D-Mannose and Cancer – Research Review

Researched and written by Keith Bishop, Cancer Coach, Clinical Nutritionist, Retired Pharmacist

D-mannose, a simple sugar, has been studied for its potential anti-cancer actions. Below, we explore its mechanisms, effects on cancer treatments, and considerations for its use based on scientific research. Mannose cancer research is in the early stages and limited to laboratory cancer cell studies, a few animals, and even fewer human studies.

The Warburg Effect and D-Mannose

The Warburg effect is where cancer cells rely heavily on glycolysis (glucose) for energy production, even in the presence of oxygen. Research indicates that D-mannose can disrupt glycolysis, affecting the Warburg effect and reducing cancer cell proliferation. A study published in Nature Nature link shows how D-mannose interferes with glucose metabolism, impairing tumor growth.

D-Mannose's Impact on Glucose Metabolism

D-mannose alters glucose metabolism by inhibiting pathways like the pentose phosphate pathway, which is critical for cancer cell survival. According to findings in Cell Metabolism, Cell Metabolism link leads to reduced production of essential metabolites for cancer cells.

Anti-Cancer Effects of D-Mannose

D-mannose accumulates in cancer cells as mannose-6-phosphate, disrupting glycolysis and inducing apoptosis. This effect is highlighted in studies such as those by Cancer Research Cancer Research link. Particularly in tumors with low phosphomannose isomerase levels, D-mannose exhibits pronounced anti-cancer effects.

D-mannose has been studied for its impact on various types of cancers. Here are some examples:

• Fibrosarcoma
• Colorectal Cancer
• Glioblastoma

• Prostate Cancer
• Breast Cancer
• Lung Cancer
• Colon Cancer
• Leukemia
• Non-Hodkin’s Lymphoma – As of publication, no research
• Melanoma – As of publication, no research
• Basal cell carcinoma – As of publication, no research
• Squamous cell carcinoma – As of publication, no research
• Gastric cancer
• Oral cancer – As of publication, no research
• Head and neck cancer – As of publication, no research
• Esophageal cancer
• Bladder cancer
• Ovarian cancer
• Cervical cancer – As of publication, no research
• Uterine cancer – As of publication, no research
• Thyroid Cancer
• General Tumor Suppression: A review in Frontiers in Pharmacology discusses how D-mannose suppresses glycolysis and enhances the effects of chemotherapeutic agents across various cancer types. This review emphasizes its potential as a novel therapeutic strategy. Explore the findings here.

These studies suggest that D-mannose could be a promising complementary therapy for most but not all cancers.

Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, is associated with high phosphomannose isomerase (PMI) levels. High PMI expression in PDAC enables efficient mannose metabolism, possibly contributing to its resistance to D-mannose treatment. A study published in Cancers discusses the role of PMI in pancreatic cancer metabolism and its implications for therapeutic strategies here. Understanding PMI levels in PDAC is crucial for tailoring treatments and exploring complementary therapies like D-mannose.

D-Mannose Supplement Source

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Enhancing Chemotherapy, Radiation, and Immunotherapy

Chemotherapy: D-mannose has shown promise in enhancing chemotherapy by increasing cancer cell sensitivity to drugs like 5-fluorouracil (Journal of Experimental & Clinical Cancer Research) Journal of Experimental & Clinical Cancer Research link. Cisplatin: Research published in Cancer Discovery demonstrated that D-mannose enhances the pro-apoptotic effects of cisplatin by disrupting glycolysis and inducing apoptosis in cancer cells. You can find the study here. Doxorubicin: The same study in Cancer Discovery also highlighted that D-mannose increases the sensitivity of cancer cells to doxorubicin, leading to improved tumor response and reduced tumor growth. Learn more here. There is also a study that showed that in the early and middle stages of the development of glioblastoma multiforme (GBM), mannose can be combined with temozolomide concurrent radiotherapy (RT/TMZ) to achieve a cure (Liu et al., 2020).

Radiation Therapy (Radiotherapy): D-mannose enhanced the radio-sensitivity of esophageal squamous cell carcinoma with low MPI expression by suppressing glycolysis. It also destabilizes DNA repair mechanisms, making radiation therapy more effective (International Journal of Radiation Oncology) Radiation Oncology link.

Immunotherapy: D-mannose may improve immunotherapy by degrading PD-L1 proteins (Journal for ImmunoTherapy of Cancer). Mannose metabolism is a prominent metabolic feature of tumor precursor exhausted T cells (Tpex) crucial for maintaining T cell stemness. Their work uncovers a novel metabolic mechanism that decouples T cell proliferation from differentiation, providing valuable insights into how metabolic modulation can generate "better" T cells. Cell Metabolism Link.

Cancer Coaching

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Potential Drug Interactions and Side Effects

While D-mannose is generally well-tolerated, it may cause bloating or diarrhea in some individuals. Studies from Drug Safety Drug Safety link suggest that high doses might lead to kidney damage, and caution is advised for individuals with diabetes due to its impact on blood sugar levels.

Supplements That May Enhance D-Mannose's Effects

Some studies hint at combining D-mannose with antioxidants or other cancer metabolism-targeting compounds for potentially enhanced anti-cancer effects. However, this area requires more robust research (Frontiers in Oncology) Frontiers in Oncology link.

Plant Lectins Use with D-Mannose

Combining plant lectins with D-mannose may enhance anti-cancer effects by targeting cancer cell glycosylation patterns and disrupting tumor growth mechanisms. Lectins, such as those derived from mistletoe (Viscum album) and lentils, have been shown to bind to mannose-rich glycans on cancer cells, inducing apoptosis and inhibiting metastasis. A review in Molecules highlights the potential of plant lectins to induce programmed cell death in cancer cells, making them promising candidates for cancer therapy here. Additionally, lectins can enhance D-mannose delivery to cancer cells, amplifying its effects on glycolysis disruption and tumor suppression.

Foods naturally high in lectins include legumes (e.g., lentils, kidney beans, and soybeans), whole grains (e.g., wheat and barley), and certain vegetables (e.g., tomatoes and eggplants) here.

This combination of D-mannose and lectins represents a novel approach to cancer treatment, warranting further research to optimize its therapeutic potential.

D-Mannose Supplement Source

Discover top-quality supplements at an exclusive discount through Prevail Over Cancer's Fullscript store. Carefully curated to support your health and wellness journey, Fullscript offers a wide range of trusted products from reputable brands. Shop confidently, knowing you're getting premium supplements at a great value (10% discount) — all conveniently delivered to your door—with free delivery on orders over $50. Take a step toward optimal health today!

D-Mannose and Cancer Conclusion

D-mannose is a promising candidate in cancer research, offering potential benefits such as complementary therapy. Its ability to disrupt cancer metabolism, improve treatment efficacy, and reduce tumor growth highlights its significance. However, consult a healthcare professional before integrating D-mannose into your regimen.