How High Histamine Levels Can Occur: Key Mechanisms

Excess histamine in the body can result from three primary mechanisms: impaired breakdown, excessive intake, and overproduction in the gut. These mechanisms often overlap, leading to increased histamine-related symptoms.

Symptoms of High Histamine (Suspected Histamine Intolerance)

Since histamine receptors are present throughout the body, excessive histamine can cause a wide range of symptoms, often mimicking allergic reactions. The symptoms vary based on the affected organ system:

1. Skin & Mucosal Reactions

Flushing (redness, heat sensation, especially on the face and chest)
Itching (pruritus)
Hives (urticaria)
Swelling (angioedema)

2. Gastrointestinal Symptoms

Nausea
Vomiting
Abdominal cramps
Bloating
Diarrhea

3. Cardiovascular Symptoms

Low blood pressure (hypotension)
Dizziness or lightheadedness
Rapid heartbeat (tachycardia)
Palpitations

4. Respiratory Symptoms

Nasal congestion or runny nose (rhinitis)
Difficulty breathing (dyspnea)
Asthma-like symptoms

5. Neurological Symptoms

Headaches or migraines
Anxiety or irritability
Fatigue
Insomnia

1. Impaired Histamine Breakdown (Low DAO & HNMT Activity)

Histamine is primarily broken down by two key enzymes:

Diamine Oxidase (DAO) – Degrades histamine in the gut and bloodstream.

Histamine N-Methyltransferase (HNMT) – Works inside cells, particularly in the brain and liver, to break down histamine.

If DAO activity is low, histamine from food and the gut accumulates in the bloodstream, leading to systemic symptoms. Possible reasons for low DAO include:Genetic variations affecting DAO production. (Mušič et al., 2013)

Nutrient deficiencies (e.g., vitamin B6, copper, zinc) that impair enzyme function. (Schwelberger et al., 2013)
Chronic gut inflammation (IBD, leaky gut, dysbiosis) reducing DAO activity. (Schnedl et al., 2020)
Certain medications (e.g., NSAIDs, antihistamines, antidepressants, metformin) inhibiting DAO. (Befani et al., 1995)
Hormonal fluctuations, as estrogen can modulate DAO levels (e.g., histamine intolerance worsening premenstrually). (Maintz & Novak, 2007)

2. High Histamine Intake (Dietary Sources)

Certain foods naturally contain high levels of histamine or trigger histamine release in the body.

Histamine-rich foods: Aged cheese, fermented foods, processed meats, alcohol, shellfish.
Histamine-releasing foods ("liberators"): Citrus fruits, tomatoes, chocolate, vinegar.
Alcohol worsens histamine accumulation by inhibiting DAO. (Zimatkin & Anichtchik, 1999)

Since food histamine levels vary widely due to storage, ripeness, and processing, strict dietary avoidance is often impractical. (Taylor et al., 1986)

3. Excessive Histamine Production in the Gut (Microbiota Dysbiosis)

Gut bacteria can both produce and degrade histamine, influencing overall histamine balance.

Histamine-producing bacteria (e.g., certain strains of Lactobacillus, Klebsiella, Morganella) can increase histamine levels. (Ferstl et al., 2014)
Dysbiosis (gut flora imbalance) can lead to histamine intolerance, especially when beneficial bacteria that degrade histamine (e.g., Bifidobacteria) are low. (Smolinska et al., 2014)
Leaky gut syndrome may allow more histamine to enter circulation, increasing systemic effects. (O’Mahony et al., 2011)

Treatment & Management Options

A comprehensive approach is needed to optimize histamine metabolism and reduce symptoms.

1. Dietary Adjustments

Short-term elimination of high-histamine foods, followed by reintroduction to determine individual tolerance.
Avoiding histamine liberators (e.g., citrus fruits, tomatoes, chocolate) that may trigger symptoms.
Limiting alcohol, as it inhibits DAO.
Eating fresh foods, as histamine levels increase with aging and fermentation.
(Wöhrl et al., 2004; Cornillier et al., 2018)

2. Supporting DAO Activity & Histamine Breakdown

Ensuring adequate levels of DAO cofactors:

Vitamin B6
Copper
Zinc
Magnesium

Probiotics: Selecting strains that degrade histamine (Bifidobacterium infantis, B. longum) instead of producing it (Lactobacillus casei, L. reuteri).
Addressing gut health: Treating dysbiosis and leaky gut to restore microbial balance.
(Schwelberger et al., 2013; Smolinska et al., 2014)

3. Medication & Supplement Considerations

Antihistamines (H1 & H2 blockers): Can provide symptomatic relief. (Worm et al., 2009)
DAO enzyme supplements: Controversial; scientific evidence is limited. (Schnedl et al., 2019)
Gut-healing protocols: Address inflammation and intestinal permeability. (Schnedl & Enko, 2021)

Final Thoughts

Since histamine intolerance lacks definitive biomarkers, a personalized approach focusing on gut health, dietary balance, and enzyme support is the most effective strategy. More research is needed, but individualized management—rather than unnecessary food restriction—remains the best path forward.

Treatment Success Factors:

Accurate Diagnosis (Essential for 100% Success)
- Histamine intolerance is often misdiagnosed. Keeping a food and symptom diary is critical.
- Up to 80% of suspected cases are linked to other conditions like allergies, mast cell disorders, or gut dysbiosis. (Maintz & Novak, 2007)
Dietary Adjustments (75-90% Symptom Improvement in Studies)
- A low-histamine diet leads to significant symptom relief in 75-90% of patients within 4–8 weeks. (Wöhrl et al., 2004; Schnedl et al., 2019)
- Over-restriction can lead to nutrient deficiencies, so reintroduction is essential.
Enzyme Support (40-50% Efficacy for DAO Supplements)
- DAO enzyme supplements may help in cases of DAO deficiency but show inconsistent efficacy (40-50%). (Schnedl et al., 2019; Mušič et al., 2013)
- Best combined with dietary adjustments rather than used alone.
Probiotics & Gut Health (60-80% of Gut-Related Histamine Issues Improve)
- Some probiotics degrade histamine, while others produce it.
- Best strains for reducing histamine: Bifidobacterium infantis, Bifidobacterium longum (Smolinska et al., 2014)
- Worst strains for histamine intolerance: Lactobacillus casei, Lactobacillus reuteri (Ferstl et al., 2014)
Medication Review (25-40% of Patients Affected by DAO-Blocking Drugs)
- NSAIDs, antihistamines, metformin, and antidepressants can block DAO or increase histamine. (Befani et al., 1995; Taylor et al., 1986)
- Adjusting medications (if possible) improves symptoms in 25-40% of cases.
Stress & Hormone Management (50% Report Worsening Symptoms Under Stress)
- Stress and hormonal fluctuations (e.g., estrogen dominance) increase histamine release. (Maintz & Novak, 2007)
- 50% of women with histamine intolerance report worsened symptoms premenstrually. (Mušič et al., 2013)

Take Control of Your Histamine Intolerance – Address the Root Cause

Managing histamine intolerance requires more than just avoiding trigger foods. Long-term relief comes from identifying and treating the underlying causes, such as gut health issues, hormone imbalances, and chronic stress.

Book a comprehensive consultation to assess your symptoms, test for DAO function, gut health imbalances, and hormonal disruptions.
Download the Low-Histamine Diet Guide to learn how to adjust your nutrition without unnecessary restrictions.
Enroll in stress management coaching to reduce histamine-triggering stress and support overall well-being.

Start your journey to better health today.

Download Dr. Haucke's Elimination Diet Guide now to start your gut healing journey

References:

Befani O, et al. Inhibition of diamine oxidase activity by metronidazole. Biochem Biophys Res Commun. 1995.
Cornillier H, et al. Chronic spontaneous urticaria in children—a systematic review on interventions and comorbidities. Pediatr Allergy Immunol. 2018.
Ferstl R, et al. Histamine receptor 2 modifies dendritic cell responses to microbial ligands. J Allergy Clin Immunol. 2014.
Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr. 2007.
Mušič E, et al. Serum diamine oxidase activity as a diagnostic test for histamine intolerance. Wien Klin Wochenschr. 2013.
Schnedl WJ, Enko D. Histamine intolerance originates in the gut. Nutrients. 2021.
Smolinska S, et al. Histamine and gut mucosal immune regulation. Allergy. 2014.
Taylor SL, et al. Histamine food poisoning: toxicology and clinical aspects. Crit Rev Toxicol. 1986.
Worm M, et al. Exogenous histamine aggravates eczema in a subgroup of patients with atopic dermatitis. Acta Derm Venereol. 2009.
Zimatkin SM, Anichtchik OV. Alcohol-histamine interactions. Alcohol Alcohol. 1999.