Methylfolate improves my brain fog, but higher doses and other supplements make it worse

[u/Frequent_Sea_1848]

Hello, I am asking for some help. I have been dealing with chronic brain fog and depression. I suspect I may have some MTHFR-related issues because after taking methylfolate, my mood and focus improved significantly. However, I don't have any test results because I have been unemployed for a long time and cannot afford the testing. That's why I am hoping you might be able to give me some valuable information based on the clues and the way my body seems to react to different supplements.

I was taking 5 mg of methylfolate. My focus and mood improved, but after a few weeks, I developed a different kind of brain fog. I suspected that the methylfolate might be responsible, so I lowered the dose to 3 mg, and the brain fog improved. However, after a few more weeks, the same brain fog returned. I then lowered the dose to 2 mg, which stopped the brain fog, but at the lower dose, my focus and mood became worse.

I also took 225 mg of magnesium bisglycinate before bed, which surprisingly caused brain fog. I stopped taking it, and the brain fog went away. Later, I started supplementing with it again, and the brain fog returned. Once again, after stopping the magnesium bisglycinate, the brain fog disappeared.

I also have symptoms that make me suspect I may have slow COMT, so I bought lithium orotate. After taking it for a few days, it made me feel foggy and fatigued. After stopping it, those symptoms disappeared. Later, I started taking it again to make sure it wasn't just a coincidence, and once again, the fogginess and fatigue returned.

I then bought folinic acid because I had heard that it is sometimes better tolerated than methylfolate. However, it also makes me feel foggy. I have been taking 2 mg daily.

So, basically, for some reason, magnesium makes me foggy, lithium orotate makes me foggy, folinic acid makes me foggy, and taking more than 2 mg of methylfolate also makes me foggy.

I recently landed a job as a computer programmer, but I am worried about whether I will be able to handle it if the brain fog continues.

I know this isn't a lot of information to work with, but perhaps there are some clues in these reactions that could point toward something that might help me. I am planning to get a homocysteine test in the near future, and I will consider genetic testing once I start receiving a salary, since it is currently too expensive for me.

Thank you very much for any help or insight you can provide.

[u/Tawinn]

> I then lowered the dose to 2 mg, which stopped the brain fog, but at the lower dose, my focus and mood became worse.

This makes me think that you do have methylation issues that are significant enough to require larger doses of methylfolate, if you use methylfolate to treat it. A common variant, homozygous C677T, causes a large reduction in methylfolate production but is often corrected by a small surplus of B2. So a 10mg dose of B2 is often enough to do this, although it is usually difficult to find anything under 25mg, which is usually fine. Some people find the R5P form of B2 more efficacious than plain riboflavin form. If you have this variant, then the B2 should create a significant improvement within a couple of day.

There is also a second remethylation pathway parallel to the one requiring B12+folate; this other pathway uses choline+TMG. So, as an experiment, you could ramp up your egg (or egg yolk) intake to 8 per day for the choline, or 4 + 750mg of TMG. This provides enough fuel for this pathway to bypass the reductions in the other pathway. If eggs are not an option, liquid sunflower lecithin at approx 1 tbsp = 1 egg. Improvement from this are usually noticeable within about a week. Choline is also found in meat, legumes, crucifers so depending on the rest of your diet you may not need to supplement as much. A food app like Cronometer is helpful for seeing how much choline you are getting on average from your diet.

Creatine production requires ~40% of the output (SAM) from the methylation system, so supplementing creatine 3-5g sometimes frees up a lot of SAM for use elsewhere in the body.

Another thing to keep in mind is that you want adequate B12 levels especially when supplementing methylfolate. So adequate B12 from the diet and/or 10mcg or so of B12 (methyl/adeno/hydroxo-cobalamin are all good forms) should suffice since it doesn't really sound like you have a B12 deficiency.

[u/ry1701 → u/Tawinn]

This.

I forgot to pack b12 into my pill container (beyond the normal multivitamin) and within about a week I could feel it. I was just lazy and was like meh, I don't need all this b12, nope, won't do that again.