Do you frequently suffer from diarrhea, cramps, gas, bloating, pain or heartburn? Do you often get headaches with or without associated dizziness, nausea or feeling of vomiting? Are sneezing attacks, runny nose, hives, flushing and itching uninvited guests in your life that embarrassingly appear without warning? Does your heart race often and workup by a cardiologist has been negative? All of these could be an indication that you have an excess of histamine known as histamine intolerance.
What is histamine? Histamine is a potent, essential compound that is produced naturally in our body by various cells in the body including mast cells, basophils, platelets, special histamine releasing nerve cells and some others, to help it work effectively. Though the most important role of histamine is to respond to an acute injury which could be in the form of ingestion of a wrong food, or contact with an environmental allergen like poison ivy or a bug; it does also function in increasing blood supply to some areas of the body, regulation of stomach acid, muscle contractility, hormonal functions, body temperature, neurotransmitter function in the central nervous system, as well as balancing of special chemicals known as cytokines in the body. While histamine has important beneficial physiological effects, too much of it can be a problem in some, especially if they are intolerant to the histamine effects. Each individual’s tolerance to histamine varies according to their genetics as well as other physiological and pathological factors in the body. This is complicated by the fact that histamine is present in many of the foods that we eat commonly, and if one is genetically predisposed to having a lower threshold for histamine tolerance, you may experience symptoms with even a small to moderate amount of those foods.
Our body has inbuilt mechanisms to breakdown histamine, whether it is from the foods that we eat, or produced endogenously. The main enzyme in our small intestine that breaks down histamine from the food we eat is known as diamine oxidase (DAO). If we produce less DAO or there is an excess of histamine in our diet, symptoms and signs of histamine intolerance begin to show up. A secondary enzyme responsible for histamine breakdown is called histamine–N–methyltransferase (HNMT).
Signs and symptoms of histamine intolerance 
- Diarrhea, stomach pain, cramping, gas and bloating
- Canker sores
- Runny nose, sneezing, nasal congestion, chronic sinusitis
- Headache (migraines and menstrual migraines)
- Frequent nausea, vomiting
- Dizziness /vertigo
- Shortness of breath, wheezing, coughing, asthma
- High blood pressure or low blood pressure
- Palpitations, irregular heartbeat
- Itching, hives, flushing, rash, eczema , anaphylaxis
- Painful menses, abnormal menstrual cycles
- Joint pain, inflammation, arthritis
- Fatigue during or after a meal, general lack of energy, memory issues
- Sudden shivering and chills all over the body with or without pain
- Panic attacks, anxiety and mood changes during or soon after a meal
- Difficulty falling asleep and staying asleep, changes in circadian rhythm
- Inflammatory Bowel Disease
- “Sensitivity to everything”
It is important to remember that histamine intolerance is not a food allergy, although the symptoms of the two can be very similar . This is because during an allergic reaction to food too, a large amount of histamine is released. A food allergy is an immune mediated IgE reaction which happens within seconds to minutes after consumption of the allergenic food, whereas histamine intolerance is a non-immune mediated, relatively delayed response, the clinical presentation of which is based upon the person’s threshold for histamine tolerance. The DAO enzyme does not impact the symptoms of food allergies, for example those due to shellfish or peanuts.
We hear a lot about histamine excess but low histamine levels can also be a problem! This may be a cause for depression or fatigue. Altered levels of histamine have also been noted in neurological and psychiatric disorders including narcolepsy, some forms of seizures and also in Alzheimer’s disease. Brain levels of histamine have been found to be decreased and the latter.
Foods can either be naturally rich in histamine or they can increase the liberation of histamine.
Foods rich in histamine are:
- alcoholic beverages which are fermented like wine (especially red) and beer
- Smoked meats and fish
- Tomatoes, ketchup
- Citrus foods
- Cocoa, chocolate
- Fermented foods like sauerkraut, kombucha, yogurt, kefir
- Soy sauce, fish sauce
- Some species of fish like sardines, mackerel, tuna, mahi-mahi
- Spoiled foods: Microbial fermentation can convert histidine in high-protein foods to histamine so its content increases with the time of storage
Factors that increase endogenous production of histamine are:
- Nuts, sunflower seeds
- Wheat germ, buckwheat
- Green and black tea
- Spinach, eggplant, avocado, mushrooms
- Olives, mustard, vinegar, pickles
- Shellfish, crustaceans
- Fruits like cherries, strawberries, pineapple, kiwi, banana, mango, raspberries, pears, papaya, dried fruits, all citrus fruits
- Nutrient imbalance (excess or depletion) in the body
- Immune challenges due to a severe infection or bodily injury
- Emotional stress leading to excessive histamine release
- Hormonal imbalances in the body
- Exposure to an consumption of chemicals and toxins like caffeine, nicotine, chemical cleaning supplies
- Allergies to inhalants in the environment for example dust, pollen, pet dander, mold
Factors that can reduce DAO production are:
- Damage to the gut lining and leaky gut due to any reason, including food allergies and sensitivities. Wheat, gluten, dairy, soy, eggs, peanuts, shellfish and corn can be highly allergenic.
- Imbalance or overgrowth of bacteria, yeast or parasites in the gut leading to damage.
- Alcohol (especially red wine and champagne)and its degradation product, acetyldehyde 
- Medications which damage the gut lining like aspirin, ibuprofen
- Many drugs including anti-depressants and anti-psychotics, blood pressure and heart medications, drugs which modulate the immune system, histamine blocking drugs (this is counterintuitive). It is ironical and very plausible that these medications may be used to treat the very symptoms of histamine intolerance that they will further increase by reducing the DAO production!
- Genetic variations known as single nucleotide polymorphisms (SNPs) in the DAO gene  can be present, and depending on environmental factors there can be varied expression of these genes
Management of histamine intolerance:
- Healing the gut should be the primary focus whenever there is an imbalance of histamine to the amount of DAO. Many products with gut soothing and mucus-generating herbs are available which help repair and soothe the gut lining and decreased irritation. In my clinic we use GI Support Powder with aloe, glutamine, DGL, slippery elm which help “heal and seal” the gut lining.
- Reduction in consumption of histamine-rich foods as well as histamine-liberating foods, and an attempt towards increasing DAO levels should be the goal. It goes without saying that food sensitivity/allergy testing and comprehensive digestive stool analysis looking for imbalance and overgrowth of bacteria yeast, parasites is imperative to find out the root cause of poor gut function as without that no other treatment will have long-term efficacy. An elimination diet can be extremely useful during this process.
- The levels of histamine and DAO can be tested in the blood. Low DAO in plasma can diagnose histamine intolerance although high histamine levels even when the DAO levels are normal can present with the same symptoms. Therefore, a ratio of DAO to histamine is extremely helpful.
- DAO is available commercially for supplementation and it can help the breakdown of histamine if taken 15-20 min. before meals. In my practice , I find this extremely useful, especially in the initial phase of trying to heal the gut in patients with symptoms of histamine intolerance who also show an imbalance between histamine and DAO on testing. Once the gut has had a chance to heal, the integrity of the gut mucosa improves and our body is able to produce its own DAO.
- Omega-3 fatty acids improve the activity of DAO so I highly recommend supplementation, especially if lab testing or my clinical exam suggest low omega-3 levels.
- Probiotics are beneficial bacteria and yeast that are extremely helpful for gastrointestinal health and rebalancing of the immune function. In patients with significant histamine intolerance I usually start high doses of multi-strain probiotics for the first 1-2 months after which time lower doses will be sufficient.
- I commonly use medical foods which are anti-inflammatory, gut healing and supportive to both phases of detoxification and biotransformation. These provide an excellent array of easily absorbable amino acids, phytonutrients and antioxidants which support healing of the gut lining, reduce inflammation, and provide the raw material as well as cofactors for a healthy detoxification process.
- Vitamins C supplementation in doses of 1-3 g per day (to include bioflavonoids) can increase the activity of DAO.
- Supplementation with methylation cofactors in the form of the activated forms of vitamins B12, B6, methyl folate, trimethylglycine (TMG) can help degrade histamine by the alternative pathway of HNMT, the secondary enzyme involved in histamine breakdown. I find this especially useful in cases where my testing shows that DAO level is normal but histamine level is high and mental/neurological symptoms predominate. Of course this should be done under the guidance of a physician trained in methylation support [http://praanaim.com/about/dr-manisha-ghei/] as not everyone can tolerate high doses of these cofactors/vitamins.
- Stress levels, sleep and exercise habits should also be reviewed and addressed due to their impact on gut and adrenal health, inflammation and immune function.
- Avoid eating leftovers. Eat only freshly cooked meat, fish and poultry and fresh fruits and vegetables except those listed above. Use healing fats and oils like coconut oil, Ghee, and olive oil.
- Work with your medical practitioner to remove all nonessential prescription and over-the-counter medications that might be contributing.
Histamine intolerance can be one of the most frustrating conditions to deal with, but working with a functional medicine practitioner who can clinically assess and test for imbalances, and help support all of the areas of the functional medicine matrix that might be contributing, can be truly beneficial, especially when symptoms are severe and persistent as chronic “pseudo-allergies”.