DAO, high histamine, thiamine

Unrecognized DAO Problems, High Histamine, and Low Thiamine

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I am a 33 year old female, who has always been very fit. I worked as a personal trainer for several years and I have always eaten well with very little processed food of any kind. I have been on a long, complex health journey that hit a crescendo this year. In January of 2026, after years of brain fog, anxiety, and depression, I found that I had genetically low diamine oxidase enzyme (DAO) function on a gene panel and went on a low histamine diet. I had previously been taking AG1 daily as my primary multivitamin because I seemed to tolerate it well initially, whereas I usually had over-methylation reactions to other active B complexes. When I went on the low histamine diet, I felt a massive and immediate improvement in my mood and cognitive function. It was such a huge improvement that I thought I had completely solved my health challenges and felt like a totally new person.

Untangling Reactions to Food and Supplements

Then, since there was much less ‘static’ in my system with my histamine bucket no longer overflowing, I found that I was having reactions to my multivitamin, AG1. I stopped taking it and did not replace it with any other B complex or multivitamin because I could not find one I tolerated well. A couple months later, I started taking high dose vitamin C to attempt to further stabilize my mast cells and at the same time I happened to be eating a lot of beef. For reference, I have one copy of the HFE gene variant that puts me at a slightly increased risk of hemochromatosis. I knew this at the time but didn’t realize that high doses of vitamin C can increase iron absorption by 4-5x. I ended up experiencing acute iron overload resulting in severe fatigue, full body muscle twitching, muscles aches, panic, and nerve pain in my arms and legs. I could no longer tolerate any exercise other than walking and felt like a shell of myself.

At the time of my labs, they also tested my zinc, copper, and ceruloplasmin. My copper came up on the low side of normal and my ceruloplasmin was slightly low at 19. For some reason, I became convinced that my symptoms were due partly to low copper and tried taking a copper supplement and eating high copper foods like liver. I then experienced extreme free copper symptoms that included severe psychiatric distress and significantly worsened muscle pain. After this episode, I had to go on an extremely restricted diet because even small amounts of copper in foods would cause intense insomnia and panic. I believe this was due to a hyperactive dopamine beta-hydroxylase (DBH) enzyme as a result of the high free copper.

For about two months I experienced a wide variety of symptoms, including chronic fatigue, severe muscle burning in my quads after almost any physical movement, even just standing to cook dinner, full body muscle twitching, nerve pain in my arms and legs, severe depression, insomnia, waking with panic, and brain fog. Even after my free copper levels dropped substantially after a couple months of a low copper diet, I only saw moderate improvement in my symptoms.

Food Sensitivities and Low Thiamine

I tried expanding my foods, but also found I was so severely sensitive to food-based folate such that even a bowl of romaine lettuce would send me spiraling into a severe crash and psychiatric distress. My food sensitivities were so severe that for weeks, I could only eat chicken, rice, zucchini, blueberries, and carrots.

I started working with a functional medicine practitioner who ordered an Organic Acids Test. The results showed major mitochondrial dysfunction. I had borderline high pyruvate and undetectable succinate levels, indicating a complete shut-down of the Citric Acid Cycle. I also had high formiminoglutamate, suggesting very poor methylation, and high benzoate suggesting poor Phase II liver clearance and/or gut dysbiosis.

Introducing Thiamine and Other B Vitamins

With the high pyruvate and low succinate, my practitioner and I deduced I was likely very low in B1 and B2. I tried starting with B2 at only 5mg but had huge crashes in my cognitive function with this. So I added in a microdose (1mg) of sublingual TPP (thiamine pyrophosphate) and 1mg of B2 diluted in water and measured with a liquid syringe. This actually did improve my function. My quads no longer burned so severely, my nerve pain decreased, and my energy improved. Importantly, I also tried this water dilution and microdose approach with several other B vitamins including B6, B5, and B12 but I could not tolerate any of these and had significant reactions to all of them. The reactions were essentially what you would expect to see with taking an extremely large dose of each, yet I took true microdoses of each, usually around 2mg. I also have not tried an isolated folate supplement since I was having bad reactions to even food based folate.

Some Improvement Then a Huge Crash

I stuck with the B1 and B2 microdoses and improved quite a bit. I was able to expand my foods slightly to include larger servings of romaine lettuce, whole milk, and a few fruits. My energy actually improved so much over that month that I attempted to return to weight lifting. However, after just one week of modified workouts, I had a huge crash resulting in air hunger, incomplete yawning, extremely cold hands and feet, chest pains for which I went to the ER. All tests came back normal. During this time, I also experienced fatigue, brain fog, severe anxiety, and noticed that my joints, which have never had problems with hypermobility, felt extremely loose and lax.

Where I Am Now and Putting It All Together

It has been a few weeks since that severe crash after the increase in exercise and I am still experiencing all of these symptoms, though the chest pain and cold hands and feet have improved. After doing further research, I learned that B1 is uniquely susceptible to oxidative damage and free iron and copper have devastating effects on it. I realized that this likely explains most of my symptoms. This would also explain my reactions to other isolated B vitamins since without thiamine and sufficient ATP, the cells can’t process other nutrients. This would explain why I have not tolerated other isolated B vitamins other than the B2 I am currently taking and why I am struggling to handle food based copper and iron since processing them in the liver requires significant ATP.

Per my functional provider’s recommendations, I have increased my sublingual TPP to 18mg per day over the last couple days. I have noticed a significant decrease in my anxiety and slight improvement in my brain fog but that is about it so far. I also realize that the research suggests sublingual TPP is not well absorbed. It does seem that my body is absorbing some since I have had an immediate and noticeable improvement of some symptoms. I do intend to try the Optimized Nutrition TTFD though but I am concerned about a paradoxical flare. I tend to be extremely sensitive to supplementation of any kind.

Also, an important note is that I did try thiamine HCL a couple months ago before I tried the TPP microdose. I took about 10mg of pure thiamine HCL powder from Bulk Supplements and had an unpleasant paradoxical flare. I felt extremely tired, brain foggy, and had full body nerve pain for about 24 hours. So, I intend to start extremely slowly with the TTFD.

Other Important Information

My current safe foods:

  • Chicken breast
  • White rice
  • Zucchini
  • Romaine
  • Carrot
  • Blueberries
  • Cooked apple
  • Cantaloupe
  • Celery
  • Butter lettuce
  • Corn
  • Dairy butter

Current supplements:

  • 18mg sublingual coenzymated TPP (Source Naturals)
  • 2mg water diluted B2 (R5P)
  • 270mg Magnesium (citrate/malate combo)
  • Zyrtec (anti-histamine)
  • 5mg Melatonin (before bed)
  • Electrolytes (LMNT and Dr. Berg’s)

Genetic variants:

  • One DAO SNP
  • Two MTRR SNP’s
  • One copy of MTHFR C667T
  • Two PEMT SNP’s
  • Two NOS3 SNP’s
  • One HFE SNP

Questions for the Community

  • What are your experiences with introducing TTFD? What dosage did you start with?
  • When you introduced B1, were you then better able to tolerate other B-vitamins and nutrients?
  • For people with a variety of B vitamin deficits, what order did you introduce them in?

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Photo by Thought Catalog on Unsplash

My name is Shannon, I am a graduate student in philosophy studying AI ethics and AI alignment. In my free time, I enjoy rock climbing with my husband and spending time with our two dogs.

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