D-MANNOSE

BACKGROUND

Ingredient Type: Metabolite

Also Known As: Carubinose, D-Manosa, Mannose, Seminose, D-Mannopyranose, Mannopyranose (1)

D-mannose is a simple sugar that occurs in microbes, plants, animals, and fruit including oranges, peaches, and apples. Human plasma also contains around 50μM mannose. D-mannose plays an important role in metabolism (i.e. protein glycosylation). Mannose’ high-mannose-type oligosaccharides have proved to play an important role in protein quality control (2,3,4,5,6,7,8).

In 1921, the original industrial source of mannose was in ivory nut shavings. Ivory nuts composed of β-mannans were used to carve and manufacture buttons. In 1998, it has proven its therapeutic efficacy in glycosylation-deficient patients. This discovery opened the doors to searches in understanding its metabolism at cellular and organismic levels. At the same time, the stringent regulation of D-mannose metabolism has been noted to be of critical importance due to its complexity in serving as therapeutic and a non-antibiotic treatment for certain bacterial infections while also having the ability to become lethal and teratogenic (2).

TRADITIONAL USES

D-mannose has been used to treat inherited metabolic disorders such as carbohydrate-deficient glycoprotein syndrome (CDGS), to reduce the recurrence of urinary tract infections (UTIs), and reduce the bleeding disorders.

WHAT DOES SCIENCE TELL US?

D-Mannose Might Help Support a Healthy Urinary Tract:

Three clinical trials and one review has been found on D-mannose’s influence on reducing the recurrence of urinary tract infections (UTIs). Positive but insufficient evidence exists supporting D-Mannose’s use in preventing UTIs. The studies found consider D-mannose as an alternative therapy to antibiotic therapies. A recent review (2017) has reviewed two studies in which D-mannose was found to be a useful prophylactic therapy for recurrent UTIs. All three studies conducted in 2000s concurred on D-mannose effectiveness in preventing UTIs, while warranting further investigation to confirm the positive outcomes.

D-mannose has been investigated to reduce the recurrent UTIs in women (recurrent defined as at least two UTIs in six months or three UTIs in one year). Due to the D-Mannose efficiency during in vitro studies to locally reduce the adherence of Escherichia coli, Pseudomonas aeruginosa and Streptococcus zooepidemicus, it was proposed for a clinical trial with 308 women (>18 years of age, with acute UTI, with a history of recurrent UTIs).  Subjects were first received an antibiotic treatment of the acute UTI (500 mg of ciprofloxacin twice daily for 1 week). After the treatment, they were divided into three groups and given either 2 g/day of D‐mannose powder for the duration of six months, 50 mg/day of nitrofurantoin, or no prophylaxis. Post-assessment results of the treatment revealed,

• a significantly higher rate of recurrent UTI in the no prophylaxis group (60%) in comparison with D‐mannose (15%) and nitrofurantoin (20%) groups;
• a significantly higher risk of recurrent UTI episodes in the no prophylaxis group in comparison with active prophylaxis groups (relative risk 0.24 and 0.34);
• a significantly lower risk of side effects in the D-mannose group in comparison with the nitrofurantoin group.

The study concluded D-mannose’ effectiveness as a prophylactic in women of younger age with acute UTI and with a history of recurrent UTIs. While the results were promising, the positive outcomes warrant further investigations in which the exact dosage and the optimum regimen for D‐mannose would be analyzed (18).

A 16-months pilot study investigated D-mannose as a promising support for acute urinary tract infections (UTIs) in women. Because D-mannose is a simple sugar, it is deemed to have the ability to hinder bacteria adhesion to the urothelium. The study’s aim was to determine D-mannose efficacy standalone in treating UTIs as well as its potential to manage future recurrences. D-mannose was first administered twice daily for 3 days and then once a day for 10 days, following a randomization with a 6-month prophylaxis (to either receive or not). Post-assessment results of the treatment revealed a significant improvement of the majority of symptoms (p < 0.05), a significant positive effect on UTIs’ resolution and quality of life as measured via a specifically validated questionnaire (UTISA) (p = 0.0001), and promising results when administered as prophylactic agent (4.5% vs. 33.3% recurrences in treated and untreated patients respectively).

The study concluded D-mannose potential in becoming an effective aid in acute cystitis management as well as a successful prophylactic agent in a selected population. Given that this was a pilot study, the positive results warrant further investigation of mannose as UTIs treatment, management, and prophylaxis (19).

In seeking a natural remedy for reducing the use of antibiotics in urinary tract infections (UTIs), an analysis of studies was conducted on mannose’ influence on UTIs. Two studies were reviewed where D-mannose efficacy was compared to an antibiotic therapy. Even though a significant difference was not found between nitrofurantoin and D-mannose supplementation, it was noted that the antibiotic therapy led to considerable side-effects. One of the studies noted a significant decrease in UTIs recurrence in the D-mannose group in comparison with the trimethoprim/sulfamethoxazole group. The analysis concluded D-mannose’ potential in becoming a useful prophylactic therapy for recurrent UTIs. Although positive, the evidence presented is insufficient warranting further studies for the proposed alternative therapy (20).

SAFETY

D-mannose is generally safe when used in the prescribed dosages. Caution is advised during pregnancy (2,3,12,13,14,21).

Interactions:

No known interactions

Side-Effects:

• Excessive amounts may be toxic to the kidneys (12)
• Higher doses have been noted to cause mild gastrointestinal discomfort (15)
• Diarrhea (18)
• Studies on animals reported d-mannose as potentially teratogenic (22)

REFERENCES

1. D-Mannose. National Center for Biotechnology Information PubChem Compound Database. https://pubchem.ncbi.nlm.nih.gov/compound/18950#section=Top.  Accessed April 26, 2018.
2. Sharma V, Ichikawa M, Freeze H. Mannose metabolism: More than meets the eye. Biochem Biophys Res Commun. 2014;453(2):220-228. doi:10.1016/j.bbrc.2014.06.021.
3. Niehues R, Hasilik M, Alton G, et al. Carbohydrate-deficient glycoprotein syndrome type Ib. Phosphomannose isomerase deficiency and mannose therapy. J Clin Invest 1998;101:1414-20. DOI: 10.1172/JCI2350
4. Kranjčec B, Papeš D, Altarac S. D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial. World J Urol. 2013;32(1):79-84. doi:10.1007/s00345-013-1091-6.
5. Sharma V, Nayak J, Derossi C, et al. Mannose supplements induce embryonic lethality and blindness in phosphomannose isomerase hypomorphic mice. FASEB J. 2014;28:1854–69. DOI: 10.1096/fj.13-245514
6. Buchanan T, Freinkel N, Lewis NJ, Metzger BE, Akazawa S. Fuel-mediated teratogenesis. Use of D-mannose to modify organogenesis in the rat embryo in vivo. J Clin Invest. 1985;75:1927–34. DOI: 10.1172/JCI111908
7. Falcone G, Nickerson WJ. Cell-wall mannan-protein of baker’s yeast. Science. 1956;124:272–3.
8. Harms HK, Zimmer KP, Kurnik K, et al. Oral mannose therapy persistently corrects the severe clinical symptoms and biochemical abnormalities of phosphomannose isomerase deficiency. Acta Paediatr. 2002;91:1065–72.
9. Congenital Disorders of Glycosylation – NORD (National Organization for Rare Disorders). NORD (National Organization for Rare Disorders). https://rarediseases.org/rare-diseases/congenital-disorders-of-glycosylation/.  Accessed April 25, 2018.
10. Congenital disorder of glycosylation type 1B – Conditions – GTR – NCBI. Genetic Testing Registry. https://www.ncbi.nlm.nih.gov/gtr/conditions/C1865145/.  Accessed April 26, 2018.
11. Carbohydrate-deficient glycoprotein syndrome type I – Conditions – GTR – NCBI. Genetic Testing Registry. https://www.ncbi.nlm.nih.gov/gtr/conditions/C0349653/.  Accessed April 26, 2018.
12. de Lonlay P, Cuer M, Vuillaumier-Barrot S, et al. Hyperinsulinemic hypoglycemia as a presenting sign in phosphomannose isomerase deficiency: A new manifestation of carbohydrate-deficient glycoprotein syndrome treatable with mannose. J Pediatr 1999;135:379-83.
13. Westphal V, Kjaergaard S, Davis JA, et al. Genetic and metabolic analysis of the first adult with congenital disorder of glycosylation type Ib: long-term outcome and effects of mannose supplementation. Mol Genet Metab 2001;73:77-85. DOI: 10.1006/mgme.2001.3161
14. Hendriksz CJ, McClean P, Henderson MJ, et al. Successful treatment of carbohydrate deficient glycoprotein syndrome type 1b with oral mannose. Arch Dis Child 2001;85:339-40
15. Alton G, Kjaergaard S, Etchison JR, Skovby F, Freeze HH. Oral ingestion of mannose elevates blood mannose levels: a first step toward a potential therapy for carbohydrate-deficient glycoprotein syndrome type I. Biochem Mol Med. 1997;60:127–33.
16. Mayatepek E, Schröder M, Kohlmüller D, Bieger WP, Nützenadel W. Continuous mannose infusion in carbohydrate-deficient glycoprotein syndrome type I. Acta Paediatr. 1997;86:1138–40.
17. Kjaergaard S, Kristiansson B, Stibler H, et al. Failure of short-term mannose therapy of patients with carbohydrate-deficient glycoprotein syndrome type 1A. Acta Paediatr. 1998;87:884–8.
18. Altarac S, Papeš D. Use of d-mannose in prophylaxis of recurrent urinary tract infections (UTIs) in women. BJU Int. 2013;113(1):9-10. doi:10.1111/bju.12492.
19. Domenici L, Monti M, Bracchi C, et al. D-mannose: a promising support for acute urinary tract infections in women. A pilot study. Eur Rev Med Pharmacol Sci. 2016;20(13):2920-5.
20. Stompro, K. The efficacy of D-mannose in the prevention of recurrent urinary tract infections compared to long-term antibiotic therapy. School of Physician Assistant Studies. 2017; 610. 
21. Akazawa S, Metzger BE, Freinkel N. Relationships between glucose and mannose during late gestation in normal pregnancy and pregnancy complicated by diabetes mellitus: concurrent concentrations in maternal plasma and amniotic fluid. J Clin Endocrinol Metab. 1986;62:984–9. DOI: 10.1210/jcem-62-5-984
22. Freinkel N, Lewis NJ, Akazawa S, et al. The honeybee syndrome – implications of the teratogenicity of mannose in rat-embryo culture. N Engl J Med 1984;310:223-30. DOI: 10.1056/NEJM198401263100404

See the Michigan Medicine Health Library entry for D-mannose, this WebMD article on D-mannose, or the RXList entry for D-mannose for more information.