Inositol Hexaphosphate

• How It Works

  Inositol hexaphosphate may be useful in reducing side effects from chemotherapy.

  Inositol hexaphosphate (IP6) is a molecule found naturally in cells, where it performs important messenger roles and affects numerous cellular processes. In laboratory experiments, it inhibited events involved in blood clotting. When various types of cancer cells were incubated with IP6 in a Petri dish, it slowed their replication. IP6 may also turn cancer cells into more “normal” cells. However, it is unknown whether these effects can take place in the human body.

  A small study of breast cancer patients showed that IP6 in combination with inositol may reduce chemotherapy side effects. Myo-inositol may have chemopreventive effects in some patients with chronic lung disease. Large-scale studies are needed to confirm these effects.

• Purported Uses
  • To treat heart disease
    Some laboratory studies suggest that inositol hexaphosphate (IP6) might act as a blood thinner, but clinical trials are lacking.
  • To prevent and treat cancer
    Laboratory studies show that IP6 slows the replication of isolated cancer cells. Myo-inositol may have chemopreventive effects in patients with bronchial dysplasia. Large-scale confirmatory studies are needed.
  • To reduce chemotherapy side effects
    A small study of breast cancer patients showed that IP6 in combination with inositol may be effective in reducing chemotherapy side effects. Larger studies are needed.
  • To treat depression
    No scientific evidence supports this use.
  • To treat kidney stones
    This claim is not backed by research.
• Patient Warnings
  • IP6 binds calcium, iron, magnesium, zinc, and copper in the stomach, and may reduce their absorption.
• Do Not Take If

  Your are taking mineral supplements: Phytic acid can bind with calcium, iron, magnesium, and zinc in the stomach and reduce their bioavailability.
  Your are taking anticoagulants/antiplatelet agents: IP6 has antiplatelet activity and may increase the risk of bleeding.

• Scientific Name

  Inositol-1,2,3,4,5,6-hexakisphosphate

• Clinical Summary

  A ubiquitous intracellular molecule present in mammalian cells and obtained from various dietary sources such as grains and legumes, inositol hexaphosphate (IP6) is used to prevent and treat cancer and heart disease. Metabolites of IP6 enter the inositol phosphates pool and perform secondary messenger roles, extracellular signaling, and additional cellular signalling transduction ⁽¹⁾.

  IP6 was shown to be useful against sickle cell disease in vitro ⁽¹⁴⁾ and in mice ⁽¹⁵⁾. Several in vitro and animal studies also suggest anticancer ^{(1) (3) (4) (9) (10) (12)} and antiangiogenic ⁽¹⁶⁾ effects.

  Preliminary studies in humans indicate that a combination of IP6 and inositol may alleviate chemotherapy side effects and improve quality of life in breast cancer patients ⁽¹¹⁾, and that myo-inositol may have chemopreventive potential in patients with bronchial dysplasia ⁽¹³⁾. Large-scale studies are warranted to determine safety and efficacy ^(7) (8).

• Food Sources

  Cereal, grains, legumes, meat

• Purported Uses
  • Cancer prevention and treatment
  • Chemotherapy side effects
  • Cardiovascular disease
  • Depression
  • Kidney stones
• Mechanism of Action

  IP6 can be synthesized from inositol or obtained from the diet. Metabolites and derivatives of IP6 perform secondary messenger roles, including mobilization of intracellular calcium for mitosis. Extracellular signaling also has been demonstrated. IP6 interacts with both tyrosine kinase and PLC-coupled growth factor receptors. IP6 also enters the inositol phosphates pool, is subsequently dephosphorylated, and contributes to additional cellular signal transduction and intracellular functions ⁽¹⁾. In vitro and animal studies suggest that IP6 reduces initiation and/or promotion, inhibits proliferation by chelation of metalloproteins, causes G0/G1 arrest, and induces differentiation of various cancer cell lines ^(3) (4). IP6 also may inhibit in vitro platelet activation with ADP, collagen, and thrombin by interacting with platelet cytoskeletal reorganization, P13-K activity, or agonist-induced platelet aggregation ⁽²⁾.

• Herb-Drug Interactions

  Mineral supplements: Phytic acid can bind with calcium, iron, magnesium, and zinc in the stomach and reduce their bioavailability ⁽¹⁷⁾.
  Anticoagulants/antiplatelet agents: IP6 has antiplatelet activity. It may increase the risk of bleeding when used with other anticoagulants or antiplatelet drugs ⁽²⁾.

• References

  1. Shamsuddin AM, Vucenik I, Cole KE. IP6: a novel anti-cancer agent. Life Sci. 1997;61:343-54.

  2. Vucenik I, Podczasy JJ, Shamsuddin AM. Antiplatelet activity of inositol hexaphosphate (IP6). Anticancer Res. 1999;19:3689-94.

  3. Shamsuddin AM. Metabolism and cellular functions of IP6: a review. Anticancer Res. 1999;19:3733-6.

  4. El-Sherbiny YM, et al. G0/G1 arrest and S phase inhibition of human cancer cell lines by inositol hexaphosphate (IP6). Anticancer Res. 2001;21:2393-403.

  5. Grases F, et al. Absorption and excretion of orally administered inositol hexaphosphate (IP6 or phytate) in humans. Biofactors. 2001;15:53-61.

  6. Sakamoto K, Vucenik I, Shamsuddin AM. [3H] Phytic acid (inositol hexaphosphate) is absorbed and distributed to various tissues in rats. J Nutr. 1993;123:713-20.

  7. Fox CH, Eberl M. Phytic acid (IP6), novel broad spectrum anti-neoplastic agent: a systematic review. Complement Ther Med. 2002;10(4):229-34.

  8. Vucenik I, Shamsuddin AM. Protection against cancer by dietary IP6 and inositol. Nutr Cancer. 2006:55(2):109-25.

  9. Raina K, Rajamanickam S, Singh RP, Agarwal R. Chemopreventive efficacy of inositol hexaphosphate against prostate tumor growth and progression in TRAMP mice. Clin Cancer Res. 2008 May 15;14(10):3177-84.

  10. Gu M, Raina K, Agarwal C, Agarwal R. Inositol hexaphosphate downregulates both constitutive and ligand-induced mitogenic and cell survival signaling, and causes caspase-mediated apoptotic death of human prostate carcinoma PC-3 cells. Mol Carcinog. 2009 Jun 18.

  11. Bacic I, Druzijanic N, Karlo R, Skific I, Jagic S. Efficacy of IP6 + inositol in the treatment of breast cancer patients receiving chemotherapy: prospective, randomized, pilot clinical study. J Exp Clin Cancer Res. 2010 Feb 12;29(1):12.

  12. Williams KA, Kolappaswamy K, Detolla LJ, Vucenik I. Protective effect of inositol hexaphosphate against UVB damage in HaCaT cells and skin carcinogenesis in SKH1 hairless mice. Comp Med. 2011 Feb;61(1):39-44.

  13. Lam S, McWilliams A, LeRiche J, et al. A phase I study of myo-inositol for lung cancer chemoprevention. Cancer Epidemiol Biomarkers Prev. 2006 Aug;15(8):1526-31.

  14. Lamarre Y, Bourgeaux V, Pichon A, et al. Effect of inositol hexaphosphate-loaded red blood cells (RBCs) on the rheology of sickle RBCs. Transfusion. 2012 Jul 15. doi: 10.1111/j.1537-2995.2012.03779.x.

  15. Bourgeaux V, Aufradet E, Campion Y, et al. Efficacy of homologous inositol hexaphosphate-loaded red blood cells in sickle transgenic mice. Br J Haematol. 2012 May;157(3):357-69.

  16. Raina K, Ravichandran K, Rajamanickam S, et al. Inositol Hexaphosphate Inhibits Tumor Growth, Vascularity, and Metabolism in TRAMP Mice: A Multiparametric Magnetic Resonance Study. Cancer Prev Res (Phila). 2013 Jan;6(1):40-50.

  17. Hurrell RF. Influence of vegetable protein sources on trace element and mineral bioavailability. J Nutr. 2003 Sep;133(9):2973S-7S.