Cystitis vs Interstitial cystitis

Cystitis (also known as a urinary tract infection or UTI) is an inflammation triggered by bacteria on the bladder wall. This leads to an increase in the breakdown of urea (a component of urine) to ammonia which in turn causes irritation, inflammation and an increase in white blood cell production.

Cystitis (UTI)  is a common infection amongst women due to the shorter urethra in comparison to men. It is usually caused by a bacterial infection and the bacteria is often E.coli from the colon. The transfer of bacteria can be due to the close proximity to the colon from the two excretion points, where bacteria can spread easily, especially as a result of back-to-front wiping on the loo, or increased sweating. Lots of physical activity or a simply an exceptionally hot day can increase bacteria. In a warm environment bacterium can multiply in a process called binary fission where they replicate every 20 minutes. Due to this rapid replication, symptom onset is generally very fast.

Non-Nutritional Factors that increase risk of UTIs/ Cystitis:

-Synthetic materials increase sweating. Wearing non-synthetic underwear can be a better choice.

-The temperature required to kill bacteria is around 70 degrees, but bath water doesn’t reach higher than just above body temperature so it’s not enough to kill the bacteria but may instead provide a perfect breeding ground for them to grow. If you are at risk of repeated UTIs, then having showers rather than baths may be advisable.

-Sex can also be a trigger due to increase sweating and fluid production. It’s good practice to shower before sexual intercourse where possible and being sure to urinate after.

-Over-hygiene is also a factor. Using too much soap around the genitals can be damaging to the microbiome of the urinary tract. Some of the bacteria from soap will out compete with the good bacteria that would prevent E.coli naturally. Perfume soaps can be irritating and cause inflammation in these areas. Avoiding products that are anti-bacterial that claim to kill of germs may have the opposite effect that was intended.

-Men tend to only be vulnerable to a UTI if there is an underlying issue with the prostate or injury. For example, a cystoscopy intended to check the function of the bladder can cause damage and increase risk of infection.

Symptoms of UTIs include:

Burning
Pain
Discomfort when urinating
Disrupted flow
Excessive flow
Cloudy Urine
Mucous (women) (less common)
Blood in urine
Odour in urine

Cloudy Urine is due to the increased presence of white blood cells. Due to the inflammation, white blood cells travel to the area but cause aggravated inflammation. White cells don’t belong in the urine, so this is a clear indicator.

The odour is due to the presence of the bacteria itself. The urine is made up of water and electrolytes, but also uric acid, urea, and creatinine, all of which are nitrogenous waste which the bacteria can metabolise. The body changes ammonia into urea for urination but bacteria can also break down and metabolise urea and convert it back into ammonia which causes the burning sensation and smell.

The presence of blood in urine can be caused by the damage from ammonia or by the bacteria penetrating deeper into the bladder walls. This damage can be from the urethra or the bladder itself.  

Bacteria

In the bladder wall, we have the protective layer called GAG (or glycosamino glycans such as Hyaluronic acid) which maintain structural integrity (same as various other places in the body such as the gut and skin) and cell signalling.

On a molecular level, GAGs are proteins with a sugar attached to it. You may have heard of glycosylation elsewhere in the body where sugar binds to and thus damages proteins. This is an accidental binding due to a high sugar diet. However, in the bladder this is not the same thing as these GAGs naturally have a sugar bound to them. The most common sugar is D-mannose which has the same chemical formula of sugar (glucose). The difference is in the structural arrangement. Glucose is used in energy, but D-mannose is used in structure.

Bacteria use their pili (hair like protrusions on the surface) to adhere to the lining of the urinary tract and each other so they can form multiply. The bacteria adhere to the GAGs on the bladder wall and once this happens, they won’t be swept out in the urine. The force created when urinating is usually enough to rid the bladder of the bacteria, but once this adhesion occurs, it is no longer effective. As a result, they can then multiply and in severe cases, even penetrate deeper into the lining of the bladder and if left untreated long enough, can spread to the kidneys creating an infection which would be much more serious. A warning sign for this is kidney pain and fever, if this is the case you should seek help from your GP immediately.

D- mannose

Why then, would we use D-Mannose when it’s D-mannose that the bacteria adhere to in the bladder?

The kidneys are responsible for processing glucose and glucose can be identified in the urine by lab tests. In a healthy individual you won’t see glucose because the glucose would have been reabsorbed by the mechanics of the kidneys back into the blood stream. However, the kidneys can only process so much glucose (specifically 9mmol/L). So, if you have more than this being processed by the kidneys, they excrete them rather than reabsorb. This is also what is seen in diabetes. Large amounts of glucose in blood means the kidneys have a large amount to process. So, using D-mannose is a way to hack the body. If we give large amounts of D-mannose than the kidneys have no choice but to start excreting it out.

The D-Mannose already found in the bladder is bound to the glycoproteins (the bladder wall). It has been structurally created by the body to be bound to the cell wall. However, the supplemental D-mannose is not bound to a glycoprotein or a cell, it is just sugar passing through the bladder. The bacteria want to bind to d-mannose, be it on the cell or passing through, so this method gives us a better chance of clearing the bacteria from the urinary tract.

One method, is to give high doses (2-4g) of D-mannose every few hours until the infection is cleared to force the kidneys to have to expel the sugar, giving the bacteria less likely-hood to bind to the cell wall of the bladder. In recurrent cystitis you would do this for a longer period.

There is controversy around D-mannose because it is still a form of sugar. It has the same chemical formula as sugar, but the arrangement is different, so the body doesn’t recognise it as an energy source. Because of this, it shouldn’t aggravate sugar dependant conditions like SIBO as it is a simple sugar not used as an energy source. Despite this, it is still a sugar and high doses of sugar in the body can cause glycosylation reactions (sugars binding to proteins) and so individuals with diabetes will have an increased risk of these reactions with D-mannose if you do a high dose course long-term. They will see HBA1c blood levels go up on lab results and may also affect pre-diabetics. Studies are conflicting around this topic, so the general census is that if you can use D-mannose short term with these conditions but not as an on-going remedy in chronic cystitis cases. If an individual is getting recurrent cystitis or UTIs rather than just one-off bouts, then it could be for other issues. Be sure to check in with the causes above but also consider issues with the immune system. Of course, always consult your GP if you have diabetes, insulin resistance or PCOS.

Cranberry extract

Cranberries is often a go to remedy for UTIs as they contain proanthocyanins which are also present in grapefruit juice, blueberries, blackberries, or any fruit with a dark reddish colour. Proanthocyanins also bind to bacteria and prevent adhesion by enveloping the pili on bacteria. Cranberries also contain benzoic acid (benzoates) and quinic acid (quinates), both can be metabolised by bacteria and our tissue to hippuric acid which lead to the expulsion of the bad bacteria, acting as an anti-microbial agent. Cranberry extract may be a preferrable option as opposed to the juice because the juice is high in oxalates which if there is a problem with the kidneys, could cause kidney stones.

Nettle leaf extract

Nettle leaf is often used to support particularly men against the inflammation caused by UTIs and increase urinary output by which the force can help to expel bacteria.

Other recommendations

-Temporarily reduce intake of protein – conversion of urea to ammonia can cause most of the irritation and the more protein you have the more urea is created. This will help symptoms during the UTI but not stop it.

– Avoid caffeine, alcohol, and refined sugars as they are irritants to the bladder.

– Consume anti-inflammatory foods, fruit and vegetables and keep omega 6 low.

-Keep hydrated

-Reduced stress where possible.

-Support the TH1 arm of the immune system (quercetin, medicinal mushrooms).

Interstitial Cystitis

This is where it gets tricky! Interstitial cystitis can look initially like recurrent UTIs. This type of cystitis is not caused by bacteria. Instead, it is inflammation of the ‘Lamina Propria’ layer of the bladder wall (see below). This inflammation is of a different nature to cystitis and UTIs. In this case you may still experience blood in the urine, but you won’t have a cloudy urine sample with white blood cells. Often this type can also be identified by the lack of improvement in symptoms from antibiotic use if initially thought to be a regular cystitis flare. Symptoms are like UTIs but consist mostly of significant loin pain and pain on urination.

Interstitial cystitis can be likened to ‘leaky gut’ but for the bladder wall. What happens is that potassium crosses through in large amounts and is thought to be due to a disturbance in the GAG layer we talked about in the UTI section.

This condition is driven by electrolyte imbalance and the disturbance in the bladder wall. Normally, sodium and potassium are tightly regulated in the cell and they are usually oppositional to each other. Where there is sodium there is more fluid and less potassium presence. When there is too much potassium the fluid is dysregulated. Based on this imbalance, something called prostaglandins arrive to try and respond to the sodium and potassium imbalance. However, they themselves will cause inflammation and neurogenic pain (nerves that innovate the bladder).

Interestingly, regular cystitis will benefit from benzoates in cranberries because they help with the bacteria, but with interstitial cystitis where there is no bacteria, benzoates are an irritant and promote inflammation and a histamine response. So, it’s very important if you have interstitial cystitis not to confuse it with regular cystitis or you could make matters worse. Identifying the condition as soon as possible is ideal.

Interstitial cystitis can be aggravated by:

• Stress
• Autoimmunity I.e. Lupus and IgE allergies
• Bladder cancer treatment which causes injury to the GAG layer

Treatment for severe cases can be done professionally via your GP with Hyaluronic acid flushes (direct flushing into the bladder) to stimulate the GAG layer. However, most patients will not be allowed this treatment so instead we can support with GAGs in supplemental form:

Glucosamine sulphate

Chondroitin sulphate

MSM

Hyaluronic acid (not as effective as flush as they can be distributed elsewhere in the body)

Kegels exercise

Histamine intolerance diet