More and more people suspect they suffer from histamine intolerance suffer from histamine intolerance. Or they have been diagnosed through blood tests. The symptoms range from headaches and reddening of the skin to digestive problems and palpitations after eating certain foods. But is histamine really to blame? And what are the benefits of a low-histamine diet or a DAO enzyme preparation? New scientific studies from 2023 to 2025 provide surprisingly clear answers – and show that the truth is very complex.

Study 1: Not every supposed histamine intolerance is also a histamine intolerance

A major ^study1 by Bent et al. (2023) put the subject of histamine intolerance to the test. 59 people with suspected HIT were given either histamine or a placebo orally on different days without knowing what they were receiving. The aim was to objectively test whether symptoms were actually caused by orally ingested histamine.

The result was clear:

• 75% showed fewer symptoms with a low histamine diet. However, complete freedom from symptoms was not achieved.
• There were no anaphylactic shocks in the group that was administered histamine. Incidentally, some of these were very high doses, higher than normally achieved through food intake.
• Only 15% actually reacted to histamine.
• 85% showed no reaction, although they were previously convinced that they were affected.
• Even with placebo, those not affected, who only believed they had HIT, often experienced symptoms. The placebo effect for histamine intolerance was almost 63% in this study. We are familiar with this phenomenon in HIT, and it was confirmed here once again.

A PRICK test was also carried out, i.e. a test in which histamine is injected into a small crack in the skin. The test turned out to be inconclusive. We already knew this, but it was systematically confirmed here.

The DAO activity measured in the blood serum, i.e. the enzyme that breaks down histamine, was also not a reliable indicator. Some with low DAO (<10 U/mL) had no symptoms, others with normal values reacted strongly. We always point this out here: a DAO blood test cannot provide a valid diagnosis. What is new: It could be that a value greater than 16U/mL rules out histamine intolerance.

Conclusion of the study:
Genuine histamine intolerance is much rarer than many people think. The suspicion should only be confirmed after a placebo-controlled provocation – not solely on the basis of laboratory values or self-tests. A DAO blood test cannot diagnose HIT, but it can help to rule it out. Values above 16 U/mL could rule out HIT.

Study 2: No laboratory value can clearly prove histamine intolerance

A new ^study2 from Spain, published in Nutrients in 2025, investigated the biochemical and genetic basis of histamine intolerance. The team led by Duelo et al. analyzed DAO activity, various histamine metabolites in urine and gene variants in affected individuals compared to healthy controls.

The result: neither DAO activity in the blood nor certain genetic variants were able to reliably differentiate between affected and healthy individuals. The concentration of histamine breakdown products in the urine also showed no consistent correlation with symptoms.

The researchers emphasize that histamine intolerance is not a clearly measurable metabolic disorder, but a multifactorial process. In addition to genetic influences, diet, the intestinal microbiome, hormone levels and stress reactions probably play a decisive role.

A single blood value is not enough to confirm or rule out histamine intolerance. Diagnosis and treatment must be holistic – with precise dietary observation, exclusion of other causes and individual consideration of the microbiome. In other words, a scientific confirmation of what we have suspected for several years and what I have described in my book

Study 3: What we really know about symptoms, diagnosis and treatment

A recent ^review3 by Jochum (2024) summarizes what research knows so far about histamine intolerance – and where the greatest uncertainties lie.

The author describes histamine intolerance as a multifactorial process in which the absorption and release of histamine exceed the body’s own degradation capacity. The decisive factor here is diamine oxidase (DAO), the enzyme that breaks down histamine in the intestine. If it is inhibited – for example by medication, alcohol, nutritional deficiencies or intestinal inflammation – typical symptoms can occur: Abdominal pain, bloating, reddening of the skin, headaches, palpitations or breathing problems.

But diagnosis is difficult. According to Jochum, there is no single reliable test.

• The DAO activity in the blood fluctuates greatly and only incompletely reflects the situation in the intestine.
• Although genetic variants in the DAO gene can play a role, they only explain a portion of the cases.
• Provocation tests and skin reactions provide contradictory results, and the reaction to a low-histamine diet also varies from person to person.

Jochum therefore advises a multi-stage, clinically guided diagnosis: a careful medical history, the exclusion of other causes and structured nutritional monitoring are currently the best tools.

Therapeutically, the review recommends a temporary low-histamine diet, accompanied by a later reintroduction of individual foods in order to determine the personal tolerance threshold.
DAO preparations or antihistamines can have a supportive effect, but have not yet been sufficiently scientifically proven. It is also important to correct nutrient deficiencies (e.g. vitamin C, copper, zinc, B6) and to keep an eye on the intestinal microbiome.

What we can learn from the new studies

Current research is shedding new light on histamine intolerance. It exists – but it is not an easy disease to grasp. Neither a blood test nor urine tests or a genetic marker can provide a reliable diagnosis. Instead, it is clear that histamine intolerance is a complex interplay of various factors – between diet, enzyme activity, intestinal microbiome, hormonal influences and stress.

For those affected, this means that the path to recovery does not lie in quick tests or blanket bans, but in attentive self-observation, scientifically sound nutritional strategies and an individual approach.
A temporary low-histamine diet can help to alleviate symptoms and better assess your own tolerance threshold. However, it is crucial not to restrict the diet too much in the long term – otherwise there is a risk of deficiency symptoms and a weakening of the microbiome.

DAO supplements can be supportive pieces of the puzzle, but are not a substitute for medically supervised diagnostics. A blood test for DAO activity in serum can help rule out HIT (>16U/mL), but cannot be used to confirm it (<10U/mL).

In the end, it is confirmed that histamine intolerance is not a rigid clinical picture, but a dynamic balance – one that can be positively influenced by diet, lifestyle and targeted microbiome care.

Briefly summarized conclusion

What the new research shows

1. true histamine intolerance is rare.

Only around 10-15% of those who believe they have HIT actually react to orally ingested histamine. Many complaints are due to other causes or the placebo effect.

2. no test can clearly prove HIT.

DAO blood values, genetic analyses or urine measurements do not provide a reliable diagnosis for histamine intolerance. This is scientifically well supported.

3. more than an enzyme problem.

Histamine intolerance results from a complex interplay of diet, microbiome, enzyme activity, hormones and stress – not from a single defect.

4. observe instead of guessing.

A temporary low-histamine diet with subsequent reintroduction is the scientifically recommended way to recognize the personal tolerance threshold.

5. think holistically.

A balanced diet, micronutrient supply and intestinal health are crucial. DAO preparations can provide support, but are no substitute for a sound diagnosis.

Tip

The FITT method from the book “Understanding and mastering histamine intolerance” observes these principles and can help you to get your histamine intolerance under control.

The studies

1 Bent, R. K. et al. Placebo-Controlled Histamine Challenge Disproves Suspicion of Histamine Intolerance. The Journal of Allergy and Clinical Immunology: In Practice 11, 3724-3731.e11 (2023).

2 Duelo, A. et al. Pilot Study on the Prevalence of Diamine Oxidase Gene Variants in Patients with Symptoms of Histamine Intolerance. Nutrients 16, 1142 (2024).

3 Jochum, C. Histamine Intolerance: Symptoms, Diagnosis, and Beyond. Nutrients 16, 1219 (2024).