Factors that lead to histamine intolerance cause the following:
- An increase in how much histamine a person's digestion releases.
- A decrease in the effectiveness or abundance of diamine oxidase, or DAO, the primary enzyme that breaks down ingested histamine.
- A decrease in the effectiveness or abundance of histamine-N-methyltransferase, or HNMT, an enzyme that helps break down histamine within cells.
What are the causes?
Medications may affect enzymes that break down histamine.
Many foods and drinks contain histamine.
Usually, the enzyme DAO, and to a lesser extent HNMT, breaks down ingested histamine, preventing it from being absorbed in the gut and entering the bloodstream.
Some factors can, however, interfere with how DAO and HMNT work, or how much of these enzymes are present in the gut.
Common factors that interfere with DAO and HMNT levels include many prescription drugs, for example:
- airway medications, such as theophylline
- heart medications
- muscle relaxants
- pain medications
- gastrointestinal medicines
- nausea and gastroesophageal reflux disease, GERD
- malaria drugs
- tuberculosis medications
The list also includes over-the-counter (OTC) and prescription anti-inflammatories (NSAIDs) and painkillers, such as:
- acetylsalicylic acid (aspirin)
- indomethacin (Indocin)
- diclofenac (Voltaren)
Other influencing factors include:
- intestinal conditions or injuries that compromise the gut lining and affect digestion
- liver conditions
- vitamin B-6, vitamin C, copper, or zinc deficiencies
- extreme or chronic stress
- low oxygen states
- injury or trauma
- temperature extremes
Some people are predisposed to developing histamine intolerance because of hypersensitivity to OTC medications, for example, NSAIDs.
When the body does not break down histamine from foods, and it leaks through the intestinal lining, it enters the bloodstream and can cause an immune response.
A person's allergic response symptoms are likely to be more severe the more histamine they have accumulated in their bloodstream.
People with histamine intolerance tend to have a variety of symptoms that can make it difficult to determine the source.
What are the symptoms?
The symptoms of histamine intolerance vary but tend to mimic those of other allergic reactions.
Common symptoms include:
- chronic headache
- flushing, especially of the head and chest
- irritable bowel syndrome or IBS
- congested, runny, or itchy nose
- red, itchy, or watery eyes
- shortness of breath
- hives or red, raised, itchy, burning bumps
- very itchy skin
- unexplained anxiety
- stomach cramps or pain
- chronic constipation
- nausea and vomiting
- gas or bloating
- unexplained exhaustion
- very dry, patchy, or scaly skin (eczema)
- irregular or increased heart rate
- severe menstrual pain
Less common symptoms include:
- low blood pressure
- sleep problems
- swelling around the lips, eyes, and occasionally the throat
- loss of consciousness
How does diet play a role?
Citrus fruits are high in histamines.
Most people associate histamine with immune responses in the body.
But almost all foods and drinks contain some level of histamine, and these usually increase as the food ages, spoils, or ferments.
Some foods and drinks also contain compounds that help release histamine in the body or block the production or effectiveness of the enzymes DAO and HMNT.
Researchers are still working out how much histamine is in most foods and drinks, as well as precisely how some nutrients impair DAO and HMNT activities.
According to the current research, everyday foods and drinks rich in histamine include:
- aged cheeses
- canned, pickled, and fermented foods
- smoked products, such as sausage, ham, bacon, or salami
- legumes, such as chickpeas, soybeans, and lentils
- many prepared meals
- salty snack foods
- sweets with preservatives
- chocolate and cocoa
- green tea
- most citrus fruits
- canned fish, such as mackerel and tuna
- chili powder
Foods that may trigger the release of histamine include:
- most citrus fruits
- cocoa and chocolate
- wheat germ
- additives, preservatives, and dyes
- beans and pulses
Foods that may interfere with DAO and HMNT levels or actions include:
- energy drinks
- green tea
- black tea
- mate tea
- raw egg whites
- some yogurt, depending on bacteria type
Many kinds of bacteria, especially common food contaminants, can also produce a type of histamine in the gut. If these bacteria colonize the gut and multiply, they can generate enough histamine to cause symptoms.
People who may have histamine intolerance or are looking to reduce or reverse the condition will often need to go on a low-histamine diet. Usually, this means limiting the intake of histamine-rich foods rather than excluding them entirely.
People with histamine intolerance should also focus on increasing their intake of foods and drinks low in histamine.
Foods and drinks with low levels of histamine include:
- skinned fresh chicken
- cooked egg yolk
- fresh or flash-frozen meat and fish
- most fresh vegetables except tomatoes and eggplants
- most fresh fruits and berries besides citrus fruits, strawberries, and cherries
- fresh, pasteurized milk and milk products
- whole-grain noodles, breads, crackers, and pastas
- coconut and rice milk
- cream cheese
- most non-citrus based juices and smoothies
- most herbal teas except black, green, and mate tea
- most leafy greens except spinach
- most cooking oils
Several vitamins and minerals are necessary for the proper activity of DAO. So, people with histamine intolerance may benefit from including more foods and drinks rich in these nutrients in their diet.
People can take supplements if it is too difficult to get some nutrients because of low-histamine diet restrictions or availability.
Vitamins and minerals that may be good for people with histamine intolerance include:
- vitamin B-6, which helps DAO break down histamine
- vitamin C to help lower histamine blood levels and help DAO break down histamine
- copper, which helps raise DAO blood levels slightly and helps DAO break down histamine
- magnesium that can raise the allergic response threshold
- manganese that can enhance DAO activity
- zinc to help DAO break down histamine (it may also have anti-inflammatory and anti-allergic properties)
- calcium to help reduce hives and skin flushing
- vitamin B-1
- vitamin B-12
- folic acid
A doctor may recommend switching or avoiding certain medication.
Aside from dietary changes, there is no set treatment for people with histamine intolerance.
But most people with the condition benefit from a few different medical treatments, depending on their symptoms or the cause of the condition.
Some of the most common medical treatments include:
- taking antihistamine medication
- taking DAO enzyme supplements
- switching prescription medications
- avoiding medicines associated with histamine intolerance, such as most anti-inflammatory and pain drugs
- taking corticosteroids
In a small 2016 study, 13 out of 14 people with histamine intolerance reported a reduction in at least one symptom after taking one capsule of DAO supplement 15 minutes before lunch and dinner for at least 2 weeks.
How is it tested?
There is no single, conclusive way that doctors can diagnose histamine intolerance. Ruling out all other potential medical causes is how they diagnose most people.
An allergist or immunologist will often begin by testing someone for food allergies and intolerances if they suspect they may have histamine intolerance.
A specialist called a gastroenterologist might test people with chronic intestinal symptoms for intestinal conditions, such as:
People with suspected histamine intolerance are also often asked to keep a food diary for at least 2 to 4 weeks so a doctor can identify symptom and diet patterns. Doctors can also request a blood test to check people's DAO levels and enzyme activity levels.
Lastly, researchers have proposed a skin-prick test for diagnosing histamine intolerance, but it is not widely used and has not been proven repeatedly reliable.
Outlook and takeaway
In most cases, making dietary changes, as well as taking anti-histamines or enzyme supplements, may help manage histamine intolerance within a few weeks.
But to keep symptoms at bay, most people need to limit or avoid histamine-rich foods for a few months. People recovering from histamine intolerance will also generally need to avoid or limit the use of medications known to trigger histamine release for a similar time.
Focusing on fresh, non-packaged or prepared foods is also crucial if someone is recovering from histamine intolerance by limiting histamine levels found in everyday foods.