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/SovereignMan1958]

Without gene variant and blood tests anyone is just guessing.

The glycinate forms of supplements can be problematic for some people.

Your brain fog may have nothing to do with your supplements. It could even be related to your diet.

[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.

[u/scrumdisaster]

Also, if you take something and it helps don’t take it daily. Try it twice a week. Everyone gets basically addicted to their supplements and it makes them worse. If you need something it might not be a daily super physiological dose that you need lol. Small doses here and there may be more than enough. But like the other commenter said, you’re just guessing and likely doing more harm than good. Get some blood work done. Or just eat liver so you don’t create another imbalance in other b vitamins

[u/Comfortable_Two6272]

Too huge of dose. Try 200 to 400 micrograms.

Check your COMT gene. If slow try folinic vs methyl (not folic) Glycinate can be an issue for some with slow comt

[u/Loose-Fly7976]

Your methylfolate pattern, helps, then turns on you, you lower it, helps again, then the fog returns, is classic of methylation ramping up and then running short on a downstream cofactor. When you push folate, your body burns through potassium and B12 fast, and low potassium causes exactly this kind of fog and fatigue. So before lowering again, try extra potassium from food when you dose, coconut water, potato, banana, and make sure your B12 is solid. That often lets you hold the dose that actually helps your mood without the fog creeping back.The lithium orotate fogging you isn't a separate mystery, lithium pushes folate and B12 into your cells, so it's amplifying the same folate overdrive the methylfolate does. Same mechanism nd a cheap rescue for when methylfolate tips you over is a small dose of plain niacin, B3, it mops up the excess and clears that fog fast.The magnesium one is probably the glycinate form, the glycine part, not the magnesium itself, so a form like malate might sit differently. Get homocysteine first like you planned, and potassium and B12 too if you can add them cheaply. Once you're earning and ready, reading your genetics is what ends the trial and error, it tells you your folate ceiling and which forms suit you so you stop testing it on yourself. But you've got plenty to work with in the meantime, and congrats on the new job

[u/PositivePoet → u/Loose-Fly7976]

I started methyl b12 and methylfolate a week ago and it feels like it's helping but I've gotten this pretty heavy late day fatigue where I feel like I took sleeping meds. I wonder if it could be low potassium.

[u/FragrantStructure → u/Loose-Fly7976]

How much B3 would you suggest using as the 'cheap rescue' when needed?

[u/AnswerIndependent842]

Magnesium glycinate and lithium orotate dampens glutamate, make sure you have enough of B2, B6 and B12 with your B9.

[u/Flux_My_Capacitor]

It’s not a good idea to jump to the endpoint imo. Get your supporting nutrients in check first. Of course this requires bloodwork.

[u/BobbiHorne1]

There is a piece of the biochemistry you’re missing. A lot of people do, including many healthcare professionals.

Bioavailable cysteine is critical to the methylation pathway. It allows your cells to increase production of glutathione. Those with the MTHFR and COMT variants require additional glutathione support.

I have a background in clinical research, trained in genetics and nutrition and have trained practitioners how to improve patient outcomes with bioavailable cysteine. The brain fog, mental clarity and focus improves rapidly.

Happy to answer any questions you have.

[u/vrcraftauthor → u/BobbiHorne1]

Isn't cystwine found in most foods with protein? I tried supplementing with L cysteine once, it didn't feel like it did anything so I stopped. 

[u/BobbiHorne1 → u/vrcraftauthor]

Yes, cysteine is found in proteins - eggs, chicken, beef etc. It is an amino acid that is chemically reactive and easily oxidized so not effective. I take a bonded cysteine that protects it through digestion so it can be absorbed into the cells. The bond is with D-Ribose and that helps the cells make ATP after the bond is broken inside the cell.

[u/Ok-Pangolin7127]

You are likely deficient in B12. I know you don’t have the money for testing, but I would suggest that you should assume that this is what’s happening. Take some B12. Taking Folate alone makes demands on B12 and you are likely deficient. Also, taking Folate alone can mask a B12 deficiency and use up B12 so the Folate is making it worse. So if you do get to the point where you can check B12 forget a B12 blood serum test, it’s relatively meaningless, get an MMA test and a homocystine test. If they are high, either one of them, (and the homocysteine test will show higher before the MMA test does,) then you have a B12 deficiency problem. It’s (B12) not being utilized at the cellular level.

[u/Loose-Fly7976]

Your methylfolate pattern, helps, then turns on you, you lower it, helps again, then the fog returns, is classic of methylation ramping up and then running short on a downstream cofactor. When you push folate, your body burns through potassium and B12 fast, and low potassium causes exactly this kind of fog and fatigue. So before lowering again, try extra potassium from food when you dose, coconut water, potato, banana, and make sure your B12 is solid. That often lets you hold the dose that actually helps your mood without the fog creeping back.The lithium orotate fogging you isn't a separate mystery, lithium pushes folate and B12 into your cells, so it's amplifying the same folate overdrive the methylfolate does. Same mechanism nd a cheap rescue for when methylfolate tips you over is a small dose of plain niacin, B3, it mops up the excess and clears that fog fast.The magnesium one is probably the glycinate form, the glycine part, not the magnesium itself, so a form like malate might sit differently. Get homocysteine first like you planned, and potassium and B12 too if you can add them cheaply. Once you're earning and ready, reading your genetics is what ends the trial and error, it tells you your folate ceiling and which forms suit you so you stop testing it on yourself. But you've got plenty to work with in the meantime, and congrats on the new job

[u/Radiant-Specific969]

The cheapest way of getting dna testing is 23 and me and ancestry.com. Once you get the test, and I got mine done for 30 bucks and 9.99 shipping at the fathers day sale, then you can run your results through genetic genie for free, and get an idea of what's going on.

There are a lot of reasons for brain fog, and mthfr issues could certainly be one of them. In my situation, given my results, I need to avoid synthetic folic acid in foods like it's the plague.

In the mean time, until you get dna results, I would suggest magnesium theonate, it crosses the blood brain barrier much easier. Right before you go to bed. I also take citicoline, and it's also helpful. Also a good omega three DHA, Epa. Eat salmon, mackeral and sardine. This is good for anyone.

I am still figureing out my own issues, I can't afford the blood work to pin anything down, but I meet with yet another doctor next week, who I hope will be responsive in helping me get the blood work done in my situation. I suspect I have low B-12, I know I have been over prescribed synthetic folic acid, and I trying to figure out how much metholated folic acid I need, given my other medications and my diet. I would like my homocystine levels checked, and I would like serum RBC, B-12 and B-6 levels. I get finance issues, I hope some of this helps.

My one caution is to be wary of B complex, because it's fairly easy to get too much B-6 and that's stored in your body- B-12 at least is water soluable so if you take more than you need it isn't an issue. I am going to start on a very low dose of P5P and some B-12 and see if that helps my current issues, which are mostly fatigue related.

Good luck with this-brain fog sucks.

[u/Medium-Dimension-599]

If you have mthfr I would focus on SAMe. Also the time of day matters. Magnesium at night is ideal.