So when you get home that night, you plop in front of your computer and type “blue cheese and sick.” Food poisoning, you’re thinking. That tricky mold finally got to you. Or maybe you’re coming down with the flu. To your surprise, Google has another idea, directing you to a site about histamine intolerance. If you’ve never heard of such a thing, you’re in good company. Until 10 years ago, histamine intolerance was barely a blip on the radar in the medical community. “Histamine intolerance is a disorder of the 21st century,” says Oriol Comas-Basté, a researcher in the nutrition, food sciences and gastronomy department at the University of Barcelona in Spain, and leader author of a new report in the scientific journal Biomolecules. In fact, about 80 percent of the scientific literature on histamine intolerance has been written in the last decade, he notes, with the bulk of it in the past five years. “An increased interest in food allergies and food intolerance in the general population may play a role in this,” he says, “as well as new tools and analytical methods that have allowed a better understanding of the condition.” The growing interest in histamine intolerance and diet goes hand in hand with an increased awareness by healthcare professionals about the existence of this condition. “It’s still a fairly rare diagnosis—about one percent of people in the world have it,” says Elizabeth Bradley, M.D., medical director of the Center for Functional Medicine at the Cleveland Clinic in Ohio. “But in our world of functional medicine, it’s more common than you might think.” OK, so it’s new, it’s buzzy and it just might be the source of your disagreement with the charcuterie board the other night. But what exactly is histamine intolerance?

Understanding histamine intolerance

Let’s start with the basics: Histamine is a naturally occurring chemical messenger in your body. “It’s a byproduct of food but is also made in the body by certain cells, like mast cells, and is produced as a neurotransmitter in the brain by nerve cells,” says Tania Dempsey, M.D., a specialist in autoimmune diseases and mast cell activation syndrome in Greenwich, Connecticut. There is nothing inherently bad about the chemical—its primary function is to protect the body against allergens and foreign substances (like viruses) it perceives to be a threat. But if levels of histamine in the body become too high, it can trigger an allergic-type reaction. It’s easy to see how histamine intolerance could get lumped with other 21st century diet “intolerances”—namely, gluten and lactose—conditions that skeptics say far more people think they have than actually do. But histamine intolerance is different. For starters, despite what it sounds like, histamine intolerance does not mean that your body can’t tolerate histamine itself (the way a gluten-intolerant person can’t handle wheat). Rather, it means that your body is unable to process histamine, leading to a pile-up in your system that then causes adverse symptoms. “There are various mechanisms that we have in our body to metabolize histamine and a malfunction in any of those could cause histamine intolerance,” says Dr. Dempsey. 10 Severe Allergy Symptoms You Should Take Very Seriously

Is histamine intolerance real?

As case numbers rise, skeptics question where these new diagnoses have suddenly come from. Is it simply a case of people hopping on the condition-du-jour bandwagon? Possibly, but not likely, say experts. Instead, they attribute the increase to a better understanding of the condition itself. “The improvement of techniques to facilitate clinical studies is providing more accurate information for physicians to make an evidence-supported diagnosis of this disorder,” says Comas-Basté. “The prevalence has always been there, but in the past, affected individuals may have had to search for an explanation due to lack of awareness and information.” Still others believe an increase in the number of histamine-intolerant people is a reflection of the current times. “There are many environmental factors that can serve as a driver for this condition, including the quality of food, medications, stress and hormones,” says Dr. Dempsey. So if you’re having allergy-style symptoms—but have no known allergy—histamine intolerance is something worth talking with your doctor about.

Histamine intolerance causes

A week after your ill-fated wine and cheese outing, you’re lounging at home in front of the TV, noshing on last night’s leftovers while watching the game. By halftime, your face is flushed, your skin itches and you’re struggling to breathe. If this is histamine intolerance, what the heck is causing it? Well, it could be one of several things. “Histamine intolerance is a vague, umbrella term for a group of symptoms caused by histamine, but it does not tell you why the patient is actually intolerant,” says Dr. Dempsey. “The root cause must be determined in order for someone to be successfully treated.” Among the possible explanations for your recent rounds of illness:

Diet

Food is a leading trigger for histamine intolerance, says Dr. Dempsey. All food has some histamine in it, but the amount varies (more on that in a minute). In general, fermented and aged foods are high in histamine (why that cheese might have set you back), as are canned foods and leftovers. Many people do just fine eating high-histamine foods, but if your body is not able to metabolize histamine effectively, consuming these items can trigger symptoms like itching and hives.

DAO Deficiency

Your body produces an enzyme called diamine oxidase (DAO). Its job is to break down histamine from food in the GI tract to neutralize its effects. If you don’t produce enough of this enzyme, the histamine levels in your body rise, says Dr. Dempsey. Factors affecting DAO include:

Your genes: Single nucleotide polymorphisms (SNPs)—a fancy way of saying variations in the genetic building blocks of DAO—can lead to a deficiency in this enzyme.Medications: Certain antibiotics and blood pressure meds may lower DAO levels.GI disorders: The DAO enzyme lives in the GI tract, so inflammatory bowel disease, a leaky gut, non-celiac gluten intolerance or infections can compromise the integrity of the gut lining, leading to a deficiency in DAO.

HNMT Deficiency

Another enzyme, known as histamine N-methyltransferase (HNMT), also serves to break down histamine in your body, transforming it into a compound you can excrete through urine. Low amounts of HNMT can cause histamine to build up in the body.

Mast Cell Activation Syndrome (MCAS)

Mast cells are responsible for triggering an immune response in your body, and if they are mistakenly activated, they may cause excessive production of histamine. “If you have symptoms of histamine intolerance and do not respond to dietary changes or other simple interventions, get tested for MCAS,” says Dr. Dempsey. “Research shows 17 percent of the population has MCAS.” Although MCAS and histamine intolerance share symptoms, MCAS is its own disorder and treatment may differ.

Histamine Intolerance Symptoms

By now, you know all about the itchy, flushed, throat-constricting part. “If histamine intolerance is caused by your diet, you’ll feel it fairly soon after eating,” says Dr. Bradley. “Within an hour or so, it’s oh my God, I’m itching, my lips feel funny—you might even get hives—and you’ll say, what’s going on?” Histamine intolerance can manifest itself in other, less obvious, ways as well. For instance, you may have an unsettled feeling like a rush of adrenaline, says Dr. Bradley. Remember, when things are running smoothly, the role of histamine is to identify and kick out foreign “invaders” in your body, and the easiest way to do that is to make your eyes water and your internal passageways swell, cause your stomach to become unsettled and tell your GI tract to get a-move-on. For that reason, these are common symptoms of histamine intolerance:

AnxietyBloatingBreathing troubleCongestionDiarrheaFatigueFlushed skinGasHeadacheHivesInflammationItchingRednessUnsettled feelingWelts

Diagnosis and treatment for histamine intolerance

Despite advances in understanding this disorder, histamine intolerance is still tricky to diagnose. There is no single test your doctor can give you, but a battery of exams and blood panels can rule out things like food allergies, helping your physician zero in on the real culprit. “Diagnostic criteria includes the appearance of two or more typical symptoms of histamine intolerance and their improvement or remission after following a low-histamine diet, plus the exclusion of other related disorders like food allergies,” says Comas-Basté. There are a few diagnostic tools your doc might consider, including a test for certain genetic changes, or polymorphisms, that have been associated with lower levels of DAO activity. Doctors may also be able to identify biomarkers of histamine metabolism in your urine. But the tests are not 100 percent conclusive, and there may be other reasons for receiving positive results, so for now, clinical symptoms and the elimination of other possible causes are your best bet. If you are diagnosed with histamine intolerance, your doctor will talk with you about several treatment approaches, including dietary changes, supplements and possibly medication. “Using a food diary can help you track your symptoms, especially when it might not be clear which foods are causing the problem,” says Dr. Dempsey. You may also be asked to follow an elimination diet, where you systematically remove certain foods high in histamine from your meals, to see if you get relief from your symptoms. Should your physician determine that you are deficient in the enzyme DAO, there are supplements you can take before a meal to help your body break down histamine in food. One small study found 13 out of 14 people with histamine intolerance who took a DAO supplement experienced relief in their symptoms. Changing your diet and taking supplements may bring relief; if not, your doctor might suggest medications. “Some people respond well to medication that blocks either or both histamine receptors, H1 and H2, especially when other interventions are not successful,” says Dr. Dempsey. “H1 blockers are drugs in the antihistamine class and H2 blockers are drugs that block histamine receptors in the stomach—sometimes thought of as ‘antacids.’” Examples of H1 blockers include loratadine (Claritin) and fexofenadine (Allegra); H2 blockers available over the counter include famotidine (Pepcid) and Cimetidine (Tagamet).

Histamine intolerance diet

While no food is truly “histamine-free,” different foods have different levels of the chemical, and if you are dealing with histamine intolerance, a nutritional plan that focuses on low-histamine foods while limiting high-histamine foods is worth exploring. In fact, researchers in Seoul, Korea, found that following a low-histamine diet for four weeks reduced the severity of histamine intolerance symptoms like hives by 36 percent. These are some of the foods you may want to reduce or add to your diet.

High-Histamine Foods

If you’re looking to cut back on foods high in histamine, the Journal of the Academy of Nutrition and Dietetics suggests eliminating the foods below from your meals entirely, noting any difference in symptoms, then adding them back one by one to see if symptoms reappear or worsen:

Aged and fermented foods (kimchi, cheeses, yogurt, processed meats, sauerkraut)AvocadoCanned foodCertain seasonings (chili powder, cinnamon, cloves)CherriesEggplantFrozen or smoked fishGround meatLeftoversSpinachStrawberriesTomatoesWine and beer

Low-Histamine and Antihistamine Foods

Elimination diets may help you ID foods causing your symptoms, but “you can’t do a low-histamine elimination diet for a long period because it is too restrictive,” notes Dr. Bradley. A better long-term approach? Seek out the foods below, which are naturally low in histamine levels, or contain compounds like bromelain and quercetin, antihistamines that block the production of histamine:

AlmondsApplesBroccoliCarrotsChickenCoconut milkCooked eggsCucumbersHerbal teaLeafy greensLentilsMelonsOatsPearsPineappleRice (white or brown)TurkeyTurmeric (research shows turmeric may inhibit the release of histamine by mast cells)

Histamine-releasing foods

Certain foods are not high in histamine themselves, but aid in the release of histamine in the body or block the ability of DAO to break down histamine in your body. The Histamine Intolerance Awareness Organization lists these foods as ones to watch out for:

Black and green teaChocolateCitrus fruitsKiwiMilkMost vinegarsNutsRaw egg whitesSome preservativesWheat germ

Probiotics for histamine intolerance

A final piece in the histamine intolerance puzzle? The quality and quantity of healthy bacteria in your gut. Here’s the deal: The composition of your so-called gut microbiome helps determine the health of your gut lining, which in turn can affect the ability to properly process or remove histamine. A study in the Journal of Physiology and Pharmacology found that people with histamine intolerance had less diversity in their gut bacteria and greater impairment in their gut lining, compared to those without histamine intolerance. “Stress, poor diet and medication can all cause a disruption in the integrity of the intestinal wall,” explains Dr. Bradley. “That can lead to inflammation of the gut, which makes symptoms even worse.” Enter: Probiotics. These microorganisms can decrease gut inflammation, support your gut lining, increase good bacteria in your gut and reduce the amount of non-beneficial bacteria. (Prebiotics—foods like onions, garlic and ginger that support probiotics—may be beneficial as well, says Dr. Bradley.) Probiotics can be taken as food or in supplement form, but which ones you use matters, so read the labels carefully. “Certain probiotic strains are known to produce histamine, which could make the situation worse,” says Dr. Dempsey. “But other strains can help lower histamine levels.” Look for following probiotic strains, which have research supporting their ability to decrease histamine levels:

Bifidobacterium infantis 

Bifidobacterium longum 

Lactobacillus plantarum 

Lactobacillus rhamnosus

Lactobacillus gasseri

Bifidobacterium breve

If probiotics aren’t making a big difference in your symptoms, don’t give up. Histamine intolerance can be complicated to address, due the many possible causes for the disorder, but most people eventually figure out their triggers and how to avoid them. You might be taking a pass on wine and cheese in the future, but there are plenty of foods you can enjoy—minus the hives. Piña colada, anyone? For more good-for-you foods, check out this list of anti-inflammatory eats your body will love.

Sources

Oriol Comas-Basté, researcher in the nutrition, food sciences and gastronomy department at the University of Barcelona in SpainElizabeth Bradley, M.D., medical director of the Center for Functional Medicine at the Cleveland Clinic in OhioTania Dempsey, M.D., a specialist in autoimmune diseases and mast cell activation syndrome in Greenwich, ConnecticutAllergologia et Immunopathologia: “Histamine, Histamine Intoxication and Intolerance.”Biomolecules: “Histamine Intolerance: The Current State of the Art”American Journal of Clinical Nutrition: “Histamine and Histamine Intolerance”International Journal of Immunopathology and Pharmacology: “Serum Diamine Oxidase Activity in Patients with Histamine Intolerance”Annals of Dermatology: “A Histamine-Free Diet Is Helpful for Treatment of Adult Patients with Chronic Spontaneous Urticaria”Molecular and Nutritional Food Research: “Immunomodulatory Effects of Curcumin in Allergy”Journal of the Academy of Nutrition and Dietetics: “Is There a Diet for Histamine Intolerance?”Histamine Intolerance Awareness: “Food List”Journal of Physiology and Pharmacology: “Microbial Patterns in Patients with Histamine Intolerance” Histamine Intolerance and Diet  What Is a Low Histamine Diet  - 13