Do you have difficulty falling asleep? A bit of anxiety? Headaches? Any sort of digestive issue? A low-histamine diet may be for you!

So claims a blog post on one of the many websites promoting this diet, which is meant to treat a condition called histamine intolerance. The word “histamine” will be familiar to anyone who deals with allergies. After all, over-the-counter medications for allergic reactions like hay fever are called antihistamines. They counter the action of histamine, a molecule held inside of special blood cells called mast cells. When an allergen is detected inside the body, these mast cells get activated: like plants releasing their pollen into the wind, these blood cells burst forth with histamine, and the consequences are itching and sneezing.

But histamine is not just a mediator of allergies, nor is it only produced by the body; it can also be found in food and beverages. Some people believe they are intolerant to it, that the dose they are getting from their diet can’t be processed by their body and they get symptoms that are similar to a combination of seasonal allergy and a food hypersensitivity like lactose intolerance. Their nose runs, they sneeze, they get itchy red skin, but they also suffer from bloating, diarrhea, and sometimes even vomiting.

The fact that histamine is said to be involved here may make you think that this is an allergic reaction, but it’s not. Much like how lactose intolerance is distinct from an allergy to dairy products, histamine intolerance is said to be a nonallergic food hypersensitivity. Allergies involve the immune system and even tiny amounts of the allergen can cause severe reactions; food intolerances, however, are typically manifested in the digestive tract and symptoms are proportional to the amount consumed.

But is histamine intolerance even real? Reading its scientific literature in chronological order, I recognized a pattern we often see when new phenomena are alleged to exist: early findings from small studies convince a tiny group of researchers, who start evangelizing for its existence… until, years later, larger studies done by other scientists fail to reproduce this preliminary body of work.

Because if someone claims that ingesting histamine wrecks their body and they exhibit those symptoms while drinking a tea that has little histamine in it, we’ve probably been barking up the wrong tree.

The myth

To its believers, histamine intolerance is pretty clear-cut, and the way you will see it described will come with an unearned degree of confidence.

Its symptoms are many and can include, on top of the ones previously listed, dizziness, a rapid heart rate, a low level of muscle tone, swelling, even collapse. This is all due to the consumption of certain foods that contain high amounts of histamine: cheese, fish, wine, eggs, strawberries, bananas, and anything that has been fermented. There is a diagnostic test you can get that will measure your blood’s ability to metabolize histamine. Because if your body can’t break histamine down, it will leak through the lining of your intestines and into the blood and cause a mock allergic reaction. The treatment? Avoiding foods high in histamine.

HIT has been a darling of Central Europe, for reasons that are not clear to me, and many scientific papers from Germany, Switzerland, Slovakia, and Slovenia can be propped up as proof that the condition is real. We even know, apparently, what causes this dysfunction. Histamine can be metabolized in the body in two ways, and one of these ways involves an enzyme called diamine oxidase, or DAO for short. In people with HIT, the DAO enzyme is said to not function adequately—maybe because the gene that codes for it is mutated—so unprocessed histamine leaks into the bloodstream.

Many people on a low-histamine diet report that their symptoms go away, while others take DAO as a supplement: the enzyme is isolated from pig kidneys and sold as a pill to be taken half an hour before a meal, much like how lactase can be gulped down as a supplement before drinking a glass of milk. Antihistamines also get a mention, but they are not recommended for continuous use.

This confidence in describing histamine intolerance, however, should hit a wall when confronted with recent studies.

The reality

To be fair, there is a well-established grain of truth to the idea that the histamine content of what we eat can mess with our body. It was originally called scombroid fish poisoning, after the Latin names for the families of fish initially blamed for it, or the mahi-mahi flush. Certain fish contain a lot of histidine, one of the many building blocks of proteins. If this fish is not properly refrigerated, bacteria will turn the histidine into histamine. Within 10 to 60 minutes of eating said fish, histamine poisoning happens: flushing, nausea, diarrhea, dizziness. Sounds familiar?

Histamine intolerance is different from histamine poisoning, though, because the claim is that the food contains “normal” amounts of histamine, has not been spoiled, and only certain susceptible people will become ill from it.

The first crack we should notice in this armour of confidence is in the food list. Websites tell you which food items and beverages contain concerning amounts of histamine for people living with HIT. But when these products have their levels of histamine measured by different labs, the answers vary greatly. This means that some scientific papers on low-histamine diets will suggest avoiding milk, lentils, chickpeas, soybeans, and mushrooms, while many more will not. Items like eggs, nuts, and chocolate appear in between 20 and 60% of such lists, while cured cheese, dry-fermented meat products, and alcohol show up on the majority of these lists. The histamine content of food changes a lot based on how it is processed and stored and how ripe it is. What is a dietitian supposed to do with this inconsistent information when helping a client?

Moreover, there is evidence that histamine may not be the only culprit in some people’s symptoms and that other molecules can *potentiate *its impact, like accomplices helping a criminal commit a robbery. And it’s not just foods containing histamine but also those that don’t contain histamine but that trigger the release of histamine within the body, like citrus; and medications that impinge on the body’s ability to process the histamine it releases, a long list that includes nonsteroidal anti-inflammatory drugs, morphine, at least one antidepressant, many antibiotics, and vitamins B1 and C. When the inventory of triggers is so large, any symptom can somehow be tied back to histamine, regardless of whether or not histamine should be blamed. Histamine intolerance becomes a claim that cannot be disproven because histamine is always there, directly or indirectly.

Oral provocation studies have cast serious doubt that these symptoms—which are real—have anything to do with the much-condemned histamine molecule. A 2011 paper reported on a study done at four Austrian medical centres with 39 patients suspected of having histamine intolerance. They first gave them histamine dissolved in a peppermint tea (which is naturally low in histamine) and told them what it was: if they experienced symptoms, they were enrolled in the next phase where they were given peppermint tea that was either spiked with histamine or not, and the participant did not know. Nearly two-thirds of participants had at least one symptom after drinking the peppermint tea that had not been spiked.

A similar study out of the University of Munich was published in 2023 and reported the same result. When looking at participants who only reported symptoms when drinking the histamine-laced tea, we get a measly 7% of their 59 participants. The authors had to wonder if, for the majority of their participants, these symptoms were psychosomatic in nature as they resemble those of anxiety. (Of course, you will find people online who will argue that peppermint tea actually has salicylates, which block the metabolism of histamine, so even this herbal concoction isn’t safe for people with a histamine intolerance.)

Oh, and that diagnostic test that measures your blood’s ability to process histamine? It turns out we may have to go back to the drawing board on this one. The test focuses on the DAO enzyme found in the blood and how much histamine it can properly metabolize. The problem is that the histamine found in food is not metabolized by DAO in the blood but rather by DAO found on the lining of our intestine, and the amount of enzyme circulating in the blood may not represent how much there is in our intestine. When the diagnostic test was applied to over 1,000 Swedes who did not have histamine intolerance, nearly half of them were found to have DAO levels in the blood that are said to indicate a histamine intolerance. Prior to this study, the test had never been formally used in a large group of people without the intolerance to see what normal levels look like.

Major German specialist bodies have confirmed that there is no reliable way to diagnose “adverse reactions to ingested histamine.” This “serum DAO test,” as it’s called, is thus useless at diagnosing a food intolerance that may not even be real.

A questionable diagnosis

Lactose intolerance is what histamine intolerance wishes it was: a medically recognized condition that is fully understood biologically, can be diagnosed using validated tools, and for which evidence-based recommendations can be made. We know that lactose intolerance is normal. We know that certain people have a specific mutation that causes their body to continue producing the lactase enzyme into adulthood, and that this enzyme breaks down the milk sugar lactose into simpler sugars. We know that when the body stops producing lactase, gut bacteria feast on the milk sugar and release gas, which leads to bloating and diarrhea. We can tell lactose-intolerant people which foods to avoid or suggest they take lactase supplements before a meal.

Histamine intolerance, however, is looking more and more like chronic Lyme disease, where the symptoms are real but the idea of a persistent Lyme infection is not supported by scientific evidence. It is still possible that *some *people are indeed intolerant to the histamine content of certain food items, perhaps because of mutations in the gene that codes for DAO. Indeed, many such mutations have been found, although few have been shown to cause problems in how the enzyme behaves. But it’s also likely that the very concept of histamine intolerance is not real, unlike histamine poisoning linked to fish that has gone bad.

Some will say that switching to a low-histamine diet—whatever that means for them, since the histamine levels of a particular food item varies significantly—took care of their symptoms. If so, great, but the potential problem here is significantly restricting your diet for no good reason. Without proper dietary supervision, these diets can create nutritional deficiencies.

Histamine intolerance joins a growing list of questionable diagnoses. Some of them will be proven to be real, while others will be shown to be mistaken attempts at explaining a constellation of nonspecific symptoms. Stuck in the middle of this tug-of-war between evangelizing researchers and more skeptical ones are the patients who suffer without a clear idea of what’s wrong with them. It feels good when our symptoms are given a name and a solution. We just need better science to make sure these oases of relief are not mere mirages.

Take-home message:

• Histamine intolerance is said to be a condition that affects certain people who develop symptoms like skin rashes and stomach upset after consuming food that has a high histamine content, like fermented products, fish, and cheese
• A low-histamine diet is difficult to define because the histamine content of a particular ingredient can vary a lot depending on storage, ripeness, and processing
• The main diagnostic test for histamine intolerance (the serum DAO test) is not reliable, as many healthy people also test positive
• In studies where people suspected of having histamine intolerance are given a tea that has not been spiked with histamine, the majority develops symptoms of histamine intolerance, casting doubt on the diagnosis

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@‌jonathanjarry.bsky.social