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Dietary Supplement Information for Physicians with Naturokinetics℠ D-Mannose 500 mg Product Code: P2811 Categories: Urinary Tract Support TECHNICAL SUMMARY Chemical Name: D-Mannose Structural Formula: Molecular Formula: C6-H12-O6 Molecular Weight: 180.156 Product Composition: D-Mannose, Gelatin (capsule), Stearic Acid (vegetable source), Magnesium Stearate (vegetable source), Silica and Rice Flour. Allergen Statement: Contains no salt, starch, yeast, wheat, gluten, soy, milk, egg, shellfish or preservatives. Delivery Form: Capsule. ROLE AS A NUTRIENT 1 Essentiality: D-Mannose is a non-essential nutrient. Dietary Sources: Cranberries, black currant, peaches, green beans, and 2 tomatoes. Typical Consumption: Unknown. Factors Affecting Nutrient Status: Individuals with carbohydratedeficient glycoprotein syndrome lack the enzyme phosphomannose isomerase, which is required to generate mannose from fructose-61 phosphate, and might require mannose supplementation. 3 Methods of Evaluation: D-Mannose levels can be evaluated in plasma. Structural and Functional Role: Mannose is a sugar required for N-glycosylation that plays a role in the synthesis of proteins 1 associated with connective tissue, and also for glycophospholipid anchor synthesis in multiple tissues in the body. It has also been shown to bind to mannose-specific sites of various potentially pathogenic microorganisms, particularly E. coli, 4 thereby preventing their adhesion to various tissues in the body, including the epithelium of the urinary system. RECOMMENDED USE Healthy Urinary Tract Support: Isolates from the urinary tract of women with recurring urinary tract infections were used to test whether D-Mannose was effective in preventing adherence of E. coli to epithelial cells of the genitourinary tract in vitro. Researchers tested 73 strains of E. coli isolated from the urine, vaginal introitus, and anal mucosa of 34 women. Strains were assessed in a 2.5% combined concentration of D-Mannose and epithelial cell culture. Of the 73 strains of E. coli tested, 66 demonstrated adherence to epithelial cells. Among the strains that adhered to the cells, D-Mannose completely 5 inhibited the adherence of 25 strains and partially inhibited 11 strains by 50%. Dietary Supplement Information for Physicians with Naturokinetics℠ SM NATUROKINETICS Liberation: Dissolution test results are not available. D-Mannose 500 mg P2811 passes the standard disintegration test in water (<60min). Absorption: D-Mannose is absorbed by sodium-dependent transport, and in the 1 small intestine. Following oral administration in healthy volunteers, blood DMannose levels increase in a dose-dependent manner with peak concentrations 3 (Tmax) 1 to 2 hours after administration (Figure 1). Distribution: Absorbed D-Mannose is predominantly incorporated into glycoproteins, particularly in the liver (70%), intestine (11%), and serum (15%) within the first hour of supplementation with less than 10% apparent in the 1 kidneys. Metabolism: D-Mannose is phosphorylated by hexokinase into mannose-6phosphate (M-6-P) and is also transformed to fucose for integration into 2 glycoproteins. 3 Excretion: D-Mannose is excreted in urine with a t1/2 of approximately 4 hours. SAFETY INFORMATION Fig. 1. Blood mannose concentrations after a single dose of mannose for 3 subjects. Doses of (0.07, □), (0.14, ▲), and (0.21, ○) g mannose/kg body weight were consumed as a 5% solution in ENSURE or placebo (●).2 Tolerability: D-Mannose is generally well tolerated. Side effects associated with 3,6 supplementation include loose stool and bloating and usually occur at doses greater than approximately 1.5 g/day. Contraindications: D-Mannose can increase levels of glycosylated hemoglobin and worsen glucose control in persons with 7 diabetes. Also, individuals who have carbohydrate-deficient glycoprotein syndrome should be closely monitored when 8 using this product as it could adversely affect the kidneys. INTERACTIONS Drug Interactions: No known interactions. Supplement Interactions: No known interactions. Interaction with Lab Tests: D-Mannose may adversely affect the kidneys and cause serum and urinary creatinine levels to 8 7 rise. D-Mannose may also increase levels of glycosylated hemoglobin. Stability and Storage: Store in a cool dry environment in a tightly sealed container. References 1. Alton G, Hasilik M, Niehues R, et al. Direct utilization of mannose for mammalian glycoprotein biosynthesis. Glycobiology 1998; 2. 3. 4. 5. 6. 7. 8. 8: 285-95. Herman RH. Mannose Metabolism I. Am J Clin April 1971, 24: 488-498. 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 Apr; 60(2): 12733. Martinez JJ, Mulvey MA, Schilling JD, Pinkner JS, Hultgren SJ. Type 1 pilus-mediated bacterial invasion of bladder epithelial cells. EMBO J. 2000 Jun 15; 19(12): 2803-12. Schaeffer AJ, Chmiel JS, Duncan JL, Falkowski WS. Mannose-sensitive adherence of Escherichia coli to epithelial cells from women with recurrent urinary tract infections. J Urol. 1984 May; 131(5): 906-10. 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. Davis JA, Freeze HH. Studies of mannose metabolism and effects of long-term mannose ingestion in the mouse. Biochim Biophys Acta 2001; 1528: 116-26. 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.