Systematic Review Of The Effect Of Dmannose With Or Without Other Drugs In The Treatment Of Symptoms Of Urinary Tract Infections/cystitis
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Urinary tract infections are a commoncondition. Among them, cystitis is the most frequent disease.Treatment for UTI/cystitis ranges from over-the-counter medicationsto antibiotics if the cause is an infection. In such patients,antimicrobials are often inappropriately prescribed, and their useis associated with the selection of antimicrobial-resistantorganisms colonizing or infecting the urinary tract .
The rise in antimicrobial resistant organisms isbecoming a relevant clinical and public health issue. Worldwide, ithas been estimated that ~10,000,000 deaths by 2050 will beattributable to antibiotic resistance .
Among these molecules, several studies haveidentified D-mannose ,which is characterized by a non-pharmacological, non-metabolic,non-bacteriostatic or bactericidal, but biomechanical mechanism ofaction and does not affect antibiotic resistance .
2. Mechanism of action of D-mannose in theprevention and treatment of UTI
3. Literature search methodology
Abstract And Full Text Review Data Extraction And Quality Assessment
Abstracts from the systematic literature search were independentlyscreened by two authors using the stated eligibility criteria. Fulltext of selected abstracts were independently reviewed by the same two authors.Data extraction was also independently performed by two authors. In the event ofdisagreement, the two authors reviewed the study together and a third reviewerwas available if a consensus could not be made. Each of the clinicaltrials.gov search results wasreviewed to ensure that any known unpublished data were included in our MA. Atthe beginning of data extraction, an application for Prospero registration wassubmitted with our a priori protocol. Due to the extended timeline forprocessing and reviewing the application, this study was not selected to beregistered as the registry felt the study was too close to completion by thetime the application was reviewed.
We assessed the methodologic quality of each study using predefinedcriteria from a three-tier system in which studies were graded as good, fair, orpoor based on scientific merit, the likelihood of biases, and the completenessof reporting. This grading was completed according to the Cochrane Risk of Biastool and relevant questions from theNewcastle-Ottawa Scale.22,23 Selective study reportingwithin studies was assessed as part of the risk of bias assessment.
How Do Bacteria Cause A Urinary Tract Infection
In order to cause an infection, bacteria must first adhere to the cells lining the urinary tract. They do this using hair-like fimbriae that protrude from their surfaces. The fimbriae attach to specific receptors on your cells. D-mannose helps to prevent infections by interfering with the ability of the fimbriae to latch onto your cells.
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Best Remedies For An Urinary Tract Infection: What Is A Uti
Urinary tract infections can be quite painful and uncomfortable, but thankfully, there are plenty of remedies available to help relieve symptoms and speed up the healing process.
UTI symptoms can range from a burning sensation when urinating to bladder pain or pressure in the lower abdomen and back.
While there are medications available to treat UTIs, some people prefer more natural remedies.
In this post, well discuss the 3 best remedies for treating a urinary tract infection.
What Are The Possible Side Effects Of Using D
D-mannose is generally well tolerated by children and adults. However, there have been no studies done to confirm whether D-mannose is safe during pregnancy or breastfeeding.
Manufacturers of D-mannose state that possible side effects include bloating and loose stools.
In addition to the lack of general knowledge about D-mannose on its own, how D-mannose may interact with other medications and supplements is not well studied. Its always best to talk to your doctor if you are concerned.
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Study Selection And Eligibility Criteria
Abstracts and full text publications were screened with a predeterminedlist of eligibility criteria. Inclusion criteria were as follows: a.) originalclinical research for women receiving care in anoutpatient setting for rUTI b.) participant age of 18 years or older and c.) a study armincluding D-mannose as a UTI prevention intervention. Exclusion criteriaincluded: a.) laboratory or animal-based research b.) publications written inlanguages other than English c.) duplicate publications and d.) publishedstudy protocols. If a study met all criteria, it was included. For ourmeta-analysis , we only included studies with clearly stated D-mannosedosing, follow-up time â¥6 months, and a comparator arm. Studies thatlacked follow-up, a comparator arm, or combined D-mannose with additionalsupplements were included in the systematic review but not the MA.
Can I Eat Enough Cranberries To Get An Active Dosage Of D
Another source of D-mannose is cranberries. However, D-mannose makes up just 0.04% of the dry weight of cranberries. This is quite low in comparison to other sources, even the spent coffee grounds.
Needless to say, you would need to eat a ton of cranberries for your body to gain anything close to a protective dose of D-mannose. So this is not recommended as a method of ingesting D-mannose.
Watch our expert video series to learn more about D-mannose for UTI.
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What Is An Urinary Tract Infection Aka Uti
A urinary tract infection is a common kind of infection that can affect any part of the urinary system, including the kidneys, bladder, and urethra.
UTIs are caused by bacteria and other germs that enter the body through the urethra and cause inflammation in the urinary tract.
If left untreated, a UTI can cause serious complications such as kidney damage and infections of the bloodstream.
Causes Of Urinary Tract Infections
Urinary tract infections are usually caused by bacteria from poo entering the urinary tract.
The bacteria enter through the tube that carries pee out of the body .
Women have a shorter urethra than men. This means bacteria are more likely to reach the bladder or kidneys and cause an infection.
Things that increase the risk of bacteria getting into the bladder include:
do not use scented soap
do not hold your pee in if you feel the urge to go
do not rush when going for a pee try to fully empty your bladder
do not wear tight synthetic underwear, such as nylon
do not drink lots of alcoholic drinks, as they may irritate your bladder
do not have lots of sugary food or drinks, as they may encourage bacteria to grow
do not use condoms or a diaphragm or cap with spermicidal lube on them try non-spermicidal lube or a different type of contraception
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Can I Take Cranberry And D
Yes, you certainly can take cranberry and D-mannose at the same time! One 2020 study¹¹ concluded that administering D-mannose with cranberry extract showed an increase in effectiveness when used in combination with empirical treatment for uncomplicated UTIs. So, not only is it safe to take both together, but the overall treatment looks to be more effective.
Strengths And Limitations Of This Study
Based on current literature, this will be the first large publicly funded randomised controlled trial of D-mannose for prophylaxis of recurrent urinary tract infections.
This study is the first to use a placebo control in evaluating the benefit of D-mannose.
Obtaining the primary outcome by medical notes review will ensure data completeness.
The trial may not be powered to detect a secondary outcome of symptom burden which is also of value to patient decision making.
Although participants report weekly on their study product usage there are no objective measures available to confirm accuracy of reporting.
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Information Sources And Search Strategy
A comprehensive literature search was performed with a medical librarianusing search strategies, standardized terms, and keywords for the concepts ofrecurrent urinary tract infection and mannose. These strategies were executed inOvid Medline 1946-, Embase 1947-, Scopus 1823-, Cochrane Library, Web of Science1900-, and Clinicaltrials.gov. All searches werecompleted on February 5, 2018, March 5, 2019, and again on April 15, 2020.Database-supplied English language limits were applied. Endnote was used fordeduplication. Manual checks and comparisons were also performed to determinewhether abstracts were unique or duplicates. If there was any uncertainty at theabstract level, the two authors reviewed the full-text article and came toconsensus. The full search strategies can be found in the appendix and they followed a similar strategy as theone used for Ovid-Medline April 2020 search: or or bacteriuria or pyuria or schistosomiasishaematobia or cystalgia or cystitis or pyelocystitis or exp cystitis/or AND .
Study Aims Research Questions And Outcomes
The primary aim of MERIT is to assess the effectiveness of daily use of D-mannose compared with placebo in preventing symptomatic UTI in women.
The primary outcome of the trial will be the proportion of women experiencing at least one further episode of clinically suspected UTI for which they contact ambulatory care within 6 months of study entry.
Secondary outcomes will include :
Number of days of moderately bad symptoms of UTI.
Time to next consultation with a clinically suspected UTI.
Number of clinically suspected UTIs.
Number of microbiologically proven UTIs.
Number of antibiotic courses for UTI.
Report of consumption of antibiotics using diary during periods of infection.
Proportion of women with a resistant uropathogen culture during an episode of acute infection.
Hospital admissions related to UTI.
Quality of life and healthcare utilisation related to UTI.
Healthcare utilisation recorded in the participant diary and during a notes review.
Acceptability and process evaluation conducted via telephone interviews .
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Other Applications For D
Other uses of D-mannose include reversing the effects of metabolic syndrome and support for intestinal problems.
Infants and children who have a rare inherited disorder called carbohydrate-deficient glycoprotein syndrome type 1b take D-mannose.
People with this condition have a deficiency of a specific protein in their intestines, the symptoms of which are reversible with dietary supplementation of D-mannose. In these cases, D-mannose improves liver function, lowers blood sugar levels, and helps prevent blood clotting disorders.
Some studies show that D-mannose may act as a prebiotic and may therefore help regulate the gut microbiome.
A prebiotic is a food substance that is non-digestible to humans, but provides a food source for good bacteria in your digestive system.
What The Science Says
E. coli bacteria cause 90 percent of UTIs. Once these bacteria enter the urinary tract, they latch on to cells, grow, and cause infection. Researchers think that D-mannose might work to treat or prevent a UTI by stopping these bacteria from latching on.
After you consume foods or supplements containing D-mannose, your body eventually eliminates it through the kidneys and into the urinary tract.
While in the urinary tract, it can attach to the E. coli bacteria that may be there. As a result, the bacteria can no longer attach to cells and cause infection.
There isnt much research on the effects of D-mannose when taken by people who have UTIs, but a few early studies show that it might help.
A 2013 study evaluated D-mannose in 308 women who had frequent UTIs. D-mannose worked about as well as the antibiotic nitrofurantoin for preventing UTIs over a 6-month period.
In a 2014 study, D-mannose was compared to the antibiotic trimethoprim/sulfamethoxazole for treatment and prevention of frequent UTIs in 60 women.
D-mannose reduced UTI symptoms in women with an active infection. It was also more effective than the antibiotic for preventing additional infections.
A 2016 study tested the effects of D-mannose in 43 women with an active UTI. At the end of the study, most women had improved symptoms.
A lot of different D-mannose products are available. When deciding on which one to use, you should consider three things:
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How To Take D
As of right now, there is no standard dosage for D-mannose for UTIs. To add to the confusion, each study has used slightly different dosages. As a few examples:
- 2 grams daily for six months
- 1.5 grams twice daily for three days, then once daily for 10 days
- 1.5 grams twice daily for 16 weeks
- 1 gram three times a day for two weeks, then twice daily for 22 weeks
- 1 gram three times a day for five days
- 500 milligrams twice a day for seven days
Talk to your doctor to determine how much D-mannose to take, how often, and for how many days.
When you look at supplements, try to find ones that are third-party verified. This means theyve been independently tested to confirm that the dietary supplement contains what the label says it contains, at the amount the label states, and that nothing else other than the ingredients listed are in the supplement. This is important because the FDA does not regulate dietary supplements.
You can find D-mannose in capsules or as a powder. If you use the powder, mix it with water as directed on the package. Be sure to check how much D-mannose each capsule or scoop of powder provides so that you take the correct amount.
Data Collection And Analysis
Data extraction was independently carried out by two authors using a standard data extraction form. Methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and crosschecked by another author. The certainty of the evidence was assessed using the GRADE approach.
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What Do We Know About D
Heres the short answer: We dont know enough about D-mannose for UTI. As mentioned above, there is a clear lack of studies into whether D-mannose for UTI is beneficial.
Studies that do exist have not tested appropriate dosage, and limited studies exist for the effectiveness of D-mannose for females who experience recurrent UTIs.
Most look at D-mannose against a microorganism in vitro, that is, on the lab bench, and not in females with symptoms, so we dont have a lot of information about D-mannose out in the real world .
The largest and most heavily referenced study in humans we have found involved 308 women.
In this study, the prophylactic use of D-mannose significantly reduced the risk of recurrent UTI, and was shown to be as effective as nitrofurantoin, an antibiotic.
What Is A Uti
UTI the dreaded urinary tract infection. Usually it likes to make its presence known by causing an eye-watering sting while you wee, dull abdominal pain and the constant need to sprint to the loo! It seems unfair that something so common can have such irritating symptoms.
The first port of call for treatment is typically an antibiotic, but factors such as the rise of antibiotic resistance and unpleasant side effects have resulted in increasing interest in other possible treatment options. In this article, were going to compare one of the most long-standing home remedies for UTIs, the humble cranberry, with one of the newer kids on the block, D-mannose, which is available to buy directly from The Lowdown!
A UTI is a collective term to describe an infection which involves the bladder, kidneys, ureter or urethra. Up to 90%of all cases are due to the bacteria Escherichia coli,² which is common in the urinary tract. Many of us experience recurrent UTIs, which is where you experience 2 UTIs in a 6 month period. In fact, studies suggest that there is a 27% chance³ of a second infection within six months after the first.
It is important to note that if UTI symptoms rapidly worsen, or do not respond to treatments , within a couple of days it is important to contact your healthcare team as the infection can spread to the kidney and result in complications. Important signs of worsening infection include fever, vomiting and pain over the kidney area or loin.
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Regulatory Aspects Relevant To Borderline Medical Devices And Medicinal Products
D-mannose is contained both in the EU and the United States in different types of healthcare products, such as food supplements , and class IIa medical devices. The rational of such healthcare products has its bases on several clinical studies demonstrating the efficacy of D-mannose for the prophylaxis of UTIs .
From both definitions, the medical application of medicinal products and medical devices is evident. Moreover, the EU jurisprudence clarified that, for having a therapeutic activity, a healthcare product should act not only on the human body, but also on microorganisms inducing a response that has a direct impact on functions of the human being. As an example, in the judgment on the case of chlorhexidine containing mouthwash, the EU Court states that such a product shall not be considered as a cosmetic one since the mechanism of action of chlorhexidine is pharmacological . Indeed, even if such substance has not a direct pharmacological interaction with a human cellular constituent , its interaction with the bacteria, viruses, or parasites influences positively on the physiological functions of the constituents of the buccal cavity.
Other Ways To Prevent Some Utis Coming Back
If you keep getting a bladder infection , there’s some evidence it may be helpful to take:
- D-mannose a sugar you can buy as a powder or tablets to take every day
- cranberry products available as juice, tablets or capsules to take every day
Speak to your doctor before taking any of these during pregnancy.
Be aware that D-mannose and cranberry products can contain a lot of sugar.
If you’re taking warfarin, you should avoid cranberry products.
Page last reviewed: 22 March 2022 Next review due: 22 March 2025
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Safety Of Supplemented D
Despite the potential benefits of D-mannose in UTI, some mice studies have shown that prenatal mannose supplementation causes embryonic lethality and eye defects among the mice who survived . In this trial, the dose ranged from 1 to 5% in the drinking water. In humans, safety and tolerability of a D-mannose containing product has been tested in a so called maximal tolerated dose design study . This study showed that the product containing D-mannose was well-tolerated up to 90ml of study product . Of note, the main ingredient in the product was cranberry liquid. In the above reviewed clinical trials where D-mannose was investigated as a single active ingredient with a daily dose between 2 and 3g , no serious adverse events were associated with the use of D-mannose. In addition, a systematic review and meta-analysis by Lenger et al. concluded that D-mannose was well tolerated with minimal side effectsonly a small percentage experiencing diarrhea. The occurrence of adverse events is likely to be dose-depended as daily doses exceeding 0.2g/kg of body weight may cause diarrhea and bloating . Of note, in human diabetics, blood glucose balance could potentially be disturbed by mannose supplementation . This should be taken into account when considering D-mannose supplementation among diabetics and pregnant women.