Effectively Treat Histamine Intolerance

The Reason Why You May Have New Allergies 

Histamine intolerance comes from an imbalance of eaten/produced histamine and ability to break it downR

Mast cells, food poisoning, histamine metabolism/liberators and more can exacerbate histamine intolerance.



Most people with histamine intolerance will appear to have allergic reactions to everything, especially foods high in histamine

Allergic-like symptoms from histamine can vary and may include:

  • Itchiness (of eyes, skin, throat)
  • Nausea
  • Diarrhea
  • Headaches
  • Insomnia
  • Anxiety
  • Vertigo
  • Vomiting
  • Runny nose
  • Coughing
  • Sneezing

Histamine plays a role in:

  • Mastocytosis R
  • Mast cell activation disorder (MCAD)
  • Allergic reactions (and food allergies) R R
  • Anapylaxis R
  • Arthritis (in psoriasis and rheumatoid arthritis) R
  • Inflammatory conditions R
  • Skin Disorders (like psoriasis, eczema, vitiligo, etc) R R R
  • Gastric secretion and appetite R
  • Regulating the sleep-wake cycle R R
  • Learning and memory R R
  • Motor system R R
  • Muscle contraction R
  • Neurological Disorders R
  • Cancer Progression R

Click here for the benefits and negatives to histamine.



Dysbiosis, or an imbalance of the gut bacteria, can cause problems with histamine

Inflammasomes are sensors that regulate the gut.

When their message gets scrambled or their communication gets damaged, bacterial overgrowth can happen.

One example of communication scrambling is with inflammation, and it hijacks the communication of the bacteria, SIgA, and mast cells.

If there is an overgrowth of histamine producing bacteria, then you have excess histamine.

Mast Cells


Mast cells are located all over the body and release all sorts of molecules including histamineR

Stress (corticotropin-releasing hormone or CRH) can cause mast cells to degranulate producing excess histamine. R

CRH along with IL-6, IL-8 and other inflammatory cytokines can increase blood brain barrier's (BBB) permeability. R

Lectins (like ConA) can activate mast cells, since they make the gut leakier (easily getting into the blood stream) and exacerbate histamine intolerance and giving you a IgE like response. R R R R

Leptin and leptin receptors are found in human mast cells (in skin lungs, gut, urogenital tract).

Leptin, which makes you feel full after eating, can be inflammatory by possibly activating mast cells. R R R R

Ghrelin, which makes you feel hungry, can also activate mast cells. R

Nerve growth factor (NGF), unlike BDNF, CNTF, and GDNFcan activate of mast cells. R

It stimulates histamine release and sensitizes transient receptor potential V1 (TrpV1). R

Estrogen stimulates mast cells to make more histamine. R

Substance P induces release of histamine via binding to NKR on mast cells. R

VIP, neurotensin and secretin also stimulate histamine release. R

Somatostatin stimulates histamine release from human mast cells. R 

Food Poisoning

Histamine fish poisoning is caused by histamine-producing bacteria. R

For example, when you eat fish, it usually takes a couple hours or days before it reaches your plate and you eat it. R

This allows enough time for bacteria to grow and produce histamine, while degrading the meat producing extra histidine. R

Metabolism Of Histamine




Diamine oxidase (DAO) and n-methyltransferase (HMT) are two enzymes that breakdown histamine. R

DAO (which is dependent on P5P) breaks down histamine into histadine. R

Histamine is usually excreted via urine and metabolites (such as n-methylhistamine). R

Histamine-Releasing Factor

Histamine-releasing factor (HRF), or B cell growth factor, can stimulate histamine release and IL-4 and IL-13 production from IgE-sensitized basophils and mast cells. R

It can also stimulate secretion of IL-8 and inhibit cytokine gene expression of T cells.  R

This makes the body shift towards a TH2 dominant immune reaction. R


Biomarkers And Tests

Common biomarkers:

  • Alpha-MSH (to make sure it's histamine and not overactive a-MSH levels since MSH can cause flushing) R
  • N-Methylhistamine R
  • Tryptase R
  • Neurotensin R
  • Estrogen
  • Progesterone
  • Complement C4a R
  • TGF-b1 R
  • IL-6 R
  • IL-8 (this chemokine causes release of histamine attracting neutrophils) R R
  • Leptin R

You can order these tests here.

Protocol To Treat High Histamine

1. Eat a Low Histamine Diet

Avoid all these:

  • Fish, Shellfish, and other seafood (crustaceans too, fish oil capsules are fineR
  • Leftover Meats (including long-cooking, cured, crockpot cooking, bone broth, collagen, etc) R
  • Cheese R
  • Sausage R
  • Soy R
  • Nightshades (like tomatoes, potatoes, etc) R
  • Legumes R
  • Citrus R
  • Papaya R
  • Strawberries R
  • Pineapple R
  • Nuts R
  • Peanuts R
  • Spinach R
  • Alcohol R
  • Coffee R
  • Chocolate R
  • Additives R
  • Licorice R
  • Spices R
  • Red Wine Vinegar R
  • Fermented foods (lactic acid producing bacteria produce biogenic amines) R R
  • Carnosine R
  • Cimetidine R
  • Imidazoles - such as caffeine (promoting glutamate release in hypothalamus), nicotine, and theobromine R R
  • Turmeric (curcumin) R
  • Yeast R
  • Casein
  • Gluten R
  • Lectins R R R R

Essentially, eat very fresh.

2. Increase Enzymes to Break Down Histamine

DAO is the main enzyme that helps break down histamine in the gut.  R

Increase DAO:

  • Chronic high doses of vitamin C (liposomal/IV maybe? - if you have h. pylori, it will inhibit the absorption of vitamin C) R R
  • DAO Enzymes R
  • P5P (but can also increase histidine decarboxylase) R
  • Heparin R
  • Progesterone (to balance estrogen if it is high)

Inhibiting histidine decarboxylase (HDC) will help break down histamine faster, since it is the enzyme that converts histidine into histamine (from strongest to weakest):

Stay away from:

3. Stabilize Mast Cells

High corticotropin-releasing hormone (CRH) can degranulate mast cells, increasing histamine, even though coritsol inhibits histamine release. R R

So it's probably best to avoid stress.

Here are all the ways to stabilize mast cells. I take Brain Gain.

This bold list are probably the best mast cell stabilizers that work on histamine:

4. Lower Blood Histamine

I take BH4 to lower histamine levels and to supplement for my a1298c methylation problem.

These will all lower blood histamine:

Also, be weary of neurotransmitters substance P and vasoactive intestinal polypeptide (VIP), as they are potent histamine liberators. R

Histamine also increases estrogen, which causes a positive feedback loop to increase histamine from mast cells and decrease DAO production. R

5. Fix Dysbiosis

Check out here to effectivly fix dysbiosis.

In gram-positive bacteria, HDC activity is pyruvoyl-dependent, whereas in gram-negative bacteria and in animals, this is a P5P enzyme. R

Avoid histamine (and dysbiotic) producing bacteria:

  • Bacillus licheniformis A7 R
  • Bacillus coagulans SL5 R
  • Candida R
  • Citrobacter (koseri) R
  • Clostridium perfringens ATCC 13124 R
  • C. perfringens R
  • E. coli (certain types see below) R
  • Enterobacter R
  • Enterococcus faecalis CNRZ 238 R
  • H. pylori R
  • K. pneumoniae R
  • Lactobacillus 30a (ATCC 33222) (encoded by hdacA and hdcB) R
  • Lactobacillus buchneri ST2A R
  • Lactobacillus delbrueckii bulgaricus R
  • Lactobacillus casei (controversial) R
  • Lactobacillus hilgardii (IOEB 0006) R
  • Lactobacillus reuteri (may actually help long term, still doing research on this) R R R
  • Micrococcus sp. R
  • Morganella morganii R
  • Oenococcus oeni IOEB 9204 (formerly Leuconostoc oenos 9204) R
  • Proteus mirabilis R
  • Pseudomonas aeruginosa R
  • Raoultella planticola R
  • Raoultella ornithinolytica R
  • Staphylococcus R
  • S. thermophilus PRI60 R
  • Tetragenococcus muriaticus JCM 10006 R

It is also a good idea to add histamine degrading probiotics:

Probiotics without an impact on histamine:

  • K. oxytoca R
  • Lactobacillus acidophilus R
  • Lactobacillus lactis R
  • Lactobacillus plantarum R
  • Lactobacillus sakei CRL1862 R
  • Lactobacillus plantarum Tensia R
  • Lactococcus lactis R

*Please post in the comments if you know better places to get these probiotics.*

6. Other

  • Decrease Nerve Growth Factor (NGF can activate mast cells) R R R
  • Decrease IL-6 R
  • Decrease IL-8 R
  • Decrease Ghrelin R
  • Control Leptin R R R
  • Avoid fluoride R
  • Avoid birth control and other things that increase estrogen (like sugar)
  • ACE inhibitors (such as Aloe, Grape Seed Extract, Bromelain) R R R

Problems With OTC Anti-Histamines




There are four different histamine receptors, named H1R through H4R. R

H1R is involved in the allergic response, smooth and endothelial muscle contraction, and neurotranmission. R R

H2R is expressed in many immune cells, parietal cells and nerve cells. It is mostly targeted for gastric, neurological, and cancer therapies. R R

H3R regulates histamine production in the central nervous system (CNS), regulating neurotransmitters. R R

H4R is regulates the immune system in blood and the CNS. R

The problem with most over the counter anti-histamines is that they don't address all histamine receptors. R R R R

For example, benedryl (diphenhydramine) only works on the H1 receptor. R

Antihistaminics may contribute to cognitive impairment because they block the action of histamine, which is a neurotransmitter involved in cognition, memory, learning, and motivation. R

Blockade of the H1R or H2R may shift histamine to activating the H3R autoinhibitory receptors in the brain, further limiting histaminergic transmission. R




Technical R

  • All four receptors belong to class A family of G-protein coupled receptors (GPCRs).
  • H1R couples Gαq/11 proteins, leading to phospholipase C activation, production of inositol phosphate and calcium mobilization.
  • H1R is also expressed in nerve cells, vascular smooth and endothelial cells among others, and takes part in neurotransmission and cellular adhesion respectively.
  • H2R is expressed in many immune cell types, parietal cells and nerve cells.
  • H2R mediates its effects by coupling GαS proteins, stimulating adenylate cyclase and increasing intracellular cAMP levels.
  • H2R in regulates histamine synthesis and cytokine production in immune cells.
  • This prevents stem cells in the bone marrow from differentiating and can even induce stem cells to undergo apoptosis.
  • Due to its broad localization, antagonists of this receptor have been used for treating gastric and neurological disorders, as well as in antitumour therapy.
  • H3R, when located in the presynaptic membrane of histaminergic cells, regulates the production of Hia in the CNS.
  • H3R also regulates the release of many neurotransmitters, acting as a presynaptic heteroceptor.
  • H3R couples to Gαi/o proteins and inhibits cAMP accumulation.
  • It has been demonstrated that several active isoforms of this receptor exist in humans, although their function remain unknown.
  • H4R is expressed in certain immune cells of haematopoietic origin and in the CNS.
  • H4R couples to Gαi/o proteins and inhibits cAMP formation.
  • H4R has been recently targeted as a key component of the immune response as well as being responsible for the mobilization of immune cells.
  • Histamine's regulates both IL-6 production and mRNA expression in mice mast cells via H4R activation.

Ketotifen Fumarate is a H1 antagonist with little side effects. R



D-amino acid oxidase is an enzyme that breaks down histamine into histadine. R

Mutations in this gene are associated with:

  • Ulcerative Colitis R
  • Schizophrenia R
  • Migraines R
  • Sensitivity to NSAIDs R
  • Schizophrenia R
  • Bipolar Disorder R

rs10156191 - Each T allele means you have reduced DAO activity. R
rs1049742 - Each T allele means you have reduced DAO activity. R
rs2052129 R
rs2268999 (reduced activity)
rs2071514 (protective)
rs1049748 (protective)
rs2071517 (protective)


Histidine decarboxylase converts L-histidine to histamine (via P5P). R

HDC is expressed by mast cells and other immune cells, gastric enterochromaffin-like cells (ECLCs) and histaminergic neurons. R

Mutations in this gene are associated with:

  • Breast Cancer and Cancer Growth R R
  • Chronic Heart Failure R
  • Tourette Syndrome R
  • Bile Acid Secretion R
  • Atherosclerosis R
  • Scleroderma R
  • Rhinitis (TT allele of rs2073440)


Histamine N-methyltransferase regulates histamine methylation. R

SAM-e should help increase this gene as a methyl donor. R

Mutations in this gene are associated with:

  • Asthma R
  • Allergic Rhinitis R
  • Breast Cancer R
  • Bronchiolitis R
  • Pick's Disease R
  • Down Syndrome R
  • Intellectual disability R
  • Huntington's Disease R
  • Parkinson's disease R R
  • Better Outcome in Ischaemic Stroke R
  • Schizophrenia protection  R
  • Myasthenia gravis R
  • Anxiety R
  • Aspirin intolerant chronic urticaria R 
  • Alcoholism R

rs1050891 - AA will increase histamine and may worsen ADHD. R

Histamine Receptors


Histamine Transporters



Being heterozygous or homozygous for either C677T and/or A1298c will predispose you to further histamine problems.

Each allele for both mutations adds the burden for detoxing excess histamine.


The Vitamin D Receptor acts as a transcription factor and target for H1R (histamine 1 receptor). R

More Research

  • For mackerel, at 0 degrees C, neither histamine former nor histamine production was detected up to 14 days of storage. R
  • Mast Cell Activation Symptomatology (Part 1 of 3) V
  • How to Treat Histamine Intolerance and High Histamine Levels R
  • Histamine vs Tyramine producing bacteria in cheese. R