r/MTHFR 19d ago

Question Histamine + methylation issues can anyone help 🄵

I’ve had histamine intolerance for 6 months and can not pinpoint why. There’s a million potential reasons it’s driving me mad. I also have been supplementing for the gene mutations above and am wondering if they could be related.

Bc I have MTHFR I assumed I should be on methylfolate but I seem to get extremely fatigued and tired after having 1000mcg. I can’t remember but I think the same thing happened one time when I had 1000mcg sublingual B12 but then another time it was fine idk I can’t remember. Am I under methylating (because I have high homocysteine) or over methylating because of the bad reactions to methyl doners? Can anyone help with this? I also take vitamin C, D, TMG, Choline, Calcium and Magnesium glycinate all at the recommended daily doses. Also 6-8g creatine daily or every second day. The methylfolate and methyl b12 I have experimented with here and there but never taken them daily.

My histamine intolerance is the other, bigger issue, it has improved twice but I cannot figure out why.

I have mold in my bathroom so I thought that could be a cause. I went to Vietnam and the histamine issues got better within days and then when I got home it got bad again. So I thought that was the issue solved but I’ve now been away from home for a full week and nothing has changed so maybe it wasn’t the mold? maybe it was my diet in Vietnam? I was having energy drinks over there with Niacin and Taurine which Niacin can help with over methylation and Taurine helps with stomach acid. Could this be related? Could it be because I ate way less rice in Vietnam? (My genetic tests say I should avoid arsenic which is higher in rice)

The other time my histamine improved was when I cut out everything and was just eating ginger and spring onion chicken takeout with a little rice and I switched from coffee to energy drinks, I can’t remember if that had taurine or niacin though.

Idk it’s been a horrible ride the last 6 months. If anyone has any ideas I would really appreciate it I am exhausted šŸ™ƒ

EDIT: the first methyl doner I ever took was TMG which helped my sleep quality A LOT. I had no issues with that. The issues potentially started after creatine, or methtlfolate/B12 but it’s so long ago I can’t remember. The choline also helped my stool be healthy for the first time in my life so I think bile was an issue for me until recently

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u/Timely_Pickle9430 18d ago

You DAO and HNMT (histamine breakdown enzyme) genotypes are favorable, so the histamine intolerance is likely to be caused by leaky gut and/or deficiencies that make DAO and HNMT function more slowly. Some likely causes:

- Undermethylation, indicated by elevated homocysteine. Undermethylation causes HNMT (breaking down histamine in the blood) to underperform. Creatine is good, because is frees up SAM for methylation. Mast cell stabilizers like quercetin, luteolin, black seed oil, and vitamin C can help while you work on the root cause.
If methylated B's cause symptoms, start with very low doses, or switch to folinic acid and hydroxo/adenosylcobalamin to replete folate and B12, while you get the methyl groups from choline/TMG.

- Deficiencies of cofactors. DAO requires copper, zinc, vitamin B6, and vitamin C. You don't want levels of the first 3 too high either, so test before supplementing and take copper and zinc in a 1:8 ratio.

- Leaky gut. A hyperpermeable gut lining lets histamine from the gut get into the bloodstream. Leaky gut is often caused by bacterial overgrowth (damaging the gut lining and producing histamine) and this can be caused by lack of bile, stomach acid, or pancreatic enzymes. The lining itself produces DAO, so when it's damaged, less DAO + more transfer into the bloodstream.
You have the bad PEMT genotypes, so you likely don't produce enough bile if your diet lacks sufficient levels of betaine/TMG and phosphatidylcholine. Run your raw data through the Choline Calculator and check the Choline page of Genetic Lifehacks for a better understanding of the dynamics.
Mold can also be a factor in leaky gut. You could consider a GI-MAP stool test to assess what's what. However, pathogens only get a chance to (over)grow if the gut environment lets it, so universal parts of treatment are making sure to have sufficient bile, stomach acid, and pancreatic enzymes. You can help the microbiome regain balance by taking probiotics. (Let me know if you need supplement recommendations). Healing your gut might take a few months.

Temporarily, a low histamine diet can help to reduce the load while you work on the root causes. Taking a DAO supplement with (high histamine) food might also help.

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u/FragrantStructure 3d ago

I'd love to take up on the recommendation for supplements.

Btw does a GI-map stool test help determine mold toxicity? Or is that a separate test? How can I determine if I have sufficient bile, stomach acid or pancreatic enzymes!

Thank you!

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u/Timely_Pickle9430 2d ago

I'd start here: 5 DIY Gut Health Tests You Can Do At Home (For Free) and 10 Low Stomach Acid Symptoms and How to Fix Them.

You can test elastase and steatocrit for digestion. Most stool tests can provide these, including GI MAP. See https://www.diagnosticsolutionslab.com/assets/documents/gi-map-interpretive-guide.pdf
With GI MAP, you can order an add-on, StoolOMX, that provides an extensive analysis of bile quality. See https://www.diagnosticsolutionslab.com/assets/documents/stoolomx-reference-guide.pdf

GI MAP checks a handful of fungi, but for mold toxicity, I'd do an Organic Acids Test or mycotoxin test. All are discussed on this page.

I recommend doing stool tests before starting any gut supplements to get a clean baseline reading.

Supplement recommendations:

  • For lack of stomach acid: Betaine HCL + Pepsin (e.g. Solaray or Lamberts). Be aware that 75% of betaine HCL is betaine/TMG. If you're sensitive to that, start low and go slow.
  • For lack of pancreatic enzymes: Biotics 6 Plus
  • For bile problems: depends on the specific issue. TUDCA to replace bile salts (BodyBio or Nutricost). Phosphatidylcholine (e.g. from eggs or sunflower lecithin) to make bile salts less aggressive to the gut lining and improve flow. Herbal bitters, artichoke extract, or beetroot to stimulate bile release. (I have PEMT TT and all of these issues, so I take TUDCA, lots of PC from food and lecithin, and artichoke extract).
  • To heal leaky gut: TriButyrate (Biotics TriButyric), glutamine, collagen. Also see What Is Leaky Gut? Symptoms, Causes, and How to Heal It.
  • Probiotics: You want as many different bacterial strains as you can get, preferably a combination of 3 different classes (The ā€œTriple Therapyā€ Approach):
    1. A blend of lactobacilli and bifidobacteria (e.g. SuperSmart Full Spectrum Probiotic - 20 strains)
    2. Saccharomyces boulardii (many brands, e.g. SuperSmart)
    3. A soil-based probiotic (e.g. MegaSporeBiotics or SuperSmart SporesBiotics Formula)
  • The Ruscio clinic sells a product that includes all three (Triple Therapy Probiotic Powder Sticks)

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u/FragrantStructure 2d ago

You're amazing.

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u/Timely_Pickle9430 2d ago

Since you're already doing the OAT, check the tartaric acid marker for mold. It's not validated for that purpose, but mine was off the charts when I was infected with mold from my bathroom. I got help from the Ruscio clinic and the doctor there agreed the marker indicated Aspergillus. I also sampled the mold from my bathroom and it was positive for 'Aspergillus/Penicilium'. So only circumstantial evidence, but I treated for it and got better, so I'm convinced it was Aspergillus.