not take the normal steps, and go straight to increasing Glutamate. I don’t know much about the cycle to know what she means by that, but I’m guessing some of you do.

      • Issie

        August 5, 2018 at 2:46 pm - Reply

        Sorry you are having this issue too. My sister and her son does this too. We can’t seem to figure out WHY and it seems to be a key part of our puzzle. I need to take a medicine that has potential to go down this pathway and I’m in fear to start it. But it’s only thing my doc knows that may help. We will see how it goes….. even taking the amino acid glycine went down that pathway. Glutathione does too. Even transdermal GABA. With this happening with my sister and nephew – there must be some pathway breakdown that I’ve, so far, not been able to figure out. I’ve asked doctors, asked researchers – none have come up with a reason or solution.


        • Tamesin

          August 5, 2018 at 3:08 pm - Reply

          Thanks, Issie. Interesting that it runs in your family! I wonder whether this is common in other people with ME/CFS, or whether we are a subset, or have a particular gene or snp that interferes. My doc is baffled. I hope that the new med you are taking somehow is well tolerated for you. As a side note, do you have problems with NAC, ALA, and the like causing signficantly more pain? This happens to me, even though the supplements make me feel stronger and sharper and happier — but by the end of the day of taking even a small amount of any of those types of energy-giving supplements, I am doubled over with muscle spasms and GI pain. I have not found anyone with ME/CFS who has this problem, and no doc has a clue as to why this would happen.

        • dejurgen

          August 5, 2018 at 10:54 pm - Reply

          @Tamesin: for Glutathione see my comment to ISSIE about Glutathione nearby.
          NAC ups Glutathione production too.
          ALA: you are probably in the same subset as Issie and me, the one that better has a flat and intermediate blood glucose level. And ALA, if you mean Alpha Lipoic Acid lowers blood sugar in people with diabetes2 according to webmd. You may not want that.
          It is also an anti-oxidant which is good; it is however strongly dependent on NADPH depending mechanisms for recyling so if NADPH is the limiting factor ALA competes with glutathione risking decreasing glutathiones anti-oxidant power by decreasing reduced to oxidized ratio.
          Vitamine C recycling also depends on NADPH but excess vitamine C is easily discarded in urine so this may be why it seems to be better tolerated (if not causing diarrhea in the digestive tract).
          Thanks for sharing your experience; I was considering ALA and now can save expense and setback ;-).

          • Issie

            August 6, 2018 at 1:43 am -

            NAC was another one I recently tried with great diaster. Glycine was even worse. Makes me rethink last step in CIRS treatment – VIP. Glycine is supposed to up VIP. The goal with using VIP is to help brain inflammation and it is supposed to help the immune system. But if it does what glycine did – it will not be a pleasant experience. But there is only one way to find out. And I’m really wanting the inflammation down. As that can do permanent, irreversible damage.

            The “channel” I was speaking of is partially a channel – and a receptor . NMDA. It is a glutamate receptor and ion channel. Can cause excitatory response and activate sympathetic nervous system. I’ve thought there is some connection with this and POTS. I still don’t have the answers I want on this one.

          • dejurgen

            August 6, 2018 at 9:16 am -

            @Issie: I’m a noob regarding to ion channel stuff, so my ideas are only made up on the spot. I mainly checked what they are and do and their relation to ROS/oxidative stress/glutathione.

            I did find on weblink(wikipedia, nmda_receptor):
            A) “However hypofunction of NMDA receptors (due to glutathione deficiency or other causes) may be involved in impairment of synaptic plasticity”
            B) “It is generally believed that NMDA receptors are modulated by endogenous redox agents such as glutathione, lipoic acid, and the essential nutrient pyrroloquinoline quinone.”
            -> A), B) and the NMDA receptors dependency on glutamate and glycine binding seem to indicate that these receptors are strongly depending on glutathione levels or may even have some glutathione sensing functions.
            -> Supplementing building blocks for glutathione or glutathione itself may cause an “unnatural” increase in reduced glutathione while strongly decreasing it’s anti-oxidant functioning by
            far stronger increasing the pool of oxidized glutathione, leading to falling ratio reduced to oxidized glutathione. This may be a rare/nonexistent event in the natural world so not be taken into account by evolution and may fool the NMDA receptor about the glutathione state, causing it to function opposite as desired. The fooling is in it that it does not seem to sense oxidized glutathione so it might believe increased reduced one is always indicating a state of less oxidative stress.
            That’s my best and completely uneducated guess.
            -> B) imposes ALA again

            Note: if POTS is partially of the hyper-adrenergic type: see previous comments on (nor)adrenaline

      • dejurgen

        August 5, 2018 at 8:51 pm - Reply

        “I have the same problems with trying to address low GABA as Issie. It stimulates my body, and creates restless legs, pain and spasming, etc.”

        Hi Tamesin, would you happen to be on a non-keto diet? If so, it could make sense. “GABA binds to GABA receptors on the neighboring islet α-cells and inhibits them from secreting glucagon (which would counteract insulin’s effects).”

        I start to believe that increased glucose typical found in non-keto diets in ME patients is not a “mistake” but desired as long as they do not cause glucose to fat conversion. It is a potential way to activate the pentose phosphor pathway, the main source for NADPH in the body. And NADPH is the only source for both glutathione regeneration and glucose to fat conversion. So as long as you can avoid the latter, higher glucose levels combined with the proper chemistry can increase reduced glutathione and hence fight rampant ROS.

        So GABA, inhibiting glucagon, decreases glucose levels. If the body deems those to be undesirable low then the most logical step is to increase noradrenaline and adrenaline creating anxiety. They can affect pain in either direction depending on your body “type”.

        Restless legs are by the way often a good way to increase blood flow and hart prefill. Spasming with me, when it was very strong, was a way to increase body temperature up from near hypothermia. Would your body temperature be on average quite low? If so, “wasting” glucose to heat up your body could produce NADPH and reduced glutathione as a desired side effect.

        • Issie

          August 5, 2018 at 9:06 pm - Reply

          @Dejurgen, your comments never cease to amaze me. Therefore, back to my original comments – could some of what seems to be a down regulation actually be a compensation and the lessor evil. Trying to sort out what is a symptom and what is a compensation is difficult. What should or shouldn’t be addressed, at what level in the “circle”. (For example, doing what is considered the “opposite treatments” for my POTS – its what works best for me.) We have to pay close attention to our reactions and response – there could be a very good reason for it. But trying to figure the science out and the WHY is tricky and tedious. Lots of trial and error.

        • dejurgen

          August 5, 2018 at 10:33 pm - Reply

          “I can’t help but think there is a connection to glutamate and that Channel. It’s a precursor to glutathione. I think there must be some sort of connection to a high sympathetic response. I keep trying to find how it all plays in. A fault either there or too low GABA. There is also a tie in with cysteine.”
          -> I guess you want to say glutamate and cysteine supplementing do you more bad then good? Glutathione is a tripetide made from glutamate, cysteine and glycine. At first I was a bit surprised you responded poorly to glutathione (as it seems to help many), but then again it may have answered a question I’ve been wandering about: If you supplement reduced glutathione and it is used then it turns into oxidized glutathione. If glutathione recycling is more of a problem for a certain patient then production, does it not risk to create shortly after it’s administration only marginally more reduced glutathione and plenty more oxidized glutathione? If so, the ratio reduced to oxidized nosedives. And good anti-oxidant working is very strongly dependent on this ratio being high.
          So if this oxidized glutathione is not quickly enough decomposed/destroyed/burned as fuel then it likely gives a short improvement after administration (with IV, digestion may be too slow to have even that) followed by getting worse then before.
          Seems to me you might have no problem constructing new glutathione. In fact, supplementing it’s building blocks likely speeds it construction up faster then it’s discarded and does not speed up it’s recycling. That’ll make you worse.
          I guess it’s strongly patient dependent though. I would guess you don’t have slowed down speed of hair growth now (or when this glutathione thing did not work); partly same building blocks. I had a period hair barely grew anymore; guess that would be saving building blocks for glutathione but even that is unsure.
          By the way: what “Channel” do you refer too? And what is this “snp” you and others refer to?
          Note: “simulating restless leg syndrome” by rapidly doing small leg movements when I feel bad helped me getting through the night a bit better more then once; I would not be surprised that the reported symptoms are worse late at night as glucose levels tend to be lowest by then.

        • dejurgen

          August 6, 2018 at 8:15 am - Reply

          My apologies about the remark on potential slowed hair grow. I didn’t think about your cancer treatment maybe causing hair loss. As a cancer patient always check with your oncologist regarding oxidative stress and anti-oxidants to: some treatment depend on decreasing or increasing it!

    • Moira

      August 6, 2018 at 1:56 am - Reply

      Issie, good point about glutamate. Below is my theory as to what the link between oxidative stress, hypo-methylation and glutamate could be:

      -High levels of superoxide lead to inhibition of dehydrogenase enzymes. One effect is that the Krebs cycle doesn’t work properly, potentially leading to accumulation of oxaloacetate which blocks the electron transfer chain.
      -Oxaloacetate can be converted to pyruvate, alpha-ketoglutarate and citrate in the mitochondria which can be shuttled out of the mitochondria into the cytosol for example via the malate-aspartate shuttle. This is only possible if the concentration of these three substances is the cytosol is low.
      -Alpha-ketoglutarate in the cytosol is kept low by converting it to glutamate. High glutamate levels in the cytosol inhibit this conversion leading to accumulation of alphaketoglutarate which in turn leads to accumulation of oxaloactate in the mitochondria which blocks the electron transfer chain.
      -Glutamate is used to make glutathione but only if levels of cysteine are high enough. Because the Krebbs-cycle is not working properly cysteine is shuttled towards making succinyl-CoA instead, leading to low levels of cysteine leading to depletion of glutathione as well as accumulation of glutamate.
      -Low cysteine levels could lower levels of SAMe as SAMe is converted to cysteine via homocysteine. This leaves less homocysteine available for recycling back into SAMe eventually leading to a lower availability of methyl-groups.

      • Issie

        August 6, 2018 at 4:46 pm - Reply

        Interesting! But, with me trying to up cysteine with NAC that too was a diaster.
        I had felt that upping SOD wasn’t a good idea as it lowers catalyse enzyme which could contribute to vitiligo, that I have. I’ve felt there may be to much hydrogen peroxide and that’s what may cause the bleaching effect. But also wondered if that was a compensation to help kill off Lyme as it will help with that. There are others with Lyme and mold issues who have developed vitiligo too. Addressing things at different levels in this cycle has, so far, not worked. I know there is a breakdown somewhere in this line for me and my family. But haven’t been able to come up with proper solution

        • Moira

          August 6, 2018 at 11:31 pm - Reply

          Finding a solution for you nd your family may be related to combining supplements rather than taking each one separately. For example if I take glycine on its own I end up getting extremely cranky but if I combine glycine with SAMe I feel relaxed instead. I am also avoiding NAC as it seems that anything containing an acetyl group triggers a migraine. To up glutathione I combine SAMe, serine, B6 and zinc to synthesize cysteine and add glycine to support glutathione production. I have to carefully titrate glycine and SAMe though because if I get the dosages wrong I end up either feeling cranky or feeling wired. Glycine combined with SAMe should also increase creatine production and in that way lower arginine levels, thereby lowering NO production and increase blood-pressure. So far it seems to be working as my blood-pressure has been normalized, the jelly feeling in my muscles has decreased and my dust-mite allergy seemed to have disappeared. But then again, as we all have a different genetic make-up this might not work for everyone.
          Interesting point about vitiligo. Got it as well but never linked it to Catalase/SOD levels. Thank you for pointing that out. Something else to ponder.

          • Issie

            August 7, 2018 at 12:29 am -

            I take B6 (p5p) and zinc nightly. When I tried SAME years ago – wasn’t a good response. I remember I took 2 and gave them away. Maybe the correct combo would be the ticket. But figuring that out……I don’t need higher blood pressure. I’m the rare HYPERPOTS subset with higher blood pressure. It’s actually pretty variable and does some extreme swings. We don’t even address it as its all over the place and unpredictable. Not stable from minute to minute. Doc said it was the hardest POTS type to manage.

            Hmmmmm, interesting that you have vitiligo too. By any chance do you also have alopecia?


        • Moira

          August 7, 2018 at 11:06 pm - Reply

          O wow, goes to show again how different everyone is. No I don’t have alopecia. My hair has actually started to grow back. It is a bad hair day everyday because it sticks out everywhere but I am not complaining!

          • Issie

            August 7, 2018 at 11:39 pm -

            Glad that’s not an issue for you. It’s been awhile since I had a flare with it. It’s also considered autoimmune. But what did come back, came back in silver. They said that was because of the vitiligo.


  • Monne

    August 5, 2018 at 3:14 am - Reply

    Thanks Cort – beautifully explained. My latest 2 year flare of this disorder occurred due to anaesthetic – i think I was given nitrous oxide unknowingly. Given that nitrous oxide hinders methyl groups further, as do some other anaesthetics, I wonder if this study is evidence enough for an anaesthetic protocol? I’ve seen/heard of so many kiddo’s with PANS/PANDAS/ASD having the same reaction to methyl disruptors and I believe the kids are in the same neuroimmune boat with us. It doesn’t seem to matter how much folate, folinic acid, methylcobalamin we have on board, it we are stuck in this hypomethylation, we can’t provide enough methyl groups to protect ourselves.

    • Tim

      August 5, 2018 at 5:41 pm - Reply

      Monne wrote, “Given that nitrous oxide hinders methyl groups further, as do some other anaesthetics, I wonder if this study is evidence enough for an anaesthetic protocol?” The doxepin I am taking is also an anesthetic, so your comment makes me wonder whether I should be taking it. Does doxepin hinder methylation?

  • Danny Wright

    August 5, 2018 at 6:24 am - Reply

    Hi Cort, all the best with the new Pridgen Protocol you are embarking on. I’m 5 weeks ahead of you, Dr Skip has worked with me and tweeted some things because i had a few reactions to the meds at first. I hope and pray this works for you, (and me) I hope it is easy for you but Please don’t expect it to be and please don’t be disheartened if you get a lot worse before you get better. I’m on the biggest roller coaster ride I’m doing 3-4 day cycles. Crash for 4 days, reasonably bright for 3 days. The Celebrex made me feel very rough, I’m hoping it works. Dr skip is amazing. Please feel free to ask any advice of me although I’m only 5 weeks ahead of you those 5 weeks have been ….whew!!! All over the show. He told me 12-16 weeks will be up and down. I hope it’s easier for you, (selfishly because I love your articles so much, I’d hate For you to go quiet)

    • Cort Johnson

      August 5, 2018 at 12:24 pm - Reply

      Thanks Danny for the heads up. I will gird my loin and prepare for anything :). Good luck to you!

    • Issie

      August 5, 2018 at 2:54 pm - Reply

      Just word of caution on Celebrex – it can cause strokes. This happened to my mother in law. She promptly went into dementia at that point. She knew the potential danger and because it helped her pain, chose to take it. It also happened to her sister who is now paralyzed from her stroke. Makes you wonder if there is some genetics involved since they were sisters. They both said it was a great drug for pain. But, I’m not willing to take the risk with strokes in my family.


    • Perrier

      August 5, 2018 at 7:26 pm - Reply

      Dear Danny
      How sick were/are you? Were you sick for a long time? Were you bed bound? How would you have classified yourself.

      What is Dr Skip’s success rate with this illness? What does he think about it? Has Dr Ron Davis been in touch with him?

      I find it very frustrating that some treatments work for some people. It’s bizarre. And then there are people for whom nothing works. This is a horrific illness.

    • Karin

      August 6, 2018 at 10:23 am - Reply

      Same here Danny. I’m just over 2 weeks into the Pridgen Protocol and it’s been a a real roller coaster. 4 days of really dreadful, all symptoms on the dial ramped up to full notch and not knowing where to put myself. Then the pain was replaced with utter and complete exhaustion where I couldn’t move from laying position in bed for 2 days only to crawl to bathroom and hardly get back to bed. It was way beyond the normal exhaustion I’ve felt from this illness. Then 3 days of feeling really good, pain almost gone, brain fog almost gone, able to walk around freely in the house and garden. Joy. Then another crash for 3 days and on it goes. But I have noticed on the ‘good’ days that little things are different, in a good way. Anyway, Good luck to everyone who’s on this protocol. Thank you to Dr. Pridgen, he’s one of the good guys. As I mentioned earlier, it would be great if there was a forum/group for everyone on this protocol to compare and share there journey and results.

  • Aidan

    August 5, 2018 at 1:07 pm - Reply

    Cort how many people on here have been tested for the ALPHA GAL MEAT ALLERGY? It could explain why countless have issues with taking medicines, sugar processed on Bone Spurs in plant vitamins minerals chemical sensitivity it is in everything from household cleaners sprays toothpaste shaving cream shampoos detergent dish soaps foods even additives, flavors pepper, even a loaf of bread contains milk & sugar products…Vaccines as well antibiotics I have also seen this in EDS patients also one Soldier USA he got sick he was tested he was Positive very high ALPHA GAL 610…the ingredients list is so long & cross contamination in plants…If one has ALPHA GAL they are allergic to GELATIN also Magnesium Stearate…It is hidden in so many things they even use Pig blood in some cigarette filters as well so Pig is out & any foods made from Mammalian…I react to everything even hair gel…I avoid countless types of soaps…I stopped using a house candle it is in the Wax

  • Aidan

    August 5, 2018 at 1:18 pm - Reply

    Also white sugar Vegan only all brown sugar is out including Cane sugar so if someone buys products with any sugar it is likely got ALPHA GAL contamination even cooking utensils must be changed…This could also explain the Floxies from antibiotics they contain ALPHA GAL ingredients…If this is what this is we need a long serious list on safe products done from vitamins to foods medicines & we would all need at all times 2 epi pens carried…Some are helped with liquid Benadryl Steroids or Claratin some are not…Humans are NOT supposed to have ALPHA GAL in their blood & the test is cheap under $50 also an IGE TOTAL blood test but not in all…Some will say I am VEGAN it does not matter it is in their blood what counts…It is more widespread than they realize I sent my suspicions to the Team of Ron Davis they said they would pass it on to them so hopefully, they do…His Son could still possibly be fed with products containing ALPHA GAL…Even dryer products contain ALPHA GAL

    • Issie

      August 5, 2018 at 2:39 pm - Reply

      I had read about meat allergies. Didn’t realize it was due to lone tick bites that cause a reaction to certain proteins in meats. They don’t know if you eventually get over it or not. The symptoms sound similar to mast cell degranulations. Makes me wonder. One of my docs had all his patients with Lyme and another fungus/mold to go vegan. Wonder if this is why he found them to do better? Thanks for the heads up on this.


      • Aidan

        August 5, 2018 at 3:26 pm - Reply

        u r welcome Issie, yes it is tied to Mast Cell activation also Histamine issues…The Lyme Tic bites any Mammal even a Dog Cat Cow Deer all Mammals picks it up in its saliva the ALPHA GAL from Mammal next meal tick has is a human so we do not have to be in Deer Country & transfers the ALPHA GAL into our blood…Only about 3 out of 300 people average clear the Allergen but some Doctors say do not ever eat Mammals again & avoid all their products for life some say eat cheese milk etc others say do not consume any at all…Avoid future ticks bites as well…I threw out a full bottle of Vitamin D3 it contains GELATIN from an Animal source…I think we may see major changes to the Pharmaceutical industries ingredients once word really gets out n ALPHA GAL. Imagine told for years you have ME/CFS Fibro EDS etc & all along it was ALPHA GAL in your blood…We would also need to see if we have the strain bacteria in our blood as well…Some have said 20% is going to come down with this in time…There are some good Groups on Facebook & Chicken Fish Turkey safe providing they do not contain additives or were cross-contaminated…I also had to stop using a house body spray I would get headaches after so I use none now I cannot be around anyone with Cologne on I want to leave…Imagine this even in lipstick on Condoms…One person got sick she bought Vegan sausage the skin was made from Pig…Apples Fruits Vegs WAX have in some ALPHA GAL Buy Orgain Fruits Vegs, eat Bananas when out if you tolerate them…Monsanto spray I would not dought contains ALPHA GAL ingredients under different Names…McDonald’s Fries have ALPHA GAL seasoning used nothing Vegan about them…

        • Issie

          August 5, 2018 at 9:14 pm - Reply

          I have noticed more issues when I eat red meat. I just don’t seem to digest it and then hurt more. It seems that fish is my best protein. Not guessing a tick would be on a fish – and thinking the form of protein would have a different makeup. I had just recently told my hubby I needed to go back to being more vegan. Hadn’t thought of an autoimmune response due to animal proteins in regard to my tick illnesses. While we are on it – which amino acid is this connected to? Could it be connected to the glutamate/GABA issues?

          • Aidan

            August 5, 2018 at 9:57 pm -

            I am not sure Issie if an amino acid or Gabba is involved, I know I have issues swallowing narrow on pills they get stuck in my throat & one I stopped was B6 it had magnesium stearate likely from animal…shortness of breath is also another sign of this response & I do not think this lifts overnight it is going to take time…To me it also explains the overactive immune system we seem to have…I cannot imagine someone on Pig thyroid with this now if this is the Cause maybe they would in time be taken off but one thing is clear it is an autoimmune disorder & CBT/GET can take a walk on the wild side I hope they lose all fundings…Hope you find an answer I am on Facebook but blocked for a few more days under Aidan Walsh the gold Angle is my profile there

          • Issie

            August 6, 2018 at 6:08 am -

            @Aidan – here is a link I found on dietary affects of glutamate.

            Those who are sensitive or who have autoimmune response can be connected to these amino acid proteins.

            They seem to be found in some of the foods that are connected to the antibodies formed to proteins from this tick bite, to those who develop an Ige response – though it’s found to create higher Igg responses. Appears this allergic response seems to be to a sugar that attaches to fat molecules. And depending how your body breaks down fat. Not all will have this autoimmune response to the tick bite and have this antibody. But there can be a delayed allergic response hours after consuming meat and not easy to connect with what you ate hours before. I know some allergy test do delayed allergy test for this very reason.

            There have been quite a few reports of this allergic reaction to meat and a tick bite. Appears it is now in many countries. I saw it a few weeks ago on my Google news screen pop up. That’s how I knew a little bit of what you were talking about.

            Please feel free to correct my understanding if I don’t have it just right. Love learning new things. Just sad we have to have these things going on. I’m glad that this doesn’t seem to be a huge issue with me. But I know I’m better off red meat. A few hours after I eat it – I hurt worse. I’m also noticing with my elimination diet trial – I’m reacting to lectins and oxalate.

  • Kathy

    August 5, 2018 at 5:21 pm - Reply

    So what is the drug?

  • TK

    August 5, 2018 at 5:58 pm - Reply

    The study compared CFS patients with healthy controls. How do they compare with, say, people who have had mono but did not develop CFS? It’s possible that people with previous EBV infection develop similar hypomethylation even if they don’t develop CFS.

    • Moira

      August 6, 2018 at 2:52 am - Reply

      My (wild?) guess would be that people who DO NOT develop ME/CFS after a viral infection are

      (1) better able to recycle SAMe via either the B12/B9 pathway or via the betaine/glycine pathway
      (2) better able to neutralize oxidative stress via the SOD and Catalase enzymes
      (3) have better functioning detox pathways (e.g urea-cycle, carnitine, glutathione)

      than those who DO develop ME/CFS.

      But who knows, maybe it is something completely different. Am anxiously awaiting the results of the metabolic trap study of Robert Phair

  • David

    August 5, 2018 at 9:21 pm - Reply

    What about Klimas pilot trial of CFS patients…trying to reset their systems as she is doing with Gulf War Illness patients….has that trial still going ahead? Thanks Cort

    • Cort Johnson

      August 6, 2018 at 4:00 pm - Reply

      I assume it will still take place but haven’t heard anything about it recently.

      • Denise

        August 13, 2018 at 5:37 am - Reply

        Cort, My daughter is trying what we know of Pridgen’s protocol, but can’t find any reference to dosages of Celebrex or Famvir. Her doc is using the basic info in your blog post, simply giving average doses, ( 200 mg Celebrex, 500 mg Famvir, just once a day) . We want to increase the Famvir, but— to what dose? She doesn’t get any other help. Hoping to get up to see Dr. Dowell in Flagstaff somehow… If you are able to share what the doses and intervals are he has you on, that would help! Thanks again for your hard work. I’m excited you get to try his protocol. Good Luck!

        • Chris

          August 13, 2018 at 1:39 pm - Reply


          Dr Rey start at 250 mg for Famvir and works up based on the EBV numbers. I am an adult and I was on 250mg 2x 3 times a day and then she stopped once the EBV numbers were lower.

  • Issie

    August 5, 2018 at 10:08 pm - Reply

    Aidan – I don’t do Facebook, Twitter etc.

    You must be extremely sensitive. I know some Mast cell people are that sensitive. Thankfully I’m not. There are some mast cell people who have to be really careful with colors in pills, fillers and other things. I know it happens and believe it can and does with some. But, thankfully my mast cell protocol allows me a little more leniency with what I can and cannot do. I will start paying better attention and see if there are issues there with this. Hard to be the person trying to call attention to something not well known. I appreciate your bravery and efforts. Hope you can find a way to live with this. Not everyone has an immune system that has gone so wayward. Hope you can figure a way to get it to settle out.


  • Gemma Freeman

    August 5, 2018 at 10:41 pm - Reply

    Great article, thank you.

    Reminds me of Bob Miller’s genetic research into chronic lyme patients, around mTOR, methylation, detox pathways, etc – I think of a lot of his findings might be applicable to some ME/CFS patients as well.

  • Chris

    August 7, 2018 at 12:17 am - Reply

    Even though I am not on the Pridgen Protocol – I created a Facebook group because why the hell not. It would be good to have a central place for comparing notes. It will start as a Public group unless it gets trolled or something of the ilk. Feel free to join and continue the discussion.

  • Issie

    August 8, 2018 at 7:49 am - Reply

    I found a blog that explains why certain things may paradox in the glutamate /GABA Conversion and cause a paradox response. (Includes glutathione.)