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The many faces of histamine intolerance

I am astounded at how many of us unknowingly suffer from excess histamine. Some of us itch or sneeze while others get headaches, migraines, joint pain, or nausea – within minutes or several hours after exposure! Our “histamine bucket” fills up based on factors such as genetics, allergies, medication, diet, environment, nutritional deficiencies, intestinal damage, and UV exposure. When our body cannot break down excess histamine, we suffer with histamine intolerance and increased inflammation. When we realize what is really happening, we can better prevent and treat this misunderstood condition!

Most of us know histamines through antihistamine drugs that relieve our suffering from allergies to pollen, insect bites, and even foods. Histamine is naturally produced in our body by mast cells or white blood cells, and it performs different functions by binding with histamine receptors. Depending upon their location, histamine receptors control very different body functions:

  • Histamine H1 receptors: Smooth muscle and endothelial cells affecting skin; blood vessels (Benadryl and Claritin block activity of these receptors)
  • Histamine H2 receptors: Cells in the intestines control acid secretion, abdominal pain, and nausea; heart rate (Histamine H2 receptor antagonist drugs have been used to reduce symptoms of dyspepsia and GERD)
  • Histamine H3 receptors: Central nervous system controlling nerves, sleep, appetite and behavior
  • Histamine H4 receptors: Thymus, small intestine, spleen, colon, bone marrow and white blood cells; immune function and inflammation

Keep in mind, histamine is essential for us to properly function and fight off invading toxins. But when histamine accumulates faster than we can break it down, it triggers inflammation in dreaded patterns of histamine intolerance unique to each person and episode. Our battle with histamine can hide behind less obvious symptoms like headaches, foggy thinking, diarrhea, arrhythmia, sinus congestion, or itchy skin appearing within minutes or even several hours after exposure. Extreme histamine levels can trigger breathing difficulty and swelling called anaphylaxis. The concept of histamine intolerance is rarely discussed by doctors but clearly outlined in scientific research.

So why haven’t we heard about this?

Histamine intolerance is hugely underestimated in the population. Most people respond to symptoms of histamine intolerance with an aspirin, antacid, or other quick-fix pill that does not address the root problem. Sometimes histamine levels are raised due to allergy, but histamine intolerance is not a true allergy and it won’t show up on allergy tests.

Unlike allergy testing, confirming a serious histamine intolerance isn’t easy or profitable for doctors. An elaborate study discovered that “histamine-intolerant subjects reacted with different organs on different occasions.” Each person has a unique set of symptoms that may not always recur in the same location or intensity. The only true test for histamine intolerance requires a strict histamine-free diet followed by a double-blind food challenge. With a true diagnosis, the standard treatment is even more dismal – a low-histamine diet for life. But don’t give up yet!

What causes histamine levels to rise?

Reduced or inhibited enzymes:

One of the more common reasons we suffer from histamine intolerance is the lack of enzymes diamine oxidase (DAO) and histamine-N-methyl transferase (HNMT). These enzymes break down histamine and keep it in check. DAO and HNMT levels may be genetically low in some individuals, blocked by drugs, or reduced from intestinal damage or diseases such as celiac. Though human research is lacking, caffeine inhibited DAO in animal studies. Though DAO testing has typically been limited to countries outside of the United States, Dunwoody Labs in Georgia appears to offer DAO analysis of blood tests shipped from a practitioner.

Many factors affect the body’s histamine levels, and there are ways we can help reduce the load. Our exposure to allergens, diet, drug use, temperature, hormones, and nutritional deficiencies dramatically impact our histamine levels throughout the day. Imagine your histamine as a “bucket” that fills up and only reveals symptoms after overflowing.

Allergies:

Large amounts of histamine are promptly released when we are exposed to our allergens, and the most common allergens include mold, dust mites, animal dander, pollen, medications, insect stings, latex, and food. Interestingly, scientists are beginning to suspect that these allergies have developed in order to protect us from environmental toxins. It is important to avoid exposure to known or suspected allergies, especially when histamine levels are a potential problem. Get tested and avoid the triggers to start emptying the bucket!

The most common food allergies include dairy, wheat, shellfish, eggs, and nuts. Contact allergies can include a wide range of substances such as rubber, nickel (in jewelry), acrylates (artificial nails), pine resin, and sunscreen or shampoo ingredients (such as benzophenone). Some people experience an early response to allergens, while others might only notice a late-phase response that can appear up to 10 hours later. Symptoms of this delayed response can last up to 24 hours.

If any type of food allergy is suspected, consult with an allergist and start carefully taking notes about diet and symptoms. ChartMySelf.com can help you keep online records of your health. Blood tests for both immediate and delayed food allergies are available to doctors from Great Plains LaboratoryUS Biotek, and many others. Depending on the type of allergy exposure and related damage, a body may require days, weeks, or even months to fully recover.

Air pollution and pollen:

New research shows that air pollution contributes to cardiovascular disease by the increase in histamine and inflammation. Genetics also play a role in a person’s susceptibility to pollution.

These collective studies suggest that both short- and long-term PM inhalation can enhance thrombotic and coagulation tendencies, potentially via increases in circulating histamine and inflammatory cytokines and/or activated white cells and platelets. – Circulation, 2010

Interestingly, new research shows that some of us can experience inflammation from pollen without any specific allergy! Future studies will undoubtedly reveal how particles in our environment can affect our immune system beyond the classic allergy response.

Water pollution:

Studies have shown that common environmental contaminants trichloroethylene and tetrachloroethylene raised histamine levels in lab rats by increasing their sensitivity to allergens.

Drug interference:

Drugs can inhibit our vital histamine enzymes even more than food, possibly increasing the risk of food poisoning and other symptoms of excessive histamine. According to a research reportNSAIDs such as aspirin, ibuprofen and naproxen can cause histamine levels to rise. Opoid drugs and analgesics are the most common drugs used in hospitals, releasing histamine that results in uncomfortable itching for many patients. Excessive histamine can also result from drugs including (but not limited to) acetylcysteine, acetylsalicylic acid, alcuronium, alprenolol, ambroxol, amiloride, aminophylline, amitriptyline, cefuroxime, cefotiam, chloroquine, cimetidine, clavulanic acid, cyclophosphamide, D-tubocurarine, dihydralazine, dobutamine, isoniazid, metamizole, morphine, pancuronium, pethidine, prilocaine, propafenone, metoclopramide, pentamidin, thiopental, and verapamil.

Foods high in histamine:

Symptoms can often be prevented by avoiding foods high in histamine:

  • Fermented foods like wine, aged cheese, aged or smoked meats, fermented soy products (including tofu and soy sauce), vinegar (including pickles, ketchup and prepared mustard), and sauerkraut
  • Foods exposed to high amounts of bacteria such as fish/shellfish
  • Leftover meats can quickly accumulate microorganisms which result in histamine formation
  • Chocolate/cocoa, spinach, eggplant, nuts, pumpkin, tomato, strawberries, citrus fruits, and seasonings like cinnamon, chili powder, and cloves can stimulate the release of histamine
  • Wheat-based products
  • Beverages such as tea (herbal or regular) and soy milk are high in histamine
  • Any type of alcohol interferes with the body’s ability to break down histamine.
  • Prepackaged meals

A useful reference for foods and related allergies and intolerances can be found at FoodsMatter.com.

Foods high in histadine (over 1000 mg) may also be problematic, as histadine converts to histamine:

  • Game meat including buffalo, elk, moose, caribou
  • Pork including loin, chops or other cuts, ham, bacon
  • Soy protein
  • Chicken and turkey
  • Veal and beef, pastrami
  • Lamb
  • Fish including tuna, pike, cod, sunfish, perch, grouper, and others
  • Cottage cheese

Source: Nutritiondata.self.com

Foods high in fat:

New studies show that fat absorption may dramatically increase the release of histamine and contribute to chronic inflammation.

Nutritional imbalances:

When the body is low in B vitamins, vitamin C, and copper, histamine may not break down sufficiently to overcome symptoms of intolerance. Foods high in Bs include potatoes, sunflower seeds, and soybeans. Foods high in vitamin C include bell peppers, broccoli, brussels sprouts, kiwifruit, cantaloupe, and kale. Researchers found that vitamin C may work by increasing the activity of the DAO enzyme.

Copper is required to form the DAO enzyme and copper deficiency associates with low DAO enzyme activity in animals. More research is necessary to confirm that copper supplementation increases DAO activity. Foods high in copper include fresh basil, cocoa powder, cashews, soybeans (mature), herbal tea, sesame seeds, sunflower seeds, garbanzo beans, and lentils.

Some foods like potato are also high in oxalate which can release histamine in certain people. Keep in mind that while citrus is high in vitamin C, it releases histamine within the body and can aggravate symptoms. A food allergy to any of the above foods will also increase histamine.

Heat and UVB light:

Studies show that UVB light caused histamine release in vitro, though it was protected by ascorbic acid (vitamin C). Some people notice that rashes and skin conditions can worsen with exposure to sun and heat.

Exercise:

Some episodes of anaphylaxis have been triggered by moderately intense exercise, particularly in warm environments. These extreme reactions are typically related to food allergens that were consumed prior to physical activity. Strict avoidance of allergens may help prevent symptoms of histamine intolerance that occur during exercise – particularly dynamic exercises such as jogging, running, and aerobics that involve less resistance. Recent studies indicate that the amino acid L-carnosine is released during these exercises and then converted to histamine.

Hormones – including stress hormones:

Rising estrogen levels have been associated with elevated histamine, and women might notice increased sensitivity and symptoms of histamine intolerance at different times in their monthly cycle. Periods of high estrogen link to sinus sensitivity to histamine. Environmental estrogens such as pesticides, agricultural growth hormones, and PVC in plastics may also activate histamine release. Conversely, histamine appears to stimulate estrogen levels as well and exacerbate symptoms. Diamine oxidase levels are much higher in the luteal phase of the menstrual cycle, theoretically reducing the risk of excess histamine during that phase.

The “stress” hormone cortisol appears to increase histamine in stomach and intestines in lab studiesReducing stress can lower the amount of stimulating hormones that activate mast cells which release histamine and other factors of inflammation.

How can we manage a histamine overload?

At times we can reach a “point of no return” where our histamine levels start the cascade of inflammation and aggravating symptoms. Nausea, diarrhea, skin rashes, headaches, and mental distress are common ways our body expresses inflammation from excess histamine, though each person experiences this differently. Seek immediate medical attention for any signs of anaphylaxis!

• Avoid further triggers in diet and environment. Don’t take risks until seeking medical advice and getting tested for true allergies.

• Add a cold blast or slow warm-up. Ice packs can relieve affected skin and reduce histamine. Interestingly, cryotherapy is used to relieve pain with arthritis through the reduction of histamine. Frozen gel packs even helped relieve migraines in 50% of patients in one study – applied for 25 minutes – with benefits increasing in subsequent tests. Make it very cold and quick, because a short-term moderate decrease in temperature will likely increase any itching.

• Cortisone cream and colloidal silver are quick, simple remedies for skin reactions. Topical hydrocortisone cream relieves itching and may consequently help prevent infection. Avoid complex medications or herbal remedies that expose the skin to more allergens and harsh chemicals. Colloidal silver spray is a natural antibacterial remedy that helps prevent infection.

• Oral antihistamines do not reduce histamine, but they block histamine receptors tohelp us sleep, heal, and fight inflammation. First-generation antihistamines make us drowsy with occasional side effects of insomnia and confusion. Second-generation, newer antihistamines do not make us drowsy but may cause headache and dry mucous membranes. Long-term use of oral antihistamines is associated with weight gain, and oral antihistamines do not improve DAO enzyme activity.

Corticosteroids are used locally as in the case of nasal sprays or systemically in pill form. While corticosteroids may provide immediate relief for some allergy symptoms, their side effects can be dangerous, crippling, or fatal with prolonged use.

• Bee propolis as a powder from capsules can be applied to itchy skin to quickly reduce inflammation and histamine and relieve symptoms. This supplement can stain clothing so cover with a bandage or gauze. Individuals with asthma or an allergy to pollen or bee stings should avoid bee propolis.

Stinging nettle extract reduces allergic and inflammatory activity in vitro. Interestingly, experimental topical treatment also relieves osteoarthritic pain.

• Probiotics show promising signs for alleviating allergic disease, and we are beginning to learn how these “good” bacterial strains can benefit the body in different ways. Probiotics like L. reuteri help produce histamine in the gut that suppresses inflammationStudies also suggest that probiotic L. rhamnosus reduces activation of mast cells and H4 receptors. In this manner, probiotics can shift immune activity to a more “intracellular” Th1 response rather than the “extracellular” Th2 response that characterizes excessive histamine activity in allergy, asthma, and autoimmune diseases. In fact, taking different strains of probiotics including L. reuteri, L. rhamnosus, L. casei, and B. bifidum may work best to reduce the allergic response that can trigger excessive histamine.

• Flavonoids – Naturally occurring flavonoids fisetin, kaempferol, myricetin, quercetin, and rutin inhibited histamine release in lab studies. These antioxidant compounds are found in kale, broccoli, capers, buckwheat, onions, apples, and asparagus. Mast cell activity is also inhibited by flavonoid luteolin found in carrots, peppers, celery, olive oil, peppermint, thyme, rosemary, oregano, lettuce, pomegranate, artichoke, chocolate, rooibos tea, buckwheat sprouts, turnip, capers, and cucumber.

• Enzymes – Enzyme diamine oxidase (DAO) breaks down histamine internally, and routine intake of a food supplement like DAOsin and Histame can help prevent episodes in the long-term.

What other behaviors and health conditions are related to histamine?

Food poisoning symptoms – Many outbreaks of food poisoning are actually caused by excessive histamine consumption in certain high-histamine foods. Scrombroid food poisoning results from eating spoiled fish containing toxic levels of histamine – not bacteria. Histamine poisoning resembles a food allergy and is often misdiagnosed.

MigrainesThere is much evidence to support the link between allergy and migraine, including the elevated levels of histamine in blood plasma of migraine patients. Yet typical antihistamine drugs that target histamine H1 and H2 receptors have not been effective for migraine. Future studies may target histamine H3 or H4 receptors with better results.

Atopic dermatitis – This inflammatory skin disease can be relieved with a low histamine diet in some patients who do not respond to food allergy tests.

• Motivation, appetite, and addiction Fascinating research describes how diminished histamine in the brain may relate to feelings of apathy and increased appetite. In women this behavior may be enhanced by hormones, as histamine rises with elevated estrogen and luteinizing hormone throughout the monthly cycle. Indeed, women generally experience increased appetite in the last half of their cycle as their estrogen and histamine dropSimilarly, allergic symptoms can be more pronounced in mid-cycle.

Histamine feedback loops may also contribute to the success of very-low-calorie diets. In fact, histidine supplementation suppressed food intake and fat accumulation in ratsEven chewing plays a role in triggering the histamine release that reduces appetite. Chewing has even been effective for reducing fat in obese animals!

Too much of a good thing? Excessive histamine in the brain is linked to addiction and alcohol dependence in preliminary studies. Interestingly, females have higher levels of brain histamine and are more prone to addiction than males.

Cancer – Although we may suffer from an excess of histamine and consequential inflammation, exciting new research shows that histamine controls some types of cancer growth. Research shows that histamine and histamine receptors affect growth of cancers of the stomach, pancreas, colon, and liver in different ways. Certain cancer cells produce a form of histamine (histidine decarboxylase) that represses inflammatory cell activity. Other studies show that histamine and mast cells may both promote and inhibit cancer at different stages! In fact, melanoma skin cancer appears to be stimulated by histamine in lab tests and inhibited by a topical drug that blocks histamine called H2 antagonist. This type of drug has been used to treat acid reflux, ulcers, and indigestion.

Furthermore, histamine is being considered to prevent the damaging effects of cancer radiation therapy.

“…histamine significantly protects two of the most radiosensitive tissues, small intestine and bone marrow, from high doses of radiation. In addition, histamine has the ability to prevent functional and histological alterations of salivary glands exerted by ionizing radiation.” – Current Immunology Reviews, 2010

Parkinson’s Disease and brain degeneration – Accumulated histamine in the brain can cause damage to neurons through inflammation. Studies on patients with Parkinson’s Disease have shown abnormal, reduced ability to break down histamine in the brain and an accumulation of histamine methyltransferase. Furthermore, manganese exacerbated this altered histamine activity in lab rats.

Multiple Sclerosis – Recent studies revealed that multiple histamine receptors are involved in multiple sclerosis, with some receptors promoting the disease and others inhibiting it.

Inflammation – Histamine and its receptors are constantly engaged in a vital balancing act, preventing excessive inflammation while promoting homeostasis and healing. A variety of inflammatory diseases involve histamine activity.

Animal models indicate that mast cells, through the secretion of various vasoactive mediators, cytokines and proteinases, contribute to coronary plaque progression and destabilization, as well as to diet-induced obesity and diabetes. – Trends in Pharmacological Sciences, 2011

Periodontis shows high levels of histamine in inflamed gum tissue, and topical H2 antagonist drug cimetidine dramatically improves conditions. Patients with inflammatory (rheumatoid) arthritis have pain relief from cryotherapy which has been shown to reduce histamine levels for extended periods. Certain types of histamine receptors in joint tissues are suspected to play a role in chronic conditions like arthritis.

Yet histamine may also protect us by inhibiting AGE activity which contributes to chronic inflammatory diseases such as cancer, diabetes, heart disease, and brain degeneration. Researchers found that histamine and H2 receptors inhibited AGE activity that increases plaque in diabetes, proposing that stimulating H2 receptors might help prevent atherosclerosis.

Osteoporosis – Mast cells which release histamine appear important to bone health, and a deficiency or excess of them can be associated with osteoporosis. It has even been suggested that inhibiting mast cells might eventually become a treatment for osteoporosis! Estrogen deficiency (associated with calcium deficiency) may contribute to increased mast cell activity and low bone volume that leads to osteoporosis.

Dilated blood vessels – Typically histamine lowers blood pressure and dilates blood vessels which leads to low blood pressure and increased permeability. Even hemorrhoids are dilated blood vessels associated with increased mast cells and histamineAgain, histamine can switch directions and constrict and dilate arteries and cause chest pain.

Nausea and motion sickness – Histamine can play a role in symptoms like vertigo, motion sickness, and nausea, and vitamin C supplementation may provide relief. Antihistamines have also been used to reduce post-operative nausea and vomiting.

• Sleep disorders – First-generation antihistamines made us drowsy, revealing how histamine helps keep us alert. Normally, histamine H3 receptors reduce histamine activity so we can properly fall asleep or stay awake. Studies suggest that damage or deficiency of these receptors can result in permanently excessive histamine which can contribute to chronic sleep disorders.

Hypothermia – Histamine released by the hypothalamus helps control body temperature which affects various body functions. Experiments on mice showed that histamine injected in the spinal cord can even produce hypothermia. Higher histamine levels that induced hypothermia were associated with low vitamin B1 (thiamine) levels in another study.

DiverticulitisSome types of diverticulitis appear linked to allergies and histamine activity which generate massive inflammation.

• Meniere’s diseaseThis condition involves chronic dizziness, tinnitus (ringing ears), and hearing loss which are associated with histamine levels. Betahistine works to relieve symptoms in a mixed manner by inhibiting histamine H3 receptors while enhancing H1 receptors.

Vulnerability to disease – Histamine increases the permeability of the blood-brain barrier which can leave us vulnerable to bacterial infections and other diseases. Disruptions of the blood-brain barrier play a role in the development of epilepsy, Alzheimer’s Disease, meningitis, and multiple sclerosis.

Histamine on the horizon

We can now begin to imagine how to change our diet, avoid certain drugs, and adjust our lifestyles to better regulate our histamine levels. By first identifying our allergens through thorough testing, we can reduce exposure and dramatically empty our “histamine bucket” and lower inflammation. Even if we have no allergies to avoid, we can improve our ability to breakdown non-allergic histamine with B and C vitamins. Ideally we can better prepare our bodies to handle histamine “spikes” as needed for fighting disease, increasing motivation, or simply tolerating delicious leftovers.

We desperately need a way to identify and “scan” histamine content in our food and supplements prior to purchase and consumption. Packages can differ widely based on their microscopic bacteria content – even within expiration dates. Austrian scientists have made suggestions for tolerable levels for certain foods including sausage, fish and cheese, but we need global standards for all foods and awareness of the risks surrounding fish, fermented foods, canned meats, alcohol, prepackaged meals, and other high-risk products.

Similarly, daily tracking of our own histamine metabolism would help guide our diet and lifestyle. Recognizing the triggers can help us map our journey to good health and beyond!

Update July 2013 – The Hidden Accomplices of Histamine Intolerance:

Researchers are finding that histamine and its toxicity can be affected by related substances in its family of biogenic amines including putrescine, tyramine, and cadaverine. Putrescine and cadaverine in foods can prevent the breakdown of histamine and contribute to symptoms of intolerance. Putrescine is highest in spoiled food, fruits and cheeses, while cadaverine can be high in aged meats, fish and cheese. Some migraine sufferers have noted sensitivity to tyramine-rich foods which can accumulate tyramine in bodies with reduced levels of monoamine oxidase (MAO). Tyramine builds up in foods such as aged cheese, meats, fish, red wine, and soy sauce as well as high-protein foods that have been stored over time.

A limited but useful food database was been developed that identifies polyamines in food sources. Grapefruit juice, orange juice and cooked soybeans showed higher levels of putrescine, while lentil soup and cooked soybeans showed higher levels of spermidine and spermine. Mature cheddar cheese was high in all three polyamines, demonstrating how fermentation and storage can dramatically affect levels in many products. A wide range of spices can reduce polyamine activity, though some like curcumin (turmeric) may also inhibit DAO according to animal tests. Yogurt and high fat milk showed lower levels of polyamines than other milk products, though more studies are necessary to find the relationship between fat, polyamines, and histamine burden on the body.

Like histamine, biogenic amines can be produced by bacteria in food but cannot be broken down by cooking or freezing. Substances like resveratrol (found in red grape skin) and green tea can reduce histamine production and the allergic response, and interestingly these substances are also inhibiting tumor growth. Research has associated elevated polyamines (putrescine, spermidine, and spermine) in the body with cancers of the breast, colon, lung, skin, and prostate.

 

181 comments to The many faces of histamine intolerance

  • Great article – great summary. Histamine problems come in three forms a) consuming too much b) producing too much c) not metabolising enough. I’d love to see a follow up article on how to boost metabolism of histamine as many people have methylation problems that slow down histamine metabolism, not just DAO production.

  • Ann

    Wow, the feedback loop makes a lot of sense to me. I would faint every 15 weeks due to a drop in blood pressure. There was intense pain in the lower left abdomen, same place I’ve been getting the pain for 45 years. The fainting loop started when I began reducing Lamictal. I had seizures, had the surgery, became sz-free, so began reducing meds. Reduction took 4 years and I delayed med reductions once (because I didn’t want to get sick that week) and wound up fainting anyway. The cycle continued after I was off all meds until I changed my diet. I removed/reduced the high histamine foods from my diet and stopped fainting. When I removed all citrus, a few months later, my arm started to work again. I hadn’t been able to lift it above my shoulder for 4 years.

    Your info is amazing.

  • That’s a great question – the half-life of histamine and related factors certainly feels like forever when you’re itching like mad! Histamine actually breaks down within minutes. IgE antibodies to an allergen may only last hours roaming freely in the plasma, but once they attach to mast cells, it could be weeks or months! Once the reaction has started (mast cell degranulation), there is a feedback loop that causes allergic inflammation, and the body has signaling molecules that can turn the process on or off. Salicylates including aspirin and NSAIDs like Aleve can cause mast cell degranulation, so they are triggering suspects in this case. In fact, one of the contraindications for Aleve is the “Condition of Increased Mast Cells.”

    It is important to check with an allergist about a drug allergy to NSAIDs (aspirin, naproxen/Aleve, ibuprofen, etc), as some people are very sensitive and the reaction could be even worse next time. We can develop allergies at any time in our lives. Increased intestinal permeability raises the risk of developing allergies. Alcohol and NSAIDs dramatically increase the permeability of the gut, allowing the invasion of bacteria and development of allergies. It is also possible that environmental allergies (mold, pollen, chemicals) are filling the “allergy bucket.” I’ve had similar allergic incidents when accidentally consuming gluten with my celiac disease, so identifying and treating food allergies and autoimmune conditions can help.

    Researchers are hunting for substances that can stabilize mast cells and prevent the vicious cycle. Some very exciting papers have outlined the benefits of probiotics, and I mentioned that taking different strains of probiotics including L. reuteri, L. rhamnosus, L. casei, and B. bifidum may work best. A high-quality refrigerated probiotic capsule is going to be more reliable, and yogurt does not usually contain all of these.

    Besides allergy testing, diet can reduce histamine and protect the gut lining. Environmental estrogens (pesticides, heavy metals, plastics, household chemicals) can also promote allergic disease.

    Hope your streak of bad luck will eventually bring new health and awareness! Best wishes.

  • anne

    Since April of this year I have had poison ivy twice, a bee sting, and another bite/sting resulting in leg swelling. , I also had aspirin, aleve and red wine within a few days. I work outdoors. Last week I broke out in very bad hives that brought me to the ER twice. Even with prednisone and antihistimines , the hives and severe itching lasted one week.
    My question is can histamine build and accumulate in the body over a period of months before a histamine reaction occurs. Is there a threshold that when exceeded by too many triggers causes an acute response?
    Your article is awesome. Thanks.

  • This is an important point. The second enzyme that breaks down histamine is histamine N-methyltransferase (HNMT) that only occurs in tissues and not body fluid, so direct assessment does not appear possible. We are also not clear on which enzyme should take the blame (DAO, HNMT, or possibly the related histidine decarboxylase that turns histidine into histamine). One very old paper predicted that HNMT was responsible for histamine degradation in skin. Apparently HNMT works inside the tissues, while DAO gets dumped into our bloodstream in order to manage histamine levels. The highest amounts of HNMT are in the kidney and liver, and it is the most important enzyme for breaking down histamine in the lungs.

    The urine test at the Mayo Clinic or Quest Diagnostics can check for N-methylhistamine which shows increased histamine production – usually a disorder of mast cells.

    There are genetic tests that show mutations in the HNMT gene, but I could not find one publicly available. There are a few associations between HNMT mutations and atopic dermatitis, myasthenia gravis, and asthma. One company has a genetic testing kit for Mast syndrome, but I could not see that it evaluated HNMT.

    My article focused on treating symptoms of histamine intolerance (despite genetic causes) with diet and lifestyle, as we cannot alter our genes. Some gastrointestinal diseases may reduce the enzymes, so treating them appropriately (as in the case of celiac) may likely have a positive effect. Crohn’s disease and ulcerative colitis associate with low DAO activity. My personal experiences with excessive mast cell degranulation were triggered by foods or allergens that normally would have been tolerable. However, my system was disrupted by recent accidental exposure to gluten in each case, setting me up for hypersensitivity.

    The best technical paper on histamine and the enzymes is published by Amer Journal of Clinical Nutrition.

  • Ann

    I see reference to DAO enzyme but am curious as to how you can check and see if there is a problem with the H-NMT enzyme. How can it be tested and where could it be done? Is mast cell activation disorder caused by reactions to high histamine foods? I had epilepsy as well, urticaria, leg edema and a few other problems.

  • Poor kid! A prompt consultation with a naturopathic doctor is a great idea. Here is a link to the “Find a Naturopathic Doctor” service. I am not a doctor and cannot offer professional advice, but my personal experience and shared research may be helpful. The recent report on allergy remedies is worth reading as well.

    The basic IgE tests can be very limited – agave is not often tested but is known to trigger allergic reactions (not related to bees, only the agave plant). IgE in cells can last for weeks, resulting in mast cell degranulation, histamine production, and inflammation. Depending on which mast cells are activated, the symptoms can appear in the respiratory system, intestines, skin, lymph nodes, spleen, and liver.

    IgE levels increase in childhood and peak between age 10-15, so it seems important to identify as many triggers as possible right away. Thorough IgE tests should include airborne allergens like dust, mold, and pollens. While avoiding dietary and environmental allergens AND foods high in histamine (processed meat, fish, fermented foods and condiments, leftover meats, etc.) – the immune system can be boosted with B vitamins which help break down histamine. The only kid-friendly chewable B Complex supplement I found was on Amazon, and I give it to my kids.

    Vitamin C has also shown some anti-histamine effects, but all types of citrus allergies should be checked before consuming extra citrus. A natropathic doctor may advise on the safe dosage of vitamin C supplements. A diet rich in carotenoids might prevent the development of food allergies (in mice), and carotenoids are high in yellow, orange, and red plant foods like carrots, pumpkin and sweet potato. They are also high in spinach, kale, tomato, and Chinese cabbage. Again, allergenic foods should not be consumed. I do not consume much pumpkin because it is usually only available in a can with high histamine content.

    My personal experience with severe histamine reactions (lasting 2 weeks) consistently occurs after exposure to gluten (I am celiac and wheat/gluten intolerant). I become extremely sensitive to allergens within 1 weeks of accidental gluten exposure, experiencing 1-2 weeks of intense swelling and unbearable itching from allergens usually better tolerated (such as lavender or mint soaps). I benefitted from these remedies, though a simple anti-histamine drug may have been easier!
    • Soaking in cool water with 1/2 tsp of vitamin C crystals (=2000 mg from Trader Joe’s).
    • Oil pulling with organic coconut oil – this helped me with detoxification after IgE “overload” and has improved allergic skin symptoms in my sensitive son
    Bee propolis ointment or powder from capsules applied to itchy, swollen skin (this is not safe for those allergic to stings!)
    • Acupuncture actually relieved the itching, but I used a Chinese practitioner with many years of experience with unusual cases. He also gave me seed beads that I taped to points in the ear that helped reduce itching for a few days while my system calmed down.
    • No strong chemicals, soaps or shampoos.

    I did not use homeopathic remedies in these cases of “overload” but do have great success with BioAllers drops for airborne allergies in different seasons. Because I’ve had success with nearly every BioAllers product, I suspect that their common ingredient Histaminum Hydrochloricum may be part of the secret to success. The extreme dilution of histamine may somehow encourage my body to develop tolerance to histamine, reducing symptoms – just a theory. Amazon carries the Bioron homeopathic pellets of histaminum.

    If celiac was not checked, a doctor should do the blood work for this asap. Research shows some groups of people who are diagnosed with celiac following chronic urticaria (hives). Gluten-free dieting (along with avoiding the other allergens) can help some cases of chronic urticaria and has helped my family avoid problems with skin, fatigue, digestion, and mood/concentration.

    Keep me posted, and good luck.

  • Lisa Turner

    Thank you for this information. Do you have any information on histamine trigger or overload being caused by a single trauma? My 8 year old son was stung by a hornet on 7/25. His foot blew up like a club but then it went down. A week later exactly he blew up with hives so bad we had to rush him to the E.R. after he had a breakfast of pancakes drizzled with agave nectar. We initially thought he must of had an allergic reaction to the nectar (perhaps related to honey?) After a two day hospitalization and 8 weeks later he is still having chronic hives. His thumb swelled with a severe staff infection just three weeks ago in which the provider only could say “he was having a string of bad luck”. A Ige test came back with allergies to Rice, wheat, potato, tomatoes, garlic, oranges, and soy. Now today he has been nauseated, vomiting and diarrhea. I believe from H3 … His histamine levels are obviously still out of wack. I am at a loss 🙁
    Any information you may have would be much appreciated. I am going to homeopathic doctor soon to get some insight on how to build his immune system back up.

    Thanks,
    frustrated mama

  • Ask the doctor about checking DAO after all possible allergens have been tested. Sometimes we have to do our own sleuthing when tests are not available. Histamine intolerance is usually a sign of allergy overload. If the intestines are highly permeable (in the case of celiac), allergies to gluten as well as many other foods, pollens, and environmental substances can easily develop and dramatically raise histamine levels. It is known that airborne allergies can manifest as gastrointestinal symptoms, as in the case of birch pollen allergy – see research paper. An allergist might call this “pollen-associated food allergy” and it is important to identify and avoid as many allergens as possible until histamine/inflammation are under control.

    Be thorough in testing for all dietary and environmental triggers. US Biotek, for example, offers tests for 584 substances for IgE allergies. Sometimes we can narrow things down by simply leaving our environment – perhaps a weekend away and carefully noting changes in symptoms. Once the triggers are determined, look into sublingual immunotherapy as mentioned in my recent report.

  • Courtney

    Hi there,
    I’m fairly convinced I have a child (6 yrs old) with Histamine Intolerance. She looks like a textbook case to me (she has Celiac, can’t tolerate tomato, chocolate, and many many other high histamine foods). She has constant abdominal pain which gets progressively worse throughout the day. She is under the care of excellent physicians both at Children’s Hospital LA and Boston Children’s Hospital. The doctors are stumped as to what causes her pain despite a strict gluten free diet (we are excellent on this front and have done may eliminations except histamines). Still, the doctors discount my belief that she has Histamine Intolerance. I believe our allergist would order a DAO test for her. Do you know if the DAO test is accurate for children? Any other tests you suggest running at the same time? I prefer to draw blood as few times as possible from this little tyke–yet want/need as much info as possible to help her live a pain-free life! Thank you so much!

  • There may be an underlying allergy that magnifies when alcohol raises permeability and increase histamine levels. Some allergies to consider with an allergist include gluten, corn, and yeast. Beer is made with “gluten” grains like wheat, barley or rye so you may want to check for celiac or gluten intolerance. There are a few gluten free beers now. Corn can be added to beer as well. Sometimes preservatives are added to beers. Yeast may be a likely suspect as it is high in beer and wine but cannot survive in the higher alcoholic content of liquor (over 20% or over 40 proof). A good article is listed at LivingWithout.com. Alcohol consumption increases intestinal permeability which increases risk of intestinal disorders as well as allergic symptoms, including anaphylaxis.

  • Louise

    I had never heard about histamine intolerance before tonight, but after getting really sick from one drinking beer I stumbled upon this. I am curious though about histamine and alcohol because I seem to have trouble with beer, and a bit with wine, but not with liquors. Can anyone tell me if that could be a histamine problem or is it something else? Thanks.

  • Yogurt doesn’t contain all of the probiotics associated with reducing IgE (associated with histamine), but Lifeway Kefir does! Flavored kefir tastes like a yogurt smoothie and is offered at Whole Foods and health food stores. There are 12 active cultures in this kefir, and only 2-6 types of strains are available in yogurt. Some flavors of Stoneyfield and Silk Live Soy Yogurt containing the most variety (S. Thermophilus, L. Bulgaricus, L. Acidophilus, Bifidus, L. Casei, and L. Rhamnosus). So honestly, I eat different types of yogurt for taste and rely on kefir and probiotic capsules for therapeutic value.

    Dannon has tried to trademark a Bifidus strain in their yogurt, but it is simply a marketing term (Bifidus Regularis) for a strain of Bifidobacterium animalis.

    It may be easier to take capsules. Garden of Life, Innate Response, and MegaFood make capsules that contain L. reuteri, L. rhamnosus, L. casei, and B. bifidum that are mentioned in this article. When purchasing from iHerb, the Garden of Life capsules ship on ice to preserve freshness and keep more of them “alive.”

  • mary alcott

    Lit,
    I’m curious…what was the name of the yogurt you eat with the different strains?

    Thanks

  • Board certified allergists typically treat problems related to allergy – the most common reason for histamine overload. From there you can choose to suppress symptoms, use immunotherapy (see the next article), or explore underlying imbalances with a doctor of naturopathy or integrative medicine. Check out the AANP web site to find a naturopathic doctor in your area.

  • Please recommend doctors or clinics that deals with high histamine problems. I am suffering for years. I have checked with doctors up on down the US of A. still no definite diagnosis or relief. Thanks for your insightful article. Audrey

  • Yes, a bacteria-aware diet would bring us much closer to controlling our body and brain! Research is indicating that intestinal bacteria can affect our health by controlling our intestinal permeability – our body’s security gates. A starchy sugary diet as well as certain bacteria overgrowth fuels “bad” bacteria and fungus, paving a direct path to disease. Certain fermented foods such as sauerkraut and kefir may support gut health through beneficial bacteria, but some people may not be able to tolerate these items until they reduce their total histamine load (which is the objective of this article).

    You mention acid blockers and food intolerance, an interesting connection. Excessive histamine in the stomach is reduced by acid blocking drugs such as H2 (histamine 2) receptor blockers. Yet, the suppression of stomach acid interferes with our ability to break down food particles (proteins) that can lead to food allergy. Risk of food allergy is increased with these drugs, so it seems that they create a vicious cycle of dependency: acid blocker -> food allergy -> excess histamine -> more acid blocker. While we are still very much in the dark when it comes to understanding gut bacteria, new research showed that H2 receptor blockers lowered the bacterial diversity in premature infants. Bacterial diversity is vitally important to maintaining a healthy gut and preventing disease.

    Many naturopathic patients have discovered that their heartburn is actually caused by poor a digestive system rather than an overactive one! Both digestive enzymes and supplemental hydrochloric acid (betaine hydrochloride) help relieve symptoms in many cases by supporting the body rather than suppressing it.

    In summary, certain diets like GAPS may not be easy for those lacking histamine-degrading enzymes, but keep in mind that even fruits and vegetables can accumulate histamines in storage and packages. The GAPS diet focuses fresh foods which consequently reduces the total exposure to histamine in most cases.

  • Sarah

    What about histamine production from bacterial overgrowth. It is known that certain species of bacteria produce histamine (scrombroid poisoning) and there are a number of theories how gut dysbiosis is the cause of much food intolerance. For myself, I know an environmental change within myself accounts for much of my intolerance. I was only mildly intolerant to amines (I could eat some chocolate and cheese, but too much would give me symptoms), then I had acid blockers for indigestion (heredity issues with valve in my family) and my food intolerance went through the roof. The only things that have reduced my symptoms was eating a low amine diet and doing a diet protocol to heal my gut. The former alleviated symptoms but made me more and more sensitive. So much so, that I went looking for more information. The low amine diet had more refined starches and sugars that were feeding my dysbiosis and further damaging my gut. I started the GAPS diet and after a horrible start, my symptoms reduced dramatically. This diet is relatively high in histamine, which was not a problem after I healed my gut. I fell of the wagon and ate too many starches and sugars and I find myself intolerant again. Back to my diet protocol. I write this as I am concerned at how many diets inadvertently shift to higher levels of starch and sugar to avoid amines such as histamine. I think that an protocol based on changing your gut ecology should always be explored as genetic factors are not the only possibility. Especially if your symptoms have changed over the years, or are variable.

    Thank you for your in depth information.

    Sarah

  • lit

    Does this also relate to being allergic to certain medications like aspirin, ibuprofen, iodine and being unable to wear gold or silver jewelry with nickel as an alloy. These issues along with food allergies seems to run in my family.

  • lit

    This is by far the best article on this subject I have ever read. I have suffered from this since my teens and have spend countless amount of money with doctors. I have not incorporated a yogurt that has all the listed probiotics and I have seen a marked difference in my symptoms. I know eat it religiously and have told my brother to try it since he suffers as well.

  • A naturopathic doctor may be able to treat you more holistically to remove the underlying causes of disease rather than suppress symptoms. This link will help you find a naturopathic doctor: http://www.naturopathic.org/AF_MemberDirectory.asp?version=2

  • Adrienne Clarke

    Where can I go to be tested and shown vitamins I should take and foods to avoid. I have bronchoasthma, and allergys to certain shellfish. Also have urticaria and tinnitus. Any help is greatly appreciated. Frequent heartburn also.

  • Melanie

    Thank you for the very illuminating article. Very good information.

  • Yes, the FDA histamine limit of 50 ppm in a sample of fish is used for detection, as it may indicate much higher toxic levels elsewhere in the fish or sampled lot. Histamine levels vary widely in the tissue and do not break down with cooking, freezing, or canning. Symptoms of scrombroid poisoning may result at 200 ppm or higher. Tuna, mahi mahi, and Swiss cheese seem to readily acquire the bacteria that form histamine, but certainly any food could be suspect if left alone in the right environment!

  • Piao

    Thank you so much for providing such great info. Do you know why FDA established a histamine level limit of 50PPM for certain seafood? Is it dectection limit?

  • Dj

    Very helpful article. Now i understand why my body is itching and swelling, I just need to discover the source. Much of the info was over my head, lol, but I learned from it nonetheless!! Unfortunately I continue needing to postpone the allergy test as I can’t seem to go more than the required 3 days of no antihistamines before the test. Spent last night in the ER as my throat was blocked. Maybe more answers soon.
    Thank you!

  • For immediate IgE allergies, an allergist can review your symptoms and recommend a skin, blood or food challenge test. IgE allergies produce immediate, uncomfortable symptoms as a result of IgE antibody/histamine production. However, testing for IgG antibodies is not often pursued by doctors, as there is no consistent link to delayed or chronic symptoms. Some people (like myself) have great experiences eliminating foods linked to my elevated IgG antibodies, while others are disappointed. Until we have a better understanding of the body, food elimination diets and challenge tests (under professional care) are the best way to identify problem foods. I usually recommend allergists for immediate diagnosis of histamine-related symptoms and naturopathic doctors for treating the underlying imbalances that provoke allergic conditions.

  • rae

    Which test is recommend for allergy testing? Besides elimination diet. Is this through a naturopath?

    Thank you!
    Opinion on leaky gut?

  • Granuloma Annulare (GA) is a term describing a poorly understood skin reaction that may relate to [delayed] type IV hypersensitivity – but not the familiar type I hypersensitivity that produces IgE antibodies and histamine. If other high-nickel foods such as almonds, peanuts, and wheat bran also trigger symptoms, you could discuss the possibility of a systemic nickel allergy with your doctor. Chocolate and spinach are also very high in oxalate which can affect autoimmune conditions as noted by researcher Susan Costen Owens. Any kind of allergic reaction is going to stress the immune system in ways that influence other immune conditions. There is a newer paper discussing GA at http://link.springer.com/article/10.1007/s40257-013-0029-5#page-1 – hope this helps!

  • Denise

    Granuloma Annulare is a skin disorder, which in my case is triggered by excess chocolate and spinach. I always associated those foods with an internal allergic reaction due to the high content of nickel contained in them. Are you saying that these foods contain high amounts of histamine or that my body produces more histamine as a reaction to the nickel?

  • A. Winslow

    Excellent article, broadly researched, succinct and most
    informative. Thanks. We’ll be publishing an article pertinant to your interests which you might find of interest.
    AW

  • Kala

    Very useful and exhaustive info. Well presented too. Appreciate your efforts. Thank You

  • Paul

    Excellent article and much needed on any UK GP’s desk, many thanks, I am now equipped to deal with an often confusing visit to the GP’s surgery

  • Histamine plays an unclear but important role in pregnancy, and high levels of DAO enzyme (that breaks down histamine) are produced by the placenta. In fact, high progesterone levels in pregnancy inhibit mast cell secretion (including histamine). Since elevated histamine has been linked to depression in certain cases, the sudden increase in histamine could theoretically contribute to the many factors of postpartum depression. Rare cases of breastfeeding anaphylaxis within 2-3 days of birth are thought to be triggered by the drop in progesterone and rise in prolactin.

    Taking antihistamines while breastfeeding has not been linked to any adverse effects on the infant, but evidence is surprisingly scarce in recent years. There is new concern that the mother can transfer allergens to the infant, and an allergen-avoidance diet (plus fish oil and probiotics) may help prevent allergic responses in the infant. If there is a DAO deficiency (blood tested) as well as depression, it would be interesting to see if the Histame product would help alleviate symptoms.

  • Kelly

    If histamine intolerance can be triggered by a woman’s hormone levels could this be linked to baby blue or post part um disorders?

  • There are a few lists on the Internet but the primary focus is PURE FRESH WHOLE foods. If I am doing any testing with chronic symptoms, I insist on avoiding anything packaged for 2-3 weeks during the test. If you are casually lowering histamine, check out this online list of allowed foods. Avoiding chocolate and cocoa powder is important and absolute torture!

  • I wish someone would come up with a list of what we SHOULD be eating and drinking to avoid histamine symptoms. All the info about what to avoid is confusing, and confused by the things we ought to be having in order to enhance various vitamins and other elements.
    Being hypoglycaemic and coeliac the AVOID list does not leave me very much to eat !!
    Jane

  • Bec

    Thanks so much for this information on histamine – very in-depth and helps me understand how histamine behaves/functions in the body.

    Much appreciation for putting in so much effort to compile this article 🙂

  • Bill

    I agree! Best most informative site I have seen yet. Have been trying to figure out the source of migraines for years. Dr.s of western medicine were no help. Plenty of medicine if you want, but no one was looking for the root cause. Got the most help from my Naturapath . Went down the candida trail for over a year on a very strict diet and things were better. Then had igg food allergy testing, showed 17 different food allergies. Amung which, Milk, eggs, wheat gluten pepper, omit and things got better. But still the foruruner symptoms to migraines would show up, stiffness, tiredness, dizzyness, swelling of blodvessels intemples and pain. Still some food and drink cause problems gave me problems. Bingo! It was histamines. Have had this all my life. Slow learner I suppose. DAO seems to help slightly when taken, experimenting with vitamin C and quercetin. Having no red wine and only small amounts of decaff coffee. Thank you for your information.

  • Some people are having good results with DAO in products like Histame and DAOsin –
    see this discussion for testimonials. The supplements are expensive but easy to purchase on Amazon (with even more reviews) and must be taken before meals in order to work. The supplements are also not a cure in cases of underlying mast cell disorders.

  • amelia

    Thank you for what may be a lifesaver for me. I have ‘suffered like a dog’ for a few years with incredible itching…you have given me hope. What is your opinion on use of the enzyme ‘DIAMINE OXIDASE’ , WHICH SUPPOSEDLY BLOCKS THE ANTIHISTAMINE IN THE GUT? I AM AT MY WITS END…HAVEN’T SLEPT PROPERLY IN YEARS, CAN’T HANLDE THE INTOLERABLE ITCHING,. Amelia

  • mansoor ahmad

    good info

  • MrsM

    The best piece I ever read on histamine. Thank you!

  • It is safest to get thorough allergy tests as soon as possible to determine if symptoms are a result of a true allergy. Symptoms might be life-threatening with repeated exposures, and you may not be able to communicate the suspected allergies in the case of an emergency.

    The relationship between histamine and surgery is complex and might apply to many of us who have experienced unusual allergic symptoms after a procedure. A study in France found that the most common triggers for surgery-related allergy were neuromuscular blocking agents, latex, and antibiotics. Metal allergies might also aggravated by certain types of stitches and implants. I would suggest careful identification of all contact, chemical, and drug allergies through skin or intradermal tests as soon as possible – and especially before any future surgery or dental work.

    It is even more intriguing that certain anesthetic drugs can impair histamine activity in various complex ways, appearing to contribute to the coma-like effect. Similarly, enhancing histamine activity in cells can help wake animals from anesthesia. While we are lacking research on the histamine-anaesthesia connection, I would guess that any swing in histamine level might disrupt our pendulum.

  • Lorelei

    This is an incredibly helpful article; thank you so much. I have a PhD in Genetics, which means I have just enough background in Immunology to come to all the wrong conclusions. After surgery two years ago, I told doctors I must be allergic to morphine and Percocet, since both made me itch horribly. This was dutifully noted on my chart and is reviewed each time I meet with a physician – NONE of my doctors have said, “Actually, that could just be a release of histamines from mast cells.” I had surgery again last week and I refused any narcotic pain medications because I wanted to avoid itchiness, but in the last two days, I have, nonetheless, been overcome with skin itchiness, which rapidly turns into large welts. I explained it to myself as a “hyper-active immune system” during healing and have kept myself away from my dog out of fear that I will develop an allergy to her while my immune system is running rampant. Now i understand better what is really going on. Thank you so much for this excellent collection of information.

  • Perhaps mast cell disorders could be mistaken for histamine intolerance, but they typically involve very acute skin eruptions and diagnose with a series of blood and tissue analyses. We cannot yet identify our individual mast cell numbers, distribution, and underlying causes of accumulation. Mast cells, like histamine, are a deeper chain in the immune response, and we can attempt to reduce discomfort by stabilizing them and reducing their products (histamine). Genetics can also affect enzyme deficiencies and development of systemic mastocytosis (c-KIT mutation).

    Histamine intolerance (based on low DAO enzymes) is technically separate from mast cell disorders but could dramatically worsen symptoms. There is a blood test for DAO levels. Please share results if you choose to take DAO enzymes for mast cell activation syndrome or mastocystosis.

  • Amy

    If someone is being worked up for mast cell activation syndrome or other mast cell disorder… How can you tell the difference between an allergy to histamines versus a mast cell degranulation issue? Any way to properly distinguish upon testing or other assessment/interventions??

  • Bob

    Great site, thanks for the info.

  • Dunwoody Labs in Georgia can run a DAO enzyme test – they send a kit to your health care provider who will take your blood and return it properly. A company in Australia will also analyze blood tests shipped from the US – visit the ImuPro web site. I cannot verify the credibility of these testing sources. Some people prefer to try the DAO enzymes (such as DAOsin and Histame) to see if they improve symptoms.

  • Kim Craig

    Great article. Do you know anything about DAO testing in the US?

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