The potential of mannose in the pharmaceutical field is mainly concentrated in several specific directions, some of which have already been clinically applied (such as urinary tract infection prevention), while others are in the basic research or early clinical trial stage. The prospects are worth paying attention to, but more evidence is needed to support them. Describe its potential in the following areas:

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1、 Recognized/Mature Application Fields

Preventing recurrent urinary tract infections (rUTI) ?

Mechanism: Oral administration of mannose results in high concentration excretion in urine, competitively blocking the binding of FimH pilin adhesins from pathogens such as Escherichia coli to bladder epithelial cells, preventing bacteria from colonizing and being washed away by urine.

Evidence:

Multiple clinical studies, such as the comparison with the antibiotic furantoin, have shown that 1.5-2g of mannose per day is as effective as low-dose antibiotics in preventing rUTI caused by Escherichia coli in women, and has a lower risk of resistance.

The European Association of Urology (EAU) guidelines list it as an alternative to rUTI prevention (Level of Evidence: B).

Advantages: High safety (mild gastrointestinal side effects), no risk of broad-spectrum antibiotic resistance.

Limitations: Only applicable for prevention and cannot replace antibiotics in the treatment of acute infections; The effect on non Escherichia coli UTI is limited.

2、 Areas in the research stage but with clear potential

Treatment of Congenital Glycation Disorder (CDG)

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Mechanism: Some CDG subtypes, such as MPI-CDG (CDG-Ib type), lack phosphomannose isomerase (PMI), which prevents the conversion of mannose-6-phosphate to fructose-6-phosphate, leading to multiple organ failure.

Treatment: Oral administration of mannose can bypass PMI defects and directly provide mannose-6-phosphate, restoring glycoprotein synthesis.

Current situation:

The FDA has approved the use of mannose for MPI-CDG, which is one of the few treatable subtypes of CDG.

Significant improvement in liver disease, coagulation dysfunction, and gastrointestinal symptoms, but lifelong medication is required.

Potential: Explore the adjuvant therapeutic value for other CDG subtypes, such as ALG-CDG.

Antitumor immune regulation and drug delivery ???? ?(Active preclinical research)

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Mechanism:

Targeted tumor microenvironment: Tumor associated macrophages (TAMs) highly express mannose receptors (MRC1), and mannose modified drugs can be delivered to tumors in a targeted manner.

Regulating immune suppression: Mannose competitively inhibits the mannose receptors on the surface of TAMs, blocking their recognition of mannose glycated antigens on the surface of tumor cells, which may reverse immune suppression.

Enhancing chemotherapy sensitivity: In animal studies, the combination of mannose and chemotherapy (such as doxorubicin) can significantly inhibit tumor growth (possibly by interfering with glucose metabolism).

Challenge: Further research is needed on human effectiveness, optimal dosage, and delivery systems.

Antifungal/antiparasitic infection adjuvants ??

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Mechanism: Pathogens such as Candida albicans and Plasmodium rely on host mannose receptors to invade cells. Mannose can block its adhesion.

Research:

In vitro and animal models have shown that mannose can inhibit Candida adhesion to epithelial cells.

Combined use with antimalarial drugs can reduce the infection rate of malaria parasites (animal experiments).

Potential: As an adjuvant to enhance the efficacy of existing anti infective drugs and reduce drug resistance.

3、 Emerging exploration directions (potential to be verified)

Inflammatory bowel disease (IBD) and intestinal barrier repair ??

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Assumption:

Mannose may regulate gut microbiota (promote beneficial bacteria) and inhibit pathogenic bacterial adhesion.

Enhance the function of intestinal mucosal barrier proteins through glycosylation modification.

Current situation: Animal models (colitis) show certain protective effects, but human research is lacking.

Regulation of autoimmune diseases ??

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Theory: Abnormal glycosylation is involved in the pathogenesis of rheumatoid arthritis, lupus, and other diseases. Mannose supplementation may correct glycosylation defects.

Progress: Only observed in cell models or a very small number of cases, without rigorous clinical trials.

Prevention of complications of diabetes ??

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Logic: High blood sugar leads to excessive non enzymatic glycation (AGEs) of proteins, causing complications. Mannose metabolism is not dependent on insulin and does not affect blood glucose, or it can competitively reduce the formation of AGEs.

Evidence: Animal experiments show that the progress of diabetes nephropathy is slowed down, and human research is blank.

4、 Challenges and limitations

Main challenges in the field

UTI prevention is ineffective against non Escherichia coli pathogens; Long term safety data insufficient (especially renal function impact)

CDG treatment is only effective for specific subtypes; Early diagnosis and lifelong medication are required

The efficacy of tumor treatment in the human body is unknown; High doses may cause diarrhea; The toxicity risk of combining chemotherapy needs to be evaluated

Insufficient efficacy of single use of anti infective adjuvants; Need to optimize the combination therapy with existing drugs

Weak research on mechanisms in other emerging fields; Lack of high-quality clinical trials; Most of them remain in the animal model stage

5、 Future development direction

Precision delivery system development: Design mannose modified nanocarriers to enhance tumor/infectious lesion targeting.

Combination therapy optimization: exploring the synergistic effects of mannose with antibiotics, immune checkpoint inhibitors, and antifungal drugs.

Rare Disease Expansion: Screening for more CDG subtypes and lysosomal storage disorders that can be treated with mannose.

Long acting sustained-release formulation: solves the problem of frequent medication (such as daily use for UTI prevention).

Population stratification strategy: precision medication based on pathogen type (UTI) or gene mutation (CDG)