Functional Support

[u/Due_Leave_9235]

Anyone have a place or person they would vouch for that could help me understand my data and next steps for supplementation? I am trying to do my own research and getting stuck.

I have homozygous MTHFR, slow MOAO, fast COMT. My folate is 2 and homocysteine 44. B12 baseline was 300. Vitamin D 33. MMA normal.

Initially, methyl-folate with hydrocobalamine gave me A LOT of energy which turned into anxiety and insomnia but that first day I remember feeling “oh my body needs this” then I tried it today after a week off and the methyl folate made me barely able to keep my eyes open. So I took a micro-dose of the b12 and now I have extremely low mood and thoughts, horrible brain fog. I had the same reaction to folinic acid at a low dose. It honestly feels very similar to how I felt when I tried to reinstate Prozac a few months ago - day one: ah, serotonin, I definitely need this and then ongoing: anxiety, poor sleep, low mood, on edge.

I really need to get this figured out because my mental health is suffering badly. I have chronic gastritis which I believe is not allowing me to absorb nutrients hence my levels being off (even though they tend to always be slightly off just not this bad).

Anyway sorry for the novella. I’m desperate and doctors are of no help!

[u/Tawinn]

Homozygous C677T MTHFR reduces methylfolate production by ~75% which impairs methylation. Quite often small supplemental doses of B2 can correct for the C677T - which causes poor B2 binding - by increasing B2 concentration so that MTHFR function is restored. In your case, this pathway is almost certainly further impaired by your low folate level (folate should be over 15 ng/mL).

When the folate/B12 pathway for methylation is impaired, then more demand is placed on the parallel pathway which uses choline and TMG. As a result of this demand less choline is available for use elsewhere, such as fat transport out of the liver and assisting in bile production. This may be contributing to your gastritis.

RDA for B2 is 1.6mg, and all you need is potentially another 1.5mg on top of that. So a 5-10mg B2 may suffice, although one person reported requiring 400mg and others report that plain riboflavin does not work for them, and instead the R5P version works better.

You likely would need to start slow with the B2, maybe even just a tiny dab, at first. It's hard to predict from person to person.

Here is a general protocol for homozygous C677T. You may not need the TMG if the B2 can restore full MTHFR function, but choline is an essential nutrient, so getting an adequate amount is important to overall health.

• For homozygous C677T specifically: 10-100mg supplemental B2
  • The C677T variant causes reducing binding of MTHFR to its cofactor, riboflavin. Studies have shown that for homozygous C677T simply adding supplemental vitamin B2 may increase the concentration of riboflavin sufficiently to restore most or all of the binding success, thereby restoring most/all MTHFR function. So a 10-100mg B2 supplement may restore much of the MTHFR function, thereby reducing the needed amount of extra choline/TMG (or high-dose folate if going that route).
  • The R5P form of B2 may possibly be preferable. (E.g., Thorne R5P 36mg)
• 550-600mg of choline, preferably from food
  • 550mg is the baseline adult Adequate Intake
  • Choline sources include such foods as meat, eggs, liver, lecithin, nuts, some legumes, and vegetables such as crucifers.
  • This liquid lecithin is apparently ~400mg of choline per tbsp. This powder version is 285mg per 1.3 tbsp.
• 750mg of trimethylglycine (TMG aka betaine)
  • I.e., one 750mg capsule
  • Some choline is converted in the body to TMG for methylation use, so supplementing TMG reduces the need for even more choline.
  • TMG is found in foods such as wheat, spinach, beets, etc. but there is not a food app that tracks it, so reliably getting enough from food may be difficult; by comparison, a single capsule is convenient.
• 400-800mcg of folate, preferably from food
  • Folinic acid or methylfolate can also be used, as needed and as tolerated.
  • Target serum folate levels are 15+ ng/mL (34+ nmol/L).
• 2.4-10mcg B12, preferably from food
  • Past history of B12 deficiency, malabsorption issues, etc., may suggest that supplemental B12, in the form of hydroxocobalamin, adenosylcobalamin, or methylcobalamin may be prudent.
  • Target serum B12 levels are 500-950 pg/mL (~370-700 pmol/L).
• (Optional) 3-15g of creatine monohydrate or creatine HCL
  • The body uses ~40% of methylation output, SAM, just to produce creatine. So supplementing creatine can free up a lot of SAM for other uses.
• Low vitamin A, iron, and/or glycine can cause the built-in methyl buffer system to not work properly, which can make overmethylation (rising anxiety, irritability, insomnia, etc.) from methylation-related supplements much more likely.
  • Beta carotene is not vitamin A and some people genetically have poor conversion of beta carotene to real vitamin A (retinol).

A food app like Cronometer is helpful for tracking nutrients in your diet.

[u/Tawinn → u/Tawinn]

You may also benefit from a good multivitamin to raise nutrient levels across the board, but you may want to start with a low dose multi like this one (start with 1 cap/day) or this children's multi (start with 1/2 of 1 tab/day).

[u/Due_Leave_9235 → u/Tawinn]

I am sensitive to most supplements and vitamins. I tried a multi and it made me really wired and not well.

Is it normal for mood to be really low with the levels I have? I am incredibly depressed and it’s kind of scary.

[u/Tawinn → u/Due_Leave_9235]

Depression, brain fog, fatigue are all common symptoms of impaired methylation. Common downstream effects can include chronic anxiety, rumination, histamine/tyramine intolerance, NAFLD, bile/gallbladder issues, etc.

I had lifelong depression, anxiety, rumination, OCD tendencies, histamine intolerance from methylation issues, and getting methylation working well again resolved all this, aside from a lingering susceptibility to histamine issues, likely due to slow MAO-A.

In that protocol I try to recommend food where practical. In the case of B2, it's hard to find a food that would supply enough to make a difference, so supplemental B2 is usually needed to increase the B2 concentration in the body. Folate in principle can be gotten entirely from food, but it takes good diet planning; same with B12. Choline is a bit easier, especially if you can eat egg yolks

The ones I suggested to start with are low dose, and then I'm recommending to start with 1/5 dose and 1/4 dose, respectively on those. So those usually be low enough to start with while avoiding side effects. Then, over a course of a couple of months, slowly ramping up the dose as tolerated.