Histamine Intolerance & Cystitis



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I’m a Naturopath, MTHFR & Methylation Specialist. I’m dedicated to helping you achieve your health goals so you can live a vibrant & fulfilling life

Histamine Intolerance & Cystitis


Histamine contributes to the pain and inflammation in bladder conditions including painful bladder syndrome  / interstitial cystitis (PBS/IC).

You don’t have to have PBS/IC to experience bladder irritation from histamines.  Many patients describe urinary urgency, urinary frequency and incomplete emptying without the pain that is characteristic of PBS/IC.

Painful Bladder Syndrome / Interstitial Cystitis

PBS/IC is a term used to describe chronic bladder inflammation associated with lower pelvic pain, voiding dysfunction including urinary frequency, urgency and nocturia (excessive urination during the night) for more than six months in the absence of urinary tract infections.

PBS/IC is more prevalent in females and is associated with various comorbidities such as allergies, fibromyalgia, endometriosis, and pain syndromes.

The cause of PBC/IC is not very well understood, however, it’s thought that a defect in the lining of the bladder allows irritants in the urine to leak through the coating of the bladder into the intersitium where the nerves are located.  The irritants start a cascade of inflammation that releases inflammatory cytokines and histamine.  The major causes of defects of the bladder lining are chronic exposure to urinary tract infections and / or oxalates.

Histamine and PBS/IC

Clinical studies have demonstrated that patients with PBS/IC have elevated levels of mast cells in the bladder.  Mast cells are a type of immune cell that secret histamine.  Furthermore, patients with PBS/IC have elevated levels of methyl-histamine in their urine.  Methyl-histamine is a major metabolite of histamine.

Histamine contributes to all symptoms of PBS/IC being inflammation, pain, urinary urgency and frequency.

In PBS/IC the immune system responds to the bladder irritant by stimulating the release of histamine.  However, with general bladder irritation (urgency, frequency, incomplete voiding), histamine that is building up from other sources (see below) is adding to the overall load of histamine in the body, and for some people this excessive histamine will irritate the bladder.

Other sources of histamine

Histamine can build up in the body due to numerous factors including:

1. Histamine foods

Overconsumption of high histamine foods (fermented foods, aged meats and cheeses and red wine are particularly high).

2. Inflammatory foods

Overconsumption of inflammatory foods stimulate the inflammatory pathways in the body that release histamine. Inflammatory foods include gluten, sugar, fried foods, processed foods, excessive red meat and dairy.

3. Genetic DAO enzyme deficiency

The DAO enzyme degrades histamine in the gut.

4. Genetic HNMT enzyme deficiency

The HNMT degrades histamine via methylation.

Overgrowth of bacteria in the small intestine increases histamine.

6. Dysbiosis

Imbalance of bacteria in the large intestine can increase histamine.

7. Oestrogen

Stimulates the release of histamine from mast cells.


    1. Rosa AC & Fantozzi R, 2013, ‘The role of histamine in neurogenic inflammation, British Journal of Pharmacology, vol. 170, no. 1, pp. 38-45 PMID: 23734637
    2. Rudick CN et all, 2008, ‘Mast Cell-Derived Histamine Mediates Cystitis Pain’, PLoS One, vol. 3, no. 5, pp. 1-11 PMID: 18461160
    3. Ullah MW et al, 2018, ‘Painful Bladder Syndrome/Interstitial Cystitis Successful Treatment with Montelukast: A Case Report and Literature Review’, Cureus, vol. 10, no.6, pp. 1-5 PMID: 30155378
    4. Zierau O, Zenclussen A & Jensen F, 2012 ‘Role of female sex hormones, estradiol and progesterone, in mast cell behaviour’, Frontiers in Immunology, vol 19, no. 3. 

PMID: 22723800

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