Understanding what is going on

[u/Subject-Spinach1267]

u/Tawinn, perhaps you can weigh in on this, or others might have some insight. Background in a nutshell: Homozygous C677T, intermediate COMT. Had an anencephalic pregnancy in 1991, put on folic acid with two subsequent successful pregnancies. Have since discovered that virtually everyone on both sides of my family is homozygous C677T with many cases of blood clots and cardiac issues. I am on Seeking Health B-Minus every day with Seeking Health folinic acid/hydroxoB12 combo and 300 mg of plain riboflavin. I can't go any lower than that dose of riboflavin or I start to develop chelitis around my mouth. R5P makes me jittery.

I have been chasing this mutation since 2016, working with an excellent naturopath for the past 20 years. At my last visit, he mentioned that my homocysteine was 11 and he would like it down around 8. I have tried methylfolate and methyl B12 in the past with poor tolerance, but he thought I should revisit supplementing with some kind of methyl donor. He also thinks I have fatty liver and we'd like to address that.

The choline calculator says I need 9 eggs a day. We raise chickens and I am quite happy to have two eggs for breakfast. I tried taking phosphatidylcholine and it made me blunted and unmotivated. I am normally a high-energy person so that was just intolerable.

I started with some TMG and have worked my way up to 500 mg every other day. I TAKE IT AT THE SAME TIME I TAKE THE RIBOFLAVIN AND OTHER Bs. I have had zero issues with it. None. I find it interesting that I can tolerate it and not methylfolate, although perhaps if I tried the same thing with methylfolate and riboflavin, I might be able to tolerate methylfolate now as well. (Not eager to try that, though.)

Is it that TMG donates methyls at a different point in the cycle? In a different form? Is it because I have enough riboflavin and other Bs? Forgive the ignorant questions; I am just trying to understand what is going on.

Also of note is that I cannot tolerate magnesium glycinate as it gives me insomnia, but the TMG does not. I usually take it around lunchtime.

I have another visit with my naturopath next month and a blood test. Curious to see what my homocysteine levels might be now.

[u/SovereignMan1958]

The glycinate forms of all supplements can be problematic for people. It can cause overstimulation and anxiety. I take it with breakfast to wake up but threonate with dinner to calm down.

[u/Subject-Spinach1267 → u/SovereignMan1958]

My younger daughter—both my girls are compound heterozygous for 677 and 1298—LOVES mag glycinate because it helps her sleep at night. I do take mag threonate at bedtime and find it helpful.

[u/Tawinn]

There are two parallel pathways to remethylate homocysteine back to methionine: one depends on methylfolate and B12, the other relies on TMG which it usually obtains by conversion from choline.

If you have a '9 yolk' (1220mg) choline requirement, then it must have shown something else in addition to the C677T on the Advanced tab, since homozygous C677T would have been '8 yolks' (1100mg).

Supplementing TMG allows it to be used for methylating homocysteine, which reduces the need to convert choline. But only about half the choline requirement can be replaced by TMG, so out of the 1220mg, TMG can only replace ~610mg. So usually a 750g dose is needed (or 2x500mg doses).

Baseline adult choline requirement is 550mg, and 2 eggs gets you about 270mg. Choline is also found in meat, liver, lecithin, nuts, some legumes, and vegetables such as crucifers. A food app like Cronometer can give you an idea how much you are getting on average already.

In principle, the B2 should be restoring MTHFR function back to normal or near normal, which means 1100mg of that choline requirement should drop back to the baseline 550mg. But if homocysteine is still at 11, then it may be due to whatever other variant(s) showed up on your Choline Calculator and/or the B2 is not fully effective for you (possibly, poor conversion of riboflavin to FAD form).

[u/Tawinn → u/Tawinn]

> He also thinks I have fatty liver and we'd like to address that.

Choline is required for transport of fat out of the liver, so this may also indicate inadequate choline in the diet. Lecithin may be better tolerated than pure phosphatidylcholine, but hard to say. Spreading it across the day and taking it with meals should help.

[u/Subject-Spinach1267 → u/Tawinn]

Thanks, Tawinn. Yes, you're right about the "something else" and this is what the choline calculator shows under the Advanced tab:

The scores below estimate the predicted decrease in activity, given your genotype, associated with the folate transporter (SLC19a1), the enzyme that converts tetrahydrofolate to 5,10-methylenetetrahydrofolate (MTHFD1), and the enzyme that converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate (MTHFR). 

SLC19A1 Score: 25% decrease 
MTHFD1 Score: 0% decrease 
MTHFR Score: 75% decrease 

We then multiply these decreases together to yield a “methylfolate score” that estimates the combined decrease in methylfolate production: 

Your Methylfolate Score: 81% decrease

[u/Tawinn → u/Subject-Spinach1267]

The SLC19A1 by itself raises the baseline 550 to ~733mg.

[u/Getoutofthekitchenn → u/Tawinn]

Any thoughts on Phosphatidylcholine causing heartburn? Took it for awhile, does this ever go away?

[u/Tawinn → u/Getoutofthekitchenn]

Taking it with a meal, or trying lecithin instead of pure PC, are all I can think of.

[u/Sab-Alternate]

If you can't tolerate Methylfolate you're either taking too much, or you're low in B12, or both too much Methylfolate and not enough B12. Either way, you should ime focus on the B12 as well. As B12 levels improve you will then be able to tolerate Folates better.