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September is IC Awareness Month - The Mast Cell Connection

Recently, I was immersed in a book called Histamine Intolerance by Dr. Janice Joneja. It is a great book that I highly recommend to practitioners who want to learn about the subject, or to people who are suffering from known or possible histamine intolerance. While I was reading, interstitial cystitis was on my mind, knowing there can be an association with bladder pain and histamine levels. I was so happy when I got to page 105 and saw that Dr. Joneja addressed the connection between IC and histamine directly. She distinguishes 3 main ways that mast cells are involved in the symptoms of interstitial cystitis.

Loss of bladder lining increases mast cell response

The bladder wall contains mast cells. Mast cells contain histamine and other chemicals which are released during allergic reactions and some immune responses. Since interstitial cystitis involves loss of the GAG (glycosaminoglycan) layer on the inside of the bladder wall, substances such as allergens, chemicals, food preservatives, drugs, toxins, and bacteria, can penetrate the bladder tissue and activate bladder mast cells.

Mast cells are activated by the nervous system

Mast cells can also be activated by neuropeptides, released from neurons. Mast cells have been found in close contact to neurons in the bladder wall, as well as the lining of the digestive tract. Both IC and IBS appear to be activated by neurogenic factors. Acute stress can also activate mast cell degranulation via neurotransmitters.

Hormonal changes affect mast cells

There is also a hormonal connection between IC and mast cells. Mast cell activation is known to be enhanced by estradiol, and mast cells on the bladder have estrogen receptors. When estrogen levels are high, such as at ovulation, mast cells on the bladder will be activated to release histamine and other stored inflammatory mediators. According to Dr. Becky Campbell, estrogen can also decrease DAO enzyme levels. DAO (diamine oxidase) is the enzyme responsible for breaking down histamine in the body.

As you can see, there are multiple ways in which mast cells found in the bladder can be triggered to release histamine and other irritating chemicals, and there can be a cyclical nature to the pain cycle.

As an herbalist, I consider the following ways to support interstitial cystitis when histamine and mast cell destabilization are involved:

  • Healing the mucosal membrane of the bladder

  • Stabilization of mast cells

  • Nervous system support and anodynes to disrupt neuogenic messaging

  • Adaptogens if stress is a trigger

  • Hormonal modulation if indicated

Herbs and supplements can be used to support each of these physiological areas, but the most important way to address histamine-related conditions, whether IC or something else, is to eat a histamine-restricted diet, and in some cases to supplement with DAO enzyme.

Dr. Joneja describes the body as having a "bucket" that can be filled with histamine daily. As long as our DAO enzymes can keep up with the amount of histamine being consumed and produced by the body, the bucket will not overflow. But when someone is dealing with histamine intolerance, their bucket overflows beyond the capacity of their enzyme system to break it down, and a wide range of symptoms can occur. Even if the reason that histamine is high is due to endogenous production of histamine, a low-histamine diet can be both diagnostic and effective if histamine is involved in the condition.


  1. Campbell, B. (2020). Interstitial cystitis and the histamine connection. Dr. Becky Campbell.

  2. Campbell, B. (2020). Menopause and histamine: The connection. Dr. Becky Campbell.

  3. Joneja, J. (2017). Histamine intolerance; The comprehensive guide for healthcare professionals. Berrydale's Books.

Having trouble with your own Interstitial Cystitis?

About me:

My name is Jillian Bar-av and I am a Registered Herbalist and Licensed Nutritionist who works with busy women to help them have the energy to do what they love. I specialize in conditions that affect the reproductive system and urinary tract, such as PCOS and Interstitial Cystitis. I believe that it takes healthy people to create a healthy planet, and I want to make a difference for both.

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