Wednesday, April 11, 2012

Bumbling around Methylation

Are you wondering whether you should try methylation support, and if so, whose protocol to follow?  If so, this blog might help you get a handle on what to avoid and how to go about it systematically.

My history
I started this blog when I decided to try the simplified methylation program designed by Rich Van Konynenberg for people with CFS to let others know if this program ‘worked’.  Before that time, I’d spent too much money on doctors and protocols that didn’t work, or that made me substantially worse, or that only seemed to work for a short while and then left me yearning for more.  I lacked the optimism that this new ‘miracle’ protocol would turn me around, even though Rich knew more about ME-CFS than any practioner I’d ever met. 

I didn’t make fabulous progress on the methylation protocol, and unlike many on the Yahoo support group, I didn’t feel any detox.  Yet I did experience one issue repeatedly: whenever I took too much B12, whether as hydroxyB12, glutathionylB12 (made by combining OH B12 with glutathione) or methyl B12, I would always feel like I was getting a cold, usually wouldn’t be able to sleep, and sometimes would feel hyper.  Then I’d back off once again and try to build up slowly.  It frustrated me that whichever practitioner I was working with would tell me “Take more B12” except for my mainstream PCP who looked at my high serum levels and suggested I didn’t need any.  So I tried to educate myself.

I joined Amy Yasko’s forum, tried small amounts of all 3 types of B12 (methyl, adenosyl, hydroxyl), multiple types of folate (5-mthf, folinic, folic acid), and many other supplements.  No improvement, no decline.  I tried Fred Davis’ protocol (posted as Freddd on Phoenix Rising) of using only methyl B12 and 5-MTHF.  Same dismal results with the B12 as before.  It was particularly bad if I did exercise when I first got a burst of energy from B12:  I was sure to come down with a cold later in the day.  Finally, I saw Alan Vinitsky, an innovative doctor who’d patented his ideas about methylation, and decided to learn from a pro.  Proof that methylation wasn’t working properly in my body came from my high MCV on standard blood tests.  From him, I learned all the things that methylation does and was better able to identify when it wasn’t working properly.  His protocol was expensive, as it involved taking large amounts of OH B12 combined with even larger amounts of inactive folic acid, up to 20 tablets a day, but I seemed to tolerate it for the first five months.  Then things shifted and I got sicker than ever, with constant colds, sinus infections, and fatigue. 

All these stories, as well as the theories underlying the protocols, are discussed in posts from February 2011 and earlier.

On blogs and internet discussion groups, I read of others who were having tremendous detox with methylation support.  Some were experiencing huge bursts in energy after a few rocky days.  Why not me?

It was around this time that Dr. Vinitsky identified mold as an issue causing my condition and set me on the path of remediating my Ohio house. Six months later, I left it to experience life in the great outdoors where I watched many of my long-term CFS symptoms go into temporary remission. Since then, I’ve been bumbling around with methylation support, unsure which protocol to follow. When I was camping and not going anyplace, I seemed to be able to increase B12 and 5-MTHF week by week. As soon as I started looking at houses in the hope of moving beyond tent camping, I’d get hyper and decide to stop everything, or cut down on B12 until I was taking a tiny piece of a pill.  What could be blocking methylation?

A few clues
Those practicing avoidance for a long time say you have to be in a good place to get detox to occur.  What I think they mean is that, if the body is involved in a chronic inflammatory reaction, you will not detox.  I’m so sensitive that, when I enter buildings, I often get a delayed reaction hours later.  Often I don’t smell or feel anything at the time.  Sometimes I do.  Either way, I find myself hours later feeling edgy, or blue, or hyper, or congested.

Some people can stop these delayed reactions by showering and washing their hair immediately after leaving the place.  The key is to get out quickly and clean up quickly.  To do this, one has to have some ‘realization’ that the place is, or could be, an immune system trigger. My downfall is that I forget until at 3 am, I’m not sleeping and feeling miserable.

Another clue came from Dr. Ben Lynch, a naturopath with a website devoted to methylation disorders and support.  In a discussion of side effects from too much 5-MTHF, Dr. Ben notes: "if one takes methylfolate before inflammation is controlled, the methylfolate will worsen it.”  Side effects of too much methylfolate include: pain, insomnia, irritability, skin rash, achy joints, palpitations, and migraines. 

He recommends the anti-inflammatory herb, curcumin, to offset inflammation, even though it is a methyl donor.  I tried a powerful curcumin preparation while in a chronic inflammatory reaction in my old house, and had bad reactions to it.  I can take the same product now without complications.  Interesting how removing myself from immune triggers reduces inflammation to a point where I can tolerate additional support.

Yesterday I learned from Dr. Lynch that all forms of 5-MTHF are not created equal.  In his post on April 5,, he listed all the names used for methyfolate (there are about 20 of them) and then grouped them into active/effective forms and inactive/ineffective forms.  The prescription types are active and effective.  The OTC (over the counter) supplements vary.  Those that include the Merck-patented Metafolin are fine,  but they max out at 800 mcg compared to the 7.5 mg in prescription Deplin.  With the others, it’s a gamble.

Oops!  I used up my Metafolin-based supplement (Folapro) suspiciously close to the time I started getting unstable,  I also turned down a prescription for Deplin because my insurance wouldn’t pay the high cost, and ordered the least expensive methylfolate I could find.  What was really in it?

So I read more of Dr. Lynch’s blog where I learn that those supplements listing the L form or the S form of methylfolate are effectivde while those that don’t specify probably include a lot of the ineffective D form and R form of the molecule.  The chemistry of how each rotation differs from another is beyond my understanding, but I would love it if someone could explain it and let me post it as a guest blog. In the meantime, I remember that the D or R forms can be stored in the body, especially in the liver, and may inhibit regulatory enzymes related to folate metabolism.  The take home message – read labels carefully. 

I want to avoid all the dyes and fillers used by the pharmaceutical industry to make Deplin, and so I was glad to learn that Quatrefolic (available through Allergy Research Group at 800 mcg and now through Metabolic Maintenance at 10 mg) is a fine alternative to the prescription drugs. However, the cost is about the same. I check my order history and find that the brands I’ve been using in 2012 are using Metafolin. Guess that wasn’t the problem after all.

Back to Dr. Ben’s site where, in a recent post, How Much Methylfolate should you take?, he recommends titrating methyl B12 in combination with methyl folate in the ratio of the supplement he sells (how convenient!) which is 1000 mcg of methyl B12 combined with 800 mcg of Metafolin.  I, on the other hand, bumbled into trying 10,000 mcg of methyl B12 combined with 800 mcg of Metafolin.  Oops!!  (and then I tried injections of methylB12, probably getting even more.  Oops again!)

So now I try again, starting with a safe, low dose, and titrating up.  My Quatrefolic arrives tomorrow in the mail.

What about you? Are you trying to get all your folate from food?  or are you supplementing?
As a naturopath, I like the idea that fresh whole food can supply all the nutrients we need.  After all, the Greek physician Hippocrates said “Let food be your medicine” and the Bible similarly instructs us to partake of healing foods from the fruits and seeds of nature.  Yet many of us, despite an organic, whole foods diet rich in leafy greens, do not have sufficient folate in our cells for a number of reasons.  For decades, food has been fortified with artificial folic acid, a stable compound that has to be converted by an enzyme in the stomach into a useable form of folate.  When the bloodstream has high levels of unmetabolized folic acid, it’s a sign this enzyme isn’t working well (or that we’re taking more folic acid in supplements than the enzyme can handle.)  Researchers aren’t quite sure of this, but evidence points to a risk that unmetabolized folic acid has a detrimental effect on folate metabolism.  Another reason to read labels and avoid processed foods!

On top of this, many of us have genetic variants that slow down some of the methylation enzymes or cause us to use up B 12 or B5 or methyl groups too quickly.  In either case, we may find ourselves needing much larger amounts than we could ever get from food.

Even if you don’t have ME-CFS or another neuro-endocrine illness, be advised that methylation is now believed to be a key factor in preventing heart disease and cancer.  It’s an important factor in endometriosis, a healthy pregnancy, and many female syndromes that involve estrogen imbalances as well as mental disorders like schizophrenia, anxiety disorder, and depression. 

This doesn’t make methylation support a panacea for everything that ails you, but since methylation is a process that all cells in the body use to move CH2 radicals from one molecule to another, which supports over 40 different processes in the body ranging from the management of stress hormones, to immune reactions, to estrogen metabolism, to antioxidant control, a glitch in one place is bound to create a jam in another. 

Metametrix now offers a test (@ $150) for unmetabolized folic acid compared to serum methylfolate.  Vitamin Diagnostics Lab , now Health Diagnostics and Research Lab, offers a methylation panel for @ $300 which looks at all the steps in the cycle, including SAMe and SAH, reduced and oxidized glutathione.  In addition, your doctor can run serum folic acid through Labcorp or Quest to see if your levels are high or in the normal range.  But the new rage today is testing your methylation genetics and supplementing according to what you find.  The site offers extensive genetics testing for a very good price and their panel includes the important C677 and A1298 variants that could guide how you approach methylation supplementation.  When you get your results, go to Ben Lynch’s site and find out how to balance your genetics.  Or, if you’re capable of absorbing tons of information, visit the Yasko forum and dig in.


  1. Are you sure the Metabolic Maintenance Brand is made from Quatrefolic? Quatrefolic is the the brand name of 6s-L-methylfolate manufactured by Gnosis, derived from glucosamine salt. Quatrefolic and Metafolin are the only two active l-methylfolate supplements available. I'm not sure but I think the Metabolic Maintenance product may be a racemic mixture.

  2. I have Dr Ben's sublingual metafolin Mb12 supplement 800 to 1000 mcg ratio. I don't know if its me or what but I still feel a need for my 5 mg jarrow sublingual Mb12. Maybe not always but there are times when my nerves go haywire (feel like myelin is wearing off.. don't know how to explain it.. creepy, fizzling) and I need that 5 mg or at times 10 mg Mb12. I am also MTR++ and have several MTRRs+- which means I don't recycle b12 well and use inefficiently. I also think Lisa passed on info on mycotoxins using b12?

    I also have tried simplified, yasko and fred's protocol.. barely the latter.. the higher doses of metafolin really messed with my head. I was very irritable and unstable, pshychologically and physically. I felt like I was losing my balance. He may say this was a potassium crisis. I don't know. Scared me away from the high metafolin doses. I am also COMT++,++ which means methyl groups can over stimulate. We do not clear adrenaline well and I think dopamine.

    My MCV was out fo range then in range (on methylation supps) but went out of range when I was using lipo glut regularly. Fred does have a theory about glut interfering with b12 absorption into cells? I may experiement with that later. Right now my glut intake is rare. Hearing contradictory info on glut and b12 absorption.

    Thank you for the info and links. Yasko and or Rich have said only certain forms of methyltetrahydrofolate, but I have not seen any further explanation.


  3. Great questions on Dr Ben's site, Janis. Thanks.


  4. Hi R,
    Just to clarify, Dr. Ben says he doesn't know the best ration of MTHF to B12, and thinks it could be individual in any event. Just no research on this.

    Re Anonymous, here's the link to the new Metabolic Maintenance quatrefolic.
    As you'll see, it's comparable in price to Deplin, but without all the extra stuff, just some glycine.

  5. No mention of methylcobalamin donating methyl to mercury (in high mercury individuals) and bringing on your symptoms?

  6. I'd put my money into finding out what SNPs you have before finding out a symptom, like the unmetabolized folic acid in the blood. Janis, have you not done this test yet? It's about $500 and you can order it on Yasko's website.
    I was working with Ben over 6 mos. ago, but it was prior to him realizing it's not all about MTHFR and there are other things going on that need addressing first (like CBS), so I went elsewhere to Yasko's board. It sounds like you jumped around a bit too.

    You think your main issue was that mold then? it sounded like you improved so much after you left the house. How did you detect the mold?

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  8. Hi, I saw Dr. Vinitsky. He took 2 hours to explain different things including Methylation. I dont remember a thing now. He wanted me to take the combination of vitamin Bs and folic acid he created. The doze is 830,000% daily value!! I'm scared.
    Is it worth taking it? Is it worth doing all the genetic tests etc. I went to see him to figure out if my thyroid is Hypo or am I gluten intolorant and it's causing complications in my thyroid and skin due to inflamination.
    What do you suggest?

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  10. my CFS/ME specialist who has been researching this since 1985 says it's going against the body in what the body is trying to do to stay alive by pushing methylation or adrenals etc. i went down the Lynch, the Yasko rabbit holes for years and didn't get an inch better, but got a lot broke.

  11. I'm homozygous A1298c for the MTHFR defect. I've completely lost all the feeling in my feet and my ability to walk without assistance because I didn't know my body stopped absorbing B12 and wasn't getting folate for YEARS. My doctor has steered me in the direction of methyl B12/folate to address these issues, but I've stopped and started this treatment more times than I can count. Treating this issue is SO problematic. You want to take enough so it will make a difference, but then stop because it makes the symptoms so much worse. Unfortunately no one is very educated in this matter, so you play whack-a-mole treating yourself. And completely agree with the author at Ben Lynch having pricey supplements 'conveniently' available on his site. Another frustrating aspect to this whole mess, when all I really want is to try and get my life back.


Please add your comments here. If you have a question specific to your own condition, please e-mail me directly at I cannot give medical advice. If you want to suggest a product or therapy you think I should try, please let me know if you have used it, what you used it for, and how it helped you.