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 Laboratory, US 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 report, NSAIDs 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

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

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

and seasonings like Wheat-based products

Beverages such as tea (herbal or regular) and soy milk are high in histamine

are high in histamine Any type of alcohol interferes with the body’s ability to break down histamine.

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 studies. Reducing 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 inflammation. Studies 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.

• Migraines – There 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 drop. Similarly, 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 rats. Even 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 histamine. Again, 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.

• Diverticulitis – Some types of diverticulitis appear linked to allergies and histamine activity which generate massive inflammation.

• Meniere’s disease – This 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.