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.
Almost everyone with ME/CFS (and many people with other
similar illnesses) has a dysfunctional methylation process. It’s hard to tease
out cause and effect because every one of our dysfunctional systems (immune,
endocrine, nervous, etc.) causes further dysfunction in other systems. Put
simply, ME/CFS is a very complex knot of vicious cycles where each problem
worsens all the other problems. So, it is likely that the longer you have been
sick, the worse off your methylation cycle is.
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?
So, if people with ME/CFS have messed up methylation cycles,
what exactly does that mean? When the methylation process isn’t working
properly, the following problems result:
- 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).
Take a look at that list again – notice anything familiar?
It’s pretty much a list of most of the symptoms and dysfunctions that define
ME/CFS! So, now you begin to see how important methylation is to each and every
ME/CFS patient.
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).
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.)
To help with methylation and associated processes, he (and I) take the following supplements (links below), remembering that we added these very gradually and slowly:
- 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 specialist's office or online (link is to WholeScripts site, which now sells Xymogen products), 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 Note that NAC is no longer sold through Amazon and will be switching to prescription in the U.S. but companies are allowed to sell their supplement stock. You can find more brands available at eVitamins and at iHerb.
- 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.
Note: This post contains affiliate links. Purchases from
these links provide a small commission to me, to help offset the time I spend
writing for this blog, at no extra cost to you.
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