Histamine Intolerance and Endometriosis: Why Is Healthy Eating Sometimes Harmful?

You started eating better. You eliminated processed foods, introduced pickled vegetables, avocado, and tomatoes, and swapped red wine for lemon water. You did everything a classic anti-inflammatory diet recommends . Meanwhile , instead of fading into oblivion, your symptoms intensified. Worse-than-ever bloating, headaches, itchy skin, heart palpitations after meals, and pelvic pain that wouldn't go away.

If this scenario sounds familiar, you may be dealing with histamine intolerance. It's worth taking a closer look at this mechanism, as this problem is particularly common in women with endometriosis.

What is histamine and where does it come from in the body?

Histamine is a chemical compound from the biogenic amine group that occurs naturally in the human body and performs a multitude of important functions. It participates in immune responses, stimulates stomach acid secretion, acts as a neurotransmitter in the brain, and regulates the sleep-wake cycle. Therefore, it is not a foreign substance or inherently harmful. It only begins to cause problems when its concentration in the body exceeds the ability of cells to efficiently break it down.

This compound reaches us from two different directions. On the one hand, the body produces it itself, primarily in mast cells, which are part of the immune system. On the other hand, we consume histamine through food. Some foods already contain the substance, others stimulate its release from our own tissues, and still others block the enzymes responsible for its neutralization.

The main tool for neutralizing histamine from food is the enzyme diamine oxidase, or DAO for short. It is produced primarily in the small intestine and acts as a barrier protecting the bloodstream from excess histamine. When DAO activity decreases or there is too much histamine in a meal, it goes straight into the bloodstream, causing symptoms that closely resemble those of an allergy.

Where does histamine intolerance come from?

Histamine intolerance has nothing in common with a classic allergy. In allergies, the immune system produces specific IgE antibodies in response to a specific protein. The problem here lies elsewhere; it's simply an imbalance between the amount of histamine accumulated and the ability of the aforementioned DAO enzyme to metabolize it.

Weaker DAO activity can, of course, have a genetic basis, but more often it results from entirely different factors that directly damage the mucosa. Because this enzyme originates in intestinal epithelial cells, any inflammation in the gastrointestinal tract damages these cells and drastically reduces DAO production. Intestinal dysbiosis, or disruptions in the microbiome, have a similar effect. These imbalances lead to the dominance of bacteria in the intestines, which themselves produce massive amounts of histamine, further burdening the body. Furthermore, deficiencies in vitamin B6, copper, and vitamin C are essential cofactors, without which the DAO enzyme cannot function properly.

For women, a strong hormonal relationship also proves crucial. Estrogens stimulate mast cells to rapidly release large amounts of histamine, and free histamine, in turn, stimulates the ovaries to produce even more estrogen. This vicious cycle is crucial in endometriosis.

Why do endometriosis and histamine intolerance so often go hand in hand?

The convergence of these two problems is not a coincidence but stems directly from the biology of endometriosis . As a chronic inflammatory condition, the disease's foci constantly stimulate the immune system, which negatively impacts intestinal health. The inflamed epithelium produces less DAO, causing the body to become unable to cope with even small amounts of histamine in the diet.

High estrogen levels, which feed endometriosis, also sensitize mast cells. This makes them release histamine more readily and rapidly under the influence of stress or eating, which in turn fuels further hormone production, stimulating the growth of endometriotic lesions and intensifying pain.

The situation is exacerbated by the fact that endometriosis patients often struggle with intestinal dysbiosis and SIBO , or small intestinal bacterial overgrowth. Some strains of gut bacteria can convert histidine from food into pure histamine, drastically increasing its levels in the digestive tract. Furthermore, tissue studies show that endometriotic lesions and their surroundings contain significantly more activated mast cells than healthy tissues. Their stimulation triggers both local pelvic pain and generalized reactions throughout the body.

Symptoms that may indicate a histamine problem

The symptoms of histamine intolerance are nonspecific and can mimic many other conditions, causing patients to seek help from inappropriate specialists for years. They most often worsen after a meal, although the reaction time depends on the individual's tolerance threshold and the degree to which the histamine bucket is filled.

In the digestive system, this manifests as painful bloating, easily confused with a typical endometriosis belly, as well as crampy abdominal pain , sudden diarrhea, chronic constipation, or nausea. The nervous system, in turn, reacts with migraines, throbbing headaches, dizziness, chronic fatigue, and even anxiety and difficulty sleeping. The skin may experience annoying itching, hives, or sudden redness of the face and décolleté, especially after drinking alcohol or eating a hot meal. The circulatory system also often reacts with palpitations, a rapid heart rate after eating, and sudden spikes in blood pressure. Many women also complain of a chronically blocked nose, a runny nose unrelated to a cold, and a feeling of a congested throat. These symptoms significantly improve after taking antihistamines.

High-histamine foods: where is the trap?

In this case, the principles of a classic, healthy diet can be counterproductive. Fermented, long-ripened, and microbiologically processed foods contain the highest levels of histamine. These include pickles, beloved in anti-inflammatory diets, ripened cheeses like Parmesan, ripe avocados, long-ripened cold cuts, smoked fish, wine vinegar, and alcohol, especially red wine.

There's also a group of foods that don't contain much histamine themselves, but they do trigger the body to release it from cells. This list includes tomatoes, citrus fruits, strawberries, chocolate, cocoa, and nuts. Meanwhile, nonsteroidal anti-inflammatory drugs, so readily and frequently taken for endometriosis pain, directly block the action of the DAO enzyme, adding another layer to the problem.

If these disorders are suspected, the diet should be based on maximum freshness, as histamine builds up rapidly in food when stored in the refrigerator. Meat and fish should be prepared immediately after purchase, and sensitivity to specific ingredients always varies from person to person.

Modern diagnostics: do blood and saliva tests make sense?

Diagnosing histamine intolerance remains a significant medical challenge. Standard blood or skin prick tests yield negative results. While laboratories can, of course, perform tests to determine DAO enzyme activity and blood histamine levels, these results must be interpreted with caution. Low serum DAO levels suggest a problem but do not perfectly reflect enzyme activity directly in the intestinal mucosa, while histamine levels fluctuate dynamically from minute to minute, depending on stress or a meal.

In recent years, non-invasive saliva diagnostic tests, such as the French Endotest, which detect specific microRNA molecules, have gained attention in the context of endometriosis. While this represents a significant technological breakthrough, facilitating rapid diagnosis of the disease, it should be clearly emphasized that these tests do not diagnose histamine intolerance. They can be used by women who suspect endometriosis but whose standard tests are inconclusive. These tools only indicate the presence of the disease itself, but do not answer the question of how the body metabolizes biogenic amines.

For this reason, the most effective tools are a thorough medical interview and a multi-week, diagnostic, low-histamine elimination diet, guided by a clinical dietitian. Only the resolution of symptoms after elimination and their return upon reintroduction provide real confirmation. Any suspicions should be discussed with a gynecologist, as managing histamine issues directly translates to a reduction in inflammation.

A healthy diet is not one size fits all

There's simply no such thing as a universal anti-inflammatory diet. A dietary pattern that brings tremendous relief to one endometriosis patient may trigger a severe histamine-induced exacerbation in another. This doesn't mean that the general principles of healthy eating are flawed. It simply demonstrates that each woman's biochemistry requires individual adjustments. If, despite eliminating processed foods, you still feel unwell, histamine intolerance may be the missing piece of the puzzle.

Sources

• Maintz L., Novak N. Histamine and histamine intolerance. American Journal of Clinical Nutrition, 2007.
• Comas-Basté O. et al. Histamine intolerance: the current state of the art. Biomolecules, 2020.
• Vercellini P. et al. Endometriosis: pathogenesis and treatment. Nature Reviews Endocrinology, 2014.
• Olivares CN et al. Mast cells in endometriosis: innocent bystanders or key drivers of pathogenesis? Expert Opinion on Therapeutic Targets, 2020.
• ESHRE Endometriosis Guideline Development Group. Endometriosis: guideline of the European Society of Human Reproduction and Embryology. ESHRE, 2022.