I sat down to write a post about vitamin B12 supplements for people with ME/CFS and how much they have helped my son and I. I soon realized, however, that I couldn’t explain the importance of B12 without first explaining what the methylation cycle is and why it is so critical to those of us with ME/CFS (and similar illnesses). I’m no expert, but here is what I have learned:
What Does Methylation Do?
I already knew in a vague way that methylation was an important process in the body, but now I understand it is absolutely critical to multiple bodily systems. Before delving into exactly what methylation is, let’s look at its role in the body. Here are some of the vital functions of the methylation process:
- Critical to the manufacture of DNA and RNA, the body’s basic genetic material;
- Essential for several important neurological processes;
- Required for the manufacture of adrenal hormones, which affect all sorts of bodily functions, including sleep, energy, temperature regulation, and neurological functions;
- Responsible for several detoxification pathways, allowing your body to get rid of toxins, including excess medications, supplements, dead viruses or bacteria, as well as environmental toxins.
In addition, the more health problems you have, the worse the methylation process gets (more vicious cycles), so someone like my son who has ME/CFS and also Lyme disease plus two other tick infections just keeps getting worse and worse – which is what we saw with him a few years ago and again this past year. Same goes for anyone with any kind of underlying infections behind their ME/CFS (which is probably most of us).
What Happens When Methylation Isn’t Working Properly?
- Detoxification doesn’t work well (as explained above) so toxins build up in your body;
- Less serotonin, dopamine, and melatonin (all directly linked to sleep dysfunction as well as depression) are produced, as well as less of other neurotransmitters;
- Decreased production of adrenal hormones; Elevated levels of homocysteine, which can lead to cardiac problems;
- Decreased cellular energy production aka mitochondrial dysfunction, leading directly to fatigue and post-exertional malaise;
- Possibly also an underlying mechanism for depression (see note on serotonin and dopamine above).
Detoxification, one of the processes affected by methylation, becomes supremely important if you have underlying infections (as the majority of ME/CFS patients do) and especially if you are treating those infections. In that case, you need an efficient detox process even more, in order to remove toxins like dead viruses and bacteria and excess medications and supplements from the body.
Those with Lyme or those being treated with antivirals are familiar with Herx reactions, where symptoms worsen (often severely) with treatment because the body is being flooded with dead bugs and extra medication that it can not properly get rid of, causing the immune system to react against the increased presence of viruses or bacteria in the bloodstream.
When methylation is not working well (as in most with ME/CFS) and therefore detoxification pathways aren’t working well, the herx reaction can get worse and worse, until the patient is stuck in crisis mode – totally incapacitated by herx symptoms, even when the medication (antibiotics or antivirals) are severely reduced. That’s where our son was twice – first, at the end of high school a few years ago and again, this past year (sophomore year of college).
This is where it gets somewhat complicated, but even a basic understanding of the methylation process will help you understand what kinds of treatments might help. Methylation is a biochemical process in the body that uses certain raw materials (foods, vitamins, supplements) to convert molecules into other molecules. When the process is working well, all those things listed above happen as they should: DNA, RNA, and crucial neurological components are manufactured; critical hormones (for sleep, mood, healthy adrenal function, and more) are made; and the body detoxes effectively, getting rid of those things that might be harmful to you.
I find the best way to understand the methylation process is to look at it visually:
You may not recognize or understand all of the components, but this diagram shows how each step leads to another step and how interrelated the 3 different cycles shown here are to create the full methylation process. You can also see some of the important inputs to the process: proteins, amino acids, vitamin B12, folate and folic acid. And I think it is quite clear that if any one part of this process breaks down – for instance, there isn’t enough B12 or folate – then the entire process will fail, leading to the kinds of problems listed above.
Several methylation experts have emerged who understand the critical importance of the methylation cycle in people with ME/CFS and related illnesses and have made it their life’s work to try to help. Each of the experts has his or her own protocol, so there are some choices; however, they all rely on the critical components of the methylation cycle: vitamin B12 and folate (in various forms).
Dr. Amy Yasko is perhaps best known for pioneering a methylation protocol, designed to help repair dysfunctional methylation processes (and thereby improve the patient’s symptoms in a number of different areas). Interestingly, the focus of her work is in autism in children but it is equally applicable to ME/CFS (not the first time links between ME/CFS and autism have shown up). She has her own explanation of the methylation cycle, if you want to learn more, along with additional diagrams (more complicated than what I included here). Dr. Yasko advocates first getting some genetic testing done and then customizing the methylation protocol based on your results (more on that below).
With our son, we started with Dr. Rich van Konyenburg’s simplified methylation protocol, which I have written about here before. My son was in such terrible shape to start with that we had some difficulties, so I e-mailed Rich directly, and he was kind of enough to respond personally and help us through some of those challenges. Unfortunately, Rich died unexpectedly last year, leaving a big gap in our small world of expert ME/CFS resources. The last version of his simplified methylation protocol is available here, with an excellent Q&A on methylation written by one of Rich's colleagues here.
Typically, any methylation protocol begins with a good quality multi-vitamin, vitamin B12 (more on that in the next post), and 5-MTHF, a form of folate. However – and this is critically important – anyone with ME/CFS should start very slowly with tiny doses and only gradually increase, as tolerated. Any of these supplements can cause their own sort of “herx” reaction, as they get the methylation process working again, suddenly getting detoxification working again and flooding the bloodstream with toxins. As with most things in ME/CFS, low and slow is the rule. For instance, our son started with just a quarter of an 800 mcg 5-MTHF tablet every other day, very slowly working up to 400mcg per day. (Update: As of January 10, 2018, he now takes 20 mg of 5-MTHF a day).
Our son improved a bit on Rich’s protocol, but he was scheduled to start college in a month or so and was still too sick to manage it (as I mentioned earlier, his case is even more complex than most because of the 3 tick infections he is fighting along with his ME/CFS). Our Lyme doctor recommended a consultant who is a registered dietician and has an MS in biochemistry. She is brilliant and not only understands this complicated methylation process but also how that fits in with all the other complicated biochemical processes that are dysfunctional in ME/CFS and Lyme patients.
In the methylation arena, she ran a methylation panel for our son and made recommendations specifically based on his results. She also recommended dietary changes, in part because gluten, casein (the protein found in milk), and gliadin (another protein in wheat and also oats) can all block part of the methylation process. Also foods high in oxalates aren't good for people with ME/CFS (I don't fully understand why yet - still working on that one!).
With her help (and some other changes as well), our son recovered enough to start his freshman year of college alongside his peers, living on campus and taking 3 classes with enough energy left over for a social life. It felt like an absolute miracle to us, and treating methylation problems was definitely a big part of that.
We discovered, however, that you have to be diligent to stay ahead of all the complex problems in ME/CFS and Lyme. After two months, our son gave up on the restricted diet (he was feeling pretty good by then). He kept up the folate and B12 supplements, and continued with his Lyme treatment and all of the treatments for ME/CFS. Eventually, he began gradually declining again, until he was back in crisis mode and completely incapacitated during this winter break (note: this was more than methylation problems but we could tell that was part of the picture). We got back in touch with our dietician, got him back on an even stricter diet (he was so sick, he was willing to try anything). He is again recovering, back in school living on campus, and able to enjoy a social life with his friends, too. Part of his recovery is due to treating yeast overgrowth caused by his Lyme treatment, and part of it is due to getting back on track with the methylation process.
(Update: As of March 16, 2017, he continues to experience ups and downs. He knows how important diet is, but he's 22 and on his own, so it's sometimes tough for him to stick with it. He has learned, though, how important methylation is, and he knows he feels much better when he keeps up with his meds and supplements and remembers his B12 injections every other day.)
- 5-MethylTetraHydroFolate (5-MTHF) We started at 200 mcg every other day and slowly worked up to 400 mcg every day. [3/17 Update: Now, four years later, we have gradually increased to 20 mg daily for both of us.] Links at the end of this post include several options at different doses, as you work up.
- Xymogen ActivNutrients multivitamin with no Iron or Copper (rec by our dietican - apparently, it is important to leave out Iron and Copper when you have infections). We order Xymogen products at cost through our dietician's office or online (link is to Xymogen site), using a code we got from our Lyme doctor.
- Xymogen ALAMax and Resveratin to assist in mitochondrial energy support [3/17 update: my son is currently off ALA because it can contribute to yeast overgrowth]
- Calcium D-glucarate for detox support
- S-Acetyl Glutathione for detox support and energy (studies have shown people with ME/CFS to have low glutathione levels) - see also my post on glutathione for more information - we have seen big improvements in energy and immune function with glutathione injections.
- N-Acetyl Cysteine (NAC) - Critical to detox and liver support in ME/CFS and a precursor to glutathione.
- Milk Thistle - brand varies, taken throughout day and helps with detox - critical for liver support and a precursor to glutathione.
- Vitamin B12 (more info at the link) - I started with a sublingual tablet combo product, until my son told me to stop being a baby! ha ha He and I both now do subcutaneous (under the skin) self-injections every other day, alternating hydroxy- and methyl- B12. The needles are tiny and he was right - I barely feel it - and our injections are also tiny because we use a high concentration (25 mg/ml). Injections are known to be far more effective in getting the B12 to where it is needed. Sublingual pills (that melt under your tongue) are next in effectiveness, and B12 pills that you swallow or chew are very poorly absorbed. You need a prescription for injectable B12 and get it from a compounding pharmacy - it is inexpensive.
More recently, my son and I both had genetic testing done through 23andme (maybe I need another post on that!) and ran our results through Genetic Genie to find out what genetic defects we each have relative to methylation. A couple of problem areas showed up for each of us, so our next step was to work with our dietician to understand what the genetic results mean and how to adjust the methylation protocol accordingly (as Yasko recommends, too).
This post turned out much longer than I had planned, but it is a complicated and important subject. Next up is a post on the use of B12, including importance, uses, dosing, types, etc. From what I’ve read, it seems that everyone with ME/CFS can benefit from vitamin B12 supplementation, but it has to be done right in order to be effective. That one is already half-written, so I hope to post it here within the next week. [3/17 Update: you can find the B12 post here.]
Please share your own experiences with treating methylation and/or questions in the comments area. I am still learning about this critical part of ME/CFS, and I’m sure others would benefit from comments and questions also.
NOTE: Someone reminded me that I didn't mention SAMe in this summary. if you look at the diagram above, you can see that SAMe is a part of the methylation cycle; however, it is not recommended that all people with ME/CFS supplement with SAMe. My son tried it and got worse. Here's the way that Rich Van Konyenburg explained it to me:
"This was initially included in the protocol I proposed, but so many people could not tolerate it that I took it out. SAMe will come up automatically if the partial block of methionine synthase is lifted by the methylation protocol. I think that some people have difficulty dealing with all the sulfur if given NAC and SAMe. The sulfur must all pass through the sulfite oxidase reaction, and if it can't handle it, sulfite builds up and gives headaches, difficulty in breathing, and/or rashes. It also further lowers glutathione."One of the common genetic defects related to methylation causes an inability to metabolize sulfur compounds, and this is relatively common in people with ME/CFS (both my son and I both have this defect and have reacted badly to sulfa antibiotics), so perhaps this is part of the reason why supplementing with SAMe sometimes makes ME/CFS patients worse. So if you do try it in spite of Rich's warning, watch for negative reactions which may worsen over time.
NOTE: FolaPro is the 5-MTHF supplement that Rich recommends in his Simplified Methylation Protocol, linked to above. It is a low dose and comes in tablets that can be halved or quartered, so we started with that at a very low dose, as described above. As we increased the dose, we switched to other brands shown below.
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