Histamine Intolerance – Signs, Symptoms & Treatment Options

Histatime-Boardby Jill Carnahan, MD, ABFM, ABIHM, IFMCP

Histamine primarily lurks in aged, cured, fermented, cultured, and spoiled foods. From a survival perspective, it is imperative that humans have avoided rotting flesh. When animals die, bacteria from the gastrointestinal tract leaks out and starts digesting proteins. Some of the amino acids from the proteins are converted by bacterial enzymes to bioactive amines, the chief of which is histamine (formed from amino acid histamine).

At low levels, histamine increases stomach acid, which helps kill off any bacteria we may be exposed to. However, at high levels, histamine may trigger nausea, diarrhea, heart palpitations and dilation of blood vessels may cause a severe headache.


The Anatomy of a Histamine Reaction

Within minutes a person exposed to histamine may experience:
  • Flushing of face
  • Nausea
  • Headache
  • Runny nose or congestion
  • Dizziness
  • Racing heart
  • Anxiety
If the reaction continues, these symptoms may occur:
  • Hives
  • Generalized swelling
  • Abdominal cramps
  • Diarrhea
And in severe cases, there may be:
  • Panic attacks
  • Blurred vision
  • Bronchoconstriction, asthma or difficulty breathing
  • Laryngeal edema or swelling of tongue


Biogenic Amines… Histamine is One of Them!

A biogenic amine is a potent signaling molecule made from an amino acid. Histamine, for example, is made from the common amino acid histidine (amino acids are what proteins are made of). Meat and fish are rich in protein, so they are chock full of amino acids.

Here is a list of the most common biogenic amines and the amino acids they are made from.

  • Arginine—Agmatine, Putrescine, Spermine, Spermidine
  • Histidine—Histamine
  • Lysine—Cadaverine
  • Ornithine—Putrescine, Spermine, Spermidine
  • Phenylalanine—Phenylethylamine
  • Tryptophan—Tryptamine, Serotonin
  • Tyrosine–Tyramine

Many species of bacteria and yeast contain the enzyme histidine decarboxylase (HDC), which turns histidine into histamine or other biogenic amines into their active form. When meat or fish is not immediately consumed or frozen, bacteria get straight to work breaking down the amino acids within it, and one of the by-products is histamine.

For those who are sensitive to histamines, it is essential to eat meat/fish fresh or confirm that it was frozen quickly. Seems simple enough, right? But wait, there’s more. Many people go out of their way to ferment foods on purpose! We add bacteria to milk to make cheese and yogurt. We add yeast to grapes to make wine. We add bacteria to meat to make salami. In the process, these fresh foods—milk, grapes, and meat—which in their fresh forms are essentially histamine-free, become very high in histamine and other biogenic amines.

Not a problem… unless you have histamine intolerance!

Histamine intolerance is the intolerance towards “normal” levels of histamine in food caused by a decreased activity of the histamine-degrading enzymes diamine oxidase (DAO) or histamine N-methyltransferase (HNMT). In the gut the main enzyme is DAO while in other parts of the body like the skin and brain the enzyme HNMT degrades histamine.

Pseudo-Allergy from Histamine Toxicity

Dietary biogenic amines are not limited to rotten meat and spoiled fish. They are present in aged cheese, red wine and chocolate, which are all common migraine triggers. The meat we consume is not the only problem with bacteria; we all have a myriad of microbes living in our guts. When these populations become imbalanced as in the case of bacterial overgrowth, like SIBO (small intestinal bacterial overgrowth) or yeast overgrowth, the microbes in our gut can also contribute to producing too much histamine as well. Many people who suffer from histamine intolerance have either deficiencies in DAO enzyme production (which breaks down histamine) or excess of bacteria and yeast that have become histamine production factories in the gut.

What Exactly is Histamine Intolerance?

In a 2007 review article we read that histamine intolerance affects at least 1% of the population, and 80% of those affected are middle-aged. The term “histamine intolerance” was introduced as a common denominator for symptoms such as abdominal pain, flatulence, diarrhoea, headache, itching, swelling of the eyes,  hives, runny nose, painful periods, difficulty breathing, racing heart, palpitations and low blood pressure occurring after the consumption of histamine-rich foods,” according to article written in 2011 by Komericki.

Histamine intolerance may be caused by abnormally low levels of DAO. DAO is found, among other places, in the membranes of cells lining the small intestine and the upper portion of the colon, therefore people with damaged gastrointestinal systems seem to be at higher risk for histamine intolerance.

Women are more commonly affected than men by histamine intolerance. This may be because estrogen and histamine reinforce each other—histamine can increase estrogen levels and vice versa, which may explain why histamine intolerance is associated with pre-menstrual cramps and menstrual migraine and even uterine fibroids. Pregnant women may experience relief from food sensitivities during pregnancy because the placenta secretes very high amounts of diamine oxidase, or DAO, the enzyme that destroys histamine.

So What Causes Histamine Intolerance?  

Common causes include:
  • Inflammatory bowel diseases (or anything that causes damage to the enterocytes -the cells that line the gut)
  • Celiac disease
  • Intestinal dysbiosis
  • Small Intestinal Bacterial Overgrowth (SIBO)
  • Parasitic infections, like Giardia
  • Leaky gut or increase in intestinal permeability
  • Alcohol or other DAO inhibitors
  • Excess biogenic amines in diet
  • Medications that increase histamine
  • Food allergies
  • Genetic polymorphisms, like MTHFR and others that lower DAO, MAO, ALDH
  • Vitamin cofactor deficiencies – enzymes, like DAO and MAO rely on vitamin co-factors and deficiencies these can also cause abnormal enzyme activity

Working With Histamine Intolerance – Helpful Tips:

  • First treat any intestinal dysbiosis (imbalance of the gut microbes) – these could involve any of the following:
    • Fungal dysbiosis
    • Small intestinal bacterial overgrowth (SIBO)
    • Bacterial infections
    • Parasitic infections
    • Lack of healthy probiotic bacteria
  • Try natural antihistamines
    • Ascorbic Acid  1000-5000mg daily – helps degrade histamine
    • Vitamin B6 50-100mg daily – important for synthesis of DAO enzyme
    • Quercetin – 3-6grams daily (powdered works best) – natural antihistamine/mast cell stabilizer
  • Increase the activity of enzyme DAO
    • Try taking DAO enzyme, Histame with meals
  • Decrease histamine input
    • Avoid alcoholic beverages
    • Avoid raw and cured sausage products such as salami.
    • Avoid processed fish products. Use freshly caught fish and seafood instead.
    • Avoid pickles
    • Avoid citrus fruits.
    • Avoid chocolate
    • Avoid nuts
    • Avoid products made with yeast and yeast extracts
    • Avoid soy sauce and fermented soy products
    • Avoid black tea and green tea
    • Avoid energy drinks and coffee
    • Avoid matured cheese (hard cheese). Use cream cheese, mild cheese and cottage cheese instead.
    • Avoid spinach in large quantities
    • Avoid tomatoes, ketchup and tomato sauces
    • Avoid artificial food colorings & preservatives
    • Avoid certain spices: Cinnamon, Chili powder, Cloves, Anise, Nutmeg, Curry powder, Cayenne
  • Try medications that block histamine
    • H1 blockers, like loratadine
    • H2 blockers, like ranitidine
    • Cromolyn sodium
References & resources





Jill-color-4-finalAbout Jill Carnahan, MD, ABFM, ABIHM, IFMCP

Dr. Jill Carnahan emphasizes an integrative holistic approach to wellness using both conventional medicine and evidence-based complementary therapies, taking into account the whole person (body, mind, and spirit), including all aspects of lifestyle. She emphasizes the therapeutic relationship between physician and patient and seeks to give her patients a full range of healing options with an emphasis on healthy living, nutrition, and disease prevention.



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