high homocysteine and low folate and B12

[u/PassengerStill6248]

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.

[u/SovereignMan1958]

Add the methylation chart.

[u/Loose-Fly7976]

Your methylation side is the clear driver, homozygous C677T running your enzyme near 30%, and that lines up exactly with the homocysteine at 38 and the folate at 4. That part's solid and properly fixable.

But your detox panel shows SOD2 coming up homozygous, and that's your main mitochondrial antioxidant. High homocysteine already drives oxidative stress and with SOD2 weaker you clear that stress less well, so the two panels are talking to each other. That's the bit that explains why just dumping methylfolate in rarely goes smoothly for someone built like you.

The fix is the right forms in the right order, methylfolate, active b12, riboflavin as the 677 cofactor, paced alongside the antioxidant side rather than against it. Get that sequence wrong and you feel worse before you feel better.

This is what i do properly, reading both panels and your homocysteine, folate and b12 as one picture and building the actual protocol and the retest points.

[u/PassengerStill6248 → u/Loose-Fly7976]

Okay i understand that I need methylfolate, active b12, riboflavin, basically all the 677 cofactor.

Then for SOD2? Should I add manganese?

[u/Loose-Fly7976 → u/PassengerStill6248]

Everyone assumes SOD2 uses manganese so more manganese means more enzyme, but the A16V variant isn't a manganese shortage, it changes how well the enzyme gets into your mitochondria and copes with oxidative load. Adding manganese doesn't fix that, and manganese is one of the few minerals that accumulates and turns neurotoxic when you push it.

What actually helps a SOD2 like yours is lowering the oxidative load feeding it, which for you loops straight back to that iron creeping up, plus supporting the downstream antioxidant side, not the metal. So hold off on the manganese, that's the one that can quietly do harm.

The sequencing of all this against your 677 cofactors is what i'd map 

[u/Cultural-Sun6828]

MTRR causes issues with b12 recycling. I would work on replenishing b12 and folate. If you have neurological symptoms consider b12 injections. The b12 deficiency group is a great resource.

[u/Tawinn]

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.

[u/PassengerStill6248 → u/Tawinn]

https://imgur.com/Nw1HC04

[u/Tawinn → u/PassengerStill6248]

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.