D-mannose - Chronic UTI Info

D-mannose is a simple sugar that comes from mannitol which is produced from fructose, starch or sucrose from certain fruits, vegetables, plants and trees and some marine plants such as kelp. However you should only consider using D-mannose at the very beginning of symptoms. If symptoms have not diminished or completely disappeared after a short period, do not wait any longer and go to the doctor. There is a risk that bacteria are growing at a faster rate than can be cleared through D-mannose especially if the bacteria are resistant to it. There is also insufficient research at present to demonstrate D-mannose’s overall efficacy in treating recurrent and persistent cystitis.

It is found in cranberries, apples and other fruits such as gooseberries and blackcurrants. It is also present in smaller quantities in aloe vera, green beans, tomatoes, cabbage, root vegetables such as turnips. Think of it as a natural, simple sugar that is related to glucose.

However the body absorbs mannose much more slowly than glucose and does not convert it to glycogen (glycogen is the stored form of glucose) or store it in the liver. Only very small amounts of D-mannose are metabolized (processed by our digestive system), so it doesn’t interfere with blood sugar regulation. This enables D-mannose to be quickly absorbed into the bloodstream (in under an hour), through the kidneys and then excreted in urine out of the body. It is an important sugar when it comes to health and is found in most cells in the human body including that of the bladder wall (urothelium).

Why is there a link between D-mannose and the treatment of urinary tract infections?

While many bacteria can cause a UTI, the most common pathogen for both uncomplicated and complicated UTI is gram-negative uro-pathogenic Escherichia coli (E. coli) or UPEC. UPEC are responsible for 80%–90% of all uncomplicated UTI and approximately 65% of complicated UTIs.¹

Most E-coli strains live harmlessly in the the gut of humans and animals such as cattle, pigs, sheep and poultry. Strains of E-coli, as part of the gut flora, play a part in the digestive process.

UPEC can be shed in your stools, allowing them to live on the perineum or the urogenital area (the vulva and vaginal/urethral entrances). This can lead to bacteria being introduced into the urinary tract.

Upon entering the bladder, these infection causing bacteria must ensure they are able to bind to the bladder lining and/or a surface such as a catheter to establish and develop a bacterial colony. To do this, UPEC species change shape and develop adhesive pili (or hairs) on their surface. These are known as Type 1 FimH (or Fimbria) and it is these that allow these bacteria to stick and thus begin to establish colonies. Think of them as grappling hooks. During bacterial colonization, these grappling hooks bind to carbohydrate‐containing protein receptors found in the cells of the bladder wall and effective bacterial colonies can develop as these receptors provide the right nutrients for growth.

As first mentioned, mannose is found in cells all over the body including the bladder wall. UPEC love the D-mannose in these cell walls because of their glucose element allowing them to attach and replicate.

If a catheter is introduced into the bladder, fibres can develop across the surface of the catheter caused, it is thought, by the inflammatory immune system response of the body from which fibres leak into the bladder and are deposited onto the catheter. This allows UPEC to bind to the catheter and promotes growth of the infection.

D-mannose molecules in the urine may act as a competitor to the mannose cells on the bladder wall lining for bacteria as they are similar in structure and may prevent colonisation of a catheter surface via pili attachment to the fibres. The key is the dosage of D-Mannose. In sufficient concentration in the urine, if the D-Mannose is effective, the bacteria can be expelled from the bladder by urination. Any remaining infectious bacterial cells in the urine can be tackled by your immune system with the introduction of bacteria killing white blood cells and the shedding of the infected bladder wall cells to prevent re-establishment and growth.

Should D-mannose be used each time a UTI develops or to help prevent recurrent infections?

Current research available has shown that:

D-mannose may be effective for the reduction of acute or recurrent infections if taken at the very onset of the infection when symptoms are first noticed.
D-mannose may be effective against certain strains of E-coli or possibly Klebsiella known to cause UTIs to prevent bacterial attachment to the bladder wall.
D-mannose is a natural alternative remedy that may be used if the user does not wish to use daily prophylaxis or low-dose antibiotics to prevent acute infection or reinfection. Increasing bacterial resistance to low dose antibiotics has meant that many front-line antibiotics such as Trimethoprim are now resistant to strains of UPEC.
D-Mannose will not affect either the vaginal microbiome or urinary microbiome unlike antibiotics. The use of these can lead to thrush/candida.

The case against

However, there is insufficient, current research at present to demonstrate D-mannose’s overall efficacy in treating recurrent and persistent cystitis. Issues include:

Controlled trials and studies are often limited in complementary and alternative medicine and involve small numbers of participants. They are often conducted under less rigorous controls, guidelines and environments than those undertaken for the development of new pharmaceutical medications such as antibiotics. Do your research, there should be clear, peer reviewed, empiric evidence as to the efficacy of D Mannose rather than theorisation about how it may be beneficial in the treatment of a chronic UTI.
There are very limited patient research trial studies. More are needed and several are currently in trial publishing in 2020.
Length of study and size of participant groups. Current studies available have shown trials of under one year and in small patient trial groups. This study published in the World Journal of Urology in 2013 noted that in their patient cohort of 399 women those taking D-mannose powder alone showed effectiveness in preventing UTI. However it fared no better than those women taking a daily prophylactic dose of nitrofurantoin and the recurrence rate did not differ between patients who took standard Nitrofurantoin prophylaxis and those who took D-mannose powder. This lack of scientific and clinical rigor applied to study design and outcomes is common with alternative therapies.
In Vitro vs In Vivo. Most studies undertaken are either in laboratory known as “test tube conditions” or with the use of mice rather than human participants. Human behavioural, genetic, and environmental differences in comparison to those of mice mean it is difficult to compare like with like.
Different strains of bacteria. Infections are now recognised to be polymicrobial (comprised of more than one bacteria). Not all bacterial strains have these Pili (grappling hooks) and thus D-Mannose molecules in the urine won’t be effective in binding these bacteria to them and expelling them through urination. Instead the bacteria will bind to the urothelium and form bacterial colonies. Indeed certain strains of UPEC do not create Pili.
Once bacteria have attached to the cells of the bladder wall and started to reproduce, D-Mannose will not prevent the infection developing further.
There has been insufficient research into the optimum dosage for the prevention of recurrent infections.
For those with gastric issues such as Crohns or colitis, D-mannose may not be absorbed. Additionally, pathogenic e coli in the intestines may bind to most D-mannose available preventing sufficient molecules being filtered through the kidneys and into the bladder. Different people will react differently to the same D-mannose dose due to their age, weight, and overall health.
Commercial D-Mannose powder is often made from corn, particularly the less expensive versions. For those with allergies, a reaction to D-Mannose derived from corn may include a mild rash headaches and stomach aches.
Cost – as with any usage of a supplement on an intermittent or ongoing basis, there is a cost to you financially.

How will D-mannose help with a chronic embedded intracellular or biofilm infection?

Usage of D-mannose for penetration of a biofilm or an intracellular infection would not be effective. Where it may be of use is for acute attacks, when these cells release planktonic (active) bacteria into the urine and you experience a ‘flare up’ of symptoms. By using D-mannose at sufficient dosage, this may help to prevent reinfection and new colonies of infection being created on the bladder wall. But it will only work if the bacteria identified are UPEC.

Should I keep using it?

If you have used D-mannose before and found it effective previously then it is your choice as to whether you continue using it to manage an acute UTI or as a preventative.

A teaspoon of D-mannose should ideally contain around 2,000 mg of pure Mannose and a single tablet or capsule should have around 500mg. Your health practitioner should offer guidance as to the appropriate dosage.

The following points should help.

Take a half to one teaspoon of D-mannose in no more than half of a glass of water. Then wait for about 45 mins to an hour. After that, drink plenty of water. Once the D-mannose has been absorbed into the bloodstream and flushed through the kidneys, this will concentrate the D-mannose in your urine allowing it to bind to the UPEC bacteria. Continue this every two to three hours for up to five days.
Only use D-mannose at the very beginning of symptoms. If symptoms have not diminished or completely disappeared after a short period, do not wait any longer and go to the doctor. A full-blown UTI might benefit from D-Mannose supplementation, but there is a risk that bacteria are growing at a faster rate than can be cleared through D-mannose especially if the bacteria are resistant to it. Remember, D-mannose only works for UTIs caused by E. coli bacteria. A delay in seeking treatment if symptoms worsen or do not significantly improve can result in worsening the infection leading to possible kidney infection or at worse sepsis.
If antibiotics are prescribed, supplementing with D-mannose could be an option to speed up recovery, but do not stop the antibiotic treatment to switch to D-mannose. A course of antibiotics should always be completed unless side effects are experienced and a medical professional advises cessation.
Some find it beneficial to follow up a flare up or acute attack by taking a preventive D-mannose dose daily. This is usually one teaspoon 2-3 times daily. Consider taking D-mannose every time you think your vaginal flora or immune system are compromised (with the first signs of a yeast infection, after sex, illness etc.).
Take the DM away from any acidic food or drink as it will counteract its effects and the urine must be kept alkaline. This includes the use of Hiprex, a urinary antiseptic which is activated when urine is very concentrated and acidic. Gram-negative bacteria such as e coli reproduce more slowly in an alkaline environment allowing for the potential of greater attachment to the D-mannose molecules in your urine.
Initial usage of D-mannose can lead to loose stools for a few days. If diarrhoea continues, consult with your specialist as to continued usage. Users also report gas and bloating as other side effects. It may potentially exacerbate symptoms for those with small intestinal bowel overgrowth (SIBO). If this applies to you consider adjusting your dosage or discuss its usage with your consultant.

Types of D-mannose

D-mannose is sold as both as a powder or as capsules. Which type you use, is up to you and personal preference. Suppliers include

Sweet Cures – Waterfall D-mannose

Now Foods D Mannose

West Coast Mint

However it is important to understand the differences between D-mannose formulations, particularly for those with allergy issues.

Manufacturers can use various raw sources for the production of D-mannose or D-mannose can be synthetically produced. Manufacturers refer to this as pure or synthetic production. Natural sources can be from birch trees, palm kernels, potato, corn or fruits such as cranberries and pineapples. Synthetic sources such d-fructose or d-glucose or pure starch through bio-conversions are inexpensive starting materials and widely available.

For those with corn allergies, always check with the manufacturer as to the source of their D-mannose before purchasing and the environment in which the product has been packaged. If you have a known corn allergy or suffer a reaction after using D-Mannose, consider an alternate that is made from pineapples or cranberries or derived from birch/beech wood hydrolysate.

The production of D-mannose can also introduce additives, in particular if taken in capsule form. Silica, magnesium stearate, rice flour, artificial sweeteners and heavy metals can all be included as bulking agents or form the body of an individual tablet. This ensures cheaper mass production. Do your research first especially if you have allergy issues or are following a preferred regime of avoidance such as soy, gluten or GM products.

Sadly sometimes price does reflect quality of manufacture and purity of product so buyer beware.

When researching a brand look at the amount of pure D-mannose in each pot or tablet. The higher the better. A teaspoon of powder should offer around 2000 mg of D-Mannose and a tablet around 500mg. And remember Cranberry products are not the same as D-Mannose. Cranberry extract and juice has been shown not to be effective against recurrent and chronic UTI.

We debunk the cranberry myth here.

What is research now focusing on based on the behaviour of UPEC to D-mannose?

The Hultgren laboratory at the Department of Molecular Microbiology, Washington University School of Medicine in the US is now focusing on inhibitors of UPEC bacteria to attachment of the bladder wall. One area of development are mannosides. Mannosides are mannose replicates that are designed to bind with FimH and thus block UPEC from attaching to the bladder wall. Murine (or mice) studies have shown that mannosides are potent, fast acting and highly efficacious in the treatment of UTI and also catheter induced UTI (known as CAUTI). One study they have produced notes: “Mannoside treatment is especially promising as a novel antibiotic sparing therapeutic because they are effective against multi-drug resistant uropathogens. While D-Mannose and mannosides both appear to effectively block FimH-mannose interactions, mannosides have approximately a 1,000,000-fold increase in potency for inhibiting FimH, making them promising antibiotic-sparing therapeutics.” ²

Considering using a complementary medicine? Before doing so it may be worth reading the Buyer Beware information on our Natural Supplements home page.

References:

1. Foxman B. Urinary tract infection syndromes: Occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect. Dis. Clin. N. Am. 2014;28:1–13. doi: 10.1016/j.idc.2013.09.003.

Griebling T.L. Urinary tract infection in women. In: Litwin M.S., Saigal C.S., editors. Urologic Diseases in Amerca. U.S. Government Printing Office; Washington, DC, USA: 2007. pp. 587–620.

Flores-Mireles A.L., Walker J.N., Caparon M., Hultgren S.J. Urinary tract infections: epidemiology, mechanims of infection and treatment options. Nat. Rev. Microbiol. 2015;13:269–284. doi: 10.1038/nrmicro3432.

2. Adhesive Pili in UTI Pathogenesis and Drug Development Caitlin N. Spaulding and Scott J. Hultgren Pathogens. 2016 Mar; 5(1): 30.