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Dietary phytic acid/phytate/myo-inositol hexaphosphate (IP6), a phosphate reservoir in plants, was viewed as antinutrient, caused by an influence on the bioavailability of minerals through its chelating activity. However, there is a growing body of evidence indicating that IP6 has beneficial (e.g., antiinflammatory, antibacterial, and anticancer) effects on multiple biological processes. Also, IP6 and its metabolites are known to exist in mammalian cells, including human cells, and the role of IP6 as a functional molecule is attracting attention. IP6 can bind to the growth sites of hydroxy-apatite (HA) and calcium oxalate crystals to prevent their growth and hence inhibit pathological calcification. SNF472, hexasodium IP6, is currently being evaluated in clinical studies as a treatment for vascular calcification and calciphylaxis. However, since HA crystal growth within bone matrix is an essential process in bone formation, it is possible that IP6 intake may inhibit physiological mineralization and bone formation, although currently more published studies suggest that IP6 may contribute to bone health rather than inhibit bone formation. Given that IP6 and its metabolites are thought to have diverse activities and many health benefits, it remains important to consider the range of effects of IP6 on bone. [ABSTRACT FROM AUTHOR]

Phosphorylated inositol hexaphosphate (IP6) is a naturally occurring carbohydrate, and its parent compound, myoinositol (Ins), is abundantly present in plants, particularly in certain high-fiber diets, but also in mammalian cells, where they regulate essential cellular functions. IP6 has profound modulation effects on macrophages, which warrants further research on the therapeutic benefits of IP6 for inflammatory diseases. Here, we review IP6 as a promising compound that has the potential to be used in various areas of dentistry, including endodontics, restorative dentistry, implantology, and oral hygiene products, due to its unique structure and characteristic properties. Available as a dietary supplement, IP6 + Ins has been shown to enhance the anti-inflammatory effect associated with preventing and suppressing the progression of chronic dental inflammatory diseases. IP6 in dentistry is now substantial, and this narrative review presents and discusses the different applications proposed in the literature and gives insights into future use of IP6 in the fields of orthodontics, periodontics, implants, and pediatric dentistry. [ABSTRACT FROM AUTHOR]

Inositol hexaphosphate I[P.sub.6] is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plant and mammalian cells. It was recently recognized to possess multiple biological functions. A striking anticancer effect of I[P.sub.6] was demonstrated in different experimental models. Inositol is also a natural constituent possessing moderate anticancer activity. The most consistent and best anticancer results were obtained from the combination of I[P.sub.6] plus inositol. In addition to reducing cell proliferation, I[P.sub.6] increases differentiation of malignant cells, often resulting in a reversion to normal phenotype. Exogenously administered I[P.sub.6] is rapidly taken into the cells and dephosphorylated to lower-phosphate inositol phosphates, which further interfere with signal transduction pathways and cell cycle arrest. Enhanced immunity and antioxidant properties can also contribute to tumor cell destruction. However, the molecular mechanisms underlying this anticancer action are not fully understood. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, I[P.sub.6] holds great promise in our strategies for the prevention and treatment of cancer. I[P.sub.6] plus inositol enhances the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves the quality of life, as shown in a pilot clinical trial. The data strongly argue for the use of I[P.sub.6] plus inositol in our strategies for cancer prevention and treatment. However, the effectiveness and safety of I[P.sub.6] plus inositol at therapeutic doses needs to be determined in phase I and phase II clinical trials in humans. KEY WORDS: * prevention * treatment * differentiation * phytic acid

To test the hypothesis that the antineoplastic activity of phytic acid (inositol hexaphosphate (InsP(sub 6))) is a result of rapid intake by the cells and its conversion to lower inositol phosphates (InsP(sub 1-5)), thereby affecting the intracellular inositol phosphate pool, YAC-1 (mouse T cell leukemia), K562 (human erythroleukemia) and HT-29 (human colon adenocarcinoma) cell lines were incubated at 37 degrees C with (3H)InsP(sub 6). After 1 h, 31.3 + or - 3.1% of administered radioactivity was taken up by YAC-1 cells, 6.2 + or - 0.9% by K562 cells and 6.6 + or - 3.8% by HT-29 cells. Differential centrifugation and high resolution subcellular fractionation of cell homogenates demonstrated that within the various cellular compartments, 80% (HT-29) to 97% (YAC-1) of the total radioactivity was in the cytosol. Kinetic study showed that the peak of the total absorption was obtained after 30 min of cell exposure to radiolabeled InsP(sub 6), after with a plateau was reached. Analysis of the radioactivity accumulated within the cells showed variable proportions of myo-inositol and InsP(sub 1-6), with a preponderance of InsP(sub 1) and InsP(sub 2). The presence of (3H)myo-inositol and (3H)InsP(sub 1-6) suggests that InsP(sub 6) may, in some cells at least, be absorbed as such and that a variable degree of dephosphorylation of InsP(sub 6) takes place both extra- and intracellularly.

To understand the mechanism of antineoplastic action of phytic acid, we investigated the absorption and distribution of myo-(inositol-2-3H(N)hexakisphosphate in rats. The radioactivity was measured in urine, feces, blood, gastrointestinal tract contents and various organs and tissues at 1 and 24 h after intragastric administration. Of the total radioactivity, 79.0 plus or minus 10.0% was absorbed and at least 26.6% was degraded during the 24-h period following ingestion. The absorption was rapid; 11.0 plus or minus 2.6% of the radioactivity was detected in the wall of the stomach (4.4 plus or minus 3.7%) and upper small intestine (6.6 plus or minus 1.9%), 6.5 plus or minus 2.6% in the skeletal muscle and 4.0 plus or minus 1.5% in the skin after 1 h. Much of the radioactivity after 24 h was in the liver (4.0 plus or minus 0.9%), kidneys (2.2 plus or minus 1.1%), muscle (18.1 plus or minus 3.4%) and skin (10.1 plus or minus 3.3%). Analysis of plasma and urine demonstrated that most of the radioactivity was due to myo-inositol and small amounts of inositol monophosphate (InsP1). Gastric epithelial cells, however, contained inositol and various inositol phosphates (InsP1-6). Our data suggest that soluble InsP6 when administered in drinking water when administered in drinking water is rapidly absorbed through the stomach and upper small intestine, becomes quickly dephosphorylated within the mucosal cells and is distributed to various organs as inositol and InsP1. J. Nutr. 123: 713-720, 1993.

Inositol hexaphosphate (I[P.sub.6]) is a naturally occurring polyphosphorylated carbohydrate, present in substantial amounts in almost all plant and mammalian cells, with a strong anticancer activity against numerous tumors. In vitro, I[P.sub.6] affects signal transduction pathways, leading to inhibition of cell growth and transformation, reduced invasive behavior, enhanced apoptosis, and slowed angiogenesis. Uncontrolled proliferation is a hallmark of malignant cells, and I[P.sub.6] can reduce the cell proliferation rate and cause [G.sub.0]/[G.sub.1] cell cycle arrest of many cell lines, both human and rodent. Our studies using estrogen receptor-positive MCF-7 and estrogen receptor-negative MDA MB-231 human breast cancer cells show that I[P.sub.6] causes [G.sub.0]/[G.sub.1] cell cycle arrest associated with inhibition of Akt and Erk1/2 and upregulation of PKC-[delta] and cyclin-dependent kinase inhibitor p[27.sup.Kip1] As a result, phosphorylation of retinoblastoma protein was decreased, and cells were [G.sub.0]/[G.sub.1] arrested. I[P.sub.6] was selective and synergistic with standard chemotherapeutics. One important characteristic of malignancy is the ability of tumor cells to metastasize and infiltrate normal tissue. A significant reduction in the number of lung metastatic colonies by I[P.sub.6] was observed in a mouse metastatic tumor model using FSA-1 cells. In vitro, I[P.sub.6] inhibits key steps of metastasis through effects on adhesion, migration, invasion, and inhibition of metrix metalloproteinases. Tumors depend on the formation of new blood vessels to support their growth and metastasis. I[P.sub.6] inhibited the growth and differentiation of endothelial cells and inhibited the secretion of vascular endothelial growth factor from malignant cells. Apoptosis is a hallmark of action of many anticancer drugs. I[P.sub.6] induces apoptosis involving cleavage of caspase 3, caspase 9, and poly(ADP-ribose) polymerase (an apoptotic substrate) in a time- and dose-dependent manner. Being a safe, selective, and potent antiproliferative and proapoptotic agent, I[P.sub.6] should be considered in our alternative or complementary strategies for cancer prevention and therapy.