young woman stressed and in pain dealing with fibromyalgia, Dr. Rodger Murphree can help.

Fibromyalgia, Chronic Fatigue Syndrome (ME) and Methylation Cycle Block

There are numerous theories for the cause and symptoms triggering fibromyalgia and CFS. One theory, now gaining some traction, should be explored in more detail–certainly doctors should be testing their patients for Methylation Cycle Block.

Excerpt taken from my new 5th edition Treating and Beating Fibromyalgia and Chronic Fatigue Syndrome book.

A New Theory of Cause:

Glutathione Depletion and Methylation Cycle Block

young woman stressed and in pain dealing with fibromyalgia, Dr. Rodger Murphree can help.Methylation

Methylation is a key biochemical process essential for the proper function of almost all of your body’s systems. It occurs billions of times every second and is believed to operate in every cell. It helps repair your DNA on a daily basis, and it helps protect against plaque formation, arterial occlusion, heart disease, heart attack, and stroke. Methylation regulates moods and inflammation, and it helps recycle molecules needed for detoxification. It also facilitates the production of CoQ10 and carnitine, two important chemicals for energy.

When the methylation cycle is blocked, important biochemical functions are not carried out properly. A methylation block leads to a block in the folate metabolism, to which it is intimately linked, and this interferes with synthesis of new DNA and RNA, among other important effects. Perhaps the greatest problem with a methylation-cycle block is that neither the immune system nor the detox system can operate properly. If the methylation cycle remains blocked for an extended period of time, infections and toxins can be expected to build up in the body. Not good.


Methylenetetrahydrofolate reductase ( MTHFR) is a common genetic variant that causes a key enzyme in the body to function at a reduced rate. There are over fifty known MTHFR variants, and it is associated with a variety of chronic illnesses, including fibromyalgia and CFS/ME.

Rich van Konynenburg, PhD, has spent a number of years piecing together an interesting theory, one that is gaining momentum among functional medicine doctors, known as glutathione depletion and methylation cycle block. Dr. van Konynenburg proposes that in order to develop CFS/ME, a person must have When this person then is also subjected to some combination of long-term physical, chemical, biological, or psychological/emotional stressors, glutathione levels are lowered to the point that a block occurs in the methylation cycle.

This lowering of glutathione levels also simultaneously removes the normal protection that glutathione provides to vitamin B12 and allows the accumulation in the body of toxins (probably mercury, chiefly) that can interfere with the utilization of this vitamin. His hypothesis further proposes that the lowering of glutathione levels means that the level of methylcobalamin (a special form of natural vitamin B12) is too low to support the methionine synthase reaction, and it therefore becomes chronically blocked. This produces a vicious cycle that causes CFS/ME to become a chronic condition.

woman stress headacheThose with MTHFR do usually have very low glutathione levels. This makes them more susceptible to stress, including toxins that overwhelm an already poorly functioning detoxification system, leading to more stress. Glutathione is the body’s primary antioxidant and a potent detoxifier. These folks simply can’t detoxify the chemicals they are exposed to on a daily basis. As time goes on, they find they become more and more chemically sensitive. They have “funny” (not so funny, really) reactions to meds, aversions to strong odors, and seemingly random sensitivities.

Rich van Konynenburg’s idea is that ineffective methylation is a major cause of fatigue. There are many possible reasons for this connection, but some become obvious when we look at the many different functions of methylation:

  • to produce vital molecules such as CoQ10 and carnitine.
  • to switch on DNA and switch off DNA by activating and deactivating genes.


When viruses attack our bodies, they take over our own DNA in order to replicate themselves. If we can’t switch DNA/RNA replication off, then we become more susceptible to viral infection. This “switching” role is also essential for protein synthesis. And proteins, of course, make up our hormones, neurotransmitters, enzymes, and immune factors and are fundamental to good health.

  • to determine the rate of synthesis of glutathione, which is essential for detoxification.
  • to produce myelin for the brain and nervous system.
  • to control sulphur metabolism of the body, not just glutathione but also cysteine, taurine, and sulphate. This is an important process for detoxification.
  • to serve as part of folic-acid metabolism. This also switches on synthesis of new DNA and RNA.
  • to assist in normal immune function.


The methylation cycle is essential for cell-mediated immune function, and blockages here will mean that infections will not be adequately dealt with.

Senior couple relaxing outsideFactors that Affect Your Methylation Process

  • Genetics: Like an estimated 20 percent of us, you could be genetically predisposed to high homocysteine levels, which affect your methylation process.
  • Poor diet: B vitamins come from eating leafy greens, beans, fruit, and whole grains to get adequate levels of vitamins B 6 and B 12, betaine, and folate. Egg yolks, meat, liver, and oily fish are the main dietary sources of vitamin B 12, so long-term vegan diets can also be a problem. Plus, certain compounds can raise levels of homocysteine and deplete the B vitamins: excess animal protein, sugar, saturated fat, coffee, junk food, and alcohol.
  • Smoking depletes vitamin B 6.
  • Decreased stomach acid: Aging and other conditions can reduce stomach acid, and therefore absorption of vitamin B 12.
  • Malabsorption: Conditions like digestive diseases, food allergies, and even aging can reduce absorption of nutrients.
  • Other conditions: These include hypothyroidism, kidney failure, having only one kidney, cancer, and pregnancy.
  • Medications: Drugs like acid blockers, methotrexate (for cancer and arthritis and other autoimmune diseases), oral contraceptives, HCTZ (for high blood pressure), and Dilantin (for seizures) can all affect levels of B vitamins.


The overall effect here  is that if the methylation cycle doesn’t work, the immune system malfunctions, the detoxification system malfunctions, the antioxidant system malfunctions, and our ability to heal and repair is reduced.

Measuring Your Own Methylation Process

To find out if your methylation process is optimal, ask your doctor for the following tests:

  • Complete blood count: Red blood cells with a mean corpuscular volume (MCV) greater than ninety-five can signal a methylation problem.
  • Homocysteine: The normal level is less than thirteen, but the ideal level is likely between six and eight.
  • Serum or urinary methylmalonic acid: This is a more specific test for vitamin B 12 insufficiency. Your levels may be elevated even if you have a normal serum B 12 or homocysteine level.
  • Plasma blood test: Along with the above, I use this test from Doctor’s Data that measures six primary indicators of methionine metabolism.

dreaming of being healthy and fibro free

I strongly encourage you not to embark on treating MHTFR without the help of a functional medicine doctor trained in MHTFR. When your body starts to detox properly, which is the goal of correcting MHTFR, you’ll most likely have die-off reactions from the killing of unwanted viruses, bacteria, yeast, etc. These reactions can be severe and at best, very uncomfortable. It is best to work with a health-care professional who can walk you through the process slowly but surely.  The first step in this treatment, however, is to be properly These reactions can be severe and at best, very uncomfortable. It is best to work with a health-care professional who can walk you through the process slowly but surely. The first step in this treatment, however, is to be properly tested. If you’ve only been in the traditional medical world, I bet you’ve not been properly tested.

26 replies
  1. Teresa Linger
    Teresa Linger says:

    Wow! This makes so much sense. My children and I have FM, CFS and a slew of other issues. We found out a few years ago, when my daughter was tested for MTHFR after several miscarriages, that we all had MTHFR. They have two types, I have one, which means, if I understand correctly, their father has the other type. He also was diagnosed with CFS.
    Very interesting! Gotta get this book!
    Thank you!

  2. Charlie Watson
    Charlie Watson says:

    Nice info. I doubt my PCP would agree??? How to you find a functional doc trained in MHTFR?

    Also, you need some editing on above article, regarding “the first step”

  3. Barbara Donley
    Barbara Donley says:

    Very timely information. Both my daughter and I have fibro/cfs and recently had genetic methylation panels done.
    We are both very ill with this, and nothing we have tried has had any traction.
    Do you take patients? We live in Nashville, if there is anyone to recommend, else we can come to you.
    Thank you
    Barb Donley

    • Dr. Rodger Murphree & Team
      Dr. Rodger Murphree & Team says:

      Barb sorry to read you and daughter aren’t doing well. 90% of my practice is phone consults with patients throughout N. America. I also see patients at my clinic in Birmingham AL. Please call my assistant Juno she will happy to help set up a consult 205-879-2383.

  4. susan fuchs
    susan fuchs says:

    I go see a endocrinology,my TSH is 0.o28,my cortisol is high sertonin is real low.Been sick over 20yrs with cfs.I also have a pitiary tumor for long time.I’m ready to give up,just getting older,more things go wrong.Can you help?

  5. Loe Masson
    Loe Masson says:

    This one of the best explanations I have seen to date on FMS/CFS in all of my readings. I shall share this with as many people and support groups as feasible. Thank you!

  6. Patty
    Patty says:

    Dear Dr. Murphree, I am very happy about this news about Fibro! The problem is my Dr. + insurance probably will not run these tests, so how do I find a Dr. who will run this blood work? I am on disability right now + it is very hard for me to get the help I really need! I have taken the supplements you recommended and it helped somewhat, which means you are on to something, I tell everyone about you! I thank you for going through all this trouble for all of that are suffering + Drs. + family think we are crazy! Well thank you Dr. again + believe me I listen to all your tapes over + over again, some day I will call you when finances get better.
    Thanking you,
    Patty Drolet

    • Dr. Rodger Murphree & Team
      Dr. Rodger Murphree & Team says:

      Dear Patty glad you are doing better. I want to help anyway I can. I’m in process of launching a doctors training program and site for people to find these doctors trained in my protocols until then please call the clinic 205-879-2383 and find out about setting up a phone consult.

  7. Patty
    Patty says:

    Dear Dr. Murphree, I was wondering is there some kind of de-tox I can buy to help get rid of the build up of what you are talking about? I was using Spirulina for awhile, do you think this would help?

    Thanking You,
    Patty Drolet

  8. Annamaria
    Annamaria says:

    My issues goes way back as s child. Trauma age of 7 I started OD with moms meds nothing happen. But in my sleep I would vomit. During gym when we have to run. Right upper rib the pain dizziness. Psin grew my batter body going through hell by hirs smack so on. Yet I continue to OD. My grew stronger. Diagnose with Chronic pain no meds giving. Off the shelf tynol over used then advil. My life has been so tired with illness I have. Here is the list what my body goes through none stop.
    Chronic pain

    Now I found out last week I have high cholesterol iron is 12
    My liver always been the issue. If doctors read back on your own medical history my liver was never strong prone to cyst. I was given injections age 18yrs protect my liver from any viruses or diseases. Well level of my liver is high. Last month was told he can’t help me anymore. My morphine perks aren’t perscribe as last Tuesday visit. Mean while his writing a letter to the Government for a drug that ain’t covered. Meaning there is no subscription to take. I’m forest to take brand name meds off shelves. I’m band off tynol. Doc cannot control what I buy. I know abuse myself by over takingb them to get right dosage to help. Then my system will fight off t he drug then nothing works. These disease I deal with. I hope my heart will stop beating as I . Everything will be at peace. Body mind soul heart will finally rest to sleep with all the loss of sleep I be set free no more pain….
    Thank you…

  9. Mary allen
    Mary allen says:

    I have all the symptoms . I was told in 1997 that I have Fibromyalgia but I haven’t found a doctor who will treat me. I don’t have a job or any income to find a doctor at this time.

  10. Jan
    Jan says:

    This article makes so much sense! My Fibro/CFS doctor gets it! She started me on glutathione therapy when I first started seeing her, about 3-4 years ago. She has been studying & treating this for 20+ years. (she is located in Houston) I go back every 3 months for a visit and med refills. I think I need to get back on the glutathione therapy cause the FM/CFS is kicking my tail lately! Thanks for all you do to help with these debilitating syndromes!!

  11. Sue Kleeman
    Sue Kleeman says:

    Great info for chronic disease, ea individual seems to encounter such a variety of symptoms, the fight is exhausting n without many “good”days. Why is this disorder so difficult to understand n conquer. Added stress includes the ignorance of insurance companies in accepting a Fibromyalgia diagnosis n the extent to which a person is deemed disabled! Been battling fatigue n immune deficiency all my life but post pregnancy I felt every symptom n have spiraled downward since 2000, having to leave my Teaching position by 2009. Never able to receive long term disability, however I havebeen under various MD care since leaving my job teaching. As passionate as I was I could not function properly in the classroom. Very disappointing. Help!?

    • Dr. Rodger Murphree & Team
      Dr. Rodger Murphree & Team says:

      Sue I understand your frustration. Most doctors are down on what they aren’t up on….I do phone consults and would to help 205-879-2383. Please call if would like to know more, my staff is happy to answer any questions and help anyway they can.

  12. Ginny K.
    Ginny K. says:

    I’m a soon-to-be 56-yr-old female. I have had episodes of mild depression, anxiety and extreme tiredness since my teens. I have had “muscle-contraction migraines” for nearly 20 years. Symptoms include severe sensitivity to light, sound, motion, and an extreme inability to mentally function and, needless to say, irritability. The episodes often would be so severe that I could not keep down food or water which resulted in dehydration. After going through chemo and radiation 10 years ago the frequency of the episodes have increased to, sometimes, once a month and can last several days. Of course, I have seen doctors about this and tried different medications (and, just two days ago, an MRI which came back clear) but the problem still exists. I do have a thyroid condition (and was, in fact, given a treatment of radioactive iodine approximately in 1996) but the doctors do not think that the migraines are a result of my thyroid condition. The migraines make holding on to a full-time job difficult, to put it mildly. I’m a puzzle to my doctors. After reading your intriguing article, I can’t help but wonder if this could shed some light on my medical mystery. Based on the information I listed, do you think there’s a possible link?
    Coincidentally, I have a slightly older friend (retired) that has been diagnosed with FM, IBS, depression and other issues. I will forward your article to her in the hopes that she benefits from it.


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