D-mannose is a natural sugar very similar to glucose. It reduces urinary tract infections and improves the symptoms of a rare metabolic genetic disorder. It may also act as a prebiotic and help with weight loss. Continue reading to learn more about D-mannose, its health benefits, and side effects.
What is D-Mannose?
D-mannose (occasionally known as carubinose, seminose, and mannopyranose) is a simple sugar that occurs naturally in the body. It’s also found in animals, plants, and microbes. Although it’s a close relative of glucose, D-mannose is much less efficient at storing energy [R, R].
D-mannose acts as a health-promoting “glyconutrient” in the body. It activates proteins by binding to them (creating so-called “glycoconjugates”), which allows proteins to play out important roles in many tissues and organs [R, R].
Humans can take in d-mannose through diet or produce it from fructose. Most of the blood D-mannose that enters cells (98%) is transformed into the fruit sugar fructose. Fructose is broken down to release energy, while only ~2% is used to bind proteins. These proteins can release D-mannose back into the blood to maintain D-mannose levels [R, R, R].
The main clinical applications of D-mannose are [R]:
- Preventing urinary tract infections (UTIs)
- Correcting a genetic disorder of glycosylation
D-Mannose Blood Levels
Human blood contains ~50 μmol/L D-mannose. High D-mannose levels can be a sign of the following conditions [R]:
- Yeast infection (candidiasis) [R]
- Diabetes [R, R, R]
- Insulin resistance [R]
- Metabolic syndrome [R]
- Advanced breast and esophageal cancer [R, R]
One study associated high D-mannose levels with an increased risk of developing chronic disorders such as type 2 diabetes, heart disease, and kidney problems (albuminuria) [R].
Although high D-mannose levels are associated with advanced esophageal cancer, a study on 159 people with this cancer found that those with higher D-mannose levels had a lower risk of cancer recurrence and death [R].
Mechanisms of Action
Most UTI infections are caused by E. coli, which attaches itself to the lining of the urinary tract by small hair-like proteins. D-mannose taken orally is excreted from the body by urine. While passing through the urinary tract, D-mannose clings to E. coli proteins and detaches the bacteria. As urine leaves the body, bacteria bound to D-mannose are flushed with it [R, R].
Genetic metabolic disorders
Congenital disorder of glycosylation type Ib is a rare genetic disorder caused by a defect in the enzyme that makes D-mannose from fructose (phosphomannose isomerase). People with this condition can’t bind D-mannose to proteins and suffer from liver damage, digestive and blood clotting abnormalities. Intake of D-mannose in high amounts raises its blood levels and ensures normal metabolism [R, R].
Uses & Benefits of D-Mannose
1) D-Mannose Reduces UTIs
What are UTIs?
UTIs are bladder infections that can affect any part of the urinary tract, including the urethra and kidneys. Most of them (75-90%) are caused by E. coli, which can enter the bladder through the urethra and begin to multiply [R, R+].
UTIs are much more common in women, half of which suffer from at least one in their lifetime. Women have a shorter urethra than men, making it easier for the bacteria to travel to the bladder. The main risk factors for developing UTIs in women are [R+]:
- Being sexually active (risk increases with frequency of sexual intercourse)
- Poor intimate hygiene [R]
- Some birth control methods — diaphragms with spermicide more so than birth control pills [R]
Urinating after sex was linked to UTIs in women who previously didn’t experience them in one study, others found the opposite, while some studies did not find any link between urinating after sex and UTI risk. Maintaining good intimate hygiene seems to be more important [R, R, R].
UTIs can also affect men in rare cases. Factors that increase UTI risk in both men and women include age, weakening of the immune system, medical conditions such as diabetes or multiple sclerosis, and catheter use [R].
- Increased frequency of urination with reduced urine volume
- Burning feeling during urination
- Cloudy, dark, bloody, or smelly urine
- Pain, nausea, and fever
D-mannose for UTIs
In a clinical trial of over 300 women with recurrent UTIs, D-mannose (2g/day) for 6 months was as effective as the antibiotic nitrofurantoin at reducing UTI recurrence [R]
In another trial of 60 women, D-mannose was more effective than two other antibiotics (trimethoprim and sulfamethoxazole). It was used at a higher dose for 2 weeks (3g/day) and maintained at a lower dose for 6 months (1 g/day) [R].
D-mannose (3g/day) also reduced UTI recurrence in a clinical trial of 22 people with multiple sclerosis after 4 months [R].
In a clinical trial of 43 women with mild bladder inflammation, D-mannose resolved most symptoms and reduced their recurrence. It was given at 3g/day for 3 days followed by 1.5 g/day for 10 days [R].
Recurrent UTIs are a frequent cause of kidney stones. In a clinical trial of 25 people who underwent kidney stone removal surgery, a formulation containing 0.1 g D-mannose for 5 months reduced the formation of new stones [R].
2) D-Mannose Improves Congenital Disorders of Glycosylation
Congenital disorders of glycosylation result from genetic defects in enzymes that bind sugars such as D-mannose to proteins. The faulty, incomplete proteins can cause serious organ damage [R+].
Type Ib of this disorder is a rare defect in the enzyme that makes d-mannose from fructose. It can affect multiple organs such as the liver and brain, cause malnutrition, vomiting, and other serious symptoms [R+].
Type Ia of this disorder is caused by a defect in another enzyme in the D-mannose pathway. Although D-mannose supplementation corrected the defect in cells and mice, it has so far failed to improve the symptoms in humans [R, R, R, R, R].
3) D-Mannose Balances the Immune System (in animals and cells)
D-mannose helps build immune tolerance and may stabilize Th1/Th2/Th17 dominance. In cells, it activated Treg cells and increased their production, which is extremely important for balancing reducing all-around inflammation and autoimmunity [R].
A team of Chinese researchers recently caused a complete shift in thinking, claiming that D-mannose is a unique health-promoting substance. According to the above-mentioned study, this simple sugar may be a safe dietary supplement to balance the immune system, treat and prevent autoimmune diseases and allergies [R].
Clinical trials have yet to prove the safety of D-mannose for reducing autoimmunity and inflammation, but moderate doses could probably achieve these effects. In animals, even a 9-fold increase in D-mannose blood levels didn’t cause side effects [R].
D-mannose prevented the onset of autoimmune diabetes, asthma, and acute respiratory distress syndrome (ARDS) in animal studies. In rats, D-mannose wound injections blocked inflammation during wound healing [R, R, R, R, R].
4) D-Mannose May Prevent Other Infections (in animals)
Similarly, D-mannose prevented gonorrhea infections in rabbits [R].
Clinical trials are required to test if D-mannose can help prevent infections from these disease-causing microbes in humans.
5) D-Mannose May Act as a Prebiotic (in animals)
Prebiotics are sugars that stimulate the growth of beneficial gut bacteria. D-mannose restored a healthy microbiome in mice with poor gut flora and reduced gut inflammation. In another study on obese mice fed on a high-fat diet, D-mannose favored the growth of the weight-loss-promoting gut microbes (Bacteroidetes) [R, R].
6) D-Mannose May Help with Weight Loss (in animals)
In obese mice fed a high-fat diet, D-mannose reduced weight gain, prevented diabetes and fat buildup in the liver. It also increased fat burning and reduced food absorption in the gut (so fewer calories are absorbed) [R].
Certain gut bacteria are linked to weight gain or weight loss. D-mannose shifted the microbiome composition to enhance weight-loss-promoting gut microbes called Bacteroidetes. It did so at the expense of another strain of bacteria linked to weight gain and obesity in humans (Firmicutes) [R].
D-Mannose Side Effects
D-mannose is generally well tolerated. At the doses used to prevent urinary tract infections, most studies found no side effects and only one reported mild diarrhea in 7.8% of people [R+].
The doses used for congenital disorder of glycosylation type Ib are much higher and the following adverse effects have been reported:
- Bloating and loose stools [R+, R+]
- Diarrhea and stomachache [R]
- Seizures and reduced consciousness [R]
- Dizziness [R+]
- Lack of appetite, discomfort, and tiredness [R]
However, the effects were only seen in people exceeding the highest recommended dose of 1.2g/kg/day. This would amount to a very large dose of over 70g/day for a person of about 120 lbs.
D-Mannose Safety and Toxicity
In a child with a congenital disorder of glycosylation type Ib, the injection of extremely high D-mannose doses for 3 weeks still didn’t cause any toxicity. Even the high doses typically used for this genetic disorder didn’t cause any damage in the long term (up to 10 years) [R, R, R+, R+].
It’s important to note that no clinical studies have evaluated its safety during pregnancy and breastfeeding. Additionally, high D-mannose doses caused reduced growth, blindness, organ malformations, and increased death rates in mouse and rat embryos. Pregnant and breastfeeding women should be cautious with D-mannose [R, R, R, R, R, R].
D-mannose stimulates insulin release. It also combines forms protein-sugar complexes that may cause complications in diabetics, such as eye, kidney, brain, and heart damage. Diabetics should consult their doctors before taking D-mannose supplements [R+, R, R, R].
D-mannose is eliminated through urine and high blood levels are linked to an increased risk of kidney problems, which raised some concerns about long-term use. However, no cases of kidney damage have been reported with the typical doses [R+, R, R].
The antibiotic for fungal infections, pradimicin A, binds to D-mannose. D-mannose supplements can reduce the availability and effects of this antibiotic [R].
- 2 g 1x/day, or
- 0.5-1.5 g 2x/day
- 1.5 g 2x/day for 3 days followed by 1.5 g 1x/day for 10 days, or
D-mannose Combination Supplements for UTIs
D-mannose is often combined with plant extracts (cranberry, hibiscus, Noni) and probiotics in formulations for UTIs.
In numerous studies with over 300 people, different formulations with D-mannose were used. The ones that worked the best include:
- D-mannose (1 g/day) combined with NAC and Noni for 1 week in preventing mild recurrent UTIs [R]
- Cranberry dry extract and probiotics (Lactobacillus plantarum and Lactobacillus paracasei) with D-mannose in preventing severe recurrent UTIs. Both higher D-mannose doses (2 g/day) over 2 weeks and lower doses (0.5 g/day) over 4 months were effective [R, R].
- The same combination improved mild active UTIs after 2 months at a lower dose (D-mannose 0.25-0.5 g/day)[R]
For Glycosylation Disorders
For Cats and Dogs
Some people buy D-mannose supplements for their pets. Analyses reported the use of D-mannose for urinary tract infections in cats and dogs with good results and without any adverse effects [R+].
The human dosage can be adapted to pets based on their weight. Large dogs would probably need a dose similar to what’s used in humans, while smaller cats and dogs would require only ¼ or less (depending on their size). Check with your vet if you’re unsure.
Forms of Supplementation
D-mannose can be taken as:
- U-tract (alone)
- Mannocist (alone)
- Cystoman (in combination with cranberry extract and vitamin C)
Additionally, the following fruits are rich in d-mannose [R]:
*Although cranberries do contain some D-mannose, they mainly improve UTI symptoms thanks to their proanthocyanidin content [R].
D-Mannose Reviews & User Experiences
A lot of women take D-mannose as an alternative to antibiotics for recurrent urinary tract infections. Almost all of them reported a reduced frequency of infections, improvement of the symptoms, and absence of adverse effects. Users who rated D-mannose lower usually complained about its high price and only a few reported occasional infections despite the therapy.
Most women with active urinary tract infections were gratefully surprised to start seeing positive results after only 1-2 days, while only a few complained that the product didn’t work for them.
Loose stools and bloating were the most commonly reported adverse effects.
Limitations and Caveats
Although the results on the use of D-mannose for urinary tract infections are very promising, they are based on only a few clinical trials. Additional studies with more people are required to confirm D-mannose as a practical, safe, and effective alternative to antibiotics.
Among the studies on D-mannose use for urinary tract infections, one was funded by the manufacturer of a D-mannose formulation (Probiotica SpA) and another one was carried out by two scientists working for another manufacturer (Deakos) [R+, R+].
Because congenital disorder of glycosylation type Ib is a very rare disease (less than 50 cases reported), the benefits and potential adverse effects of D-mannose therapy have only been investigated in a few case studies [R+].
The potential application of D-mannose in inflammatory conditions, infectious diseases other than UTIs, microbiome restoration, and weight loss have only been investigated in animals and cells. Clinical trials in humans are required to confirm these health benefits.