Conditions, Interstitial Cystitis

Interstitial Cystitis and Mast Cells

Mast cells have long been reported to be raised in patients suffering from interstitial cystitis. Mast cells are a type of cell that are usually associated with allergies. Today I’m going to take a look at the relationship between interstitial cystitis and mast cells.

What is a Mast Cell?

A mast cell is a type of white blood cell that is a part of the immune system. Mast cells are most abundant in tissue that is in contact with the outside world such as skin, lungs, digestive system and eyes. But they can also be found in diseased bladder tissue.

Mast cells contain granules that are rich in the compounds histamine and heparin. These compounds are usually secreted as part of the defence mechanism of the immune system.

Normally, mast cells play an important role in the defence against pathogens, wound healing, formation of new blood vessels, immune tolerance and blood-brain barrier function.

On the other hand, they are best known for their role in allergies as they play a big role in causing the unpleasant side-effects of an allergic attack.

During an allergic response, mast cells release histamine and other pro-inflammatory compounds. These compounds are responsible for much of the allergic symptoms (such as itching and swelling). That is why antihistamine drugs can reduce allergic symptoms.

Mast cells also play a big role in anaphylactic shocks.

Mast Cells in Interstitial Cystitis

Mast cells have been found to be raised in patients suffering from IC [1].

Although mast cells are usually present in the lamina propria (the connective tissue just under the urothelium) of healthy bladders, they are found in increased numbers in the submucosal layer of the bladder wall and especially in the muscle layer (detrusor muscle) surrounding the bladder in interstitial cystitis sufferers [1].

Mast cells are especially rich in IC bladders with ulcers [1].

As a result, interstitial cystitis bladders also contain about double as much histamine as healthy bladders. Histamine plays a role in inflammation.

Increased numbers of activated mast cells are also referred to as mastocystosis.

Mastocytosis is a mast cell activation disorder caused by the presence of high numbers of mast cells, leading to a high level of mast cell degranulation (inflammatory compounds are released from mast cell granules, including histamine).

Apart from histamine, mast cells can also release the inflammatory chemical Interleukin-6 (IL-6). IL-6 release can be triggered by bacterial lipopolysaccharide (LPS), a toxin released by pathogenic bacteria [2].

Interestingly, IL-6 has also been found to be raised in IC bladders [2], raising the question whether IC is in fact a bacterial infection (see ‘intracelullar bacteria’).

What about mast cells and regular cystitis?

There is also evidence that at least in mice mast cells play a role in the lower urinary tract symptoms experienced in a bout of cystitis (urinary tract infection) [3].

Mast cells and other diseases

As mentioned above, mast cells are highly implicated in allergic conditions and autoimmune diseases.

People with increased mast cell can be prone to skin conditions, swelling and itchiness.

Increased mast cell counts can also be present in conditions such as irritable bowel syndrome (IBS) [4].

This explains a possible connection between IC and other conditions.

What activates Mast Cells?

Many patients will find that one or more of the following aggravates their symptoms. This is because they activate mast cells:

  • Estrogen [1]: Estrogen levels rise in the first half of the female cycle, just after the period. Hormonal birth control also usually contains estrogens. This could explain flares of symptoms at certain times of the cycle.
  • A damaged urothelium (bladder lining) [2]: a damaged or dysfunctional urothelium produces certain chemicals that can activate mast cells.
  • Stress: Hormones that are released in response to physiological or emotional stress destabilize mast cells and cause them to release their inflammatory chemicals [5].
  • Coli: Pathogenic e. coli that have adhered to the bladder wall have the ability to activate mast cells [2].
  • Bacterial, Fungal, Viral and Parasitic Infections: All types of infections and pathogenic overgrowth can activate mast cells in the body [6].
  • Heavy Metal Toxicity: Heavy metals such as mercury, aluminium, lead, cadmium and bismuth can activate mast cells [7].

Natural Ways of Reducing Mast Cell Activation

Ultimately, the root cause of increased mast cells would have to be found and addressed. In the meantime, the following measures may help provide some relief:

  • Low Histamine-Diet: For those with high levels of mast cells histamine from food could exacerbate symptoms, as the body is most likely already high in histamine. A low histamine diet is part of my customization plan for a healing diet (read more about diet here and here).
  • Nutrients/Herbs that may help stabilize mast cells: Selenium, Vitamin C, holy basil, peppermint, ginger, thyme, turmeric, quercetin, bromelain, nigella sativa, nettle and butterbur.
  • Chondroitin Sulfate and Quercetin: Synergistically help to inhibit mast cell activation [2].
  • Stress reduction techniques: meditation, deep breathing exercises, yoga, Mindfulness Based Stress Reduction (MBSR), Tai Chi, walks in nature, massage, acupuncture, flotation tanks, reflexology, sauna etc.

Now I’d like to hear from you: Do you think your mast cell levels are raised? Have you done anything to deal with it? Let me know in the comments.

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  1. Theoharides, Theoharis C et al. Mast cell involvement in interstitial cystitis: a review of human and experimental evidence Urology June 2001 [Volume 57 , Issue 6 , 47 – 55]
  2. Sant, Grannum R. et al. The Mast Cell in Interstitial Cystitis: Role in Pathophysiology and Pathogenesis Urology 2007 [Volume 69 , Issue 4 , S34 – S40]
  3. Xu Wang et al Evidence for the Role of Mast Cells in Cystitis-Associated Lower Urinary Tract Dysfunction: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Animal Model Study Plos One December 21, 2016
  4. Pang et al Mast cell and substance p-positive nerve involvement in a patient with both irritable bowel syndrome and interstitial cystitis Urology [Volume 47, Issue 3, March 1996, Pages 436-438]
  5. Spanos, Constantine et al. Stress-Induced Bladder Mast Cell Activation: Implications for Interstitial Cystitis The Journal of Urology 1997 [Volume 157 , Issue 2 , 669 – 672]
  6. Saluja R, Metz M, Maurer M. Role and Relevance of Mast Cells in Fungal Infections. Frontiers in Immunology. 2012 [3:146.]
  7. Bent, S., Göttsch, C., Braam, U. et al. The effects of heavy metal ions (Cd2+, Hg2+, Pb2+, Bi3+) on histamine release from human adenoidal and cutaneous mast cells Agents and Actions (1992) [36(Suppl 2): C321.]


  • Reply

    Sheryl Chan

    May 17, 2017

    Fascinating research, articulated so simply and covered so thouroughly as always! Very interesting piece, never thought about mast cells connection. I do get a lot of random outbreak of hives. My bladder irritation is quiet for now, but nobody even knows what the cause was. Now I’m wondering if mast cells have to do with anything else 😉 Thanks for the insight!

    • Reply


      May 18, 2017

      Thanks, Sheryl! Some researchers believe that mast cell activation disorders could be at the root of many conditions, I believe the book ‘never bet against Occam’ that has been recently reviewed on the CIB network deals with this topic (although I haven’t read it myself).

  • Reply

    Kelley PALOMINO

    September 11, 2017

    How would one test for Mast cells in the urine?

  • Reply

    Maria K

    October 17, 2017

    Thanks for a great article.
    I have a massive amount of mast cells in my bladder biopsy and therefore diagnosed with IC.
    I am in daily pain. I wonder of mastocytosis treatment would help me..
    Antihistamines and gastrocom…

    • Reply


      October 18, 2017

      Hi Maria, I heard from others that antihistamines can help reduce pain – it makes sense as histamine is one of the chemicals secreted from mast cells that is responsible for inflammation and pain and since antihistamines would block this it may well help. Would be interested to hear how you get on.

  • Reply

    Yakov Mirkin

    May 22, 2018

    Dear Layla,
    Thanks for outstanding article!!!
    I’m urologist from Russia and I evaluate NGF/Cr, IL-6/Cr level in urine for diagnostic IC/BPS.
    I completely agree with you – IC is the part of mast cells activation syndrome.
    It’s interesting that I noticed decreased amount of mast cells in bladder biopsy after BOTOX injections into the bladder trigone… I don’t know, how can I explain this fact…

  • Reply


    April 4, 2019

    I don’t even know where to start when explaining all this…it started out fantly when I was in my young teens, i would go to the bathroom (#2) and right after I’d had this horriable bladder irritation. I use to think ohhh greatt here come another bladder infection(I use to get them a lot when I was young) and it wouldn’t would literally go away after like and hour. But now for some reason of my 28 years of living this horriable horriable feeling has stayed with me every single bloody day since January 2019. I have been back and forward with my doctor..we have done urine cultures, blood work, examinations. And nothing! Apparently it is a hard disease to rule out from your I sat down with my doctor and really explained to her how I’m really feeling, trying to really study my body and what I’m feeling..and I told her I really think I have Interstitial Cystitis and she more so kinda agreed and wanted to do more testing…but wth why…she is wasting my time and money..I am struggling everyday and work and sleeping..I’m popping my back pills (Tramadol) for any relief I can get..I am sick of living like this I’m 28 years old and I have no life…I can’t live like this anymore..oh and where I live is pretty much 5:00A.M now, I’ve been up since 3:03..this is my new life now.. 🙁 I can’t live like this

    • Reply


      April 8, 2019

      Hi Kelly, I’m really sorry you’re going through this. I know how it feels, I have had the same issue. But I don’t have it anymore, so there is some hope for you. I have many articles on the blog that may help you understand better what could be going on and also some tips on actions to take. Wishing you all the best!

    • Reply

      Pam Arthur

      July 22, 2020

      Kelly, If you see this post, I am having the same issue. After I have a BM, I feel like I have to pee for an hour or so. Did you ever figure out what caused it? thanks

  • Reply


    August 26, 2019

    Hi Layla,
    Thank you for the article. I have episodes that mimic Interstitial cystitis and UTIs, but I also have Systemic Mastocytosis. In my case, one of the ways I know it is my mast cells acting up is that urine cultures are negative. I have found only 1 thing that helps, and that is taking Midol Complete. It must be the Pyrilamine antihistamine in it that helps. I am on an awful lot of different antihistamines but this 1 does the trick for some reason. Let me know if anyone else is helped by this medicine. Thanks, Ra

  • Reply


    March 7, 2020

    Thank you for this article. It has raised some interesting theories for my family and myself. I have suffered from chronic cystitis my adult life, worse while breastfeeding. 2 of 3 children have significant food allergies, the 3rd has grown out of them. I wonder if the Mast cell levels in my body my have contributed to this…. it is a theory /link that hasn’t been explored (to my knowledge). Have you heard of such a link?

    • Reply


      March 9, 2020

      I haven’t heard of such a link but it’s an interesting idea. Not sure how mast cell levels in your own body could affect your children…

  • Reply


    April 17, 2020

    Hi Layla,

    Did you combine AIP with the above diets all at once? I have done AIP but not combining low oxalate/low histamine. The thought of looking at multiple lists when trying to shop/cook is so stress inducing!

    • Reply


      April 19, 2020

      Hi Chelsea, I initially did the GAPS diet and later with low Fodmap. I only learned about AIP later and followed a low oxalate Diet more recently (combined with a paleo type diet plus white rice).
      I would not recommend doing such a restrictive diet as it can be stressful, which is counterproductive. A few months on AIP can be useful if you also have autoimmune problems, otherwise I’d try a more standard paleo approach. You could test for oxalates and histamine to find out if this applies to you.

  • Reply

    Susan Fisch

    June 5, 2021

    I am a DES daughter and I have suffered from UTIs for my entire life. In 2016, I was diagnosed with IC and pelvic floor dysfunction. I have been seeing a urologist who has been studying IC ad pelvic floor dysfunction but has yet to find a cure. This year, I was diagnosed with mast cell activation syndrome. One doctor believes that I have IC and the other is positive that I have mast cell syndrome. I am not in the medical profession, but I think that I have all of the conditions. I have been in unbearable pain every day for so many years and I have lost the quality of my life! I am in desperate need of intervention and assistance. Since there is nothing to do to help with IC and the pelvic floor except for PT which I have found to not really give me relief, I am going to try to take OTC medication for the mast cell activation syndrome.

  • Reply

    beverly J Chetney

    June 17, 2021

    I am an 80 year old lady who is on two heart meds. (Can’t take antihisamine meds with heart meds.) Just went through two days of high amount of urination day and night. Been outside with daughter weed wacking my flower gardens. Upstate NY. Blood pressure went high. Pain in right temple. Scared I was going to have a stroke. Prayed for an answer and learned about Interstitial cystitis and Mast cells. I have taken a Homeopathic antihistamine called Rhinallergy (get it on Amazon. read forum) So once I learned that my bladder could be troubled by all the grass pollen etc. around my home, I popped two under my tongue (been taking a couple a day, but not enough). Woke up in the middle of the night (to pee) and pain in temple was less. Took two more Rhinallergy’s. (Follow instructions on package for first use) This morning I took two more, and will stay indoors to get my histamine level down. I feel so much better already. Lots of friends and family use it now. I just did not have runny nose etc. , but did have slight pain near my nose, so I did not take it like I should have to decrease the histamine level before it did the badder and temple pain thing. Love your articles. Will give it to others.

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