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Methylation - Tried It All, No Luck?

I've tried all the ideas I know of to methylate and be functional but I'm stuck.


A few years ago, I began experience bronchitis-like symptoms and the symptoms didn't stop for over a year. I spent a lot of time getting treatment and diagnosis from pulmonary, immune, and allergic doctors with no luck. After 2 years, I was sick with a dozen or more symptoms and could hardly breath despite taking prednisone, theophylline, and 50 doses of albuterol every day.

I moved to an area without allergens, hired a private babysitter so that my kid wouldn't get me sick, and started working from home. I still felt the same, and couldn't escape my symptoms.

That's when I came to understand that I had CFS, and I ordered a 23andme and test. Using selfdecode, geneticgenie and other sites, I learned that I have several mutations for genes related to methylation. Fast forward one year, and I've read dozens of posts on this forum, including much of Freddd and Dr. Rich's protocols as well as Dr. Yasko's work. I've tried several methylation protocols, and I'm still sick. I'm hoping that someone on here recognizes my symptoms and can help me restart my methylation.

What's Wrong With Me?

I experience these symptoms on a regular basis:
  • Malaise
  • Brain fog
  • Inability to handle stress
  • Blurry vision or difficulty focusing my eyes
  • Night blindness
  • Mood swings
  • Allergies
  • Poor sleep
  • Chronic lung inflammation and phlegm (bronchitis-like)
  • Difficulty breathing
  • Weekness in arms
Add it all up, and I generally don't feel like myself. It's stressing me out everyday to be pushed beyond my limits and still feel like I'm barely holding a full-time job.

My Methylation Hell

I'm a problem solver, so I began trying methylation protocols on myself last year but I haven't had much luck. The one exeption was when I first took choline.


I tried a choline pill and, within 3 hours, it was like all my symptoms disappeared. I kept taking choline, increasing the dose from 500mg to 3000mg spread throughout the day, and felt amazing. My lungs stopped producing phlegm and I no longer needed the high-dose steroids to be able to breath. My brain felt better and I began feeling like myself for the first time in years. I was smarter, happier, healthier, and had more self control.

Adding Methylfolate

This is where things went wrong. After 3 weeks, I decided that, because I'd done so well on choline, I should get ahead of my MTHFR mutations and take methylfolate. I took a 10mg pill and experienced what I call a "crash" within an hour. I wound up writhing in bed for 1 day from intense pain in my brain and body.

The following day, I took 2.5mg of methylfolate and, though not as bad, crashed. I tried 1mg the next day and crashed again.

Finding the Answers

I stopped methyfolate for a couple weeks but never returned to health. I started to have headaches. My reading led me to think that my body wasn't using the choline I was taking for methylation, and that my brain's levels of acetylcholine were too high. I tried an SSRI for a couple days (I read that serotonin reduces acetylcholine), and the headaches stopped. My phsical symptoms hadn't changes however.

MTHFR Protocol

My reading on this forum and on Dr. Yasko's site led me to try a more robust methylation protocol for MTHFR, including tapering the dose of methylfolate slowly over the course of weeks, culminating in...

800mg potassium
1g magnesium
10mg manganese
20mg methylcobalamin
4800mg fish oil
100 mcg K-2
200mg CoQ10
2g curcumin
2g resveratrol
5mg lithium
10mg D3
200mg zinc
500mg choline
2g C
4 Jarrow B-Right pills
3mg of adenosylcobalamin once/week

I sometimes took:

1g acetyl L-Carnitine
600mg NAC
SAMe (would cause the same type of crash as initially taking methylfolate)
Extra B2
Extra Niacin

I started with small amounts of methylfolate after reaching 1600mcg from the B-Right pills. I stopped getting bronchitis-like symptoms but that was about the only change on this protocol.

After a month, my total dose of methylfolate was up to 3mg. At that point, I noticed signs of methylation (improvements to my brain and physical function). I kept the dose of methylfolate constant, and felt 50% better for 3 days. Each time I took methylfolate, however, I'd get a runny nose and start to have allergic symptoms. On the third day of feeling improved, I crashed.

I repeated this cycle for several month, trying to find the right combination of support and slowing my dose changes to avoid the "crash." I kept crashing over and over however.

Hail Mary

I stopped taking all supplements related to MTHFR methylation. My idea was that, if I got off MTHFR supplements, my body might begin to methylate with choline using the BHMT pathway. Without methylfolate, methylcobalamin, lithium, adenosylcobalamin, B-Right, etc., I got bad lung inflammation within days. I stuck with the new "choline protocol" for a month but never shook the inflammation.

TMG was the next thing I tried, and I've had a roller coaster of results since taking it. After a week on TMG, I had 2 days of pretty good health, followed by poor health. My improved again for 2 days after 1 week, then went back to being being poor for the past month. This is where I'm at today.

I don't know what's going on. Ideas? You'll be my hero if you can solve this.


Senior Member
Sounds similar to what I’m going through with regard to the breathing issues, but I don’t have any answers. Hopefully someone else can chime in.


Senior Member
Check this post from Rich:

The BHMT reaction takes place in the liver and the kidneys, and it is an alternative pathway for converting homocysteine to methionine. Dr. Amy Yasko refers to this as the "short-cut" pathway. The other pathway is the methionine synthase pathway, and that is the one that is partially blocked in ME/CFS.
Dr. Yasko advocates boosting the short-cut pathway at first, using TMG or Choline, and then, after B12 and methylfolate supplements have been added for a while, to switch to DMG, in order to slow the short-cut pathway and shunt more flow into the methionine synthase pathway. So one possibility is that the DMG is cranking up your methionine synthase.

The other thing that DMG does is to donate a methyl group to tetrahydrofolate to produce 5,10 methylene tetrahydrofolate. This is the substrate for the MTHFR reaction, which produces 5L-methyl tetrahydrofolate, which is a reactant for the methionine synthase reaction. So that could also act to boost the activity of methionine synthase.



Senior Member
Pacific Northwest
@jtex Exactly how did you come up with the protocol you outlined above? The doses on your list are like hitting your body with a sledgehammer, which could be producing unwanted symptoms.

Methylation should be personalized to your needs and ramped up gradually, and not applied like using some recipe out of a cookbook. Unbalanced methylation is not a good thing - see all the big red dots in Figure 4 indicating areas where imbalance can drive cancer:


Immune dysfunction, neurotransmitter dysfunction, brain symptoms, and many other unfortunate things can result from methylation imbalances. Optimizing it for you can make a tremendous difference and support improvements in your health.

The best way to personalize a methylation protocol is to do some lab testing, and not just go by your genes. The test my doctors have used over the past 9 years is the Genova Diagnostics NutrEval:


It gives guidance on what to take, and after 9 years of working with it doing the crest every 9-12 months, my experience has been that one's needs can change dramatically over time.

In general, you need to get your digestion working properly and be ingesting plenty of water. Then you work backwards, starting with transsulfuration pathway nutrients (B1 and molybdenum), then make sure you have nutrients to produce glutathione - amino acids and B6. Then you add in B12, with supporting nutrients for the methionine cycle - B6, B2, TMG, magnesium, and maybe potassium. And in some cases, methionine. And then you add folate.

If you get the amounts and proportions right, you shouldn't have any mood symptoms and should feel pretty good. Some people need to increase the amounts slowly to optimize function and to help the body handle stressors.

Also, almost everyone has some toxicity. If you start up methylation suddenly, you could be mobilizing toxins, and if you can't get rid of them fast enough, you can resbsorb them from your digestive tract and can feel sick. I've gotten headaches, a sick feeling and intestinal discomfort when this happens. Helping digestion , using binders to bind the toxins, backing off methylation a bit, or adding a support like curcumin can all help ease the discomfort.

Just for comparison, I'm in a very heavy, doctor supervised protocol optimized for my needs. I won't detail all of it, but you can compare what's working for me to your protocol just to get an idea of the difference in proportions between the nutrients.

3mg 5-MTHF
10mg MB12
350mg P5P (B6)
300mg R5P (B2)
500mg benfotiamine (B1)
500mg niacinamide (B3)
2g TMG
800mg magnesium malate
50mg zinc
1mg molybdenum
1.5g NAC
4.5g glycine

But you need to test and find out what's right for you.

Good luck!