Inositol Hexaphosphate (IP6): Fiber-Derived Support for Mutagenic, Cardiovascular, Antioxidant, and Immune Concerns

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Fiber-Derived Support for Mutagenic, Cardiovascular and Immune Concerns

By Kimberly Pryor

We live in a delicate state of balance. Ironically, we depend on our cells’ ability to commit suicide in order for us to continue living. This process is called apoptosis and it’s the body’s way of weeding out once healthy cells that have turned cancerous. When our state of balance is disrupted, the body loses its ability to block the malignant transformation of normal cells by sentencing them to die before they become cancerous.
Once a cell has become cancerous, it’s virtually unheard of for it to revisit its previous state of normalcy. However, a substance derived from dietary fiber known as inositol hexaphosphate (IP6) or phytic acid, forces malignant cells to revert to a non-cancerous state, a phenomenon observed in human colon cancer cells and other cell lines.
Scientists discovered IP6’s novel ability to turn back the clock on cancer cells through looking at a tumor marker expressed on malignant and premalignant cells. This marker, however, is absent on normal cells. Following IP6 treatment of cancer cells, the tumor marker was significantly suppressed, and in most IP6-treated cells the marker was completely absent. IP6 also caused a decreased rate of cell proliferation.[1-2] It also has been suggested that IP6 can regulate heart rate and blood pressure and keep platelets from clumping together.[3-6]
Dietary IP6
IP6 occurs in fiber-rich foods—particularly cereals and wheat bran, along with corn, soy beans, nuts (especially peanuts), oats, seeds and rice. Scientists have recently discovered that IP6 is a powerful antioxidant and cancer-modulating agent,[7-9] but when administered in the diet, IP6 binds with proteins, forming insoluble complexes less readily metabolized and absorbed compared to when it is taken alone. In fact, one group of researchers stated: “Thus, IP6, an active substance responsible for cereal’s beneficial anticancer effect, is clearly more effective than 20 percent bran in the diet…. Intake of IP6 may be a more pragmatic approach than gorging enormous quantities of fiber for cancer prophylaxis.”[10-11]
Proposed Anticancer Mechanisms
IP6 exerts its effects on the body by controlling cell division. IP6 reduces the rate of cellular proliferation, both in vivo and in vitro, and has exhibited an ability to reduce DNA synthesis.[12-14]
Scientists have suggested that one way IP6 may exert this cellular control is by interfering with mineral absorption, since iron and other minerals are important in gene regulation.[15] Studies have shown a possible link between excess iron and an increased risk of cancer in animals and humans, particularly colon cancer.[16] IP6 has been shown to interfere with iron absorption and reverse iron-dependent augmentation of colorectal tumor initiation. IP6 also suppresses iron-caused oxygen generation, and almost totally inhibits iron-caused lipid peroxidation, the process where lipids turn rancid.[17-18]
A concern in this regard is the possibility that IP6 may deplete the body’s mineral stores. Yet, in numerous studies, researchers have noted no significant differences in the level of serum or bone minerals in rats, even after lengthy treatment with IP6 and inositol.[19]
AbulKalam Shamsuddin, MD, PhD, a researcher who has extensively studied IP6 and the author of IP6: Nature’s Revolutionary Cancer Fighter, stated that “Certainly, its [IP6’s] hypothetical harm connected to chelation is far less than that of other compounds of similar usage (e.g., cancer chemotherapeutic and chemopreventive agents) and are far outweighed by the plethora of benefits.”[20]
The questions that arise in regard to IP6’s ability to chelate minerals suggest that other anticancer actions are at play. These actions include boosting natural defense mechanisms through the augmentation of natural killer (NK) cells that defend the body against tumor initiation;[21] blocking PI-3 Kinase, an enzyme necessary for tumor promotion;[22-23] altering cellular communication necessary for tumor growth;[24-25] and stimulating tumor suppressor gene p53.[26] New animal and cell culture experiments also have indicated that IP6 works primarily by inhibiting metastases and blocking angiogenesis, the process of forming new blood vessels that feed tumors.
Angiogenesis depends on the interaction between endothelial cells (cells that line the blood vessel walls) and tumor cells. For angiogenesis to occur, endothelial cells on the blood vessel walls must multiply or proliferate. Consequently, Shamsuddin and colleagues investigated IP6’s effect on both endothelial and tumor cells.
During the in vitro experiment, IP6 inhibited the proliferation and growth of endothelial cells. The combination of IP6 and an agent with anti-angiogenic activity was even more powerful in reducing cell growth. IP6 also inhibited the proliferation of endothelial cells derived from human umbilical veins. In addition, IP6 significantly reduced the action of a growth factor involved in vessel formation. In human liver cancer cells, exposure to IP6 for eight and 24 hours resulted in a dose-dependent inhibition of another growth factor involved in vessel growth (vascular endothelial growth factor or VEGF). “Thus, IP(6) has an inhibitory effect on induced angiogenesis,” the researchers wrote.[27]
In two other studies, Shamsuddin and his fellow researchers also showed that IP6 influences key events that stop the spread of cancer cells.[28-29] These potential mechanisms of actions explain the outcome of a number of studies showing IP6’s anti-mutagenic potential in a number of different cancers.
Colon Cancer
In 1988, Shamsuddin first reported in the journal Carcinogenesis the stunning effect IP6 had on large intestinal cancer in rats. Researchers fed 1 percent sodium inositol hexaphosphate (Na-IP6) to one group of animals one week prior to inducing cancer, and to another group two weeks after the last dose of a carcinogen was administered. Rats who took the IP6-laced drinking water prior to carcinogen treatment exhibited a 35 percent decrease in large intestinal cancer compared to the control carcinogen group. The group fed IP6 after receiving the carcinogen showed a similar reduction.[30]
Phytic acid (IP6) was also effective at reducing the incidence of colon tumors in conjunction with a high-risk, high-fat diet. Colon tumor incidence in carcinogen-treated rats plummeted from up to 70 percent in the control groups to 30 percent in the groups fed a high-risk diet (HRD) plus phytic acid (IP6).[31] IP6 may also increase its ability to inhibit colon cancer when combined with green tea.[32]
Liver Cancer
In the January-March 2005 issue of the Asian Pacific Journal of Cancer Prevention, researchers in Seoul, Korea investigated the effect of IP6 and/or inositol on liver cancer in mice. The researchers gave the animals either inositol or IP6 or a combination of both, starting one week prior to administration of a chemical carcinogen to induce liver cancer.
Supplementation with IP6, inositol or both resulted in a significant decrease in the size and the number of a precancerous marker for liver cancer.[33] Patients suffering from Hepatocellular carcinoma (HCC), a common liver cancer, usually have an extremely poor prognosis. In the first of two experiments, Shamsuddin and colleagues compared the in vitro effects of IP6 on HepG2, a human liver cancer cell line. Compared to other cancer cell lines, HepG2 cells were extremely sensitive to IP6, experiencing a dose-dependent, 50 percent inhibition of cell growth. IP6 also weakened HepG2’s ability to form colonies.
The sequel to the experiment demonstrated that IP6 regressed pre-existing human liver cancer cells transplanted in mice back to their normal, non-cancerous state, when IP6 was injected into the transplanted tumor cells. In addition, the tumor weight in IP6-treated mice was 86 percent to 1180 percent less than that in control mice.[34-35]
Prostate Cancer
In the last several years, a number of in vitro and animal studies have explored IP6’s potential role in supporting a healthy prostate. In the September-October 2004 issue of the journal Neoplasia, University of Colorado researchers investigated the growth-inhibitory effect of IP6 in androgen-dependent human prostate carcinoma cells. IP6 treatment strongly inhibited cancer cell growth and triggered apoptosis in the cancer cells.
According to the researchers, whose 2003 study on IP6 and androgen-independent prostate cancer also showed similar results, this latest study using androgen-dependent prostate cancer cells indicates “IP6 has promise and potential to be effective against prostate cancer.”[36,37]
Breast Cancer
IP6 has been shown to inhibit carcinogenesis in all types of mammary cancer cells—those that require estrogen for growth and those whose growth is independent of the female sex hormone. It accomplishes this by inhibiting DNA synthesis and cell growth, and inducing differentiation of the cancer cell lines.[38-40] IP6 also enhances the anti-cancer effects of the drugs tamoxifen and adriamycin. In a study published in 2003, Shamsuddin and colleagues investigated IP6’s ability to inhibit cancer growth in vitro in combination with adriamycin or tamoxifen. The researchers tested the three substances against an estrogen dependent human breast cancer cell line, an estrogen independent human breast cancer cell line, and an adriamycin-resistant breast cancer cell line.
After 96 hours of treatment, much lower concentrations of IP6 were required to inhibit the growth of adriamycin-resistant breast cancer cells than to inhibit the estrogen-dependent human breast cancer cells. The estrogen independent human breast cancer cells were also highly sensitive to IP6. Cancer growth was markedly suppressed when IP6 was administered prior to the addition of adriamycin. This inhibition of cancer cell growth was especially notable in the estrogen-dependent breast cancer cells. In all three cell lines studied, IP6 acted synergistically with tamoxifen.
According to the researchers, “Our data not only confirm that IP6 alone inhibits the growth of breast cancer cells, but it also acts synergistically with adriamycin or tamoxifen” and is particularly effective against estrogen-independent breast cancer cells and adriamycin-resistant cells.[41]
Leukemia
In a study published in 2002, researchers analyzed IP6’s effects on human leukemia cell lines and leukemia cells originating in bone marrow. IP6 dose-dependently triggered cancer cell death in all of the leukemia cell lines tested. IP6 exposure caused an extensive down modulation of genes involved in leukemia development and an upregulation of genes that inhibited leukemia’s cell cycle. IP6 treatment of fresh bone marrow samples where the leukemia cells originated decreased proliferation of the cancerous cells, but had no effect on the normal bone marrow specimens. “Taken together, our results confirm the antiproliferative activity of IP6,” wrote the researchers, “and suggest that it may have a specific antitumour effect also in chronic myeloid leukemias, via active gene modulation.”[42]
Skin Cancer
When we first reported on IP6 in 2000, a study of mouse skin cancer indicated that IP6 prevented skin papillomas when given during cancer initiation. After initiation however, IP6 exerted little effect.[43] Since then, a study published in 2003 showed that topical application of IP6 to the skin of mice with induced skin cancer had a dramatic effect. Topical IP6 inhibited skin tumor development significantly in a dose-dependent manner.[44]
Lung Cancer and Asbestos-Induced Fibrosis
Scientists have also received positive results with IP6 in regards to lung cancer and asbestos-induced fibrosis and carcinoma. Studies have shown that fibrosarcoma cells in mice treated with IP6 resulted in a significant inhibition of tumor and size as well as improvement of survival over the untreated controls. In addition, IP6 treatment of mice with experimental lung metastasis resulted in a significant reduction in the number of metastatic lung colonies.[45]
Due to its antioxidant properties and its ability to chelate iron, in another study IP6 diminished the asbestos-induced oxidative damage that results in inflammation and fibrosis in the lungs of exposed animals, from six- to 30-fold less than in control groups.[46]
Rhabdomyosarcoma
IP6 has suppressed the growth of rhabdomyosarcoma, the most common soft tissue sarcoma in children. Cell line growth was reduced by 50 percent in vitro in a dose-dependent fashion. After two weeks, IP6-treated mice experienced 25-fold smaller tumors and a 49-fold reduction in tumor size after five weeks.[47]
Kidney Stones, Platelet Aggregation, Heart Attacks and HIV
IP6 has been shown to support a number of other conditions. Researchers at the Harvard Medical School and Massachusetts General Hospital in Boston successfully used pure Na-InsP6 to treat idiopathic hypercalciuria, which is associated with a high incidence of kidney stones.[48]
Other research points to IP6’s usefulness in preventing platelet aggregation (sticky platelets), a prime cause of heart attacks and strokes. In one in vitro study by the same researchers, stickiness was induced in human whole blood taken from healthy volunteers. IP6 reduced clotting by 50 percent, or eliminated it altogether.[49]
IP6’s role may also extend to controlling the damage inflicted upon the myocardium (heart muscle) during heart attacks. After a heart attack, doctors reperfuse (fill) the heart area with oxygenated blood. This poses its own set of risks, because the oxygen can churn out free radicals, damaging the blood vessels and heart muscle. Researchers successfully used IP6 to protect the heart muscle from superoxide damage during reperfusion.[50-51]
As more studies unfold, additional properties of IP6 have been revealed. Otake and colleagues demonstrated that IP6 inhibited the cell destruction induced by HIV as well as the HIV specific antigen expression.[52]
Synergistic Effect
In his book, IP6: Nature’s Revolutionary Cancer Fighter, Shamsuddin, calls IP6 combined with inositol, “an anticancer cocktail.” IP6 combined with inositol exerts an even more powerful suppression of cell proliferation and colorectal cancer than with either agent alone. This potent “cocktail” has also been used to suppress carcinogenesis in mammary and metastatic tumor models.[53]
Shamsuddin and colleagues wrote in an IP6 review published in the November 2003 Journal of Nutrition. “The data strongly argue for the use of IP6 plus inositol in our strategies for cancer prevention and treatment.”
References
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