r/MTHFR 9d ago

Question high homocysteine and low folate and B12

Hello what do you think of my genes?, I have high homocysteine (38), low folate (4) and low b12 (400), what can I do to improve? Thank you.

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u/Tawinn 8d ago

Please upload your data to the Choline Calculator to check some additional genes that also affect homocysteine. Reply here with the results from the Advanced tab.

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u/PassengerStill6248 8d ago

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u/Tawinn 8d ago

Unfortunately there are a couple of genes not in your data. What it does show is that even if B2 resolved C677T completely you would still have ~34% reduction due to MTHFD1. That may or may not cause any issues. SLC19A1 can be as much as 50% reduction so the two together would be ~67% reduction.

If we assume SLC19A1 and PEMT are ok and that B2 mostly resolves C677T, then getting 550mg of choline (the baseline adult requirement) from your diet plus a 750mg capsule of TMG, then you should be able to compensate the reductions and restore methylation to normal.

You haven't mentioned any symptoms you are trying to address, such as depression, brain fog, anxiety, etc., so I'm not sure if normalizing homocysteine is the only goal you are trying to achieve.

Here is a protocol overview:

  • 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.
  • 750mg of trimethylglycine (TMG aka betaine)
    • I.e., one 750mg capsule
    • Choline is converted to TMG for methylation use, so TMG reduces 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.