Histamine

Comprehensive Overview: Histamine, Immunity, and Mast Cell Activation Syndrome (MCAS)



1. What is Histamine? Histamine is a biogenic amine involved in local immune responses, gastric acid secretion, and neurotransmission. It is synthesized from the amino acid histidine by the enzyme histidine decarboxylase.

2. Where is Histamine Found?

  • Stored in mast cells and basophils
  • Present in the brain as a neurotransmitter
  • Found in the skin, lungs, gastrointestinal tract

3. Histamine Receptors and Their Effects:

  • H1 Receptors: Allergic symptoms (itching, swelling, bronchoconstriction)
  • H2 Receptors: Gastric acid secretion
  • H3 Receptors: Regulate neurotransmitter release in the CNS
  • H4 Receptors: Immune cell chemotaxis and inflammation

4. Histamine Metabolism and Enzymes

  • DAO (Diamine Oxidase): Main enzyme for degrading histamine in the gut
  • HNMT (Histamine-N-methyltransferase): Degrades histamine intracellularly, mainly in the liver, kidneys, CNS

5. Causes of Histamine Intolerance

  • DAO deficiency (genetic or acquired)
  • Gut dysbiosis, SIBO
  • High histamine foods
  • Chronic inflammation
  • Medications that block DAO (e.g., NSAIDs, antibiotics)

6. High Histamine Symptoms by System:

  • Skin: Flushing, hives, eczema, itching
  • GI: Bloating, diarrhea, reflux, nausea
  • Respiratory: Congestion, asthma, sneezing
  • Neurological: Headaches, dizziness, insomnia, anxiety
  • Cardiovascular: Tachycardia, low or high blood pressure
  • Reproductive: Painful periods, hormonal sensitivity

7. Testing for Histamine and Related Conditions:

  • Plasma histamine
  • DAO activity (serum)
  • Urine histamine/metabolites (e.g., N-methylhistamine)
  • Tryptase (elevated in mast cell activation)
  • Chromogranin A
  • 24-hour urine methylhistamine
  • IgE, IgG, IgA testing (for food/environmental allergies)
  • Genetic testing for DAO, HNMT polymorphisms

8. Mast Cell Activation Syndrome (MCAS) A condition where mast cells release excessive chemical mediators (including histamine) inappropriately.

MCAS Symptoms:

  • Episodic flushing, tachycardia, abdominal pain, brain fog, anxiety, allergic-type reactions
  • Often overlaps with POTS, EDS, autoimmune conditions

MCAS Diagnosis:

  • Elevated tryptase, chromogranin A, or urine methylhistamine
  • Response to mast cell stabilizers

9. Functional and Integrative Approaches

  • Supplements:
  • DAO enzyme
  • Vitamin C (natural antihistamine)
  • Quercetin (mast cell stabilizer)
  • Bromelain, NAC, Magnesium, Omega-3
  • B6, Copper (cofactors for DAO)
  • Diet:
  • Low-histamine diet (avoid aged cheeses, wine, smoked meats, fermented foods)
  • Fresh foods, anti-inflammatory choices
  • Avoid leftovers (histamine increases with time)
  • Gut Health Support:
  • Address dysbiosis, leaky gut
  • Probiotics (choose strains low in histamine production, e.g., Bifidobacterium infantis)
  • Digestive enzymes, L-glutamine

10. Medications for MCAS and Histamine Intolerance

  • H1 blockers (e.g., cetirizine, loratadine)
  • H2 blockers (e.g., famotidine)
  • Mast cell stabilizers (e.g., cromolyn sodium)
  • Leukotriene inhibitors (e.g., montelukast)

11. Fun and Important Facts:

  • Estrogen increases histamine release, explaining symptom flares around menstruation
  • Histamine also influences circadian rhythm and alertness (why high histamine may cause insomnia)
  • Some people have both histamine intolerance and MCAS

12. Monitoring and Ongoing Care

  • Keep a symptom and food journal
  • Elimination and reintroduction to identify triggers
  • Regular labs to track inflammation and nutrient deficiencies



Conclusion Histamine plays a vital role in immune function, but imbalance or intolerance can lead to widespread, multisystem symptoms. Understanding histamine metabolism, proper testing, and integrative management strategies can significantly improve quality of life for those affected by histamine-related disorders or MCAS.

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