Why Histamine Intolerance Is Hard to Diagnose and What New Research Says

Editoral Team
Feb 9
5 min read

Updated: Feb 17

Introduction

Histamine intolerance (HIT) is a complex and often misdiagnosed condition, with symptoms that overlap with allergies, IBS, and mast cell activation syndrome (MCAS). Many individuals struggle with unexplained reactions to food, yet standard allergy tests fail to identify histamine as the culprit.

A 2024 study, Measurement of Diamine Oxidase (DAO) During Low-Histamine Diets (European Journal of Clinical Nutrition), explores the diagnostic challenges of histamine intolerance, investigating how DAO levels fluctuate under different dietary conditions and whether histamine exposure reliably triggers symptoms in affected individuals.

Below, we break down what this research reveals about the difficulties in diagnosing HIT and what it means for patients and practitioners.

Person receives skin test on arm. Doctor applies liquid with dropper near numbered grid. Brown bottles and white surface in background. — Testing for histamine intolerance: A patient undergoes a skin test, highlighting the intricate challenge of diagnosing conditions like HIT, where symptoms mimic other disorders but standard tests may not identify the true cause.

What Is Histamine Intolerance?

Histamine intolerance occurs when histamine accumulates faster than the body can break it down. The two main enzymes responsible for degrading histamine are:

Diamine Oxidase (DAO): Active in the gut, breaking down dietary histamine.
Histamine N-Methyltransferase (HNMT): Functions in other tissues, like the brain and liver.
For individuals with low DAO activity, consuming histamine-rich foods can lead to an

imbalance between histamine intake and clearance, triggering widespread symptoms.

Common Symptoms of Histamine Intolerance

Since histamine affects multiple systems, symptoms vary widely, making it difficult to pinpoint as the underlying cause. According to the study, common symptoms include:

🔥 Skin reactions: Flushing, hives, itching, eczema.

🧠 Neurological: Migraines, dizziness, anxiety, brain fog.

💨 Respiratory: Nasal congestion, wheezing, asthma-like symptoms.

💓 Cardiovascular: Palpitations, low blood pressure, rapid heart rate.

🌿 Digestive issues: Bloating, nausea, diarrhea, acid reflux.

Because these symptoms overlap with allergies, IBS, and MCAS, many individuals undergo extensive testing without clear answers.

Why Histamine Intolerance Is Hard to Diagnose

Unlike allergies, histamine intolerance does not involve an immune response, meaning standard allergy tests cannot detect it. Instead, HIT is a metabolic issue, where the body struggles to break down histamine efficiently. For these reasons, histamine intolerance Is hard to diagnose.

Key Diagnostic Challenges Identified in the 2024 Study

1️⃣ DAO Levels Alone Do Not Always Predict Symptoms

Some individuals with low DAO had no symptoms, while others with moderate DAO levels still reacted to histamine exposure.
This makes DAO testing an unreliable standalone diagnostic tool.

2️⃣ Symptom Variability Complicates Testing

Different individuals reacted differently to histamine-rich liquids, suggesting that other factors (such as gut health, inflammation, and genetics) influence histamine tolerance.
No single threshold for histamine intolerance was identified.

3️⃣ Current Testing Methods Are Limited

DAO enzyme tests provide some insight, but the study suggests that they cannot diagnose HIT alone.
Elimination diets remain the most reliable approach, but they require careful implementation.

These findings reinforce that no single test can definitively diagnose histamine intolerance, and a combination of symptom tracking, dietary trials, and DAO testing is required.

The Role of Diet in Diagnosis

The 2024 study examined DAO activity levels in individuals following a low-histamine diet and after a controlled histamine challenge to determine if dietary changes could predict histamine intolerance.

Findings:

✅ Participants who followed a strict low-histamine diet saw significant symptom improvement.

✅ Histamine exposure triggered symptoms in some participants but not in others, reinforcing the individualized nature of HIT.

✅ DAO supplementation helped some individuals but was not universally effective, depending on their baseline DAO activity.

This suggests that a structured elimination diet remains the most effective diagnostic tool for histamine intolerance.

Management Strategies for Histamine Intolerance

While there is no cure for histamine intolerance, the study reinforces several key management strategies to reduce symptoms:

1️⃣ Low-Histamine Diet

Avoiding histamine-rich foods can help reduce symptoms. Common triggers include:

🚫 Aged cheeses and fermented foods

🚫 Alcohol (especially red wine & beer)

🚫 Smoked & processed meats

🚫 Tomatoes, spinach, avocados

🚫 Certain fish (tuna, mackerel, sardines)

The study found that low-histamine diets significantly reduced symptoms in most participants.

2️⃣ DAO Supplementation

For individuals with low DAO activity, taking DAO enzyme supplements before meals may help break down histamine and prevent symptoms. The study showed mixed results, with effectiveness depending on the severity of DAO deficiency.

3️⃣ Antihistamines & Mast Cell Stabilizers

H1 and H2 antihistamines may help manage skin, digestive, and respiratory symptoms. Additionally, quercetin and vitamin C were noted for their mast cell-stabilizing effects, reducing histamine release.

4️⃣ Gut Health Optimization

The study reinforces that gut health plays a critical role in histamine metabolism. Strategies include:

✔ Probiotics & prebiotics (carefully selected strains)

✔ Reducing inflammation through diet

✔ Ensuring adequate nutrients (Vitamin B6, Copper, Magnesium)

Since gut dysbiosis can worsen histamine sensitivity, restoring gut balance may improve long-term tolerance.

Study Limitations

While this study provides valuable insights, the authors acknowledge several limitations:

📉 Small Sample Size – The study did not include a large enough group to capture individual differences in genetics and gut health.

🔬 Controlled Histamine Exposure vs. Real Food Intake – The study used liquid histamine, which may not reflect the body’s response to histamine-containing foods.

🧩 Other Factors May Contribute to Symptoms – DAO levels alone did not always predict severity, suggesting mast cell activation and gut microbiome imbalances may play a role.

Despite these limitations, the study reinforces the importance of DAO in histamine metabolism and emphasizes the need for further research into HIT diagnosis and treatment.

Final Thoughts

Histamine intolerance remains underrecognized, largely due to overlapping symptoms and a lack of standardized testing. However, growing research is helping to clarify its mechanisms and improve management strategies.

This 2024 study highlights that tracking DAO levels and histamine responses can provide useful insights, but should not be the sole diagnostic tool. Instead, a combination of dietary management, enzyme support, and gut health optimization offers the best approach to reducing symptoms and improving quality of life.

For those struggling with unexplained reactions to food, considering histamine intolerance as a possible cause may be an important step toward finding relief.