Overactive Bladder? Read This — Mast Cells and Bladder Function

Pelvic pain, bladder pain, frequent urination, and so on. Over 1 in every 10 people knows the uncomfortable symptoms of interstitial cystitis, overactive bladder, and similar bladder symptoms (1). Though it’s more common in women, men can experience these uncomfortable bladder problems.

Bladder problems can become chronic and seriously interfere with one’s life. Increasing research evidence suggests that mast cell activation and histamine intolerance may be one of the underlying conditions behind interstitial cystitis and other bladder dysfunction. In this article, I want to discuss the role of histamine and mast cells in bladder function and offer you some natural strategies to improve your symptoms.

Common Bladder Problems

Interstitial cystitis may also be referred to as bladder pain syndrome (BPS), painful bladder syndrome (PBS), or chronic pelvic pain (CPP). It is a bladder condition characterized by bladder pressure or pain, pelvic pain, and increased urgency or frequency of urination. Though interstitial cystitis mostly affects females, it can happen to anyone regardless of gender, age, race, or ethnicity (2).

Symptoms of interstitial cystitis may range from mild to severe. They can be uncomfortable and in many cases, they may seriously impact one’s quality of life. Symptoms of interstitial cystitis may include:

  • Pain in the pelvis and chronic pelvic pain

  • Pain in the vagina or vulva (vulvodynia) in females

  • Pain between the vagina and anus in females and between the scrotum and anus in males

  • Pain in the lower abdomen or lower back

  • Pain when the bladder is full and feeling relief after urination

  • Pain that feels similar to a urinary tract infection without the presence of an infection

  • Persistent and urgent need to urinate and frequent urination with urinary frequency up to 60 times a day

  • Painful intercourse

Overactive bladder (OAB) is a bladder condition that happens when your bladder squeezes urine during the wrong time. Overactive bladder may be characterized by two or all of these symptoms (3):

  • Urinating 8+ times a day and 2+ times during the night

  • Experiencing a sudden and urgent need to urinate

  • Urine leak after a strong and sudden urge to urinate

People with overactive bladder may also be experiencing urinary incontinence (UI). Urinary incontinence is characterized by a loss of bladder control or an inability to control urination. It is a common problem that may be a minor issue for some and a serious problem severely impacting one’s daily life in others. There are different types of urinary incontinence that may be caused by a variety of things, including stress, weak pelvic floor muscles, nerve problems, too much fluid, poor bladder emptying, disabilities, and various health issues (4).

What Are Mast Cells

Your mast cells are a type of white blood cells found in your connective tissues, including your digestive tract, skin, respiratory tract, urinary tract, reproductive organs, surrounding your nerves, and near your blood vessels and lymph vessels. Your mast cells store histamine and other inflammatory mast cell mediators. When your body encounters an allergen, irritant or harmful pathogen, your mast cells will release these mediators to protect your body.

What Is Mast Cell Activation Syndrome?

Your mast cells are essential for healthy immune system function and overall health. Overactive mast cells, however, may increase the risk of mast cell disorders, including mast cell activation syndrome (MCAS). MCAS is a complex health condition that can lead to inflammation, symptoms, and health problems across your entire body, including hives, itching, eczema, skin issues, headaches, migraines, fatigue, nervous system symptoms, digestive issues, and bladder problems (5, 6, 7, 8).

Bladder Function and Mast Cells: The Connection

Your bladder function and mast cell health may be closely connected. Bladder problems, including interstitial cystitis and overactive bladder, may be linked to mast cell activation and histamine intolerance. Increased mast cell count and elevated mast-cell-derived histamine levels are common in those with interstitial cystitis pain and bladder dysfunction. A clinical trial from Germany has found that about 75% of participants with interstitial cystitis had elevated histamine levels and nearly 50% had histamine-producing vaginal bacteria (9). A 2008 study published in PLoS One has found that interstitial cystitis symptoms may be linked to increased mast cell count and mast-cell-derived histamine mediates cystitis pain (10). Researchers found that histamine released by your mast cells may act on your bladder sensory nerves and may increase pelvic pain. A 1994 review published in The Urologic Clinics of North America has found that mast cells activation may lead to bladder mucosa damage and inflammation causing symptoms of interstitial cystitis or other bladder problems (11). Since then, various newer research studies, including a 2007 study published in Urology, pointed out the role of mast cell activation in interstitial cystitis pathophysiology (12). A 2016 study published in Translational Andrology and Urology has found that mast cells may play a role in the sensitization of nerve fibers perpetuating hypersensitivity and pain, and possibly causing a difficult-to-treat neurogenic inflammation and neuropathic pain (13). A 2020 study published in The FASEB Journal has found that mast cell degranulation and histamine release may increase interstitial cystitis and bladder problems (14). Researchers found that histamine may lead to the contraction of the urinary bladder smooth muscle contributing to symptoms of bladder issues. A 2020 article published in the American Journal of Physiology, Renal Physiology has found that histamine may cause a sensory outflow in the bladder causing a sensation of bladder fullness (15). All this suggests that mast cells and histamine may be a therapeutic target in interstitial cystitis, overactive bladder, and other bladder issues. A 2016 study published in PLoS One has found that mast cell inhibition may be beneficial for those with bladder inflammation and interstitial cystitis (16). A 2019 study published in BMC Urology has found that antihistamine therapy may be an effective treatment option for bladder pain and interstitial cystitis (17).

Recommendations for Better Bladder Function


ELMIRON® is a prescription medicine used to treat bladder pain or discomfort associated with interstitial cystitis. The product monograph itself says “serious side effects have been reported with the use of ELMIRON® ”, which makes many patients leery. Addressing mast cell activation and histamine intolerance may be an effective way to improve bladder function and improve interstitial cystitis, overactive bladder, or other bladder symptoms, without the same risks.

Follow a Low-Histamine Diet

Follow a low-histamine diet for 3 to 4 weeks with plenty of anti-inflammatory, nutrient-dense, low-histamine foods. Avoid inflammatory foods, such as refined sugar, refined oil, artificial ingredients, gluten, heavily processed foods, and junk food. Avoid high-histamine foods that can trigger histamine release, or may act as diamine oxidase or DAO enzyme blockers, and increase histamine levels as described in this article. Reduce acidic foods that may be triggering interstitial cystitis and bladder pain, including chili, spicy foods, green apples, pineapple, nectarines, peaches, tomatoes, tea, and vinegar (18). Eat plenty of low-histamine, anti-inflammatory, nutrient-dense whole foods, such as greens, vegetables, herbs, fruits, eggs, pasture-raised poultry, grass-fed beef, and wild-caught fresh fish. For patients in my clinical practice this diet change on its own has often times resulted in marked improvement in symptoms.

Reduce Your Histamine Bucket

Following a low-histamine diet may not be enough to reduce your symptoms. You have to reduce your histamine bucket by paying attention to other lifestyle and environmental factors. Avoid medications, chemicals, environmental toxins, heavy metals, and other irritants that may trigger mast cell activation. It is particularly important to be mindful of any chemicals that come in contact with the local area, including clothing. Reduce your stress and anxiety. Exercise and move your body regularly. Improve your sleep.

Try Quercetin

Quercetin is a powerful flavonoid that’s found in a variety of plants, including blueberries, cranberries, cherries, grapes, black currant, black plums, pepper, cruciferous vegetables, cabbage, romaine lettuce, kale, asparagus, snap pea, sprouts, olive oil, and various herbs. One of the main superpowers of quercetin is its ability to lower histamine and allergic responses.

A 2001 clinical trial published in Techniques in Urology has found that quercetin may help to improve interstitial cystitis (19). According to a 2002 review published in Reviews in Urology, quercetin may be an effective part of a natural approach to interstitial cystitis (20). If you are dealing with interstitial cystitis or similar bladder problems, you may benefit from eating plenty of quercetin-rich low histamine foods and taking a quercetin supplement.

Try Nutraceuticals

Nutraceuticals are food-derived supplements that may improve your health. I have mentioned the powers of quercetin before. You may also try some other nutraceuticals that may improve bladder issues. L-arginine, bioflavonoids, mucopolysaccharides, magnesium-potassium citrate, calcium glycerophosphate, and gamma-aminobutyric acid (GABA) may also improve interstitial cystitis and bladder problems (21, 22, 23).

Try Mast Cell-Stabilizing Foods and Supplements

Try foods that may help to stabilize your mast cells, including watercress, moringa, chamomile, Thai ginger, apples, Brazil nuts, peaches, nettle, onion, fiber-rich foods, and quercetin-rich foods (24, 25, 26, 27, 28, 29, 30, 31, 32, 34, 35, 36). You may try supplementation with natural antihistamines and mast cell stabilizers, such as quercetin, resveratrol, curcumin, vitamin C, nettle leaf, and luteolin. DAO enzyme may be helpful (37, 38, 39, 40, 41, 42, 43).

A Recent Patient with Vulvodynia

This symptom can be very troubling, for many reasons. It can also be very stubborn to try to manage, mostly because it is not as well understood as it needs to be. As the studies above support, I suspect mast cell activation of the local tissue (44) is a significant factor for many that suffer with it, also influenced by abnormal vaginal flora. Recently, after doing some research to assist a patient with longstanding vulvodynia, I came across a paper (45) that looked at the combination of Baclofen and PEA in a compounded cream for topical use in the local area of pain. Within a week her symptoms subsided considerably, with her exclaiming “you’re brilliant!”. If nothing else I am resourceful. More importantly, this treatment holds some promise, especially since PEA (palmitoylethanolamide) is studied as a mast cell stabilizer (46, 47).

Next Steps

Are you experiencing symptoms of interstitial cystitis, overactive bladder, frequent urination, or other bladder issues, or other symptoms of histamine intolerance or MCAS? Working with a healthcare practitioner knowledgeable about histamine intolerance and MCAS may be the best way to get to the root cause of your symptoms and to create an individualized treatment plan. I welcome you to start a personalized functional medicine consultation with me for further guidance to improve your health. You may book your consultation here. Check out my Histamine Intolerance Course here. Learn on your own time, from anywhere. Get an inside look at the most helpful functional medicine tests for pinpointing imbalances, ways to identify and manage the most common (and sometimes surprising) mast cell triggers, and learn what to eat, what to avoid, and why.