Conditions, Interstitial Cystitis

Could Your Interstitial Cystitis Be Caused By A Damaged GAG Layer?

The so-called GAG layer plays an important role in protecting the bladder lining (epithelium) against anything that enters the bladder.

When this protective layer is disturbed, the sensitive bladder lining is exposed to irritation and attack. From this, sensitivity, pain and other problems can arise.

A damaged GAG layer has been established to play a big role in the pathogenesis of interstitial cystitis.

What is the GAG layer?

GAG is short for glycosaminoglycans. GAGs are mucopolysaccharides, meaning they are long chains of sugars (similar to starch) interspersed with some amino acids that attract water to form a kind of mucilage (similar to mucus).

GAGs mainly contain the molecules hyaluronic acid, chondroitin sulphate, keratin sulphate, heparin, heparin sulphate and also the amino-sugars glucosamine and galactosamine.

GAGs can be found on skin tissue (including the lining of organs), cartilage and bones, where they play a protective and cushioning role.

In the bladder, GAGs are secreted from cells of the bladder lining – similar to mucus.

The GAG layer in the bladder

Urine contains many waste products that the body needs to excrete. The more waste products it contains, the more irritating the urine would be.

The GAG layer, however, has the ability to repel these substances.

By binding to underlying cells, the GAG layer creates an electrically neutral barrier to protons in the urine. These are positively charged – meaning that without the GAG layer the protons could cause ‘electrical shocks’ in the epithelial cells of the bladder lining.

Moreover, an intact GAG layer can prevent bacteria from adhering to the bladder wall, so that they can be washed away in urine.

How does the GAG layer get damaged?

Bacteria: If there is a high pathogenic burden or the GAG layer lacks integrity, growing bacteria may start to produce enzymes that help them adhere to tissues. The higher the number of bacteria, the more enzymes would be secreted. These enzymes may erode the GAG layer, making it possible for the bacteria to adhere to the bladder lining where they can set up biofilm colonies.

Lack of raw materials: To build a strong GAG layer the body needs sufficient raw materials. These include amino acids such as glutamine, sulphur, water and glucose to name a few. If these raw materials are not sufficiently provided through the diet, the GAG layer may lack integrity.

Toxins and drugs: Free radicals, environmental toxins (e.g. chemicals such as Glyphosate), certain foods, bacterial toxins and certain drugs (e.g. statins, bacteriostatic antibiotics and radiation) may contribute to GAG and epithelium damage in the bladder.

Inflammation: The damaging effect of toxins and certain drugs is probably due to the inflammation they can cause. Certain foods and drinks can also increase inflammation (e.g. Omega 6 oils from vegetable fat, food additives, refined sugars).

Stress: Stress may play a role in most chronic diseases. Long-term, it can suppress the immune system, allowing pathogens to take hold and cause damage. Moreover, dietary absorption of nutrients may be reduced, potentially reducing the availability of raw materials for the GAG layer.

A damaged GAG layer and interstitial cystitis

When the GAG layer is damaged, the bladder lining is no longer protected from urine and the waste products contained in it. This may lead to several problems:

  • The electrically positive-charged protons present in urine interact with the epithelium, potentially establishing a small electric current across the cellular membranes. This may manifest in a pain feeling like tiny ‘electric shocks’.
  • The exposed epithelial cells of the bladder lining can become damaged by urine and its toxins and may begin to ‘leak’ (‘leaky bladder’). Ions from urine get through the barrier that would normally only get through if the bladder was full. This can give an early signal to void to the nerves located between the cells, potentially leading to the frequency, pressure, cramping and urgency associated with interstitial cystitis.
  • The delicate epithelial cells are exposed to acid urine urinary toxins that may cause burning. The bladder would probably try to rid itself of the burning urine as quickly as possible through spasms. Long-term ‘burning’ may contribute to scarring and shrinking of the bladder.

How to support the GAG layer

  • GAG replenishment therapy has shown promise for interstitial cystitis relief in a few studies. Intravesical (directly into the bladder) administered hyaluronic acid or a hyaluronic acid-chondroitin sulphate combination seem to be effective.
  • Mucilageous herbs such as aloe vera or slippery elm may bring some relief and protection to the bladder lining in absence of a functional GAG layer. However, they will not repair the GAG layer.
  • Eating a nutrient dense diet can help supply the raw materials needed to make a strong GAG layer (check out the interstitial cystitis diet protocol).
  • Removing toxins and irritants may help to reduce further damage and irritation.
  • Drink bone broth every day. Bone broth contains GAGs and all the building blocks needed to make them. It is the one thing I contribute my recovery from interstitial cystitis to the most.

Do you think a damaged GAG layer could be involved in your interstitial cystitis? Let me know all about it in the comments!

Pin it for later:


Hauser, PJ et al Abnormalities in Expression of Structural, Barrier and Differentiation Related Proteins, and Chondroitin Sulfate in Feline and Human Interstitial Cystitis. J Urol. 2015 Aug [194(2):571-7] available at:

Hauser, PJ et al Abnormal expression of differentiation related proteins and proteoglycan core proteins in the urothelium of patients with interstitial cystitis. J Urol. 2008 Feb [179(2):764-9] available at:

Christopher D. Engles et al Intravesical Chondroitin Sulfate Inhibits Recruitment of Inflammatory Cells in an Acute Acid Damage “Leaky Bladder” Model of Cystitis Urology February 2012 [Volume 79, Issue 2, Pages 483.e13–483.e17] available at:

Ömer Gülpınar, MD et al Clinical comparision of intravesical hyaluronic acid and hyaluronic acid-chondroitin sulphate therapy for patients with bladder pain syndrome/interstitital cystitis Can Urol Assoc J 2014 [8(9-10):e610-4] available at:

Jody A. Charnow Bladder Pain Syndrome/Interstitial Cystitis Linked to Statins December 2015 Issue of Renal And Urology News

Dr Jeremy Jones and Radswiki et al. Radiation and chemotherapy induced cystitis 2017

Gillespie, Larrian You don’t have to live with cystitis (New York: Avon Books, 1996), p. 61-67

Daniel, Kaayla T. and Fallon, Sally, Nourishing Broth (New York, Grand Central Life & Style, 2014)





  • Reply

    Roy A Wagner

    January 17, 2017

    Very interesting article that seems to be completely coherent with our experiences. This explains the bio-mechanics of what we had observed in our story from several months back. We hope your article gives hope and encouragement to people who are still suffering from IC.
    Thinking back on my wife’s experience with IC, I am reminded of a line from the movie “National Treasure” where Nicholas Cage asks: “Could it really be this simple?”
    Joy2U and your readers.

  • Reply


    January 17, 2017

    Thanks, Roy!

  • Reply

    Sheryl Chan

    January 17, 2017

    Hi Layla,

    Thanks for writing this very helpful guide backed with sources. I am sure it will help many others out there!

    On a side note, I’ve been having bladder irritation for months now (like having a UTI, but without the bacteria ;)), but my doc brushes it aside and says IC doesn’t usually present in the way I describe to him. Just wondering, in your vast knowledge in relation to such issues, if you have a clue of anywhere I could start looking for an answer to? I do have Lupus, Sjögren’s, and lots of other conditions which might play a part.

    Thank you for your time! ?

    • Reply


      January 17, 2017

      Hi Sheryl! Thanks, I do really hope it will 🙂
      I’m so sorry to hear you are dealing with bladder pain! And all the other conditions!
      It has been proposed that IC should be called ‘Bladder Pain Syndrome’ because similar to IBS it doesn’t manifest in the same way in every person affected – unfortunately some doctors will only recognize a ‘disease’ once it has progressed far enough to show the typical symptoms…From my research I have gathered that in most cases there is probably a damaged GAG layer, which then potentially turns into a damaged bladder lining (‘leaky bladder’ – article forthcoming…). Take a look as this study that explains how that can cause the early symptoms of IC, that aren’t classed as IC:
      Another thing would be biofilm infections (I wrote an article about this) or bacteria/yeasts in the bladder that aren’t picked up by the lab.
      IC often seems to come with autoimmune disorders (I have Hashimotos as well) and allergies, so there is a theory that it has also to do with immune dysfunction and/or a mast cell disorder.
      Autoimmunity seems to have a lot to do with gut health: and for me focusing on diet and gut health has resolved the IC and a lot of other symptoms. You could also look into some of the treatments for a GAG layer issue.
      For my autoimmune issues I’m currently trying helminthic therapy and have had FMT (fecal microbiota transplant) in the past, both therapies you could look into (there are some very helpful FB groups for both of these) – both have good research behind them but have not been approved by the medical establishment.

      I hope any of this helps, just brainstorming a bit 😉

      Good luck with your recovery!

      • Reply


        February 16, 2017

        Hi Layla,

        Apologies for the late response, I only just saw it. Thank you so much for your help, I truly appreciate it! I will definitely look into the links and also research on the knowledge you have shared.

        On another note, they referred me to a proper urologist who thinks it might be to do with the Lupus. Perhaps it’ll just be guesswork (as usual) but let’s see what the results show. Thanks so much once again, and keep up with your fantastic writing.

  • Reply


    January 13, 2018

    I believe my GAG layer damage caused my interstitual cystitis. Similar to your other article about antibiotics, I was on Macrobid several times in 2 months. The last time I was on it I got a severe reaction: chest pain and throwing up. Wishing a few days that’s when severe burning and my interstitial cystitis symptoms started.

  • Reply


    January 31, 2018

    I had surgery in 1995 for a nerve graft and was given anseph to prevent infection. The night it was given to me I started urinating every 20 minutes and had a bad reaction to it. My bladder was never the same. Do you think the anseph could of caused my ic, and if so what can I do to get my life back?

  • Reply


    January 31, 2018

    I had surgery in 1995 for a nerve graft and was given anseph to prevent infection. The night it was given to me I started urinating every 20 minutes and had a bad reaction to it. My bladder was never the same. Do you think the anseph could of caused my ic, and if so what can I do to get my life back?

    • Reply


      February 2, 2018

      Hi Emilie,
      I don’t know much about anseph, is it an antibiotic? My own problems got kicked off by antibiotics but I can’t say for sure in your case. You might want to read this article about antibiotics and bladder health:

  • Reply


    March 9, 2018

    Hi Layla,

    I’ve had a history of recurrent UTI, but didn’t have an infection in 5 years. The in September i got another one and took macrobid, but it didn’t kill the infection so I took levaquin. Follow up cultures showed the infection was gone but i was stuck with awful bladder irritation. After a few weeks of altered diet (no alcohol, coffee, sugar), it went away and I totally had my life back and could consume whatever.

    I just got another UTI in early February and nitrofurantin cleared it (culture confirmed), but AGAIN I’m left with the terrible bladder irritation and this time it is not going away. Again, I’ve noticed it’s worse after consuming acidic foods (coffee, alcohol, tomatoes) and I’ve tried to avoid them but have slipped up from time to time. I’m getting a a cystoscopy in a week.

    It sounds like my GAG layer may be damaged after repeat infections and use of antibiotics (i got UTIs almost monthly as a kiddo). How long did it take of altered diet + bone broth/supplements to notice an improvement? Are you able to now consume what you like? Do you make your own bone broth… I’ve been a vegetarian for 14 years so this will be a tough adjustment.

    Furthermore, due to the recurrent UTIs I’ve been prescribed nitrofurantin to take post-coital. I feel like I need the antibiotics to avoid the UTIs which then caused this IC-like issue.

    Any tips or hope would sure help! Thank you!

    • Reply


      March 10, 2018

      Hi Alexa, I’m so sorry to hear you’re struggling. It took me 6 months for my bladder pain to improve and can now eat most things without getting bladder issues. Yes, I did make my own Bone broth but you can now also buy it in many countries (although it tends to be expensive). Bear in mind that this is what worked for me, it doesn’t necessarily mean it’ll be exactly the same for you – we’re all individuals. The problems with antibiotics is that they disturb the balance of bacteria, which also affects good bacteria. I now believe that the most important thing is to restore balance (using fibre as food for beneficial bacteria, plus certain beneficial bacteria supplements) and to help immunity by eating nutrient-dense foods and avoiding stress. I have blog posts on many of these topics. Also, be aware that a negative urine culture doesn’t mean theres no infection – these tests miss a lot of infections.

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