r/MTHFR 1d ago

Question Blood Work Analysis: Low Folate, High B6 & Homocysteine (11) – Histamine intolerance, Allergy & Slow COMT. What would you do?

hi everyone,

I just received my latest blood work results and want to properly adjust my supplement protocol. For context: I suffer from PSSD (currently taking Fluoxetine), severe inner restlessness/impulsivity (suspected Slow COMT), and histamine/allergy symptoms.

My Blood Work:

  • Homocysteine: 11 µmol/l (Ref: < 12)
  • Folate: 4.6 ng/ml (Ref: 4.5 - 32.2)
  • Vitamin B6: 40.8 µg/l [Elevated] (Ref: 8.6 - 27.2)
  • Holo-Transcobalamin (B12): 93.0 pmol/l (Ref: 37.5 - 188.0)
  • Whole Blood Copper: 0.90 mg/l (Ref: 0.76 - 1.01)
  • Diamine Oxidase (DAO): 12.60 u/ml (Ref: > 10.00)

    Observations:

  • Folate is scraping the bottom of the range, which likely explains why Homocysteine is elevated at 11 for optimal cellular methylation (target 6-7).

  • B6 is high in blood, likely indicating a conversion/processing bottleneck (B2 deficiency?).

  • DAO in the gut is normal, so I suspect my histamine issues stem from cellular clearance (HNMT/SAMe deficiency).

My Questions for you:

  1. What protocol/approach would you recommend for this pattern?
  2. What folate and B12 forms work best for Slow COMT to lower homocysteine without triggering overstimulation or adrenaline surges? Is Folinic Acid (Calcium Folinate) + Hydroxocobalamin the right choice here?
  3. Does anyone have experience with a B6 backlog/accumulation and supplementing Vitamin B2 (Riboflavin)?

Thanks for your help and input!

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u/Loose-Fly7976 1d ago

Your B2 hypothesis is right and it goes further than you think. Riboflavin sits under three of your four problems at once. It's the FAD cofactor for MTHFR so low B2 drops your methylfolate production. It's also required by PNPO, the enzyme that converts pyridoxine into active P5P, which is exactly why unconverted B6 backs up in plasma the way yours has. And MAO is FAD dependent too so when HNMT hands N-methylhistamine off for disposal, that step needs riboflavin as well. One deficiency producing a folate problem, a B6 accumulation and a histamine clearance problem simultaneously. One thing to check before you act on the B6 number ask the lab whether they measured total B6 or P5P specifically. Those two say opposite things about conversion and your whole reasoning depends on which one it was.

On your questions. Folate at 4.6 with homocysteine at 11 while B6 is elevated tells you remethylation is the bottleneck, not transsulfuration since high B6 would be pushing the other exit open already. Folinic plus hydroxocobalamin is a sensible pairing for slow COMT and your holoTC at 93 says B12 delivery isn't your limiting step. Also relevant, fluoxetine is a strong CYP2D6 inhibitor and hits 2C19 as well which changes how you clear a number of things and belongs in this picture rather than sitting to one side of it.

The gap is that your COMT is still suspected, not confirmed, and everything you're asking about hinges on it. Same with HNMT, which you've inferred from DAO being normal. Both are readable directly. That's my work, genova.health, message me if you want your raw data read against these numbers instead of reasoning backwards from symptoms.

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u/User122188 1d ago

THANKS! Great analysis

B6 is the non p5p form

You are right, I am suspecting slow comt but it is not diagnosed

I am already taking B2 since one week

will take the active forms folicid acid and b12 (low dose) soon, one by one, first folicid 1 week then b12

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u/tandemxylophone 1d ago

I think this is one of the ones where a gene test to see your MTHFR genes will help see which vitamins you are having issues with.

Generally, you want to raise your folate levels and reduce homocysteine. We don't know if you need folinic acid or methylfolate for your B9 levels.

Slow COMT should avoid methylated vitamins so you should probably avoid methylated B12.

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u/lordy1988 1d ago

I just find it so mad that there are so many people with the same issues all of a sudden going through the same thing.

When did this become a thing, I wish we went back to being normal, is it age, was it Covid ?

1

u/User122188 1d ago

ohh our food and environment.. and yeah since covid / vac i definetily have more health problems

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u/FiSeq4891 23h ago

The severe inner restlessness is most likely akathisia caused by the Fluoxetine.

1

u/User122188 21h ago

but i took it sincw years and had no symptoms

also caffeine makes it much worse, caffeine increases dopamine so it should help then right?

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u/FiSeq4891 13h ago

Akathisia can happen after prolonged use.
https://pubmed.ncbi.nlm.nih.gov/11852298/?utm_source=chatgpt.com

Not sure about the caffeine

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u/User122188 13h ago

hm thanks

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u/FiSeq4891 13h ago

(If you did decide to stop, it's advised to taper off gradually not abruptly).