Query: phytic acid

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The effect of inositol hexaphosphate on the expression of selected metalloproteinases and their tissue inhibitors in IL-1β-stimulated colon cancer cells <=SEP=> Introduction Matrix metalloproteinases (MMPs) have repeatedly been shown to play a very active role in extracellular matrix degradation associated with tumor invasion and metastasis. Tissue inhibitors of MMPs (TIMPs) are well-known for their ability to inhibit MMP activity thereby inhibiting malignant progression. Inositol hexaphosphate (IP6 phytic acid) has been recognized to have both preventive and therapeutic effects against various cancers including that of colon. In in vitro studies, IP6 has been demonstrated to inhibit cancer cell adhesion and migration. In the present study, the effect of IP6 on the expression of MMP and TIMP genes was evaluated in unstimulated and IL-1β-stimulated colon cancer cell line Caco-2. Materials and methods Real-time QRT-PCR was used to validate the transcription level of selected MMP and TIMP genes in Caco-2 cells after treatment with 1 ng/ml of IL-1β, 2.5 mM of IP6, and both for 6, 12, and 24 h. Results Stimulation of cells with IL-1β only resulted in an overexpression of MMP and their TIMP mRNAs. A significant decrease in MMP-13, MMP-3, MMP-2, and TIMP-1 basal expression was achieved by IP6. IP6 was also an efficient downregulator of MMP-1, MMP-9, and TIMP-2 genes transcription stimulated by IL-1β in 6 h lasting culture. After 12 h, IL-1β-induced MMP-2 mRNA expression was significantly reduced by IP6. Conclusion Proinflammatory cytokine IL-1β upregulates MMP and TIMP mRNAs expression in colon cancer epithelial cells Caco-2. IP6 (2.5 mM) influences constitutive expression of both MMP and TIMP genes and downregulates IL-1β stimulated transcription of some of these genes. IP6 exerts its anti-metastatic activity through modulation of MMP and TIMP genes expression to prevent cancer cell migration and invasion.

High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial <=SEP=> Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.

Efficacy of IP6 + inositol in the treatment of breast cancer patients receiving chemotherapy: prospective, randomized, pilot clinical study <=SEP=> Background Prospective, randomized, pilot clinical study was conducted to evaluate the beneficial effects of inositol hexaphosphate (IP6) + Inositol in breast cancer patients treated with adjuvant therapy. Patients and methods Patients with invasive ductal breast cancer where polychemotherapy was indicated were monitored in the period from 2005-2007. Fourteen patients in the same stage of ductal invasive breast cancer were involved in the study, divided in two randomized groups. One group was subjected to take IP6 + Inositol while the other group was taking placebo. In both groups of patients the same laboratory parameters were monitored. When the treatment was finished, all patients have filled questionnaires QLQ C30 and QLQ-BR23 to determine the quality of life. Results Patients receiving chemotherapy, along with IP6 + Inositol did not have cytopenia, drop in leukocyte and platelet counts. Red blood cell counts and tumor markers were unaltered in both groups. However, patients who took IP6 + Inositol had significantly better quality of life (p = 0.05) and functional status (p = 0.0003) and were able to perform their daily activities. Conclusion IP6 + Inositol as an adjunctive therapy is valuable help in ameliorating the side effects and preserving quality of life among the patients treated with chemotherapy.

Effect of inositol hexaphosphate (IP(6)) on human normal and leukaemic haematopoietic cells. <=SEP=> Inositol hexaphosphate (IP(6)), a naturally polyphosphorylated carbohydrate, has been reported to have significant in vivo and in vitro anticancer activity against numerous tumours, such as colon, prostate, breast, liver and rhabdomyosarcomas. To confirm this activity in haematological malignancies and to characterize some of the mechanisms of IP(6) action, we analysed its effects on human leukaemic cell lines and fresh chronic myelogenous leukaemia (CML) progenitor cells using a combined cellular and molecular approach. IP(6) had a dose-dependent cytotoxic effect on all of the evaluated cell lines, with accumulation in the G2M phase in two out of five cell lines tested. At the molecular level, cDNA microarray analysis after IP(6) exposure showed an extensive downmodulation of genes involved in transcription and cell cycle regulation and a coherent upregulation of cell cycle inhibitors. Furthermore, IP(6) treatment of fresh leukaemic samples of bone marrow CD34+ CML progenitor cells significantly inhibited granulocyte-macrophage colony-forming unit (CFU-GM) formation (P = 0.0062) in comparison to normal bone marrow specimens, which were not affected. No differentiating effect on HL60 cells was observed. Taken together, our results confirm the antiproliferative activity of IP(6) and suggest that it may have a specific antitumour effect also in chronic myeloid leukaemias, via active gene modulation.

Protection against cancer by dietary IP6 and inositol. <=SEP=> Inositol hexaphosphate (IP(6)) is a naturally occurring polyphosphorylated carbohydrate, abundantly present in many plant sources and in certain high-fiber diets, such as cereals and legumes. In addition to being found in plants, IP(6) is contained in almost all mammalian cells, although in much smaller amounts, where it is important in regulating vital cellular functions such as signal transduction, cell proliferation, and differentiation. For a long time IP(6) has been recognized as a natural antioxidant. Recently IP(6) has received much attention for its role in cancer prevention and control of experimental tumor growth, progression, and metastasis. In addition, IP(6) possesses other significant benefits for human health, such as the ability to enhance immune system, prevent pathological calcification and kidney stone formation, lower elevated serum cholesterol, and reduce pathological platelet activity. In this review we show the efficacy and discuss some of the molecular mechanisms that govern the action of this dietary agent. Exogenously administered IP(6) is rapidly taken up into cells and dephosphorylated to lower inositol phosphates, which further affect signal transduction pathways resulting in cell cycle arrest. A striking anticancer action of IP(6) was demonstrated in different experimental models. In addition to reducing cell proliferation, IP(6) also induces differentiation of malignant cells. Enhanced immunity and antioxidant properties also contribute to tumor cell destruction. Preliminary studies in humans show that IP(6) and inositol, the precursor molecule of IP(6), appear to enhance the anticancer effect of conventional chemotherapy, control cancer metastases, and improve quality of life. Because it is abundantly present in regular diet, efficiently absorbed from the gastrointestinal tract, and safe, IP(6) + inositol holds great promise in our strategies for cancer prevention and therapy. There is clearly enough evidence to justify the initiation of full-scale clinical trials in humans.

IP6: a novel anti-cancer agent. <=SEP=> Inositol hexaphosphate (InsP6 or IP6) is ubiquitous. At 10 microM to 1 mM concentrations, IP6 and its lower phosphorylated forms (IP(1-5)) as well as inositol (Ins) are contained in most mammalian cells, wherein they are important in regulating vital cellular functions such as signal transduction, cell proliferation and differentiation. A striking anti-cancer action of IP6 has been demonstrated both in vivo and in vitro, which is based on the hypotheses that exogenously administered IP6 may be internalized, dephosphorylated to IP(1-5), and inhibit cell growth. There is additional evidence that Ins alone may further enhance the anti-cancer effect of IP6. Besides decreasing cellular proliferation, IP6 also causes differentiation of malignant cells often resulting in a reversion to normal phenotype. These data strongly point towards the involvement of signal transduction pathways, cell cycle regulatory genes, differentiation genes, oncogenes and perhaps, tumor suppressor genes in bringing about the observed anti-neoplastic action of IP6.

The role of phytic acid in legumes: antinutrient or beneficial function? <=SEP=> This review describes the present state of knowledge about phytic acid (phytate), which is often present in legume seeds. The antinutritional effects of phytic acid primarily relate to the strong chelating associated with its six reactive phosphate groups. Its ability to complex with proteins and particularly with minerals has been a subject of investigation from chemical and nutritional viewpoints. The hydrolysis of phytate into inositol and phosphates or phosphoric acid occurs as a result of phytase or nonenzymatic cleavage. Enzymes capable of hydrolysing phytates are widely distributed in micro-organisms, plants and animals. Phytases act in a stepwise manner to catalyse the hydrolysis of phytic acid. To reduce or eliminate the chelating ability of phytate, dephosphorylation of hexa- and penta-phosphate forms is essential since a high degree of phosphorylation is necessary to bind minerals. There are several methods of decreasing the inhibitory effect of phytic acid on mineral absorption (cooking, germination, fermentation, soaking, autolysis). Nevertheless, inositol hexaphosphate is receiving increased attention owing to its role in cancer prevention and/or therapy and its hypocholesterolaemic effect.

Effect of IP6 on human neutrophil cytokine production and cell morphology. <=SEP=> Inositol hexaphosphate (IP6) has anti-cancer properties, but recently other extracellular functions have been observed for IP6, including enhancing superoxide production and phagocytosis by neutrophils in the presence of microbial stimuli. This study investigated other inflammatory functions of IP6 on adherent neutrophils. The effect of IP6 on the release of IL-8, tumour necrosis factor (TNF-alpha) and IL-6 by neutrophils attached to either plastic or laminin for up to 6 hours in response to stimulation with lipopolysaccharide or N-formyl-Met-Leu-Phe (fMLP) was investigated. An increase in IL-8 secretion by stimulated cells occurred in the presence of IP6. The incubation of cells attached to laminin with IP6 alone (100-250 BM) did not effect cell morphology, but in the presence of 10(-7) M fMLP altered cell shape. A direct effect of IP6 on cell function was to trigger a sustained assembly of F-actin. Thus, exposure of neutrophils to low levels of IP6 appears to modulate selective neutrophil functions.

Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis. <=SEP=> The article gives an overview of phytic acid in food and of its significance for human nutrition. It summarises phytate sources in foods and discusses problems of phytic acid/phytate contents of food tables. Data on phytic acid intake are evaluated and daily phytic acid intake depending on food habits is assessed. Degradation of phytate during gastro-intestinal passage is summarised, the mechanism of phytate interacting with minerals and trace elements in the gastro-intestinal chyme described and the pathway of inositol phosphate hydrolysis in the gut presented. The present knowledge of phytate absorption is summarised and discussed. Effects of phytate on mineral and trace element bioavailability are reported and phytate degradation during processing and storage is described. Beneficial activities of dietary phytate such as its effects on calcification and kidney stone formation and on lowering blood glucose and lipids are reported. The antioxidative property of phytic acid and its potentional anticancerogenic activities are briefly surveyed. Development of the analysis of phytic acid and other inositol phosphates is described, problems of inositol phosphate determination and detection discussed and the need for standardisation of phytic acid analysis in foods argued.

In vitro investigations of the potential health benefits of Australian-grown faba beans (Vicia faba L.): chemopreventative capacity and inhibitory ... <=SEP=> The functional properties, including antioxidant and chemopreventative capacities as well as the inhibitory effects on angiotensin-converting enzyme (ACE), α-glucosidase and pancreatic lipase, of three Australian-grown faba bean genotypes (Nura, Rossa and TF(Ic*As)*483/13) were investigated using an array of in vitro assays. Chromatograms of on-line post column derivatisation assay coupled with HPLC revealed the existence of active phenolics (hump) in the coloured genotypes, which was lacking in the white-coloured breeding line, TF(Ic*As)*483/13. Roasting reduced the phenolic content, and diminished antioxidant activity by 10-40 % as measured by the reagent-based assays (diphenylpicrylhydrazyl, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) and oxygen radical absorbance capacity) in all genotypes. Cell culture-based antioxidant activity assay (cellular antioxidant activity) showed an increase of activity in the coloured genotypes after roasting. Faba bean extracts demonstrated cellular protection ability against H₂O₂-induced DNA damage (assessed using RAW264.7 cells), and inhibited the proliferation of all human cancer cell lines (BL13, AGS, Hep G2 and HT-29) evaluated. However, the effect of faba bean extracts on the non-transformed human cells (CCD-18Co) was negligible. Flow cytometric analyses showed that faba bean extracts successfully induced apoptosis of HL-60 (acute promyelocytic leukaemia) cells. The faba bean extracts also exhibited ACE, α-glucosidase and pancreatic lipase inhibitory activities. Overall, extracts from Nura (buff-coloured) and Rossa (red-coloured) were comparable, while TF(Ic*As)*483/13 (white-coloured) contained the lowest phenolic content and exhibited the least antioxidant and enzyme inhibition activities. These results are important to promote the utilisation of faba beans in human diets for various health benefits.

Anti-angiogenic activity of inositol hexaphosphate (IP6). <=SEP=> A significant anticancer activity of the naturally occurring carbohydrate inositol hexaphosphate (IP(6)) has been reported against numerous cancer models. Since tumors require angiogenesis for growth and metastasis, we hypothesize that IP(6) reduces tumor growth by inhibiting angiogenesis. Because angiogenesis depends on the interaction between endothelial and tumor cells, we investigated the effect of IP(6) on both. IP(6) inhibited the proliferation and induced the differentiation of endothelial cells in vitro; the growth of bovine aortic endothelial cells (BAECs) evaluated by MTT proliferation assay was inhibited in a dose-dependent manner (IC(50) = 0.74 mM). The combination of IP(6) and vasostatin, a calreticulin fragment with anti-angiogenic activity, was synergistically superior in growth inhibition than either compound. IP(6) inhibited human umbilical vein endothelial cell (HUVEC) tube formation (in vitro capillary differentiation) on a reconstituted extracellular matrix, Matrigel, and disrupted pre-formed tubes. IP(6) significantly reduced basic fibroblast growth factor (bFGF)-induced vessel formation (P < 0.01) in vivo in Matrigel plug assay. Exposure of HepG2, a human hepatoma cell line, to IP(6) for 8 h, resulted in a dose-dependent decrease in the mRNA levels of vascular endothelial growth factor (VEGF), as assessed by RT-PCR. IP(6) treatment of HepG2 cells for 24 h also significantly reduced the VEGF protein levels in conditioned medium, in a concentration-dependent manner (P = 0.012). Thus, IP(6) has an inhibitory effect on induced angiogenesis.

Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic. <=SEP=> Inositol hexaphosphate (IP6) 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 IP6 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 IP6 plus inositol. In addition to reducing cell proliferation, IP6 increases differentiation of malignant cells, often resulting in a reversion to normal phenotype. Exogenously administered IP6 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, IP6 holds great promise in our strategies for the prevention and treatment of cancer. IP6 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 IP6 plus inositol in our strategies for cancer prevention and treatment. However, the effectiveness and safety of IP6 plus inositol at therapeutic doses needs to be determined in phase I and phase II clinical trials in humans.

Diet and colorectal cancer: a case-control study in Greece. <=SEP=> A case-control study probing the role of diet on the incidence of colorectal cancer was undertaken in Athens, Greece, in a population characterized by ethnic homogeneity but substantial heterogeneity with respect to dietary habits. The case series consisted of 100 consecutive patients with histologically confirmed colorectal cancer admitted to two large hospitals of Athens during a 16-month period; the control series consisted of orthopaedic patients, admitted to the same hospitals during the same time period, individually matched to the index cases by age and sex. Dietary histories concerning the frequency of consumption (per month or per week) of about 80 food items were obtained by the same interviewer. Cases reported significantly less frequent consumption of vegetables (particularly beets, spinach, lettuce and cabbage) and, independently, significantly more frequent consumption of meat (notably lamb and beef). Between the two extremes (high-vegetable, low-meat diet versus high-meat, low-vegetable diet) a risk ratio of about 8 appears to exist, sufficient (in size and direction) to explain a substantial part of the international variation in the incidence of colorectal cancer. Significant associations were not found with beer or other alcoholic beverages, and significant interactions were not noted with respect to age, sex and anatomic localization (colon vs. rectum).

Dietary suppression of colonic cancer. Fiber or phytate? <=SEP=> The incidence of colonic cancer differs widely between various human populations. It has been suggested that dietary fiber content is of utmost importance and is inversely related to the occurrence of colonic cancer. However, high-fiber diets are not always correlated with low frequency of colonic cancer, suggesting the involvement of additional dietary constituents. Inositol hexaphosphate (phytic acid) is an abundant plant seed component present in many, but not all, fiber-rich diets. The authors have found that phytic acid is a potent inhibitor of iron-mediated generation of the hazardous oxidant, hydroxyl radical. Herein, the authors propose that inhibition of intracolonic hydroxyl radical generation, via the chelation of reactive iron by phytic acid, may help explain the suppression of colonic carcinogenesis and other inflammatory bowel diseases by diets rich in phytic acid.

Traditional non-Western diets. <=SEP=> In traditional cultures, balancing health with a balanced lifestyle was a core belief. The diseases of modern civilization were rare. Indigenous people have patterns of illness very different from Western civilization; yet, they rapidly develop diseases once exposed to Western foods and lifestyles. Food and medicine were interwoven. All cultures used special or functional foods to prevent disease. Food could be used at different times either as food or medicine. Foods, cultivation, and cooking methods maximized community health and well-being. With methods passed down through generations, cooking processes were utilized that enhanced mineral and nutrient bioavailability. This article focuses on what researchers observed about the food traditions of indigenous people, their disease patterns, the use of specific foods, and the environmental factors that affect people who still eat traditional foods.

Colorectal cancer and diet in an Asian population--a case-control study among Singapore Chinese. <=SEP=> A hospital-based case-control study of diet and colorectal cancer was conducted among Chinese in Singapore (who constitute 77% of the population). A total of 203 cases and 425 controls were included. A history of the usual dietary intake one year prior to interview was taken using a quantitative food frequency questionnaire. Daily intakes of nutrients and selected food items were computed and stratified by tertiles of the control range, to assess risk in low-, medium- and high-intake categories. Effects were adjusted in analysis for age, sex, Chinese dialect group and occupation. For cancers of colon and rectum combined, significant observations were a protective effect of high cruciferous vegetable intake (OR = 0.50, p less than 0.01) and a predisposing effect of a high meat/vegetable consumption ratio (OR = 1.77, p less than 0.05). Similar results were observed for colon cancer alone. For rectal cancer alone (only 71 cases), significant (p less than 0.05) protective effects were observed for high intakes of protein (OR = 0.61), fibre (OR = 0.46), beta-carotene (OR = 0.54), cruciferous vegetables (OR = 0.51) and total vegetables (OR = 0.51). When further assessed by multiple logistic regression, tests for trend and assessment of risk in the extreme highest and lowest quintiles of the control range, the factors consistently significant were cruciferous vegetable intake and the meat/vegetable ratio. A particularly high relative risk was also noted in association with low coffee consumption (OR = 1.59, with p less than 0.05 for trend). No consistent trends were noted for fat or fibre intakes. For non-dietary variables investigated, a history of cholecystectomy increased the risk of both cancers combined (OR = 3.43, p less than 0.05) and colon cancer alone (OR = 4.39, p less than 0.01). This study in an Asian population of countries of Southern and Eastern Asia newly undergoing industrialization and in which rapid economic change is reflected in changing cancer patterns, suggests that the protective effects of certain dietary constituents, notably the cruciferous vegetables, may be more important than the hitherto stressed carcinogenic potential of fat and protein.

Nonstarch polysaccharide consumption in four Scandinavian populations. <=SEP=> Nonstarch polysaccharide (NSP) intake was measured in representative samples of 30 men aged 50-59 in 2 urban and 2 rural Scandinavian populations that exhibited a 3-4 fold difference in incidence of large bowel cancer. Intake was measured by chemical analysis of complete duplicate portions of all food eaten over one day by each individual. NSP intakes showed a rural-urban gradient, with 18.4 +/- 7.8 g/day in rural Finland and 18.0 +/- 6.4 g/day in rural Denmark versus 14.5 +/- 5.4 g/day in urban Finland and 13.2 +/- 4.8 g/day in urban Denmark. NSP intakes were also calculated (using food tables) from weighed food records kept over 4 days, one of which was the day on which the duplicate collection was made. Intakes were 2-2.5 g/day higher with this method than with direct chemical analysis, mainly because published tables of values have become outdated and inaccurate as a result of improved methods for measuring NSP in food. Individual variation from day to day in NSP intake was considerable. Average NSP intake and intake of some of its component sugars were inversely related to colon cancer incidence in this geographical comparison. To show a relationship at the individual level between diet and cancer risk in a prospective study would require detailed and accurate methods for the assessment of NSP consumption.

Dietary risk factors for colon cancer in a low-risk population. <=SEP=> In a 6-year prospective study, the authors examined the relation between diet and incident colon cancer among 32,051 non-Hispanic white cohort members of the Adventist Health Study (California, 1976-1982) who, at baseline, had no documented or reported history of cancer. The risk of colon cancer was determined from proportional hazards regression with adjustment for age and other covariates. The authors found a positive association with total meat intake (risk ratio (RR) for > or =1 time/week vs. no meat intake = 1.85, 95% confidence interval (CI) 1.19-2.87; p for trend = 0.01) and, among subjects who favored specific types of meat, positive associations with red meat intake (RR for > or =1 time/week vs. no red meat intake = 1.90, 95% CI 1.16-3.11; p for trend = 0.02) and white meat intake (RR for > or =1 time/week vs. no white meat intake = 3.29, 95% CI 1.60-6.75; p for trend = 0.006). An inverse association with legume intake (RR for >2 times/week vs. <1 time/week = 0.53, 95% CI 0.33-0.86; p for trend = 0.03) was observed. Among men, a positive association with body mass index was observed (relative to the RR for tertile III (>25.6 kg/m2) vs. tertile I (<22.5 kg/m2) = 2.63, 95% CI 1.12-6.13; p for trend = 0.05). A complex relation was identified whereby subjects exhibiting a high red meat intake, a low legume intake, and a high body mass experienced a more than threefold elevation in risk relative to all other patterns based on these variables. This pattern of putative risk factors would likely contribute to increases in both insulin resistance (high body mass, high red meat intake) and glycemic load (low legume intake), a synergism that, if causal, implicates hyperinsulinemic exposure in colon carcinogenesis. The overall findings from this cohort identify both red meat intake and white meat intake as important dietary risk factors for colon cancer and raise the possibility that the risk due to red meat intake reflects a more complex etiology.

Prostate cancer and inositol hexaphosphate: efficacy and mechanisms. <=SEP=> There are now extensive scientific data suggesting the potential role of dietary and non-dietary phytochemicals in the prevention and control of prostate cancer (PCA) growth and progression. PCA is a disease of elderly male populations with a relatively slower rate of growth and progression as compared to most other cancers and, therefore, is a candidate disease for preventive intervention. Overall, PCA growth and progression involve aberrant mitogenic and survival signaling and deregulated cell cycle progression, accompanied by gradual accumulation of genetic and epigenetic changes over a period of years. Several mechanisms, including overexpression of growth, survival and angiogenic factors and their receptors, together with a loss/decrease of tumor suppressor p53, retinoblastoma and cyclin-dependent kinase inhibitor, have been implicated in PCA growth and progression. Therefore, phytochemicals targeting these molecular events could have a promising role in PCA prevention and/or therapy. Inositol hexaphosphate (IP6) is a major constituent of most cereals, legumes, nuts, oil seeds and soybean. Taken orally as an over-the-counter dietary/nutrient supplement, and is recognised as offering several health benefits without any known toxicity. In vitro anticancer efficacy of IP6 has been observed in many human, mouse and rat prostate cancer cells. Completed studies also show that oral feeding of IP6 inhibits human PCA xenograft growth in nude mice without toxicity. In a recently completed pilot study, we observed similar preventive effects of IP6 on prostate tumorigenesis in the TRAMP model. Mechanistic studies indicate that IP6 targets mitogenic and survival signaling, as well as cell cycle progression, in PCA cells. IP6 is also shown to target molecular events associated with angiogenesis. Moreover, IP6 has pleiotropic molecular targets for its overall efficacy against PCA and, therefore, could be a suitable candidate agent for preventive intervention of this malignancy in humans.

Suppression of colonic cancer by dietary phytic acid. <=SEP=> Large differences exist between human populations in the frequency of colonic cancer. Epidemiological evidence indicates that these differences are strongly influenced by country of residence, and a negative correlation has been found between the fiber content of the diet and frequency of colonic cancer. This has prompted the hypothesis that high-fiber diets are in some way protective. However, reanalysis of the dietary data provides equally strong support for the hypothesis that the protective element may be phytic acid (inositol hexaphosphate). This heat- and acid-stable substance is present in high concentration in many food items, including cereal grains, nuts, and seeds. Phytic acid forms chelates with various metals and suppresses damaging iron-catalyzed redox reactions. Inasmuch as colonic bacteria have been shown to produce oxygen radicals in appreciable amounts, dietary phytic acid might suppress oxidant damage to intestinal epithelium and neighboring cells. Indeed, rapidly accumulating data from animal models indicate that dietary supplementation with phytic acid may provide substantial protection against experimentally induced colonic cancer. Should further investigations yield additional support for this hypothesis, purposeful amplification of dietary phytic acid content would represent a simple method for reducing the risk of colonic carcinogenesis.

Inositol hexaphosphate (IP6) inhibits key events of cancer metastasis: II. Effects on integrins and focal adhesions. <=SEP=> BACKGROUND: We have shown that inositol hexaphosphate (IP6), a natural compound and a potent anti-cancer agent, inhibited cancer cell adhesion to the extracellular matrix (ECM) proteins, thereby leading to inhibition of cell migration and invasion. Cell adhesion to ECM is mediated by specific cell surface integrins, which transduce intracellular signals through their interaction and activation of other proteins that are recruited to the focal adhesion. We hypothesize that IP6 decreases cell adhesion by suppressing the integrin receptors and their subsequent signaling pathway. MATERIALS AND METHODS: We analyzed integrin expressions of the highly invasive estrogen receptor-negative human breast cancer MDA-MB 231 cells exposed to IP6 by flow cytometry. The expression of focal adhesion proteins was investigated by immunocytochemistry and Western blotting. RESULTS: IP6 treatment caused a significant (P < 0.005) decrease in the expression of integrin heterodimers alpha 2 beta 1 (collagen receptor), alpha 5 beta 1 (fibronectin receptor) and alpha v beta 3 (vitronectin receptor); flow cytometry showed that it was the alpha 5 subunit that was down-regulated ( < 0.001). However, the expression of the alpha 2, alpha v, beta 1 and beta 3 subunits were not affected by IP6 treatment. When the expression of integrins on the cell surface was assessed, there was a dramatic 82% decrease in the expression of alpha 5 beta 1 on IP6-treated cells (P < 0.0001), indicating a decrease in cell surface expression of the heterodimers. No effect was seen when inositol hexasulfate (IS6), an analogue of IP6, was used as a control. Immunocytochemistry showed a lack of clustering of paxillin; tyrosine-phosphorylated proteins in IP6-treated cells were discontinuous and scattered around the cell periphery, whereas the patterns were more dense and localized in control cells. Consistent with these observations, focal adhesion kinase (FAK) autophosphorylation at tyrosine-397 residue was suppressed, albeit modestly, by IP6 treatment, suggesting a down-regulation in the integrin-mediated signaling pathway. CONCLUSION: The results of this study indicate that IP6-induced inhibition of cancer cell adhesion, migration and invasion may be mediated through the modulation of integrin dimerization, cell surface expression and integrin-associated signaling pathway.

The Prevalence of Phosphorus Containing Food Additives in Top Selling Foods in Grocery Stores <=SEP=> Objective To determine the prevalence of phosphorus-containing food additives in best selling processed grocery products and to compare the phosphorus content of a subset of top selling foods with and without phosphorus additives. Design The labels of 2394 best selling branded grocery products in northeast Ohio were reviewed for phosphorus additives. The top 5 best selling products containing phosphorus additives from each food category were matched with similar products without phosphorus additives and analyzed for phosphorus content. Four days of sample meals consisting of foods with and without phosphorus additives were created and daily phosphorus and pricing differentials were computed. Setting Northeast Ohio Main outcome measures Presence of phosphorus-containing food additives, phosphorus content Results 44% of the best selling grocery items contained phosphorus additives. The additives were particularly common in prepared frozen foods (72%), dry food mixes (70%), packaged meat (65%), bread & baked goods (57%), soup (54%), and yogurt (51%) categories. Phosphorus additive containing foods averaged 67 mg phosphorus/100 gm more than matched non-additive containing foods (p=.03). Sample meals comprised mostly of phosphorus additive-containing foods had 736 mg more phosphorus per day compared to meals consisting of only additive-free foods. Phosphorus additive-free meals cost an average of $2.00 more per day. Conclusion Phosphorus additives are common in best selling processed groceries and contribute significantly to their phosphorus content. Moreover, phosphorus additive foods are less costly than phosphorus additive-free foods. As a result, persons with chronic kidney disease may purchase these popular low-cost groceries and unknowingly increase their intake of highly bioavailable phosphorus.

Effects of Polyphosphate Additives on Campylobacter Survival in Processed Chicken Exudates <=SEP=> Campylobacter spp. are responsible for a large number of the bacterial food poisoning cases worldwide. Despite being sensitive to oxygen and nutritionally fastidious, Campylobacter spp. are able to survive in food processing environments and reach consumers in sufficient numbers to cause disease. To investigate Campylobacter persistence on processed chicken, exudates from chickens produced for consumer sale were collected and sterilized. Two types of exudates from chicken products were collected: enhanced, where a marinade was added to the chickens during processing, and nonenhanced, where no additives were added during processing. Exudates from enhanced chicken products examined in this study contained a mixture of polyphosphates. Exudate samples were inoculated with Campylobacter jejuni or Campylobacter coli strains and incubated under a range of environmental conditions, and viable bacteria present in the resultant cultures were enumerated. When incubated at 42°C in a microaerobic environment, exudates from enhanced chicken products resulted in increased survival of C. jejuni and C. coli compared with that in nonenhanced exudates in the range of <1 to >4 log CFU/ml. Under more relevant food storage conditions (4°C and normal atmosphere), the exudates from enhanced chicken products also demonstrated improved Campylobacter survival compared with that in nonenhanced exudates. Polyphosphates present in the enhanced exudates were determined to be largely responsible for the improved survival observed when the two types of exudates were compared. Therefore, polyphosphates used to enhance chicken quality aid in sustaining the numbers of Campylobacter bacteria, increasing the opportunity for disease via cross-contamination or improperly cooked poultry.

Prevalence and public health significance of aluminum residues in milk and some dairy products. <=SEP=> Sixty random samples of bulk farm milk, market milk, locally manufactured processed cheese, and milk powder were collected to be analyzed for aluminum (Al) concentration using graphite furnace atomic absorption spectrometry (GFAAS). The results were compared with provisional acceptable permissible limits (PAPLs). The maximum estimated dietary intake (MEDI) of Al for the examined samples was calculated. In addition, an experimental study was conducted to determine the possible leaching of Al from cookware in milk during boiling. The obtained results showed that Al concentration in examined bulk farm milk samples was found to be negligible. In contrast, market milk revealed higher concentration, 65.0% of the examined samples were above the PAPLs. The results revealed significant difference of Al concentration among them. The Al levels in processed cheese wrapped in Al foil were significantly higher than those found in samples packed in glass containers with a significant difference of Al concentration between them. Also, 20% of the examined milk powder samples exceeded the PAPLs (0.01 to 0.4 mg/kg). The MEDI for Al in bulk farm milk, control market milk, market milk boiled in Al cookware, market milk boiled in stainless-steel cookware, processed cheese wrapped in Al foil, processed cheese packed in glass containers, and milk powder were calculated as 3.0%, 61.0%, 63.0%, 61.0%, 428.0%, 220.0%, and 166.0% from "PTDI," respectively. The results of the experimental study showed no marked significant differences of Al concentration between market milk (control group) and those boiled in Al cookware, as well as to those boiled in stainless-steel cookware. PRACTICAL APPLICATION:   The results of the present study indicate that Al level in milk kept in Al containers and dairy products packed in Al foil is beyond the permissible limits, suggesting health hazard. Therefore, all milk cans should be constructed of stainless steel, prevent the entrance of tap water into milk, and the processed cheese should be packed in glass containers and not wrapped in Al foil. Leaching of Al increased to a significant percent more during storage than during boiling, so milk should be kept in stainless steel or glass containers in the refrigerator.

Hidden sources of phosphorus in the typical American diet: does it matter in nephrology? <=SEP=> Elevated serum phosphorus is a major, preventable etiologic factor associated with the increased cardiovascular morbidity and mortality of dialysis patients. An important determinant of serum phosphorus is the dietary intake of this mineral; this makes dietary restriction of phosphorus a cornerstone for the prevention and treatment of hyperphosphatemia. The average daily dietary intake of phosphorus is about 1550 mg for males and 1000 mg for females. In general, foods high in protein are also high in phosphorus. These figures, however, are changing as phosphates are currently being added to a large number of processed foods including meats, cheeses, dressings, beverages, and bakery products. As a result, and depending on the food choices, such additives may increase the phosphorus intake by as a much as 1 g/day. Moreover, nutrient composition tables usually do not include the phosphorus from these additives, resulting in an underestimate of the dietary intake of phosphorus in our patients. Our goal is to convey an understanding of the phosphorus content of the current American diet to better equip nephrologists in their attempt to control hyperphosphatemia.

PHOSPHORUS CONTAINING FOOD ADDITIVES AND THE ACCURACY OF NUTRIENT DATABASES: IMPLICATIONS FOR RENAL PATIENTS <=SEP=> Objective Phosphorus containing additives are increasingly added to food products. We sought to determine the potential impact of these additives. We focused on chicken products as an example. Methods We purchased a variety of chicken products, prepared them according to package directions, and performed laboratory analyses to determine their actual phosphorus content. We used ESHA Food Processor SQL Software to determine the expected phosphorus content of each product. Results Of 38 chicken products, 35 (92%) had phosphorus containing additives listed among their ingredients. For every category of chicken products containing additives, the actual phosphorus content was greater than the content expected from nutrient database. For example, actual phosphorus content exceeded expected phosphorus content by an average of 84 mg/100g for breaded breast strips. There was also a great deal of variation within each category. For example, the difference between actual and expected phosphorus content ranged from 59 to 165 mg/100g for breast patties. Two 100 g servings of additive containing products contain an average of 440 mg of phosphorus, or about half the total daily recommended intake for dialysis patients. Conclusion Phosphorus containing additives significantly increase the amount of phosphorus in chicken products. Available nutrient databases do not reflect this higher phosphorus content, and the variation between similar products makes it impossible for patients and dietitians to accurately estimate phosphorus content. We recommend that dialysis patients limit their intake of additive containing products and that the phosphorus content of food products be included on nutrition facts labels.

Phosphate Additives in Food—a Health Risk <=SEP=> Background Hyperphosphatemia has been identified in the past decade as a strong predictor of mortality in advanced chronic kidney disease (CKD). For example, a study of patients in stage CKD 5 (with an annual mortality of about 20%) revealed that 12% of all deaths in this group were attributable to an elevated serum phosphate concentration. Recently, a high-normal serum phosphate concentration has also been found to be an independent predictor of cardiovascular events and mortality in the general population. Therefore, phosphate additives in food are a matter of concern, and their potential impact on health may well have been underappreciated. Methods We reviewed pertinent literature retrieved by a selective search of the PubMed and EU databases (www.zusatzstoffe-online.de, www.codexalimentarius.de), with the search terms “phosphate additives” and “hyperphosphatemia.” Results There is no need to lower the content of natural phosphate, i.e. organic esters, in food, because this type of phosphate is incompletely absorbed; restricting its intake might even lead to protein malnutrition. On the other hand, inorganic phosphate in food additives is effectively absorbed and can measurably elevate the serum phosphate concentration in patients with advanced CKD. Foods with added phosphate tend to be eaten by persons at the lower end of the socioeconomic scale, who consume more processed and “fast” food. The main pathophysiological effect of phosphate is vascular damage, e.g. endothelial dysfunction and vascular calcification. Aside from the quality of phosphate in the diet (which also requires attention), the quantity of phosphate consumed by patients with advanced renal failure should not exceed 1000 mg per day, according to the guidelines. Conclusion Prospective controlled trials are currently unavailable. In view of the high prevalence of CKD and the potential harm caused by phosphate additives to food, the public should be informed that added phosphate is damaging to health. Furthermore, calls for labeling the content of added phosphate in food are appropriate.

Lack of Awareness among Future Medical Professionals about the Risk of Consuming Hidden Phosphate-Containing Processed Food and Drinks <=SEP=> Phosphate toxicity is an important determinant of mortality in patients with chronic kidney disease (CKD), particularly those undergoing hemodialysis treatments. CKD patients are advised to take a low phosphate-containing diet, and are additionally prescribed with phosphate-lowering drugs. Since these patients usually seek guidance from their physicians and nurses for their dietary options, we conducted a survey to determine the levels of awareness regarding the high phosphate content in commercially processed food and drinks among medical and nursing students at the Hirosaki University School of Medicine in Japan. For this survey, 190 medical and nursing students (average age 21.7±3 years) were randomly selected, and provided with a list of questions aimed at evaluating their awareness of food and drinks containing artificially added phosphate ingredients. While 98.9% of these students were aware of the presence of sugar in commercially available soda drinks, only 6.9% were aware of the presence of phosphate (phosphoric acid). Similarly, only 11.6% of these students were aware of the presence of phosphate in commercially processed food, such as hamburgers and pizza. Moreover, around two thirds of the surveyed students (67.7%) were unaware of the harmful effects of unrestricted consumption of phosphate-containing food and drinks. About 28% of the surveyed students consume such “fast food” once a week, while 40% drink at least 1∼5 cans of soda drinks/week. After realizing the potential long-term risks of consuming excessive phosphate-containing food and drinks, 40.5% of the survey participants considered reducing their phosphate intake by minimizing the consumption of commercially processed “fast food” items and soda drinks. Moreover, another 48.4% of students showed interest in obtaining more information on the negative health effects of consuming excessive amounts of phosphate. This survey emphasizes the need for educational initiative to raise awareness of the health risks posed by excessive consumption of phosphate additives.

Extra-phosphate load from food additives in commonly eaten foods: a real and insidious danger for renal patients. <=SEP=> BACKGROUND: Restriction of dietary phosphorus is a major aspect of patient care in those with renal disease. Restriction of dietary phosphorus is necessary to control for phosphate balance during both conservative therapy and dialysis treatment. The extra amount of phosphorus which is consumed as a result of phosphate-containing food additives is a real challenge for patients with renal disease and for dieticians because it represents a "hidden" phosphate load. The objective of this study was to measure phosphorus content in foods, common protein sources in particular, and comprised both those which included a listing of phosphate additives and those which did not. METHODS: Determinations of dry matter, nitrogen, total and soluble phosphate ions were carried out in 60 samples of foods, namely cooked ham, roast breast turkey, and roast breast chicken, of which, 30 were with declared phosphate additives and the other 30 similar items were without additives. RESULTS: Total phosphorus (290 ± 40 mg/100 g vs. 185 ± 23 mg/100 g, P < .001) and soluble phosphorus (164 ± 25 mg/100 g vs. 100 ± 19 mg/100 g, P < .001) content were higher in products containing additives than in foods without additives. No difference was detected between the 2 groups regarding dry matter (27.2 ± 2.0 g/100 g vs. 26.7 ± 1.9 g/100 g) or total nitrogen (3.15 ± 0.40 g/100 g vs. 3.19 ± 0.40 g/100 g). Consequently, phosphorus intake per gram of protein was much greater in the foods containing phosphorus additives (15.0 ± 3.1 mg/g vs. 9.3 ± 0.7 mg/g, P < .001). CONCLUSIONS: Our results show that those foods which contain phosphate additives have a phosphorus content nearly 70% higher than the samples which did not contain additives. This creates a special concern because this extra amount of phosphorus is almost completely absorbed by the intestinal tract. These hidden phosphates worsen phosphate balance control and increase the need for phosphate binders and related costs. Information and educational programs are essential to make patients with renal disease aware of the existence of foods with phosphate additives. Moreover, these facts highlight the need for national and international authorities to devote more attention to food labels which should clearly report the amount of natural or added phosphorus. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Dietary phosphorus restriction in dialysis patients: potential impact of processed meat, poultry, and fish products as protein sources. <=SEP=> BACKGROUND: Dietary intake of phosphorus is derived largely from protein sources and is a critical determinant of phosphorus balance in patients with chronic kidney disease. Information about the phosphorus content of prepared foods generally is unavailable, but it is believed to contribute significantly to the phosphorus burden of patients with chronic kidney disease. DESIGN: Analysis of dietary components. SETTING: We measured the phosphorus content of 44 food products, including 30 refrigerated or frozen precooked meat, poultry, and fish items, generally national brands. OUTCOMES: Measured and reported phosphorus content of foods. MEASUREMENTS: Phosphorus by using Association of Analytical Communities official method 984.27; protein by using Association of Analytical Communities official method 990.03. RESULTS: We found that the ratio of phosphorus to protein content in these items ranged from 6.1 to 21.5 mg of phosphorus per 1 g of protein. The mean ratio in the 19 food products with a label listing phosphorus as an additive was 14.6 mg/g compared with 9.0 mg/g in the 11 items without listed phosphorus. The phosphorus content of only 1 precooked food product was available in a widely used dietary database. LIMITATIONS: Results cannot be extrapolated to other products. Manufacturers also may alter the phosphorus content of foods at any time. Protein content was not directly measured for all foods. CONCLUSION: Better reporting of phosphorus content of foods by manufacturers could result in improved dietary phosphorus control without risk of protein malnutrition.

Descriptive sensory analysis of broiler breast fillets marinated in phosphate, salt, and acid solutions. <=SEP=> Sensory attributes of fully aged broiler breast fillets marinated in a 6% NaCl solution containing 2% sodium tripolyphosphate (2P), 2% citric acid (2C), 2% acetic acid (2A), 1% citric acid plus 1% phosphate solution (1C), or 1% acetic acid solution plus 1% phosphate (1A) were studied. A 6% NaCl (6S) solution with no additives was used as control. Oven-cooked samples (177C degrees oven; 75 degrees C internal temperature) were evaluated by a 9-member trained descriptive analysis sensory panel that rated the intensities of 26 different flavor and texture attributes using 15-point line scales. Data were analyzed using general linear model SAS procedures to determine significant differences (P < or = 0.05) in individual sensory attributes due to marinade treatment. All sensory attributes were scored in the low intensity range (1.5 to 5.0). Brothy, vinegar, and residual particles were the only individual attributes rated significantly different (P < or = 0.05) due to treatment. Multivariate analyses indicated that all sensory attributes formed 2 dimensions that explained 57% of variation in the data. The low intensity values for texture attributes indicated possible negative consequences due to phosphates, salt, and acids when used with fully aged fillets.

Effects of polyphosphate additives on the pH of processed chicken exudates and the survival of Campylobacter. <=SEP=> Campylobacter spp. are nutritionally fastidious organisms that are sensitive to normal atmospheric oxygen levels and lack homologues of common cold shock genes. At first glance, these bacteria seem ill equipped to persist within food products under processing and storage conditions; however, they survive in numbers sufficient to cause the largest number of foodborne bacterial disease annually. A mechanism proposed to play a role in Campylobacter survival is the addition of polyphosphate-containing marinades during poultry processing. Campylobacter jejuni and Campylobacter coli strains incubated in chicken exudates collected from poultry treated with a marinade demonstrated considerable survival advantages (1 to 4 log CFU/ml) over the same strains incubated in chicken exudate from untreated birds. Polyphosphates, which constitute a large portion of the commercial poultry marinades, were shown to account for a majority of the observed influence of the marinades on Campylobacter survival. When six different food grade polyphosphates (disodium pyrophosphate, tetrasodium pyrophosphate, pentasodium triphosphate, sodium polyphosphate, monosodium phosphate, and trisodium phosphate) were utilized to compare the survival of Campylobacter strains in chicken exudate, significant differences were observed with regard to Campylobacter survival between the different polyphosphates. It was then determined that the addition of polyphosphates to chicken exudate increased the pH of the exudate, with the more sodiated polyphosphates increasing the pH to a greater degree than the less sodiated polyphosphates. It was confirmed that the change in pH mediated by polyphosphates is responsible for the observed increases in Campylobacter survival.

Original Articles: Phosphorus and Potassium Content of Enhanced Meat and Poultry Products: Implications for Patients Who Receive Dialysis <=SEP=> Background and objectives: Uncooked meat and poultry products are commonly enhanced by food processors using phosphate salts. The addition of potassium and phosphorus to these foods has been recognized but not quantified. Design, setting, participants, & measurements: We measured the phosphorus, potassium, and protein content of 36 uncooked meat and poultry products: Phosphorus using the Association of Analytical Communities (AOAC) official method 984.27, potassium using AOAC official method 985.01, and protein using AOAC official method 990.03. Results: Products that reported the use of additives had an average phosphate-protein ratio 28% higher than additive free products; the content ranged up to almost 100% higher. Potassium content in foods with additives varied widely; additive free products all contained <387 mg/100 g, whereas five of the 25 products with additives contained at least 692 mg/100 g (maximum 930 mg/100 g). Most but not all foods with phosphate and potassium additives reported the additives (unquantified) on the labeling; eight of 25 enhanced products did not list the additives. The results cannot be applied to other products. The composition of the food additives used by food processors may change over time. Conclusions: Uncooked meat and poultry products that are enhanced may contain additives that increase phosphorus and potassium content by as much as almost two- and three-fold, respectively; this modification may not be discernible from inspection of the food label.