Inositol Hexaphosphate

Health Care Professional Information

Common Name

IP-6, InsP-6, NA-InsP6, phytic acid, inositol hexakisphosphate, myo-inositol hexaphosphate, inositol-1,2,3,4,5,6-hexakisphosphate, phytate

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, perform secondary messenger roles, extracellular signaling, and additional cellular signal transduction (1).
IP6 was shown useful against sickle cell disease in vitro (14) and in mice (15).

Several in vitro and animal studies suggest anticancer (1) (3) (4) (9) (10) (12) and antiangiogenic (16) effects of IP6.
Preliminary results indicate that a combination of IP6 and inositol may be useful in alleviating the side effects of chemotherapy and improved quality of life in breast cancer patients (11); 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, and meat.

Purported Uses
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).

Pharmacokinetics

Absorption:
IP-6 appears to have rapid absorption in the upper gastrointestinal track following oral administration according to studies performed in rats. IP6 also can be synthesized from inositol (6). Studies in humans suggest that there is saturable absorption of IP6 with escalating doses that results in elimination of unabsorbed dose in the feces. The chemical used in formulating IP6 (i.e. sodium, magnesium, calcium) may also influence the rate and extent of absorption (5).
Distribution:
IP6 and its metabolites are widely distributed throughout the body to all sites including skeletal muscle and skin (6). Active transport across cellular membranes has been attributed to various binding proteins (clathrin adaptor complex AP2, AP180, coatomer of COP I coat) (1).
Metabolism / Excretion:
IP6 may be dephosphorylated to IP1-5 as it is passes through mucosal cells. There are multiple pathways for IP6 metabolism including dietary phytase. IP6 can be metabolized to IP1-5 as well as inositol. Primary route of excretion is in urine, although saturable excretion also occurs. Measured urinary levels of IP6 can be directly correlated to serum levels (5).

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).

Dosage (Inside MSKCC Only)
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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.

Consumer Information

How It Works

Bottom Line: 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. It has been studied in laboratory experiments. When various types of cancer cells were incubated with IP6 in a petri dish, it slowed their replication. It may also induce differentiation of cancer cells into more “normal” cells. IP6 also inhibited the events involved in blood clotting in laboratory studies. It is unknown whether these effects take place in the human body.

Purported Uses
  • To treat heart disease
    Some laboratory studies suggest that inositol hexaphosphate might act as a blood thinner, but clinical trials are lacking.
  • To prevent and treat cancer
    Laboratory studies show that inositol hexaphosphate slows the replication of isolated cancer cells. A small study of breast cancer patients showed that IP6 may be effective in reducing side effects from chemotherapy. Myo-inositol may benefit patients with bronchial dysplasia (chronic lung disorder). Large scale 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.
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