What is histamine?
Histamine is a chemical that is found in foods and is made in the body (1). Histamine is released from mast cells, within the immune system, when an allergen is detected by the body (1).
Histamine is also is produced in the body from the amino acid histidine, which is a type of protein (1). Histamine occurs in food as a by-product of the fermentation of histidine. It is a chemical which is produced by bacteria during fermentation, storage or decay.
Histamine plays an important role in the immune system. It causes an immediate inflammatory response. It serves as a warning to the immune system, telling the body about any potential attackers. Histamine causes blood vessels to swell, or dilate, so that white blood cells can quickly find and attack the infection or problem.
Histamine plays other roles in the body as well. As a neurotransmitter, it communicates important messages to and from the brain and spinal cord (1). These messages are related to arousal and attention. This partly explains why OTC anti-histamines that cross the blood-brain barrier, such as diphenhydramine or Benadryl, act as sedatives (1).
Histamine is also involved in stimulating the parietal cells, found in the stomach, to secrete stomach acid, which is critical for breaking down food in the stomach and for good digestion (2). Too much histamine can be one cause of excessive secretion of stomach acid. This can lead to acid reflux / heartburn (GERD).
Histamine Intolerance is an increased sensitivity to histamine and/or an excessive build-up of histamine in the body.
An excessive amount of histamine is suspected to result from various sources:
- Allergic response(s)
- Eating large quantities of histamine-containing foods or beverages
- Consumption of foods or other substances that cause histamine to be released
- Impaired ability for enzymes in the body to break it down (3)
The enzymes that can break down histamine are diamine oxidase (DAO) and histamine N-methyl transferase (HNMT) (3).
There are two primary categories of issues:
- An increased amount of histamine in the body
- Decreased activity of the enzymes that break down histamine and remove it from the body
In addition to these categories, approximately 1% of the population experience adverse reactions to what is considered a “normal” level of histamine in food (3). This typically presents more often in people who are middle-aged (3). High levels of histamine can make a person feel unwell but the majority of people tolerate the amounts found in a regular diet without any issues.
A histamine reaction is the body’s natural immune response, but if histamine is not broken down properly, it can lead to histamine intolerance (HI). This is why OTC medications like Claritin can help with an allergic histamine reaction. Claritin is an anti-histamine which blocks and decreases histamine’s action.
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What are the symptoms of excess histamine?
The onset and severity of histamine intolerance symptoms can vary greatly between individuals, but common complaints are (3):
- Migraines and headaches
- Respiratory problems including: asthma, nasal congestion, sneezing, difficulty breathing
- Skin conditions like: itching, rashes, dermatitis, hives or eczema, swelling
- Gastrointestinal problems such as: nausea, reflux, vomiting, abdominal pain/cramps, diarrhea
- Dizziness, low blood pressure, and irregular heartbeat
- Difficulty falling & staying asleep
- Abnormal menstrual cycle
- Joint pain
How is it diagnosed?
Diagnosis of histamine intolerance has been based on low serum levels of DAO (the enzyme responsible for breaking down histamine), the presence of gastrointestinal disorders and the improvement of symptoms with a low histamine diet (4). Some additional blood markers like whole blood histamine and a few others can also point to histamine issues.
What are the causes of high histamine?
Intolerance to histamine is primarily thought to be caused by previous or current gastrointestinal problems (such as SIBO or small intestinal bacterial overgrowth, dysbiosis, leaky gut, inflammation of the gut), toxic burden, and/or genetics.
There is evidence that dysbiosis, or an alteration of the gut microbiome, is related to the incidence of all food intolerances, and especially to histamine intolerance (5). Dysbiosis is an imbalance in the types and amounts of bacteria in the gut. It means there are too many pathogenic or bad bacteria and too few good or health-promoting bacteria in the gut microbiome. It is very often associated with disease.
One study analyzed the microbiome of people with histamine intolerance (5). They found increased amounts of certain pathogenic bacteria like Proteobacteria, and a reduced level of good bacteria such as Bifidobacteriaceae / Bifidobacterium (5). This imbalance and lower bacterial diversity can both point to dysbiosis, or a problematic balance of bacteria in the gut. Additionally, this study found an impaired intestinal barrier, or leaky gut, in this patient group (5).
Histamine has a negative effect on gut permeability. Dysbiosis in histamine intolerant patients may contribute to mucosal inflammation of the gut (5). This in turn could favor the development of a leaky gut as well as the reduction of intestinal DAO leading to elevated histamine levels and symptoms in sensitive people (5).
Mast Cell Activation Syndrome (MCAS)
Toxic burden can also be a cause of mast cell activation syndrome (MCAS). Mast cells are cells that produce histamine. When mast cells are activated, they produce and release a high level of histamine, in addition to other chemicals. MCAS is a condition where there seems to be overly active mast cells and high histamine levels. This creates an inflammatory response and contributes to very similar symptoms as histamine intolerance.
As mentioned, gut dysbiosis and gut conditions like small intestinal bacterial overgrowth (SIBO) can be a cause of histamine issues (including MCAS). There are also common issues where toxins accumulate and that also seems to be correlated with higher levels of MCAS. Not all of the causes of MCAS are known.
About 1 in 4 people have a genetic predisposition in which there is a change in the HLA-DR gene. This gene is involved with the immune system's ability to identify certain kinds of toxins and to eliminate them from the body effectively. In people with this genetic predisposition, there is an increased potential for these toxins to bioaccumulate and cause inflammation. In many cases mold toxins, or mycotoxins, are one of the toxins that are not appropriately identified.
This is a significant issue, given that about 1 in 2 American homes have been shown to have water damage and may have high levels of mold toxins. Because only 1 in 4 people have the gene, not everyone in the home will become ill. This makes mold toxin illness a common issue that is often underdiagnosed.
Although the reason why there is a link between MCAS and mold toxin illness remains unknown, many clinicians who treat mold issues see a high correlation between these two conditions.
Our blog post next week will focus on MCAS so be sure to look out for that article and read further on MCAS.
Enzymes involved in decreasing histamine
The main histamine enzyme in the gut is diamine oxidase (DAO), while other areas like the skin, spinal cord, lungs and other organs rely on an enzyme called histamine N-methyltransferase (HNMT) (5). Though both enzymes play an important role in histamine break down, DAO is the main enzyme responsible for breaking down ingested histamine. Any deficiency in DAO will likely result in symptoms of histamine intolerance (5).
The causes of high histamine (3, 5)
- Allergies (IgE reactions)
- Bacterial overgrowth (SIBO)
- Leaky gut (intestinal permeability)
- GI bleeding
- Gut inflammation
- Mold toxin illness
- Fermented alcohol like wine, champagne, and beer and histamine-rich foods
- Diamine oxidase (DAO) deficiency
Causes of low DAO (6)
- GI disorders such as gluten intolerance, celiac disease, leaky gut, SIBO, inflammatory bowel disease
- Inflammation from Crohn’s, ulcerative colitis, and inflammatory bowel disease
- DAO-blocking foods: alcohol, energy drinks, and black, mate and green teas
- Nutrient deficiencies for co-factors of DAO (vitamin B6, vitamin C, copper, vitamin B12, and iron)
- Genetic mutations that lead to a reduced DAO enzyme activity (common in people of Asian-descent)
- Medications that block DAO or prevent its production including: 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) and Histamine (H2) blockers (Tagamet, Pepcid, Zantac)
Although histamine blockers, a class of acid-reducing drugs, seem like they would help prevent histamine intolerance, these medications can actually deplete DAO levels in the body.
Symptoms either improve or disappear with a low histamine diet (4). One study found a significant increase in serum DAO levels in patients with strict and even occasional compliance to a low histamine diet (4). The study authors concluded that a low histamine diet not only improves symptoms in HI, but also leads to an increase in serum DAO which correlates with the degree of diet compliance (4).
It is also critical to work on gut health to alleviate histamine intolerance. We know that dysbiosis and other GI issues are often present with histamine intolerance (3, 5, 6). Eradicating any gut infections, overgrowths or inflammation will be vital for rebalancing the gut and ensuring a healthy balance of gut flora.
The Basics of the Low Histamine Diet
Eat freshly cooked and prepared real food! Packaged and processed food can have high histamine levels. Eating fresh food is important because histamine levels increase the longer food is not refrigerated. Histamine levels can also increase in left-over or fermented food.
Unfortunately, the histamine content of different foods can vary quite substantially depending on the maturity of the food, storage time, and processing (7). So histamine levels can differ considerably within the same food product. For example, the histamine content in Emmental cheese varies from <0.1 to 2000 mg/kg and in smoked mackerel from <0.1 to 1788 mg/kg (7). These variations make it difficult to estimate the histamine content of individual meals. However, it is entirely possible to decrease histamine load by concentrating on low histamine foods and avoiding foods high in histamine (like cheese and fish) or foods that block DAO activity.
Low Histamine Foods to Eat:
- Freshly cooked grass fed, wild, organic meat or poultry: red meat, steak, ham, chicken and turkey
- Freshly caught wild fish
- Cooked pastured eggs
- Gluten-free grains: rice, quinoa, corn, millet, amaranth, teff
- Pure peanut butter (although peanut butter can be contaminated with a mold toxin called aflatoxin)
- Legumes (except soybeans & red beans)
- Fresh fruits: mango, pear, watermelon, apple, kiwi, cantaloupe, grapes
- All fresh vegetables (except tomatoes, spinach, avocado, and eggplant)
- Dairy substitutes: coconut milk, rice milk, hemp milk
- Cooking oils: olive oil, coconut oil
- Leafy herbs
- Herbal teas
- Decaffeinated coffee
- Honey & maple syrup
Some tips to keep in mind for food preparation:
- Try to cook most of your own meals to avoid histamine
- Avoid or limit eating canned foods and ready meals
- Avoid heavily processed or junk foods: food dyes/artificial colors can be big triggers
- Keep the kitchen clean
- Refrigerate vigilantly as histamine forms on food as it spoils
Foods to Avoid:
To reduce histamine from food, avoid:
- Foods high in histamine
- Foods that release histamine
- Foods that suppress DAO
Unfortunately, some research says certain foods are high in histamine and other research disagrees in some cases. Some foods are consistent across research studies. For this reason, we focus on the foods that are consistent across research studies. You may find that our list does not mention foods that other lists or research say is high in histamine. However, if one research study says a food is high in histamine and another says it is low, we have eliminated that food in order not to recommend avoiding things unnecessarily. It is important to have a varied healthy diet with few food restrictions, especially when we are not sure about whether those foods have high levels of histamine or not.
Histamine-Rich Foods (3):
- Yeast or anything that contains it: alcohol, bread, pastries, and baked goods
- Fermented foods: sauerkraut, vinegar, soy sauce, kefir, yogurt, kombucha, etc.
- Vinegar-containing foods: pickles, mayonnaise, olives
- Cured deli 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
- Some citrus fruits: lemon and mandarin
- Some other fruit: pineapple, banana, and avocado
- Aged hard or semi-hard cheese including goat cheese (soft fresh cheese is okay)
- Nuts: all nuts, especially walnuts, cashews
- Smoked fish or canned anchovies
- Bone broth
- Certain spices: curry, mustard seed / mustard, and soy sauce
- Many artificial preservatives and dye
DAO-Blocking Foods (6):
In addition to alcohol releasing histamine and inhibiting DAO, there is also enzyme competition as some enzymes that can break down histamine are also involved in breaking down alcohol. The body may have to choose one of the two and this can further exacerbate histamine issues.
Probiotics and histamine: Probiotics impact histamine levels. Some increase histamine levels and others decrease histamine.
These probiotics can produce histamine – consider avoiding with histamine intolerance:
- Lactobacillus Casei
- Lactobacillus Delbrueckii
- Lactobacillus Bulgaricus
These probiotics can degrade histamine and are preferable to use in the case of histamine intolerance:
- Lactobacillus Plantarum
- Lactobacillus Rhamnosus
- Bifidobacter species
- Possibly soil based organisms like bacillus subtilis
- Some report benefit from Saccharomyces Boulardii
How to manage histamine intolerance:
- In order to manage histamine intolerance, it is useful to follow a low histamine diet for 3 months. Avoid foods that either release histamine or block the action of DAO.
- It can be helpful to take a DAO supplement.
- Experiment with supplements that are pre-cursors to endogenous DAO production: vitamin B6 (in P-5-P form), copper and B2 (7). In addition, vitamin C can help to degrade excess histamine (7). Vitamin B12 may also help in some cases (we prefer methylcobalamin form of B12).
- Some herbs like nettles and nutrients like quercetin can also help.
- Healing the gut is an important step. This involves addressing SIBO and other potential gut infections or issues (parasites, celiac, inflammation, dysbiosis or others), as well as healing leaky gut.
- Then re-introduce histamine foods, one food every 3 days, and observe reactions very carefully to see what can be tolerated without symptoms. Once symptoms are better under control and the overall histamine load is lower, it may be possible to tolerate some histamine foods, in a few months’ time.
There are many other factors involved with histamine intolerance and MCAS. For example, methylation is one issue that we did not discuss in this article, but low methylation can be associated with increased histamine. If you feel that you have several of the symptoms mentioned in this article, we recommend seeking guidance from a practitioner experienced with histamine intolerance and/or MCAS.
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- Purves D, Augustine GJ, Fitzpatrick D, et al. 2001. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001. The Biogenic Amines. https://www.ncbi.nlm.nih.gov/books/NBK11035/
- University of Washington. Regulation of Acid Secretion. https://courses.washington.edu/conj/bess/acid/acidreg.html. Accessed June 17, 2019.
- Kohn 2014. Is There a Diet for Histamine Intolerance? J Acad Nutr Diet. 114: 1860.
- Lackner S, Malcher V, Enko D, Mangge H, et al. 2018. Histamine-reduced diet and increase of serum diamine oxidase correlating to diet complance in histamine intolerance. Eur J Clin Nutr. 73, 102–104.
- Schink M, Konturek PC, Tietz E, et al. 2018. Microbial Patterns Patients with Histamine Intolerance. J Physiol Pharmacol. 69, 4, 579-593. DOI: 10.26402/jpp.2018.4.09.
- MTHFR Support Australia. 2018. DAO Deficiency and Histamine: The Unlikely Connection. https://mthfrsupport.com.au/2016/09/dao-deficiency-and-histamine-the-unlikely-connection/. Accessed June 17, 2019.
- Reese I, Ballmer-Weber B, Beyer K et al. 2017. German Guideline for the Management of Adverse Reactions to Ingested Histamine. Allergo J Intl. 26: 72. doi.org/10.1007/s40629-017-0011-5.