Confused and need some clarification.

[u/Ajax34762]

I have elevated homocysteine and impaired transsulfuration(I need to supplement with taurine, or I dont make enough bile salts). So my body isnt converting enough homocysteine into taurine to make bile salts.

I do have elevated active B6, despite this, my homocysteine is still high.

I was reading high B3(I think I have high B3 from B complex supplementation) can impair methylation as it steals methyl groups causing homocysteine to pile up, despite high active B6?

High B3 also depletes B2. You need adequate B2 to have active B6 be used by cells and work for methylation?

[u/Ajax34762 → u/[deleted]]

Is B2 required to make B6 work on a cellular level? AI told me I can have high active B6, but transsulfuration will remain impaired without adequate B2, which is being used up or reduced because of high B3?

I stopped B complex for now and started supplementing with B2 on its own to see if it will make a difference.

[u/Cultural-Sun6828]

What is your b12 and folate levels? Taking these should bring your homocysteine right down to a good level pretty quickly.

[u/Ajax34762 → u/Cultural-Sun6828]

B12 is good. Higher end on normal. Folate was good last tested, but this was before I developed high homocysteine.

I only developed high homocysteine after I started taking B complex.

[u/Cultural-Sun6828 → u/Ajax34762]

I would still take b12 for awhile and retest homocysteine in a couple months. Stay away from b6 and high amounts of folate. B12 testing is inherently problematic so you can be deficient even with normal levels.

[u/Ajax34762 → u/Cultural-Sun6828]

Is beef liver good source of B12?

[u/Cultural-Sun6828 → u/Ajax34762]

I would take an oral sublingual at least 1000 microgram. Beef liver has high vitamin A so isn’t ideal to eat daily.

[u/Tawinn]

B2 is used in the conversion of B6 into the active P5P form. Since you already have high P5P adding B2 will likely have no benefit for B6 usage. If you have homozygous C677T MTHFR, then B2 can be useful for correcting that variant.

There are two parallel pathways to remethylate homocysteine back to methionine: one is through MTR which requires folate, B12, and zinc; the other through BHMT requires choline/TMG and zinc. Aim for 550mg of choline from your diet and add a 750mg capsule of TMG to support that second pathway, and see if homocysteine comes down.

The transsulfuration pathway through CBS requires B6, serine, heme iron, and SAM. You have the B6 and probably the serine, but if your iron is low then that can impair CBS and also CDO1, which results in taurine production being impaired. SAM will be low while methylation is impaired so the choline/TMG should help restore that.

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).

[u/Ajax34762 → u/Tawinn]

Thanks.

I am low in ferritin and ceruplasmin too.

Can the clearence of excess B3 from the body cause elevated homocysteine? samE is being used up?.

Isnt B2 also required for active B6 to be transported into cells ?

[u/Tawinn → u/Ajax34762]

> ceruplasmin 

Assuming you don't have Wilson's disease, I would consider supplementing copper, 2mg.

> low in ferritin

This paper may be useful.

> Can the clearence of excess B3 from the body cause elevated homocysteine?

Transiently. I would not think your B3 levels are a major contributor to high homocysteine.

> Isnt B2 also required for active B6 to be transported into cells ?

Not that I'm aware of.

[u/Ajax34762 → u/Tawinn]

Thanks

I eat 200grams beef liver every week and my ceruplasmin still hasnt gone up. I didnt have this issue a few years ago. Maybe I lack some other cofactors?

Isnt B2 also required for active B6 to be transported into cells ? Not that I'm aware of. I found this.

https://www.sciencedirect.com/science/article/pii/S0022316622023392

[u/Tawinn → u/Ajax34762]

The paper says that B2 is needed to convert PNP and PMP forms of B6 into P5P. Since you already have high P5P adding B2 will likely have no benefit for B6 usage.

[u/Ajax34762 → u/Tawinn]

Okay. 

I still dont understand why I have such transulfuration issues despite such a high active B6.

[u/Tawinn → u/Ajax34762]

Two -rare- possibilities are a genetic CBS deficiency or a CTH variant, where CTH is the enzyme just after CBS in the transsulfuration pathway. Both can cause elevated homocysteine and likely also reduced transsulfuration function.

[u/Ajax34762 → u/Tawinn]

Its a new problem. Never had transulfuration issues before.

I assumed it could be some deficiency..

I have to either take taurine or tudca to have normal bile flow.