Methylation Protocol Effective Treatment for ME/CFS & Fibromyalgia

In my previous post, I announced the release of a great new book by Dr. Neil Nathan, On Hope and Healing: For Those Who Have Fallen Through the Medical Cracks.  In this book, Dr. Nathan discusses an effective treatment that he has found for ME/CFS & Fibromyalgia patients called the Methylation Protocol.  Dr. Nathan says:

I suspect that the words “methylation protocol” are, at first glance, intimidating. But if you will hang in with me for a few paragraphs, I would like to make this both understandable and useful.

First of all, what is most important is that we have recently shown that the use of tiny doses of very specific combinations of vitamin B-12 and folic acid, has resulted in significant improvement in patients with fibromyalgia and chronic fatigue. That’s the bottom line.

So, if you are suffering with chronic fatigue and/or fibromyalgia, you may be interested in learning more about our research, and what we learned.

Let’s start with the word “methylation” and de-mystify it. In chemistry, a methyl group is simply a carbon atom surrounded by 3 hydrogen atoms, with chemically looks like this:

C — H

This grouping acts as a unit and if we tack this unit, this methyl group, on to another molecule, that is what we mean by methylation.

According to Dr. Nathan, methylation is critical to many of the important chemical reactions that we have in our bodies.  We need methylation to create energy, glutathione, repair DNA, and to make melatonin from serotonin.  These are just a few of the necessary functions that our bodies need to “methylate”.

Through research, Dr. Nathan says that they have recently begun to understand is that many of us are genetically compromised with the ability to “methylate”.  Then when we get sick, like with CFS, Fibro, or another illness, it just adds a whole new level of difficulty to our illness and our body cannot compensate for it.  But the good news is that this can be fixed.  Nathan says:

By taking a combination of what are essentially vitamins, we can bypass these genetic “blocks” to methylation, and restore the body’s normal chemistry.

This concept was pioneered by Dr. Amy Yasko, who was working primarily with autistic children. She found that by treating methylation blocks many autistic children recovered to a remarkable extent. She suspected that other illnesses, such as chronic fatigue, fibromyalgia, Parkinson’s disease and other neurodegenerative diseases had a similar problem. Dr. Rich van Konynenburg, a biochemist, picked up on her concept and applied it to chronic fatigue and fibromyalgia. In a series of papers, he demonstrated that virtually every known biochemical imbalance known to occur in fibromyalgia and chronic fatigue could be explained by this inability to methylate properly.

How did the protocol work out after Dr. Nathan tried it on his patients? 

Hearing Rich’s lecture in 2007, and having a huge practice of fibromyalgia and chronic fatigue patients, I was excited to try out this hypothesis on some of my sickest patients. These patients had not fully responded to the treatment program pioneered by Dr. Teitelbaum, which I have utilized for over 15 years now. As soon as I got back to my office, I gave 50 patients this combination of B-12, folic acid and vitamins recommended by Dr. van Konynenburg which was based on recommendations from Dr. Yasko.

To my delight, 70% of my patients had improved within 3 months, and 20% reported that they were much better, occasionally to the point of feeling cured.

Dr. Nathan then received a private research grant and was able to conduct a more formal study that didn’t involve any of his previous study patients. The 30 new study participants took the glutathione and SAM supplements for six months and improvements were greatly noted. Initially, the study participants all were found to have abnormal results on their methylation tests. Hopefully with research and time, patients will soon be able to access basic health insurance marketplaces to obtain specific treatment. Here were how the results played out in the study:

The initial methylation testing showed that every single patient had abnormal results. The average starting value of glutathione in our patients was 3.2 mmol/L (normal being 3.9-5.5 mmol/L)), and the average starting value for SAM (the major methylator) was 218 mmol/L (normal being 221-256 mmol/L). 83% started with low glutathione levels.

Can we demonstrate that taking these supplements raises those numbers into the normal range? 


  • After 3 months, the average glutathione level was 3.8 mmol/L
  • After 6 months, the average glutathione level was 4.3 mmol/L
  • After 9 months, the average glutathione level was 4.7 mmol/L, which represents a 47% improvement, and ALL patients now had a normal level. 
  • After 3 months, the average SAM level was 227 mmol/L
  • After 6 months, the average SAM level was 238 mmol/L  
  • After 9 months, the average SAM level was 241 mmol/L, with only one patient not up into the normal range

The average improvement was rated by our patients as 48%. Note that 27% reported so much improvement that they now felt essentially well! Several, who had not worked in over 5 years, were able to resume full-time employment without difficulty. It took an average of 5-6 weeks before the supplements started to work, and we can clearly show that the longer patients stayed on this program, the better they got.

Not everyone got better, but the vast majority (86%) improved.

Out of Dr. Nathan’s original 30 patients, all 30 completed the first three months of the study and 29 patients completed the first six months.  There were a total of 25 out of the 30 who completed the full 9-month program.  Nathan says that it is rare to run a study for so long and to have this type of participation the whole way through.  The patients who dropped out:  3 left the program because they felt so well they didn’t see any need to continue; 1 left to have hip replacement surgery; and there was only 1 patient who dropped out because she didn’t see any improvement after six months. 

If this protocol proves to be amazing as this study makes it sound, maybe there is new hope for us all.  Dr. Nathan warns that while there are no known side effects to this protocol, there may be a detoxification reaction from mild to severe.  This is due to the body’s improved ability to methylate and make more glutathione.  He recommends that you do not try this program without the supervision of your physician.

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  2. Shelley Jones says:

    How best does one get diagnosed with CFS or Fibromyalgia?

  3. Mike Pfirrman says:

    You mention in the article that the patients took glutathione and SAM-E. That is incorrect. All they took was Methyl B Supplements, including 5-MTHF, a special form of folate (a vitamin B) and a more highly absorbable form of Vit B 12. Seeking Health and Thorne Research both make this type of supplement. Jarrow and a few others do too, but if you really look at their Folate type, it’s not as good as Thorne’s and Seeking Health’s. You can’t “take” glutathione and have it absorbed. Your own body has to produce it. The genetic defect, called MTHFR, makes a person unable to process regular Folic Acid and normal forms of Vit B 12, so special forms of this are needed for the body to produce their own SAM-E and glutathione.

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