Inositol Hexaphosphate (IP6) & Inositol
Inositol and its phosphorylated form – inositol hexaphophate (IP6), are carbohydrates found in fibers like grains and legumes. They and the other inositol isomers or phosphates (IP1– 5) are abundant in animal cells. They are involved in many biological functions, including membrane structure, hormone signaling and the glucuronic acid and pentose phosphate pathways. (Glucuronic acid pathway is a detoxification process in which glucuronic acid binds with excess hormones and other toxins in the liver so they can be excreted. Pentose phosphate pathway is a reducer of sugars in an alternative mechanism to glycolysis. It is also a reducer of other substances like glutathione that protects against oxidative stress. And it generates hydrogen peroxide for phagocytes that devour toxins.)
Anticancer activities of inositol and IP6 have been demonstrated in a number of studies, but strikingly more potent tumor inhibiting actions were seen when inositol and IP6 were combined. Together they reduce cell proliferation, induce cell cycle arrest and increase cell differentiation, which often results in a reversion to normal phenotype. As a team they are potent immune boosters and antioxidants. The combination of IP6 and inositol has been referred to by researchers as a “broad-spectrum antineoplastic agent (cancer chemotherapy).”
The vast amount of laboratory data accumulated so far confirms another one of our original hypotheses – that IP6 is indeed a broad-spectrum antineoplastic agent, effective against cancers of different cells and tissue systems. The mechanisms underlying the anticancer activity of IP6 and inositol may involve changes in pathways leading to cell growth and cell death. These include hormone and growth factor signaling, regulatory mechanisms of cell cycle progression, cell differentiation and apoptosis.
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Inositol works in conjunction with folate, v itamins B-6, B-12, choline, betaine, and methionine to prevent the accumulation of fats in the liver. It exists as the fiber component of phytic acid. Inositol has been found to promote healthy hair, hair growth, and help in controlling estrogen levels. It may also be of benefit in reducing blood cholesterol levels.
In his book, Too Good to Be True, Dr. Kim Vanderlinden N.D., D.T.C.M., cited the following anti-tumor activities for IP6:
Helps normalize the rate of excessive cell division
Helps normalize cell physiology
Enhances Natural Killer (NK) cells
Supports tumor suppressor gene (P53) activity
Promotes antiangiogenisis activities
In addition to suppressing cancer on its own, IP6 has been found to enhance the effectiveness of Tamoxifen and Andriamycin without increasing drug toxicity 1, 2. According to the School of Medicine at the University of Maryland, IP6 plus inositol has antioxidant properties and the ability to chelate iron and suppress oxygen and hydrogen formation. Researchers found IP6 inhibited growth of all tested cancer cell lines.
The antiproliferative activity of IP6 was further reported in human colon cancer HT-29 cells 28, estrogen receptor-positive and estrogen receptor-negative human breast cancer cells 32, cervical cancer 25, prostate cancer 15, 33, 34, and HepG2 hepatoma cell lines 31. IP6 also inhibited the growth of mesenchymal tumors, murine fibrosarcoma 39, and human rhabdomyosarcoma 38. However, cells from different origin have different sensitivity to IP6 (the leukemic cell lines seem to be highly susceptible to IP6), suggesting that IP6 may affect different cell types through different mechanisms of action.
The potential of IP6 to induce differentiation and maturation of malignant cells, often resulting in reversion to the normal phenotype, was first demonstrated in K-562 hematopoietic cells 26. IP6 was further shown to increase differentiation of human colon carcinoma HT-29 cells 28, 2 9, prostate cancer cells 33, breast cancer cells 32, and rhabdomyosarcoma cells 38.
J. Nutr. 133:3778S-3784S, November 2003
15. Zi, X., Singh, R. P. & Agarwal, R. (2000) Impairment of erbB1 receptor and fluid phase
endocytosis and associated mitogenic signaling by inositol hexaphosphate in human prostate
carcinoma DU145 cells. Carcinogenesis 21: 2225-2235.
25. Ferry, S., Matsuda, M., Yoshida, H. & Hirata, M. (2002) Inositol hexakisphosphate blocks tumor
cell growth by activating apoptotic machinery as well as by inhibiting the Akt/NF B- mediated
cell survival pathway. Carcinogenesis 23: 2031-2041.
26. Shamsuddin, A. M., Baten, A. & Lalwani, N. D. (1992) Effect of inositol hexaphosphate on growth and differentiation in K562 erythroleukemia cell line. Cancer Lett. 64: 195-202.
28. Sakamoto, K., Venkatraman, G. & Shamsuddin, A. M. (1993) Growth inhibition and differentiation of HT– 29 cells in vitro by inositol hexaphosphate (phytic acid). Carcinogenesis 14: 1815-1819.
29. Yang, G- Y. & Shamsuddin, A. M. (1995) IP6– induced growth inhibition and differentiation of
HT-29 human colon cancer cells: involvement of intracellular inositol phosphates. Anticancer Res. 15: 2479–2488.
31. Vucenik, I., Tantivejkul, K., Zhang, Z. S., Cole, K. E., Saied, I. & Shamsuddin, A. M. (1998) IP6 treatment of liver cancer. I. IP6 inhibits growth and reverses transformed phenotype in HepG2
human liver cancer cell line. Anticancer Res. 18: 4083-4090
32. Shamsuddin, A. M., Yang, G-Y. & Vucenik, I. (1996) Novel anti-cancer functions of IP6: growth
inhibition and differentiation of human mammary cancer cell lines in vitro. Anticancer Res. 16:
33. Shamsuddin, A. M. & Yang, G.- Y. (1995) Inositol hexaphosphate inhibits growth and induces
differentiation of PC– 3 human prostate cancer cells. Carcinogenesis 16: 1975-1979.
34. Singh, R. P., Agarwal, C. & Agarwal, R. (2003) Inositol hexaphosphate inhibits growth, and induces G1 arrest and apoptotic death of prostate carcinoma DU145: modulation of CDKI-CDK-cyclin and pRb- related protein-E2F complexes. Carcinogenesis 24: 555-563.
38. Vucenik, I., Kalebic, T., Tantivejkul, K. & Shamsuddin, A. M. (1998) Novel anticancer function of inositol hexaphosphate (IP6): inhibition of human rhabdomyosarcoma in vitro and in vivo.
Anticancer Res. 18: 1377-1384.
In addition to cytotoxic and cell differentiation activity, IP6 & inositol has powerful immune enhancing properties