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Q&A on the Simplified Methylation Protocol with Neil Nathan, MD

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Dr. Nathan reported to ProHealth readers recently on his successful trial of a promising protocol for ME/CFS and fibromyalgia patients. (See “A Simplified Methylation Protocol is Effective for the Treatment of Chronic Fatigue Syndrome and Fibromyalgia.”) As Dr. Nathan explained:

•  Every ME/CFS and FM patient he tested showed signs of abnormal methylation chemistry,

•  But this chemistry began to normalize, and most of the patients got much better, on a regimen of nutrients that the body employs in methylation.

The regimen is “simplified” in that it has been pared down over time from a long list of possibilities to just a few, with formulas refined collaboratively by Drs. Nathan, Rich Van Konynenburg, Amy Yasko, and Jacob Teitelbaum.

Now, to answer questions from readers about the protocol, Dr. Nathan has provided the following Q&A.


Dr. Nathan’s Preface:

I would like to emphasize that although the individual ingredients in the protocol are all natural and safe, when they work, there is the very real risk that improved methylation will dramatically improve the body’s ability to detoxify, and if the individual’s system cannot deal with a sudden release of toxins, they can get quite sick.

That’s why I emphasize the need to find a health care provider who understands this and can work with you. More information is available in the chapter on methylation in my book, On Hope and Healing: For Those Who Have Fallen Through the Medical Cracks. But unfortunately that information is not sufficient for patients to do this by themselves.


Q:  Specifically what are the vitamins that you mention in the article?

Dr. Nathan:  The supplements we used in the trial are:

Actifolate: ¼ tablet (200mcg) daily
Folapro: ¼ tablet daily

General Vitamin Neurological Health Formula: start with ¼ tablet and work up, very slowly, to 2 tablets daily

Activated B-12 Guard: 1 sublingual lozenge daily

Phosphatidyl Serine Complex: 1 softgel capsule daily (we feel this is helpful, though not as central to the protocol as the others)


* * * *

Q:  Do you offer a “package” that includes all the required supplements together, as described in the article?

A:  At my office (at Gordon Medical Associates), we have put this package together, and I believe that ProHealth has just arranged to offer the package
as well.*

* * * *

Q:  Is there specific information on this protocol in a form that I could submit to my doctor so she could monitor it?

A: You could copy the chapter in my book (pp. 153-167, “Methylation: a Key to Understanding Chronic Illness”), and you could Google “Rich Van Konynenburg” to get copies of his groundbreaking papers which outline the scientific basis for this program.

* * * *

Q:  Advice on finding a doctor or type of doctor who would be open minded about this protocol and willing to work with me in trying it? 

A: Many holistic, integrative practitioners are somewhat knowledgeable about this protocol, but many not have experience with it directly. I have presented our work to a number of scientific groups, and hope that more physicians will get interested.
In the meantime, you might look at members of ACAM (the American College for Advancement in Medicine), AHMA (the American Holistic Medical Association), or AAEM (the American Academy of Environmental Medicine) for practitioners who are more likely to know something about this.

* * * *

Q:  Is Dr. Nathan’s treatment ministered through any doctor or specialist here in the UK that you know of? Suggestions for those in the UK and elsewhere?

A: I’m sorry, but I am not aware of any specific individuals in the UK to recommend. In fact, I have heard that several UK holistic practitioners have been reprimanded recently for their work (which is distressing) – such as Dr. Sarah Myhill, who has done some excellent work in the field of chronic fatigue and fibromyalgia.

* * * *

Q:  Is the protocol a regimen recommended to maintain as long as you can as a part of a daily regimen?

A:  What we have found is that it takes 4 to 6 weeks to start seeing improvement, and then that improvement continues over a 9-month period of time, probably longer.

Some of my patients, in the study, discontinued the supplements and relapsed (and then improved again). Others discontinued the supplements and did well. So I suspect the results are dependent on individual biochemistry and that each patient will need to elucidate for themselves their optimal use of these materials.

* * * *

Q: Thanks for the encouraging report. Would the results of the 30 patients treated with Dr. Teitelbaum’s program have had an increased chance of realising a good response to Dr. Nathan’s treatment due to the fact they had a ‘good start’ having benefited from Dr Teitelbaum’s treatment?

A: That’s an excellent question, and we don’t really know the answer, since it hasn’t been studied yet. It is possible that addressing problems with the adrenal, thyroid, gut, sex hormones, food allergies, infections and heavy metal toxicity allowed the treatment to work much better. It is also possible that the Methylation Protocol would have value in a patient who had not been treated with any of these methods…. we just don’t know.

* * * *

Q: Would there be any point in starting on just one supplement, and if so which one?

A: In terms of our study, which is the only scientific data I have, it’s a package deal in terms of effectiveness. I have seen really sensitive patients who cannot take the entire program, and for them I start with the sublingual B-12 and phosphatidyl serine, then slowly add the Folapro and Actifolate next.

* * * *

Q: Is one supposed to discontinue your methylation supplements before doing a methylation panel test, and if so, how long would you need to be off them before the test? It seems to me that I would be more interested in how my body is doing while on them, since I plan on continuing to take them, but perhaps they interfere with the test?

A: I agree, it would be much more useful to get the panel done while ON the supplements, since that tells you where you are in space and time, and guides us in modifying the protocol. Because of the expense of the test, I usually will start patients on the protocol and reserve the use of the test for those who have not responded to it as I would expect.

* * * *

Q: If the problem is low glutathione in ME/CFS, why not just take that?

A: Also a good question, and an important one. Many practitioners don’t agree on this. From my perspective, if you give glutathione (which often helps, by the way), that sends a message to the body that it doesn’t need any more, and it stops making it. It makes more sense to me to give the body the raw materials it needs to stimulate it to make more glutathione, and our research indicates that this approach works.

* * * *

Q: I have fibromyalgia for 13 years, and am interested in your simplified Methylation Protocol, but my doctor tested me recently for folate and B-12, and they were at “normal” levels. Would this be an indication that the protocol probably wouldn’t do much for me?

A: Absolutely not. Those numbers have nothing to do with this protocol. The problem for most people is that they cannot methylate properly because of toxic, or genetic, effects. The full methylation panel offered by Vitamin Diagnostics** measures 11 parameters that we can evaluate, which show how well the body makes glutathione and SAMe, which is what this is all about.

Most physicians are only aware of, or prescribe, cyanocobalamin (one form of B-12) and folic acid, neither of which is particularly good at improving methylation. What we have learned is that hydoxycobalamin and methylcobalamin (other forms of B-12) and 5-methyl tetrahydrofolate and folinic acid are what are needed to start moving the cycle around.

So just looking at folate and B-12 levels does not give you what you need to figure this out.

* * * *

Q: I have suffered from fibromyalgia for over 33 years. I continue to search the Internet for new treatments and must admit that I have hope for the first time in many years of frustration and defeat. I’ve noticed new treatments in many different trial phases at this point. While reading about your discovery I wondered about where this stands regarding trial stage for the FDA approval process. Is it possible to try your new discovery without FDA approval? Please let me know… how I may benefit from this discovery now if possible.

A: We were not looking for FDA approval of this material. We were looking for answers for how to help a lot of patients like yourself. Since these are natural materials, they can’t be patented, and a pharmaceutical company cannot charge exorbitant amounts for the product… Hence, it will never be profitable enough for anyone to seek FDA approval in the usual way. Find someone who understands this chemistry and let them help you with it.

* * * *

Q: I have been doing the simplified methylation protocol and believe it has helped me. But I think I have reached a plateau. Do you suspect this is as good as it gets, or might there be something I could add to improve more?

A: You may be ready to check your methylation chemistry test results now. OR you may need to look at heavy metal (particularly mercury) toxicity as something that may be preventing it from working optimally.

* * * *

Q: I have chronic fatigue syndrome, and POTS is an important symptom for me. Might a methylation problem be involved in this?

A: It may help. To my knowledge no one has looked at this yet, but every biochemical piece of the puzzle may ad to the possibility of healing.

* * * *

Q: I have purchased your book [On Hope and Healing: For Those Who Have Fallen Through the Medical Cracks] and am underlining/making notes in the margin. Thanks for this wonderful book with its compilation of treatments. I have had CFIDS for 23 years. My new DO practices holistic medicine. Although she does not know the many specifics of this illness, she is willing to work with me on treatment modalities.
I looked up the products for methylation [pp. 153-167]. The General Vitamin Neurological Health Formula has citrate compounds (e.g., calcium citrate) which I have never been able to tolerate. What alternative product(s) would you recommend for citrate-sensitive individuals?

A: The General Vitamin formula was chosen for some of its unique ingredients, but is probably the least essential part of the program, so I suspect you could benefit without adding that specific product.

* * * *

Q: I would like to know if you have heard other people say that the B vitamins in this protocol cause migraines.

A: I am not aware that these B vitamins (primarily B-12) have ever been associated specifically with migraines. The only way that might happen would be if the release of toxins in that individual was greater than they could deal with. That might set off migraines. But having treated several hundred patients with the protocol now, I have not personally seen that reaction.

* * * *

Q: Dr. Nathan, if you add sufficient vitamin D3 (5,000-10,000 IU/day) to your protocol your patients will see an additional incremental improvement. Go to the Vitamin D Council website at www.vitamindcouncil.com for more information.

A: Measuring vitamin D levels and treating with D3 is an integral part of our program. I agree it is another important area to evaluate and treat, but was not specifically a part of the original protocol.

* * * *

Q: For Dr. Garth Nicolson’s “ATP Fuel” Trial (of a supplement with NT Factor, NADH, and CoQ10) now recruiting, would I have to stop the methylation protocol before starting it? I was accepted and didn’t think to ask about other meds or supps I’m taking.

A: When doing research, it is important that you follow the research protocol being offered to you. I am aware of Dr. Nicolson’s study, and would suggest you ask him that question before you proceed.

* * * *

Q: Do you have any thoughts on whether a methylation defect might affect thyroid or other hormonal balances?

A: Everything is interrelated. For example, we have to methylate serotonin to make melatonin, so there is an important interaction between our neurotransmitters and methylation… And I think, as we learn more, that all of our important endocrine relationships will be connected in some way to methylation. Methylation is central to over 150 important chemical reactions (that we know of, so far). More is yet to be revealed.

* * * *

Q: Do you think a methylation cycle problem could contribute to allergies, and if so might your simplified protocol help?

A: Again, everything is inter-related in the body. Improving methylation will help detoxification, but I wouldn’t recommend it as a first-line treatment for allergy.

* * * *

Q: Would the Methylation Protocol be of any benefit for individuals with Lyme disease? Would the vitamin B-12 and folic acid be good for it? My girlfriend has had Lyme disease for the past 7 years. She was diagnosed 5 years ago and has been on antibiotics for the past 4 years as of June 2011. Do you have any suggestions or directions regarding the continued use of antibiotics for the treatment of chronic  Lyme disease? Any help would be much appreciated. She has been through hell and is better but not cured of the Lyme. 

A: We treat a large number of patients with Lyme disease, and we have found that most of them (as with patients chronically ill with virtually any condition) do not methylate properly. Many of them do respond to a methylation protocol, but again, I must warn you that most of our Lyme patients wrestle with problems of toxicity and are at high risk of reacting to the protocol, initially. So I would go VERY slowly and carefully, work with someone who understands this.

* * * *

Q: For someone with a diagnosis of Lyme pathogens, would you recommend treating the Lyme first or doing the Methylation Protocol first?

A: Treat the Lyme first. If you try the methylation protocol first, you will release toxins that the individual cannot handle and you have a high risk of making them worse.

* * * *

Q: Rich Van Konynenburg wrote several years ago in the ProHealth ME/CFS/FM message board that he had a hypothesis that “Lyme disease is one route of entry into CFS for people who are genetically susceptible.” What is your current thinking on whether ME/CFS and Lyme may sometimes be linked or otherwise associated?

A: As we continue to study this, it becomes clear that many patients who have been diagnosed with ME/CFS have Lyme disease that hadn’t been looked for or diagnosed. The numbers are much higher than we had thought, so that some Lyme specialists think most patients with “CFS” actually have Lyme.

I would not take it that far, but I would agree that we should check all CFS patients for Lyme disease. We don’t want to realize three years down the road that we missed a treatment component.

* * * *

Q: What can help with the cellular detoxification that the methylation protocol vitamins encourage? Something like milk thistle? Or chlorella? What do you think the toxins are, mostly? Heavy metals, or other?

A: The toxins include heavy metals, mold, pesticides, chemicals, and the results of a wide variety of infections (Lyme, Bartonella, Babesia, viruses, mycoplasma, Chlamydia, etc.). We do use milk thistle, chlorella, and a wide variety of other materials to assist with the detoxification process – each adjusted to individual patients’ needs.

* * * *

Q: I heard a video piece by a man who was doing a mini-beet protocol for detoxification. He told of eating apple directly after drinking a beet juice combination. He said that the raw apples stopped the detox effects. Have you heard of this and do you think it would be a possibility following your protocol?

A: I am not specifically aware of this, but neither do I know that it is true.

* * * *

Q: Would soluble fiber be good to help while detoxing?

A: One valuable detoxification material is pectin; fiber does help.

* * * *

Q: In May 13 Science there’s an article on DNA methylation and epigenetics.  [Note: Epigenetics is the study of changes in gene expression produced by environmental factors.] It indicates this phenomenon adds methyl groups to specific genes, “usually silencing their expression.” This is susceptible to environmental influences, and is reversible, so silenced genes can be reactivated.

Could something like this DNA methylation be affecting gene expression in ME/CFS and fibro people, and might the methylation protocol be reversing something?

A: Yes, of course. One of the many vital functions of methylation is that it is central to repairing DNA. Part of our study related to the SNPs that represent genetic “tendencies” to impair methylation (more than 13 are known and are measured by Dr. Yasko) and the ability of this protocol to improve this.

* * * *

Q: It has been established in other studies that glutathione levels are low in ME/CFS. The question of whether ME/CFS is due to impaired methylation is doubtful. The immune signature of ME/CFS is now better understood and widely accepted by key researchers in this field. We need to be wary of simplistic biochemical explanations like this but by all means supplement with folate and B-12 as well as glutathione, even N-acetyl cysteine.

A: There is no reason to throw the baby out with the bathwater. Yes, we are learning more of the immune signature of ME/CFS, but why presuppose that methylation “blocks” are not an integral part of that story?

* * * *

Q: My Lyme doctor put me on the Methylation Protocol (I have had chronic fatigue for more than 10 years)… It made me feel like I was on speed. Any insights on this?

A: Yes. It was too strong for you. You may need to cut it way back for it to be of benefit.

* * * *

Q: I have problems with IBS and have heard that introduction of glutamine can sometimes rid these problems. In your study did any of your patients have IBS and did your methylation therapy help their IBS?

A: Glutamine is tricky: Although it may be useful for ‘leaky gut’ or IBS, glutamine is excitotoxic to the brain and may make autism or other conditions that have an irritated autonomic nervous system worse.

* * * *

Q: Dr. Nathan, I have your book and have been encouraged by your stories and your dedication. I’ve even done cranio-sacral work [discussed in the book]. Awesome! I have been on the full Yasko Protocol about 7 months and I believe I am progressing, but slowly. My question: Is it because I am 51 years of age? Does it make sense that someone older might take longer to recover?

A: I am not aware that age is an issue in methylation treatment. I had great results in my study with an 82-year-old woman, and poor results in a 27-year-old.

* * * *

Q: How can I get in touch with Dr. Yasko? I have a family member with autism and would like to have Dr. Yasko see him. [Note: Biochemist Dr. Amy Yasko pioneered the concept of addressing methylation problems in autistic children using specially formulated nutrients that she developed, with promising results. Her suggestion that methylation problems might play a role in other conditions was what inspired Rich Van Konynenburg, another biochemist, to work diligently for years adapting the protocol for ME/CFS and fibromyalgia.]

A: Dr. Yasko is unfortunately no longer seeing patients directly. She decided several years ago that she could help more patients (since the need is great) by testing them with the genomic assays available through her website, and going on line to help them understand the results of those tests and guide them with suggestions. 

ProHealth Concluding Note

Along with their questions, readers have expressed sincere gratitude to Drs. Nathan and Van Konynenburg for their untiring “commitment to healing.” In their words, “This is so very exciting. Thanks to you and Dr. Rich. You guys are heroes!”

For readers who have further questions for Dr. Nathan, he may be reached at his office with Gordon Medical Associates near Mendocino, California (www.gordonmedical.com, Email: neil@gordonmedical.com). Dr. Van Konynenburg may be reached at richvank@aol.com


* As a service to readers, ProHealth has arranged to make the Simplified Methylation Protocol supplements mentioned above available through our store; and if you have questions our Customer Service Specialists will be pleased to help.

** Now Health Diagnostics and Research Institute, South Amboy, NJ. Phone 732 721-1234. Their Methylation Pathways Panel requires an order from a medical doctor or chiropractor and costs $300 plus cost of shipping blood sample to lab, according to Rich Van K.

Note: This information has not been evaluated by the FDA. It is general information, and is not meant to prevent, diagnose, treat or cure any condition, illness, or disease. It is very important that you make no change in your healthcare plan or health support regimen without researching and discussing it in collaboration with your professional healthcare team.

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One thought on “Q&A on the Simplified Methylation Protocol with Neil Nathan, MD”

  1. camshub says:

    How would this protocol augment or compliment Dr. Pall’s treatment on excessive nitric oxide? And,can different forms of B-12 be taken (e.g., hydrox, meth) be taken in combination without causing problems? Thanks for your help.

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