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!
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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: https://www.ncbi.nlm.nih.gov/pubmed/25636658
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: https://www.ncbi.nlm.nih.gov/pubmed/18082196
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: http://www.goldjournal.net/article/S0090-4295(11)02483-6/abstract
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Dr Jeremy Jones and Radswiki et al. Radiation and chemotherapy induced cystitis 2017 https://radiopaedia.org/articles/radiation-and-chemotherapy-induced-cystitis
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)