Histamine intolerance: much searched, little proven

Healthy state

Histamine Histamine A messenger substance of the body that is also found in aged and fermented foods. Too much can cause headache, flushing or diarrhoea. is not a foreign substance but one of the body’s most versatile messengers. It is made from the amino acid histidine and stored in mast cells Mast cells Immune cells beneath the skin and mucous membranes, filled with histamine and other messengers. They raise the alarm in allergies, infections and stress. More in the chapter “Mast cells: alarm cells in the gut, histamine and the disputed MCAS”, the sentinel cells of the skin, airways and gut lining. It is also made by certain stomach cells, which use it to switch on acid production, and by nerve cells in the brain, where it helps control wakefulness and the sleep-wake rhythm. It acts through four docking sites (H1 to H4). H1 stands mainly for itching, redness, swelling and widening of blood vessels. H2 controls stomach acid. In the gut, histamine influences blood flow, fluid secretion, mucus production, gut movement and the pain sensitivity of nerves.

Histamine also arrives with food. It forms when bacteria or yeasts convert the amino acid histidine in foods, which is why the content rises with ripening, fermentation, storage and warmth. Particularly large amounts are found in long-aged cheese, salami and raw sausage, sauerkraut, red wine and sparkling wine, tinned fish and fish that is not fresh, such as tuna or mackerel. Important: cooking, frying or freezing does not destroy histamine. What you can do is slow its formation: buy fresh, store cold, freeze leftovers quickly.

The body has two breakdown routes. Diamine oxidase DAO (diamine oxidase) An enzyme in the gut wall that breaks down histamine from food before it reaches the blood. More in the chapter “DAO: the enzyme that intercepts histamine from food” (DAO) in the gut lining catches histamine from food before it reaches the blood; histamine N-methyltransferase (HNMT) breaks histamine down inside cells, for example in the gut, airways and brain. DAO is therefore only part of the system and mainly responsible for histamine entering via the gut, which is described in detail in its own chapter. In addition, histamine usually acts only briefly in the body: it is broken down within minutes.

Normally this goes unnoticed. A meal with some histamine causes no symptoms in most people because the gut wall, DAO and liver catch most of it. That is why the mix is decisive: the amount, the make-up of the meal, alcohol and the total load from body and food. Your condition on the day also plays a part.

Disrupted state: causes and effects

The classic explanation of histamine intolerance is: if more histamine arrives than DAO can break down, symptoms occur, such as flushing, headache, a blocked or runny nose, palpitations, abdominal pain or diarrhoea. Alcohol and some medicines also inhibit DAO, and certain genes (variants in the genes for DAO or HNMT) lower its activity. This is plausible but so far not convincingly proven.

The problem: the symptoms are non-specific. They overlap with IBS Irritable bowel syndrome Recurring abdominal pain linked to bowel movements, without tests finding another cause. Today it is understood as a disorder of gut–brain interaction. More in the chapter “The gut-brain axis”, FODMAP FODMAP Short for fermentable sugars and sugar alcohols that are poorly absorbed in the small intestine, such as fructans, lactose, fructose and sorbitol. More in the chapter “Doing low-FODMAP right” intolerance, food allergies, coeliac disease Coeliac disease An autoimmune disease in which gluten damages the lining of the small intestine. It is diagnosed with a blood test and usually a biopsy while you are still eating gluten. More in the chapter “Lactose, fructose, gluten: making sense of intolerances” and mast cell disorders. In studies, the DAO blood test does not reliably distinguish affected people from healthy ones, and the reaction often does not depend on the dose: in controlled challenges, affected people do not react to the same amount every time, and placebo Placebo A dummy treatment without an active ingredient. Comparing with it shows how much a remedy achieves beyond expectation and chance. can trigger similar symptoms. Expectation (“nocebo”) and stress also change perception. That does not mean the symptoms are imagined, but that the cause is hard to pin down in the individual case. How many people are actually affected is disputed; commonly cited figures are estimates.

Other players: mast cells can release histamine themselves in response to quite different triggers, such as stress, heat, infections, alcohol, painkillers or hormone fluctuations. Then the histamine does not come from the plate at all. People also speak of “histamine liberators”, foods said to irritate mast cells (for example strawberries, citrus fruits, tomatoes). This list rests largely on individual observations and lab experiments; the evidence in humans is thin. With pronounced attacks with circulatory symptoms, a mast cell disorder or allergy must be ruled out medically.

Gut bacteria can also produce histamine. One study found many histamine-producing bacteria such as Klebsiella aerogenes in some IBS patients. In mice, their histamine triggered abdominal pain via mast cells, and a diet low in fermentable carbohydrates (low-FODMAP) dampened this. In humans this link has not yet been proven. The finding does show that histamine from food is not the only factor. Small intestinal bacterial overgrowth Small intestinal bacterial overgrowth (SIBO) Too many bacteria in the small intestine, where normally few live. Bloating and diarrhoea are typical; it is usually diagnosed with a breath test. More in the chapter “When the small intestine is too densely colonised” may also contribute, because many bacteria there form histamine from histidine.

If you regularly react after red wine, aged cheese or leftovers, you can take that as an observation worth noting. It helps to keep the mechanisms in view: often several small factors add up (alcohol, ripeness, stress, lack of sleep, cycle, medicines), and a single food is only the drop that makes the barrel overflow. What matters is not to overlook other causes and not to restrict the diet permanently without need.