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. 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.
Warnings
This product is regulated by the FDA as a dietary supplement. Unlike approved drugs, supplements are not required to be manufactured under specific standardized conditions. This product may not contain the labeled amount or may be contaminated. In addition, it may not have been tested for safety or effectiveness.
There is a possibility that IP6 binds calcium, iron, magnesium, zinc, and copper in the stomach and reduces their absorption in the body.
Do Not Take If
You take warfarin or other blood thinners (In theory, IP6 may increase the risk of bleeding).
Side Effects
Flatulence
Gastrointestinal distress
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).
Several published in vitro and animal studies suggest efficacy of IP6 in various cancer cell lines
(1) (3) (4) (9) (10). A small study of breast cancer patients found that a combination of IP6 and inositol was useful in alleviating the side effects of chemotherapy and improved quality of life
(11). Large scale studies are warranted to determine safety and efficacy in humans
(7) (8).
No adverse events have been reported. Theoretically, IP6 may interact with anticoagulants such as heparin, aspirin, or warfarin
(2).
Food Sources
Cereal, grains, legumes, meat
Purported uses
Cancer prevention
Cancer treatment
Cardiovascular disease
Depression
Kidney stones
Constituents
Phosphorylated hexacarbon carbohydrate
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).
Adverse Reactions
Common: Flatulence, GI distress
Herb-Drug Interactions
Anticoagulants / Aspirin: Theoretically IP6 may have an additive effect due to inhibition of platelet aggregation.
Supplements / Diet: IP6 has been reported to bind calcium, iron, magnesium, zinc, and copper in the stomach and reduce their bioavailability although conflicting data exist.
(2)
References
- Shamsuddin AM, Vucenik I, Cole KE. IP6: a novel anti-cancer agent. Life Sci 1997;61:343-54.
- Vucenik I, Podczasy JJ, Shamsuddin AM. Antiplatelet activity of inositol hexaphosphate (IP6). Anticancer Res 1999;19:3689-94.
- Shamsuddin AM. Metabolism and cellular functions of IP6: a review. Anticancer Res 1999;19:3733-6.
- 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.
- Grases F, et al. Absorption and excretion of orally administered inositol hexaphosphate (IP6 or phytate) in humans. Biofactors 2001;15:53-61.
- 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.
- Fox CH, Eberl M. Phytic acid (IP6), novel broad spectrum anti-neoplastic agent: a systematic review. Complement Ther Med 2002;10(4):229-34.
- Vucenik I, Shamsuddin AM. Protection against cancer by dietary IP6 and inositol. Nutr Cancer 2006:55(2):109-25.
- 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.
- 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. [Epub ahead of print]
- 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.
