Histamine is a biogenic amine that is counted among the so-called tissue hormones. This substance is relevant for many physiological and pathophysiological processes in the human body. Among other things it is an important mediator for inflammatory reactions.
Chemical formula: C5H9N3. Alternative terms for histamine are: 2-(4-Imidazolyl)ethylamine, 2-(1H-Imidazol-4-yl)ethanamine or 4-(2′-Aminoethyl)-Imidazole. Structural formula:
Histamine is found almost everywhere in the human body, i.a. in the skin, lungs, the mucous membrane of the gastro-intestinal tract and the hypothalamus. Also, food contains significant histamine concentrations. Some plants use histamine as a substance for defense (e.g. stinging nettle).
Histamine arises from decarboxylation of the amino acid histidine in the human body. The conversion is catalysed by the enzyme histidine decarboxylase (HDC). Histamine is metabolised to n-methylhistamine by histamine-n-methyltransferase (HNMT) or converted to imidazole acetic acid by diaminooxidase (DAO).
In cells that contain higher doses of histamine, e.g. mast cells, histamine is being stored intracellularly in vesicles, in which it is bound to heparin.
Function and receptors
Histamine is a potent mediator, which triggers many consecutive reactions in the organism. It unfolds its effects via bonding to membrane-bound histamine receptors, of which there are 4 known ones, H1-, H2-, H3– und H4.
The most import pharmacological effects which occur in several tissues due to activation of the receptors are as follows.
1. Blood vessels
Histamine triggers via the H1-receptor vasodilatation and an increase of the vascular permeability of the blood vessels. Due to the vasodilatation the arterial blood pressure falls and the generation of adrenaline increases. Another arising effect is the emergence of edema (skin and mucous membrane). Typical abnormalities in the skin due to histamine are swellings, redness/flushing and itching. When it comes to migraines or other headaches the vasodilating effects of histamine may play a role, too.
In the bronchi histamine, also via the H1-receptor, leads to bronchoconstriction. Histamine therefore is of special importance for understanding the allergic bronchial asthma and its pathophysiology.
3. Gastric mucosa
Histamine induces a higher secretion of gastric acid via stimulation of the H2-receptors of the parietal cells of the gastric mucosa.
4. Central nervous system
In the central nervous system Histamine operates as a neurotransmitter. It influences also the release of other neurotransmitters via presynaptic H3-receptors. It has bearing on noradrenergic, serotoninergic, cholinergic, dopaminergic and glutamatergic neurones. The diverse effects of histamine in the body are the subject of intensive research and are not fully understood as of yet. Among other things histamine is involved in inducing vomiting and it also is involved in the regulation of the sleep-wake cycle.
(Cf. my own translation of: http://flexikon.doccheck.com/de/Histamin)
Definition: Histaminosis or histamine intolerance are general terms for excess histamine in the body (locally or systemically) that disrupts the well-being or the physical/mental functions. Different from an allergy, there are no antibodies involved in histamine intolerance. There are problems in breaking down histamine, therefore symptoms occur.
The term histamine intolerance, refers to a dysfunction in breaking down histamine due to a deficit in diamine oxidase (DAO).
Not only DAO (diamine oxidase) but also another enzyme HNMT (histamine N-methyltransferase) is involved in breaking down histamine.
The following graphics show that also MAO (Monoamine oxidases) play a minor role in breaking down histamine.
Due to the different enzymes operating at several spots in the body to break down histamine there are different forms of histamine intolerance – with different causes and cances of recovery.
Forms and possible causes of histamine intolerance
As of today the exact causes of histamine intolerance are still controversially disputed, especially because there appear to be various types of this ailment, depending on which histamine-receptor/s is/are affected (see above), also depending on if one was born with it or not. In any case, there is dysfunction in breaking down histamine. Read here more about possible causes.
If one is born with histamine intolerance it can last for a lifetime. In that case one will try to eat food low in histamine lifelong. This form usually is treatable, but not curable.
A dysfunction of HNMT can be caused by chemical influences (environmental toxins), it is then usually only temporary and therefore can be cured.
Most cells produce both DAO and HNMT. Yet, the amount varies considerably according to organ respectively cell type. In the central nervous system (CNS), in the bronchial mucosa and in the skin HNMT is the main way to break down histamine. Therefore these organs, especially the brain, tend to be effected strongly with malfunction of the HNMT. (Note: In these organs there are also a lot of mast cells.)
Mast cell activation disease must be considered as a possible cause, too, especially when symptoms linked to the organs named above are featured.
With a DAO deficit symptoms linked to the central nervous system are rather rare. DAO is an excretory (= releasing to the outside) enzyme, that is mainly being produced and discharged by cells of the intestinal mucosa. It degrades histamine already in the bolus/food that has been taken in, before it “hits” deeper in the body. HNMT on the other hand is degrading histamine in the body cells, especially in the kidneys and the liver (detoxication).
Due to the spatial and functional “labour devision” when it comes to histamine (enzymes active in different organs, in the cell and outside of the cell) it is likely that one enzyme is not fully able to substitute the other in case of a deficit.
Among other things, pre-existing conditions, especially when bacteria were/are involved or metal pollution, are possible causes for histamine intolerance. If the affected person is treated respectively detoxicated and if the diet is strictly low in histamine for a while this kind of histamine intolerance can be overcome. Sometimes the root cause can be found quite easily in the mouth. Nowadays outdated amalgam fillings can intoxicate the body, if the filling on top of that is carious the bacterial involvement will make it worse.
Other influences that might lead to histamine issues are antibiotics that destroy(ed) the gut flora.
Furthermore if the hormonal balance is off this may cause histamine issues, too. The biggest role here presumably plays oestrogen. The amount of oestrogen is not crucial, but rather the balance between oestrogen and other hormones, such as progesterone, testosterone, is decisive. Women are more prone to this “hormonal” type of histamine issues.
The hormonal balance can be disturbed by…
- female cycle (menstruation)
- hormonal contraception (e.g. birth control pill)
- menopause/climacteric period
- oestrogen dominance respectively progesterone or testosterone deficit
- hormones or hormone-like substances in natural foods (e.g. oestrogen in hop/beer)
- hormonally active environmental toxins, substances with hormone-like effect in everyday products such as plastics, sun screen, cremes/lotions and more
- (maybe hormones applied to animals in “food production”?)
Indications of a connection between histamine and hormones:
Considerably more women than men are affected and histamine intolerance often occurs first with the beginning of menopause. The intensity of histamine issues depends on the female cycle (menstrual cramps as a histamine symptom).
Afflictions of people sensitive to histamine can worsen OR better with hormonal contraception depending on the individual hormonal balance.
During pregnancy the DAO-level approximately rises to 300 times of what it was before to protect the embryo from histamine. With the effect that during pregnancy allergies and other histamine issues seem to improve.
These complicated connections are not fully understood, yet. One explanation might be:
For the degradation of oestrogen vitamin b6 is needed. If excess oestrogen has to be degraded it might be there is not enough vitamin b6 available for DAO and histamine degradation. Vice versa the histamine level also influences the hormonal balance. It is possible that not only DAO is affected hormonally, but also other processes of histamine degradation.
The problem with pseudoallergies
Histamine can be released from mast cells in the body and it can be taken in with food. A healthy body is able to break down histamine, so usually no problems occur. However, if the body is confronted with many histamine sources and unable – for whatever reason – to break down the histamine, then the histamine level rises in the body. (Some people tend to speak of “their histamine bucket” that can overflow.) If the individual tolerance threshold is surpassed (the bucket overflows), symptoms occur, often resembling symptoms of poisoning. One symptom might be rashes, similar to an allergic reaction, but also migraines or other headaches. The similarity in symptoms lead to the term pseudoallergy.
Different from an allergy, there are no specific IgE antibodies involved in pseudoallergies.
Just the reaction seems similar. Yet, this is one reason why histamine intolerance is still difficult to diagnose. People affected by it are often suffering for years or months until they are treated properly. Sometimes they are denounced hypochondriacs or their symptoms are linked to a psychosomatic disorder. The patient then does not receive proper treatment. The symptoms can resemble those of other intolerances and pollen allergy:
- swollen nasal mucosa, running nose, sneezing, phlegm, irritation of the throat, difficulties breathing
- digestive problems: diarrhoea, stomachache, bloating, acid reflux
- itching, skin rashes, redness
- hot flush, attack of sweating, disturbed temperature sensation
- tachycardia, rapid heartbeat, allodromy, drop in blood pressure
- headache, migraine, dizziness
- insomnia/sleep disorder, fatigue
- nausea, vomiting
- menstrual cramps
- edema (e.g. swellings)
(s. my own translation of: http://www.histaminintoleranz.ch/symptome.html)
Histamine is not any poison in the general sense. This is also important so one will not be afraid of supposedly “toxic” food. Histamine is one of the body’s own neurotransmitter with several functions as described above. In people affected by any kind of excess histamine the regulation of these processes is disturbed.
There are several causes of histamine intolerance. Furthermore the kind of histamine intolerance – more DAO or HNMT – is important for the individual cluster of symptoms. Often the first step after diagnosis is a dietary change (low histamine foods). I hope I can help you with this. Please feel free to get in touch with other people affected via this website. My main goal is it to gather yummy recipes here that will help people who got hit with HIT.
General information: diet
Most patients are advised to omit high histamine foods once they got diagnosed with histamine intolerance.
But this is usually where the problem starts. When having a common allergy then one just omits, say nuts. Products nowadays have to reveal allergens like nuts.
Also vegetarians can now often find products labelled as “vegan” or “vegetarian”.
But with histamine intolerance it is no allergy and certainly not only one food or only one food group. That would be the case for people suffering from lactose intolerance, who have to avoid all dairy products.
Moreover the body itself produces and releases histamine, because it is important for many processes, e.g. the sleep-wake cycle. Histamine is also being released in the process of digestion.
How do I find histamine in food?
How do I know if histamine is in the food? Well, actually very few foods are completely free of histamine (e.g. pure substances like water, salt or sugar). Apart from that, many foods contain histamine – sometimes more, sometimes less.
But there are also foods, which contain significantly high doses of histamine (foods high in histamine) and others which are known to trigger the release of histamine in the body (histamine liberators or triggers). Triggers often don’t contain much histamine, yet especially for people suffering from HNMT related histamine issues, triggers can cause symptoms and they certainly also fill up your “bucket”. Some (food) triggers are coffee (caffeine), cacao (theobromine) and many exotic fruits…
Furthermore there are so-called “DAO blockers“. Nicotine is such a DAO blocking substance for instance. So smoking can be an issue when having histamine intolerance.
The detective work – finding the histamine offenders – is something everybody has to do individually. Not everybody reacts the same way to every substance. Certain food lists, though, can be very helpful, especially to get started. They give you an idea what the histamine “suspects” might be. The Swiss organisation SIGHI tested a lot of foods on those affected by histamine intolerance and they also determined the histamine concentration in some foods. Here is the list.
The actual histamine concentration in food depends also on how it was produced and how (long) it was stored then. Food that needs long to ripen (like parmesan for instance), that was warmed up again (leftovers reheated), that goes bad easily (e.g. fish) or overripe food (especially fruits) should be avoided.
Besides food lists concerned with the histamine potential or concentration in food, lists concerned with the histidine concentration can be helpful, too. This is because histidine is a precursor in building histamine. Histamine develops through unspecific L-amino acid decarboxylase respectively through specific histidine-decarboxylase that is present in many tissues.
Fish, which contains a lot of protein and a lot of histidine can develop high histamine counts fast. It is important to gut the fish as soon as possible since the bacteria in the gut are the main cause for transforming histidine into histamine.
Histamine develops also easily in other foods which need microorganisms/bacteria for ripening, e.g. Sauerkraut or cheese.
When it comes to the histamine concentration in food freshness is the essential thing. Histamine is the result of spoilage. Histamine develops in huge numbers when spoilable foods that contain a lot of the amino acid histidine (e.g. fish) are colonised with bacteria and yeasts. But histamine can also develop during intended fermentation and ripening processes. What is actually intended to make the foods longer-lasting and more aromatic (e.g. Salami, cheese, Sauerkraut, wine, beer) drives up the histamine count aswell. In the course of longer storage the histamine concentration can increase, too (e.g. canned food).
Depending on individual sensitivity symptoms might not occur until several high histamine foods are combined (e.g. cheese with red wine). Also “healthy” people can develop symptoms depending on the dose. Almost everybody knows the typical feeling/headache after drinking an adulterated wine. Often it is not the bacteria that cause problems in the gut but the biogenic amines that are being released because of them. DAO is partly also in charge of breaking down other biogenic amines (besides histamine). A minor part in degradation plays the MAO. Other biogenic amines are rival to histamine when it comes to DAO, actually it is even worse, because DAO prefers other biogenic amines than histamine. The degradation of histamine slows down significantly when DAO is already occupied with breaking down other biogenic amines.
(Cf. my own translation of: http://www.histaminintoleranz.ch/histaminose.html#abbaustoerungen)
The selection of low histamine food is one thing one might look out for the other is to be aware of preparation and storage of the food. Freshness, again, is the important factor here.
There should be no interruption in the cold chain when buying or storing deep-frozen goods. I do not recommend slow defrosting (e.g. in the fridge), because this leads to more histamine again.
Avoid finished products or products that only need to be warmed up, e.g. breads that need to be finished in your oven. Many people cannot tolerate the inherent preservatives. Besides, the cold chain can often not be guaranteed during transportation.
Look out for certain food additives (e-numbers in Europe). Alcohol, vinegar and other substances (often of preservation) are being masked by those cryptic names or numbers.
When preparing meat, fish, vegetables or fruits (also from your own garden) make sure to wash it first. Histamine is temperature-resistent. It cannot be destroyed by freezing or heating up, but it is soluble in water. Therefore I recommend to drink enough water at meals.
Do not use pickled or canned food.
Do not warm up food again. If you want to use leftovers, freeze as soon as possible after cooking.
Try to avoid all foods with histamine potential (especially in the beginning):
- high histamine food
- histamine triggers/liberators
- other biogenic amines
- DAO and HNMT blockers
The individual tolerance threshold can vary depending on:
- what one eats before, at and after meals (again, drink enough water at meals)
- stress (better tolerance of food during holidays, stress as histamine trigger)
- current vitamin balance and current mineral balance
- physical labour or certain sports
- environmental toxins (smog, fine particles), smoking (nicotine) and passive smoking
- for allergy sufferers: contact with allergen(s) and cross reactions
- duration and quality of sleep, sleep pattern (jetlag)
- change in the weather (especially cold fronts and windy weather)
Sometimes symptoms occur and sometimes they don’t, although one is eating the same meal. This is a special challenge with histamine intolerance. The histamine concentration depends on how the food is prepared and stored.
Beware: Sometimes it is hard to notice the effect of histamine triggers and other biogenic amines, because they often appear delayed.
Once you started a low histamine diet over time it will get easier. You might also be able to add more foods to your diet again (once your “bucket” was emptied). You might have reacted to one thing in the beginning and therefore eliminated it from your regular diet, sometimes it is worth trying again after several months.
Please be mindful about a balanced diet respectively consult a dietician!
(Cf. my own translation of: http://www.histaminintoleranz.ch/therapie_ernaehrungsumstellung.html)
You have been eating according to the elimination diet plan respectively according to your individual food list for awhile now. Maybe it is time to test high nutrious foods you once eliminated. Please try in small amounts! Once the “bucket” is empty, the histamine strain on the body decreased, some foods are tolerated again.
My food list
meat: sausage products (especially salami, smoked and corned products), giblets, pork (high histamine/trigger), already marinated food (e.g. many meat products for barbecue in the supermarket), schnitzel or other breaded meat (because of wheat)
fish: tuna, mackerel, herring, sardine, sardelle/anchovy, iridescent shark, mahi-mahi (are often high in histamine), fish fingers (because of wheat in the coating), many shellfishes and crustaceans (spoil fast)
dairy products: hard cheese like parmesan, matured cheese camembert, cheddar cheese, Harz Mountain cheese, Emmental cheese (watch out for smelly cheese and for cheese with big holes). Generally prefer young cheese and dairy without bacteria strains, meaning sour cream, buttermilk and many yoghurts are to be avoided.
grains and pastries: products containing wheat (also couscous, Ebly/soft wheat and bulgur), products containing yeast (as yeast can feed unwanted bacteria when having SIBO, plus during fermentation before baking histamine builds up in the dough), rye can be problematic, “whole grain” does not mean without wheat (it is the term for a production method not a type of grain), the pseudocereals amaranth and buckwheat are often not tolerated
vegetables: sauerkraut, olives (when canned), capers (because it’s canned), tomatoes (also ketchup, tomato paste), eggplant, avocado, legumes that have to be cooked/soaked (lentils, beans, chickpeas (also hummus), soy), mushrooms, amaranth, celeriac, kohlrabi only in small amounts, leeks are not always tolerated, radish and horseradish are possible histamine liberators but are well tolerated here, onions are liberators and cause flatulences – fried they are tolerated in small amounts, in small amounts spring onions are better tolerated
fruits: strawberries and citrus fruits (liberators), raspberries, rosehip, mango, plum, watermelon, yellow/brown bananas (very ripe ones), pineapple, guava, papaya, passion fruit (also no multivitamin juice or other juices or smoothies that contain these fruits), jam only in small amounts (preserved food, often contains citric acid), no dried fruit (raisins, dates, figs, etc.)
nuts and seeds: most nuts, peanuts (actually they are legumes), cashew nut (only small amounts), walnut, pine nut, poppy seed only in small amounts tolerated, almonds (only small amounts), pecan nut?
spices and herbs: flavour enhancers like glutamate, soy and teriyaki sauce, mustard, dill, clover, chives, curry, chili because it is hot and might put more strain on the gut, cinnamon (strong allergen many people react to), nutmeg, ginger in small amounts
sweets: every chocolate containing soy lecithin as thickener, milk chocolate and white chocolate are usually better tolerated than dark chocolate, cacao
alcohol and other drinks: alcohol naturally contains histamine (fermentation), especially avoid red wine, whikey, sparkling wine, wheat beer, vinegar (especially from red wine), black tea, filter coffee, energy drinks, (yerba) maté and lemonades
soy products: also tofu and soy milk and several spreads that contain soy (often also in margarine), teriyaki and soy sauce
wheat products: it is not always obvious if food contains wheat. Most pasta contains wheat, couscous is usually made from wheat, cornflakes and many mueslis contain wheat (read the ingredients!), wheat is not actually high histamine, but very inflammatory and a big trigger here
oil: peanut oil, also pesto alla genovese is to be avoided due to parmesan (and pine nut?).
Low histamine alternatives:
meat: (fresh or deep-frozen) beef, lamb, poultry, partly venison, do not defrost slowly
fish: (fresh or deep-frozen) cod, trout, pollack, salmon, plaice and many other species, do not defrost slowly, some kinds of sushi and maki from an Asian restaurant you trust or if you made it yourself (freshness!) are tolerated (e.g. cucumber maki).
dairy products: mozzarella (without citric acid – read the ingredients), feta cheese, cream cheese, milk – no raw milk, plain yoghurt, cottage cheese, quark/curd, cream, butter cheese, young gouda
grains and pastries: prefer spelt products, you can also bake your own bread with baking powder instead of yeast, millet, rice, corn, hemp, coconut and spelt flour, pasta made from rice or spelt, oats and oatmeal, teff grass
vegetables: fresh vegetables like lettuce, rapunzel salad, rocket salad, cabbage and kale, cauliflower, broccoli, pumpkin, bell pepper (often a good substitute for tomatoes), carrots, potatoes, rice, cucumber, courgette/zucchini, corn (not canned), asparagus, garlic in small amounts (liberator like all leeks), pie plant in small amounts, artichoke (not from the glass), fennel, chicory, parsnip
fruits: blackberry, apple, apricot, cherry, blueberries, lingonberry, gooseberry, currant, coconut, seabuckthorn (not when allergic/intolerant to sorbitol), white grapes, no overripe fruits!
nuts and seeds: many nuts can cause problemes, but often can be substituted by seeds, e.g. pumpkin seed or sesame seed, in small amounts sunflower seeds can be tolerated (but it is a liberator), macadamia nuts are tolerated here, hemp seeds, chia seeds
spices and herbs: garlic in small amounts, many culinary herbs (often easy to grow on the windowsill), e.g. cress, southernwood/garden sagebrush, thyme, rosemary, basil, oregano, majoram, caraway seeds, blackseed, parsley, savory, sage, Baikal Skullcap, khella/toothpickwheat, melissa, mint, wild garlic/ramson, juniper… salt
sweets: prefer white chocolate before milk chocolate, avoid dark chocolate
alcohol and other drinks: generally avoid alcohol, some spirits and some beers are sometimes tolerated, white wine is better than red wine, instead drink water or curative water to meals or herbal tea, rooibos tea, espresso or cappuccino is better tolerated than filter coffee, because is contains less bitters and also less coffeine, green tea if it is steeped shortly
oil: oils for frying: coconut and olive oil, others not for frying: thistle, hemp, linseed. Sunflower seeds are triggers/liberators and therefore sunflower oil should also be avoided. Pumpkin seed oil is suitable for salads.
others: use mueslis with oats (instead of wheat), try to substitute wheat in general, e.g. with spelt or the other named grains/pseudocereals (s. above), if you would like to coat food use oats or sesame seed instead of wheat breadcrumbs
I post tips on special topics on a regular basis. You can find all tips by clicking on the category “tips” on the left side.
(artificial) colours: tartrazine (E102), quinoline yellow (E- 102), orange yellow S (E110), azorubine (E122), amaranth (E123), cochineal red A (E124), erythrosine (E127)
preservatives: sorbic acid and salts (E200-203), benzoic acid and salts (E210-213), parabens (E220-227), diphenyl and ortho phenyl (E231-232), Thrabenrudazol (E223)
others: nitrates (E251-252), glutamates (E620-625)
acidity regulators: di-, tri- und polyphosphates
antioxidants: butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT)
painkillers (active ingredients): meclofenamic acid, mefenamic acid, dipyrone, declofenac and acetylsalicylic acid
diaminoxidase (DAO) blocking medicaments: acetylcysteine, ambroxol, aminophylline, antibiotics, dipyrone, metoclopramide, verapamil, propafenone, cycloserine, pentamidine, distigmine, dobutamine, clomethiazole, salazosulfapyridine, dilazep, guanethidine
histamine triggering medicaments: mefenamic acid, diclofenac, naproxen, aspirin, X-ray contrast agents, opiate
X-ray contrast agents: iopamidol, amidotrizoic, iopodate, etc.
anesthetics: methohexital, thiopental
chemo-therapeutics: chloroquine, Resochin, stilbamidine, malaria prophylaxis
muscle relaxants: tubocurarine, suxamethonium, pancuronium
Always inform your doctor (when having surgery, x-rays or other scans, etc.) and your pharmacist (when buying medicaments) about your histamine intolerance!
painkillers (active ingredients): fenbufen, levamisole and ibuprofen
suitable medicaments (in general): e.g. Mexalen, Seractil (painkillers are for emergencies only!), watch out for non-steroidal anti-inflammatory drugs (e.g. Voltaren), antibiotic often tolerated is erythromycin, careful with Augmentan
medicaments against histamine (antihistaminika): Cetrizin, Daosin (only for emergencies, not on a regurlar basis!)
natural antihistaminika: vitamin B6, vitamin C
A tea from khella can work preventive against histamine reactions (bot. ammi visnaga). The seeds and leaves of the plant contain varying amounts of khellin which is a mast cell stabiliser. Grow your own or ask in a pharmacy for it.
A tea from Baikal skullcap can block the histamine release. It is therefore a natural antihistamine. Other natural antihistamines for instance are basil (especially tulsi) and oregano. When using herbs please watch out if you suffer from allergies, also check for possible allergic cross reactions to food.
Stomachic herbs help to digest food better, so that the gut does not overacidify. Southernwood (bot. artemisia abrotanum) is great to meat. Caraway seed (carum carvi) can be used in several foods, e.g. to potatoes or rice.
In case of a histamine shock taking medicaments can often not be avoided. For first aid it can be helpful to dab the affected person with a wet, cold cloth, especially around the neck. This might soothe the temperature, sweating and shivers that often come with a histamine reaction.
The scent of cloves can have painkilling effects and it may soothe nausea.
Please let me know what helps you. Feel free to leave a comment. I’m always trying to add useful information to this page.
last update 15/03/2017