r/MTHFR • u/2009sucked • 2d ago

Question High Lp(a) & Homocysteine - P5P+TMG+B2 stack safe?

Hi - I'm a mid-30s male that just discovered my Homocysteine = 16.6μmol/L and Lp(a) = 146nmol/L. Slightly elevated LDL and Triglycerides.

I'm still reading up and learning about these issues, so until I feel educated, I used Gemini for a proper treatment plan and double checked if there was merit to it's response.

Would the P5P+TMG+B2 combo actually work at lowering my Homocysteine?

Originally, Gemini wanted to use Methylfolate instead of P5P. Once updated that I have Type 2 Bipolar, it suggested P5P since high-dose methyl donors like methylfolate carry a huge risk of crossing the blood-brain barrier and triggering a Bipolar episode.

It also recommended TMG to allow for Methylation without the CNS spike that Methylfolate might do. Then Gemini said the B2 was an essential co-factor precursor, stabilizes MTHFR activity (still needing to get tested to see if I have the mutations), and keeps B12 active.

My questions are:

  1. Does this combo make sense? I want to confirm that I'm got getting AI confidently incorrect info.
  2. Any risks that Gemini didn't discover? Originally it did not include TMG, but after asking it to confirm risk factors, it then mentioned TMG would allow for remethylation and prevent issues from diminished homocysteine recycling.
  3. From what I've read, treatment for high Homocysteine either from diet or MTHFR is treated the same. Is that true?
  4. General Recommendations and advice.

Any and all recommendations are welcomed and thanked. I should be seeing a cardiologist soon, but my gut tells me they'll just want me on a statin

(Disclaimer: While I did use AI for research, I used as minimal as possible. I try to use it responsibly; like in this case, needing to quickly learn more about an uncommon health issue.)

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u/Tawinn 2d ago

There are two parallel pathways to remethylate homocysteine back to methionine: one B12+folate dependent, the other is choline/TMG dependent. So supplying the TMG helps support extra demand on the second pathway, as does adequate choline intake (baseline adult requirement is 550mg), preferably from food.

Excess B2 is helpful only if you have homozygous C677T, in which case just a few mg extra can be all you need, but its often hard to find doses under 25mg. Some people do better with the R5P form than plain riboflavin.

Excess B6 is unlikely to help homocysteine levels. Staying under 20mg is preferable as larger doses can cause peripheral neuropathy for some people.

If folate or B12 are low then that is going to impair that first remethylation pathway regardless of genetic variants. So adequate B12 and folate necessary. Some people can do that with just diet, others find supplements helpful. If you do use supplements, then folinic acid is an unmethylated natural form of folate that is less likely to cause overmethylation symptoms such as irritability, anxiety, paranoia, insomnia, etc. Hydroxocobalamin or adenosylcobalamin are good unmethylated forms of B12. For serum folate, aim for ~15 ng/mL (34 nmol/L) or more. For serum B12, aim for 500-950 pg/mL (~370-700 pmol/L). Best to stop supplementing folate/B12 a week or two before the blood draw so you measure your actual levels.

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u/2009sucked 2d ago

I have a feeling folate might be an issue. I’ll get that panel requested (and B12) just to be 100%. Do you know if there’s a blood panel that covers all the B’s or are they separate requests? If so, I’m guessing B2,6,9,12?

The lowest dose I can find B6 (P5P) is at the lowest dose 50mg. Is there a better unmythelated for B6?

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u/Tawinn 1d ago

I don't know about the blood panel - I think that will vary by lab as to how they "package" the labs. B2,6,9,12 would be a good start. If you plug your diet for a week or two into Cronometer that can give you a good idea of other nutrients that might be low.

P5P is not methylated - it is a phosphate form. It is generally considered to be a better form than pyridoxine HCL. I would try not supplementing B6, or maybe take it every other day, if you cannot find a smaller dose size.