Histamines (and DAO)

MCAS Aug 19, 2019

Mast cells that are overly activated will make and release more histamine but the activation comes before the histamine, not the other way around - so solving the histamine breakdown issues might solve only half, or none of your problem. You might break down histamine fine.

However, correcting deficiencies which worsen this breakdown, eating DAO rich foods, taking DAO supplements and eating a low-histamine diet is beneficial for many.

When histamine is formed, it is broken down by specific enzymes. In the central nervous system, it is metabolized by histamine N-methyltransferase (HNMT), while in the digestive tract it is broken down by diamine oxidase (DAO).

Diamine oxidase (DAO) is the major enzyme involved in histamine metabolism and is responsible for ensuring a steady histamine level required for the balance of numerous chemical reactions taking place in the body.

DAO is the key enzyme responsible for the degradation of extracellular (free) histamine, regardless of whether the histamine originates from allergy-induced processes in the body or is consumed with food.

Histamine exerts its effects by binding to its 4 receptors: H1R, H2R, H3R, and H4R on target cells in various tissues. Histamine receptors are located all over the body and have many important functions including:

  • H1 receptors: Smooth muscle and endothelial cells affecting skin; blood vessels (Benadryl and Claritin block activity of these receptors)
  • H2 receptors: Cells in the intestines control acid secretion, abdominal pain, and nausea; heart rate
  • H3 receptors: Central nervous system controlling nerves, sleep, appetite and behaviour
  • H4 receptors: Thymus, small intestine, spleen, colon, bone marrow and white blood cells; inflammatory response

What to eat for DAO?

The DAO enzyme is dependent on vitamin B6, B12, iron, copper and vitamin C, so it makes sense to increase the intake of these compounds.

Copper and Vit C are crucial components of the DAO enzyme and B6 is a key cofactor that enables DAO to degrade histamine.

Copper deficiency is another possible cause for low DAO activity, as copper is a central atom of the DAO and thus essential for its function. Because copper is essential to DAO function, copper levels should be monitored in patients with low DAO activity to avoid further DAO deterioration. Zinc levels should be checked at the same time, as zinc prevents intestinal copper absorption.

Putrescine, cadaverine, and tyramine are all substrates of the DAO enzyme, so if present in high amounts they may increase the adverse effects of histamine by competing as rival substrates or for binding sites in the intestinal mucosa [1,9,68,69]. The high putrescine contents found in citrus fruits, mushrooms, soybeans, bananas, and nuts could thus explain why patients associate their consumption with the onset of histamine intolerance symptoms. However, it should be noted that some foods with similar or even much higher putrescine contents, such as green pepper, peas, or corn, are permitted in low-histamine diets (Table 1).

Content of histamine and other biogenic amines (mg/kg fresh weight) in plant-origin foodsexcluded from different low-histamine diets [1–8]. Data obtained from own database and from differentscientific studies [5,12,34,38–42,47–55,57].

DAO vitamins and minerals

  • Vitamin C is well-known for its antihistaminic working. In a lot of cases, blood histamine levels are directly correlated to the vitamin C levels, and intake of vitamin C will lead to less histamine in a matter of days. It functions as a cofactor of DAO, just like vitamin B6 does. Vitamin C can be taken at doses of up to 3,000 mg to reduce histamine levels.
  • DAO depends on vitamin B6 to function. If there is shortage of B6, the enzyme is practically useless. The intake of vitamin B6 often leads to a higher DAO activity. According to the NIH, doses of up to 2 mg should suffice for lactating mothers.
  • Magnesium is important in the histamine metabolism. A shortage increases the activity of histidine decarboxylase in some tissues. Histidine decarboxylase is the enzyme that makes histamine from histidine. While at the same time, a lack of magnesium intake leads to reduced DAO. The NIH recommends doses of up to 400 mg and Magnesium can be bought over the counter as 500 mg tablets.
  • Copper is another cofactor of DAO and able to reduce histamine levels. It’s not often recommended to supplement.
  • Zinc inhibits the release of histamine from mast cells. Supplementation is recommended.
  • Manganese also inhibits the release of histamine from mast cells much like zinc.

Drugs that influence DAO

The changed production of DAO enzyme can be as a consequence of certain medications:

  • Non-steroidal anti-inflammatory drugs (ibuprofen, aspirin)
  • Antidepressants (Cymbalta, Effexor, Prozac, Zoloft)
  • Immune modulators (Humira, Enbrel, Plaquenil)
  • Antiarrhythmics (propanolol, metaprolol, Cardizem, Norvasc)
  • Antihistamines (Allegra, Zyrtec, Benadryl)
  • Histamine (H2) blockers (Tagamet, Pepcid, Zantac)

Foods High in Histamines:

Here is a list of high histamine foods:

  • Fermented alcoholic beverages, especially wine, champagne and beer
  • Fermented foods: sauerkraut, vinegar, soy sauce, kefir, yogurt, kombucha, etc.
  • Vinegar-containing foods: pickles, mayonnaise, olives
  • Cured meats: bacon, salami, pepperoni, luncheon meats and hot dogs
  • Soured foods: sour cream, sour milk, buttermilk, soured bread, etc.
  • Dried fruit: apricots, prunes, dates, figs, raisins
  • Most citrus fruits
  • Aged cheese including goat cheese
  • Nuts: walnuts, cashews, and peanuts
  • Vegetables: avocados, eggplant, spinach, and tomatoes
  • Smoked fish and certain species of fish: mackerel, mahi-mahi, tuna, anchovies, sardines
  • Processed foods of all types – Preservatives are high in histamines

Histamine-Releasing Foods:

These foods do not necessarily contain histamine but they block the action of DAO and therefore they potentiate the effects of elevated histamines.

  • Alcohol
  • Bananas
  • Chocolate
  • Cow’s Milk
  • Nuts
  • Papaya
  • Pineapple
  • Shellfish
  • Strawberries
  • Tomatoes
  • Wheat Germ
  • Many artificial preservatives and dyes

DAO-Blocking Foods:

  • Alcohol
  • Energy drinks
  • Black tea
  • Mate tea
  • Green tea

Low Histamine Foods:

  • Extra Virgin Olive Oil
  • Gluten-Free Grains: brown rice & quinoa
  • Fresh Fruits: Other than citrus, avocado, tomato, pineapple, bananas and strawberries
  • Fresh Vegetables (except spinach and eggplant)
  • Coconut milk, Rice milk, Hemp milk, Almond milk
  • Coconut oil & Grass-fed Butter/Ghee
  • Organic coffee
  • Almond butter
  • Leafy herbs
  • Herbal teas

Related Genes in Database

RCCX.me Database


  1. DAO Deficiency and Histamine: The Unlikely Connection
  2. Histamine and histamine intolerance, Laura Maintz and Natalija Novak 2007 American Society for Clinical Nutrition
  3. Histamine Intolerance in Clinical Practice Laura Maintz, Thomas Bieber, Natalija Novak
  4. The Differential Diagnosis of Food Intolerance Zopf, Y; Baenkler, H; Silbermann, A; Hahn, E G; Raithel, M Dtsch Arztebl Int 2009; 106(21): 359-69; DOI: 10.3238/arztebl.2009.0359
  5. Allergies and Your Genes – Histamine, Autoimmunity and DAO SNPs, Suzy Cohen (http://suzycohen.com/articles/histamine_intolerance_dao_genes_hashimotos/)
  6. Histamine intolerance, IMD Labor Berlin-Potsdam(http://www.imd-berlin.de/en/special-areas-of-competence/food-intolerances/histamine-intolerance.html)
  7. Histamine intolerance: a metabolic disease? H. G. Schwelberger Inflamm. Res. (2010) 59 (Suppl 2):S219–S221 DOI 10.1007/s00011-009-0134-3 Birkha¨user Verlag, Basel/Switzerland 2009
  8. Histamine: Allergies, Brain & Gut Health By Michael McEvoy, FDN, CNC, CMTA
  9. Histamine intolerance, diamine oxidase activity and probiotics Janice M. Joneja, Ph.D. Honorary Research Fellow June 2004 School of Biosciences University of Birmingham U.K.
  10. International Society of DAO Deficiency (http://www.deficitdao.org/en/dao-deficiency/what-is/)
  11. Are You Suffering From Histamine Intolerance? Dr. Jockers (http://drjockers.com/suffering-histamine-intolerance/)
  12. Histamine Intolerance Awareness Campaign (http://www.histamineintolerance.org.uk/)