Applications of d-Mannose
Food
Novel sugars were expected as alternative sweeteners to sucrose, because of their sweet-taste and low calories. Till now, the uses of d-mannose is limited and just used as a dietary supplement for direct consumption. As shown in Table 5, the current top-selling brands of d-mannose include NOW Foods, Source Naturals, and Vibrant Health. Most products are distributed in the form of capsules or powders containing plant-based d-mannose. Moreover, some features of d-mannose could improve food texture, such as its solubility and anti-melting capability. Because of these special properties, d-mannose has been commercially used in the food industry. d-Mannose has been added to commercially ice-cream, processed fruits, and salad dressings to improve texture (Sutton and Wilcox 1998). Among the sugar analogs tested, d-mannose has some effects in controlling decay in inoculated apple and peach fruit, which can slightly reduce lesion diameter (Elghaouth and others 1995). Takao and others (2008) presented a mannose-based compound comprised of 1 to 10 molecules of d-mannose, which could effectively reduce blood pressure and/or suppress blood pressure elevation without changing ordinary eating habits when applied in food.
Medicine
Besides the above-mentioned d-mannose physiological function used in the treatment of corresponding diseases, d-mannose is used as an inexpensive starting material for the synthesis of immunostimulatory agents (Ranta and others 2012), antitumor agents (Kamel and others 2010), vitamins (Chen and others 2007), and d-mannitol (Mishra and Hwang 2013). The global market for mannitol is estimated to have annual sales of approximately $100 million. Currently, the biotransformation of mannitol from d-mannose is becoming a new production trend for mannitol. Reduction of d-mannose with sodium borohydride or electrolysis leads to a high d-mannitol yield of over 31% (Ghoreishi and Shahrestani 2009). d-Mannitol is used in the production of drug delivery systems (Chen and others 2005) and in the synthesis of medicines such as oseltamivir phosphate (Chuanopparat and others 2012) and new drugs against AIDS (Botos and others 2002). Moreover, the addition of d-mannose to the natural cytotoxic cell assay significantly blocked cytotoxicity of the fibrosarcoma Meth A target by the effector cells at 50 mM and lower concentrations. In the natural cytotoxic system, recognition involved lectin-like structures with specificity for d-mannose. D-mannose also inhibited natural kill (NK) cell lysis of the lymphoma YAC-1 target, whereas in the NK system such lectin-like structures were less restricted (Stutman and others 1980). Peri-spinal treatment with d-mannose may optimize naked pDNA-IL-10 transgene uptake for suppression of allodynia, and is a novel approach to tune spinal immune cells toward pro-phagocytic phenotype for improved non-viral gene therapy (Dengler and others 2014).
Cosmetics
Aloe vera is good for health and beauty, and its function is closely correlated with the presence of mannose-rich polysaccharides (Eshun and He 2004). Similarly to d-glucose, d-fructose, d-ribose, and d-xylose, d-mannose is an auxiliary moisturizing agent that is widely used in skin-care products. The d-mannose units are linked to each other by β(1-4) glycosidic linkages. d-Mannose exhibits excellent moisturizing and skin feel capabilities, and leaves the skin less taut, less dry, and more moisturized (Schmidt and others 1991). Deckner and Wivell (1997) patented a product featuring components that provide both skin-cleansing and skin-moisturizing benefits. The product contains d-glucose, d-mannose, and d-glucuronate in a molar ratio of 2.8:2.0:2.0.Feed additives
Over the past several decades, antibiotics have been widely used in animal agriculture and have displayed therapeutic effects against disease to improve growth performance (Witte 1998). However, now antibiotics have come under increasing scrutiny because of the potential development of antibiotic-resistant human pathogenic bacteria after their long-term use (Allen and others 2013; Cully 2014). Indeed, there is growing concern over the transmission of resistant bacteria via the food chain (Santin and others 2001). People have begun to look for other ways to replace antibiotics as feed additives. d-Mannose could strongly inhibit the attachment of S. typhimurium to intestinal cells of day-old chickens in vitro and offer a competitive binding site for a certain class of bacteria (Oyofo and others 1989). Moreover, mannan-oligosaccharides may be used as alternative antibiotics to improve turkey health (Parks and others2001). A commercial product available for poultry contains yeast cell wall fragments derived from Saccharomyces cerevisiae after centrifugation of a lysed yeast culture, because the cell wall of yeast contains a large amount of mannans (Van Immerseel and others 2002). For now, d-mannose is the most effective sugar at blocking colonization and is used extensively in animal feeds to inhibit the growth of intestinal pathogens (Berge and Wierup 2012; Galis and others 2013).
Other applications
In modern scientific research, d-mannose plays an increasing significant role in various areas. d-Mannose can be used as a carbohydrate source in a synthetic medium or as a constituent of chemically defined media for cell culture (Wang and others 2000). In transgenic technology, scientists have used d-mannose as a marker that has enabled plant cells to grow and form new plants. d-Mannose could be an alternative to antibiotic resistance genes as markers in future transgenic crops. To date, hundreds of primary transgenic rice plants of different cultivars have been obtained from mannose-resistant cells (Datta and others 2003).
Conclusions
In conclusion, d-mannose is a common sugar existing in various foods. Because of its diversified properties, d-mannose has attracted increasing attention from the food industry and academia. This review of literature has revealed that d-mannose, as a highly potential functional and valuable ingredient, exhibits relatively impressive biological functions of great interest in the cosmetic, pharmaceutical, and food industries. The use of chemical methods in the production of d-mannose has the advantages of applying rapid and convenient processes, but some consumers do not agree with the production by chemical methods. Thus, with ongoing efforts in research and development, the biotransformation approach to d-mannose production with enzymes has gradually gained increasing interest and has become the most promising method. The results of a comparison of bio-enzymes suggest that MIases are promising enzymes for d-mannose biosynthesis; however, from a previous study, the conversion rates of reported MIases from d-fructose are inadequate (15 to 35%), and it is suggested that the exploration of novel enzymes with high conversion efficiency can significantly promote the production of d-mannose. In addition, further research is needed to evaluate the efficacy and long-term safety of d-mannose, especially focusing on its performance in food systems.
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