Category Archives: IP-6 (Phytate)

Phytate Associated with Reduced Bone Loss and Fractures in Postmenopausal Women


Protective effect of myo-inositol hexaphosphate (phytate) on bone mass loss in postmenopausal women.

The objective of this paper was to evaluate the relationship between urinary concentrations of InsP6, bone mass loss and risk fracture in postmenopausal women.
A total of 157 postmenopausal women were included in the study: 70 had low (≤0.76 μM), 42 intermediate (0.76-1.42 μM) and 45 high (≥1.42 μM) urinary phytate concentrations. Densitometry values for neck were measured at enrollment and after 12 months (lumbar spine and femoral neck), and 10-year risk fracture was calculated using the tool FRAX(®).
Individuals with low InsP6 levels had significantly greater bone mass loss in the lumbar spine (3.08 ± 0.65 % vs. 0.43 ± 0.55 %) than did those with high phytate levels. Moreover, a significantly greater percentage of women with low than with high InsP6 levels showed more than 2 % of bone mass loss in the lumbar spine (55.6 vs. 20.7 %). The 10-year fracture probability was also significantly higher in the low-phytate group compared to the high-phytate group, both in hip (0.37 ± 0.06 % vs 0.18 ± 0.04 %) and major osteoporotic fracture (2.45 ± 0.24 % vs 1.83 ± 0.11 %).
It can be concluded that high urinary phytate concentrations are correlated with reduced bone mass loss in lumbar spine over 12 months and with reduced 10-year probability of hip and major osteoporotic fracture, indicating that increased phytate consumption can prevent development of osteoporosis.

López-González AA, Grases F, Monroy N, Marí B…
Eur J Nutr Mar 2013
PMID: 22614760

IP-6 Inhibits Osteoclastogenesis and Increases Resorption of Mature Osteoclasts In Vitro


Inositol hexakisphosphate inhibits osteoclastogenesis on RAW 264.7 cells and human primary osteoclasts.

Inoxitol hexakisphosphate (IP6) has been found to have an important role in biomineralization and a direct effect inhibiting mineralization of osteoblasts in vitro without impairing extracellular matrix production and expression of alkaline phosphatase. IP6 has been proposed to exhibit similar effects to those of bisphosphonates on bone resorption, however, its direct effect on osteoclasts (OCL) is presently unknown. The aim of the present study was to investigate the effect of IP6 on the RAW 264.7 monocyte/macrophage mouse cell line and on human primary osteoclasts. On one hand, we show that IP6 decreases the osteoclastogenesis in RAW 264.7 cells induced by RANKL, without affecting cell proliferation or cell viability. The number of TRAP positive cells and mRNA levels of osteoclast markers such as TRAP, calcitonin receptor, cathepsin K and MMP-9 was decreased by IP6 on RANKL-treated cells. On the contrary, when giving IP6 to mature osteoclasts after RANKL treatment, a significant increase of bone resorption activity and TRAP mRNA levels was found. On the other hand, we show that 1 µM of IP6 inhibits osteoclastogenesis of human peripheral blood mononuclear cells (PBMNC) and their resorption activity both, when given to undifferentiated and to mature osteoclasts.
Our results demonstrate that IP6 inhibits osteoclastogenesis on human PBMNC and on the RAW264.7 cell line. Thus, IP6 may represent a novel type of selective inhibitor of osteoclasts and prove useful for the treatment of osteoporosis.

Arriero Mdel M, Ramis JM, Perelló J, Monjo M
PLoS ONE 2012
PMID: 22905230 | Free Full Text

IP-6 Effects on Osteoblasts are Complicated


Differential response of MC3T3-E1 and human mesenchymal stem cells to inositol hexakisphosphate.

Inositol hexakisphosphate (IP6) has been found to have an important role in biomineralization. Because the complete mechanism of action of IP6 on osteoblasts is not fully understood and its potential use in the primary prevention of osteoporosis, we examined the direct effect of IP6 on cell viability and differentiation of MC3T3-E1 cells and on differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs). We show that IP6 has different effects depending on the origin of the cell target. Thus, while IP6 decreased gene expression of osteoblast markers and mineralization in MC3T3-E1 cells without negatively affecting cell viability and ALP activity, an increase in gene expression of ALP was observed in hUC-MSCs committed to the osteoblastic lineage. This increasing effect of IP6 on ALP mRNA expression levels was reversed by the addition of a selective inhibitor of IP6 kinase, suggesting that the effect of IP6 might be due through its pyrophosphorylated derivatives. Besides, Rankl mRNA levels were decreased after IP6 treatment in MC3T3-E1 cells, pointing to a paracrine effect on osteoclasts.
Our results indicate that IP6 has different effects on osteoblast differentiation depending on the cell type and origin. However, further studies are needed to examine the net effect of IP6 on bone formation and its potential as novel antiosteoporosis drug.

Arriero Mdel M, Ramis JM, Perelló J, Monjo M
Cell. Physiol. Biochem. 2012
PMID: 23221481

IP-6 May Impair Bioavailability of Iron, Calcium, and Zinc in Chinese


Phytate intake and molar ratios of phytate to zinc, iron and calcium in the diets of people in China.

To assess the phytate intake and molar ratios of phytate to calcium, iron and zinc in the diets of people in China.
2002 China Nationwide Nutrition and Health Survey is a cross-sectional nationwide representative survey on nutrition and health. The information on dietary intakes was collected using consecutive 3 days 24 h recall by trained interviewers.
The data of 68 962 residents aged 2-101 years old from 132 counties were analyzed.
The median daily dietary intake of phytate, calcium, iron and zinc were 1186, 338.1, 21.2 and 10.6 mg, respectively. Urban residents consumed less phytate (781 vs 1342 mg/day), more calcium (374.5 vs 324.1 mg/day) and comparable amounts of iron (21.1 vs 21.2 mg/day) and zinc (10.6 vs 10.6 mg/day) than their rural counterparts. A wide variation in phytate intake among residents from six areas was found, ranging from 648 to 1433 mg/day. The median molar ratios of phytate to calcium, iron, zinc and phytate x calcium/zinc were 0.22, 4.88, 11.1 and 89.0, respectively, with a large variation between urban and rural areas. The phytate:zinc molar ratios ranged from 6.2 to 14.2, whereas the phytate x calcium/zinc molar ratios were from 63.7 to 107.2. The proportion of subjects with ratios above the critical values of phytate to iron, phytate to calcium, phytate to zinc and phytate x calcium/zinc were 95.4, 43.7, 23.1 and 8.7%, respectively. All the phytate/mineral ratios of rural residents were higher than that of their urban counterparts.
The dietary phytate intake of people in China was higher than those in Western developed countries and lower than those in developing countries. Phytate may impair the bioavailability of iron, calcium and zinc in the diets of people in China.

Ma G, Li Y, Jin Y, Zhai F…
Eur J Clin Nutr Mar 2007
PMID: 16929240

IP-6 Supplementation Causes Thinner Bones in Rats


Bone and faecal minerals and scanning electron microscopic assessments of femur in rats fed phytic acid extract from sweet potato (Ipomoea batatas).

Phytic acid was extracted from sweet potato (Ipomoea batatas) and fed to Wistar rats with or without zinc for 3 weeks. Animals were then sacrificed and bone and faecal minerals were assessed. The ultra-structure of the bones was examined via scanning electron microscopy. Phytic acid extract or commercial phytic acid supplemented diets (D + Zn + PE or D + PE) displayed reduced bone calcium levels (101.27 +/- 59.11 and 119.27 +/- 45.36 g/kg) compared to the other test groups. Similarly, reduced calcium were observed in the control groups (D + Zn and D) fed formulated diets with or without zinc supplementation (213.14 +/- 15.31 and 210 +/- 6.88 g/kg) compared to the other test groups. The group fed supplemented commercial phytic acid diet (D + CP) demonstrated the lowest femur magnesium (3.72 +/- 0.13 g/kg) while the group fed phytic acid extract supplementation (D + PE) recorded the highest level (4.84 +/- 0.26 g/kg) amongst the groups. Femur iron was highest in the group fed commercial phytic acid supplemented diet (D + CP -115.74 +/- 2.41 g/kg) compared to the other groups. Faecal magnesium levels were significantly higher in the two test groups fed phytic acid extract with or without zinc (D + Zn + PE or D + PE) compared to all other groups. All the groups which had phytic acid supplemented diets had significantly thinner bone in the trabecular region, compared to the groups fed formulated diet or zinc supplemented formulated diet (D or D + Zn). These observations suggest that the consumption of foods high in phytic acid may contribute to a reduction in the minerals available for essential metabolic processes in rats.

Dilworth L, Omoruyi FO, Reid W, Asemota HN
Biometals Apr 2008
PMID: 17562130

Low IP-6 a Risk Factor for Osteoporosis


Phytate (myo-inositol hexaphosphate) and risk factors for osteoporosis.

Several risk factors seem to play a role in the development of osteoporosis. Phytate is a naturally occurring compound that is ingested in significant amounts by those with diets rich in whole grains. The aim of this study was to evaluate phytate consumption as a risk factor in osteoporosis. In a first group of 1,473 volunteer subjects, bone mineral density was determined by means of dual radiological absorptiometry in the calcaneus. In a second group of 433 subjects (used for validation of results obtained for the first group), bone mineral density was determined in the lumbar column and the neck of the femur. Subjects were individually interviewed about selected osteoporosis risk factors. Dietary information related to phytate consumption was acquired by questionnaires conducted on two different occasions, the second between 2 and 3 months after performing the first one. One-way analysis of variance or Student’s t test was used to determine statistical differences between groups. Bone mineral density increased with increasing phytate consumption. Multivariate linear regression analysis indicated that body weight and low phytate consumption were the risk factors with greatest influence on bone mineral density. Phytate consumption had a protective effect against osteoporosis, suggesting that low phytate consumption should be considered an osteoporosis risk factor.

López-González AA, Grases F, Roca P, Mari B…
J Med Food Dec 2008
PMID: 19053869

IP-6 Inhibits Mineralization of Mouse Osteoblasts Cultures


Inositol hexakisphosphate inhibits mineralization of MC3T3-E1 osteoblast cultures.

Inositol hexakisphosphate (IP6, phytic acid) is an endogenous compound present in mammalian cells and tissues. Differentially phosphorylated forms of inositol are well-documented to have important roles in signal transduction, cell proliferation and differentiation, and IP6 in particular has been suggested to inhibit soft tissue calcification (specifically renal and vascular calcification) by binding extracellularly to calcium oxalate and calcium phosphate crystals. However, the effects of IP6 on bone mineralization are largely unknown. In this study, we used MC3T3-E1 osteoblast cultures to examine the effects of exogenous IP6 on osteoblast function and matrix mineralization. IP6 at physiologic concentrations caused a dose-dependent inhibition of mineralization without affecting cell viability, proliferation or collagen deposition. Osteoblast differentiation markers, including tissue-nonspecific alkaline phosphatase activity, bone sialoprotein and osteocalcin mRNA levels, were not adversely affected by IP6 treatment. On the other hand, IP6 markedly increased protein and mRNA levels of osteopontin, a potent inhibitor of crystal growth and matrix mineralization. Inositol alone (without phosphate), as well as inositol hexakis-sulphate, a compound with a high negative charge similar to IP6, had no effect on mineralization or osteopontin induction. Binding of IP6 to mineral crystals from the osteoblast cultures, as well as to synthetic hydroxyapatite crystals, was confirmed by a colorimetric assay for IP6. In summary, IP6 inhibits mineralization of osteoblast cultures by binding to growing crystals through negatively charged phosphate groups and by induction of inhibitory osteopontin expression. These data suggest that IP6 may regulate physiologic bone mineralization by directly acting extracellularly, and by serving as a specific signal at the cellular level for the regulation of osteopontin gene expression.

Addison WN, McKee MD
Bone Apr 2010
PMID: 20079473

Phytate Associated with Bone Density in Posmenopausal Women of Mallorca


[The influence of consumption of phytate on the bone mass in posmenopausal women of Mallorca].

Osteoporosis is a serious health problem in the population, mainly for postmenopausal women. Therefore, it is important to develop programs to decrease prevalence. The main objective of this study is to determine the influence of phytate consumption on bone mineral density.
The bone mineral density was evaluated in postmenopausal women by means of dual X-ray double energy absorptiometry for calcaneous (C), lumbar spine (LS) and femoral neck (FN). The results obtained were related to the consumption of phytate by means of a dietary questionnaire.
In the three different areas (C, LS, FN) we observed significantly higher values of T-score in women that consumed adequate amounts of phytate as opposed to those that did not, (C 0.1 vs. -0.5, LS -1.2 and -2.5 and FN -0.2 and -1.2). There is also an increase in the T-score as more phytate is consumed, up to a maximum of two times a week (C -0.7 in non consumers, -0.2 in those that consume phytate once a week and 0.2 in those that consume phytate twice a week; LS -2.8, -1.7 and 1.1 and finally, CF -1.3, -0.6 and -0.1).
The results obtained seem to indicate that the adequate consumption of phytate may play an important role in the prevention of bone mineral density loss in postmenopausal women.

López-González AA, Grases F, Marí B, Vicente-Herrero MT…
Reumatol Clin
PMID: 21794821 | Free Full Text

Phytate Associate with Bone Density in Postmenopausal Women


Phytate levels and bone parameters: a retrospective pilot clinical trial.

This study evaluated the relationship between phytate urinary levels and bone characteristics in a large population of postmenopausal women. The study population consisted of 180 postmenopausal women who participated in a descriptive cross-sectional study. A urine sample was collected from each subject to determine phytate levels and the volunteers were divided into two groups according to phytate urinary concentration (i.e., low and high levels). Bone mineral density was determined in the lumbar spine and femoral neck of groups with low and high phytate urinary levels. Urinary levels of phytate were linked to dietary phytate consumption. Hence, bone mineral density values were significantly higher in the lumbar spines and femoral necks of women who consumed high levels of phytate than in women with low urinary phytate concentrations. Higher urinary levels of phytate correlated with higher bone mineral density in the lumbar spine and femoral necks of postmenopausal women. This finding demonstrates the potential use of phytate in the treatment of bone related diseases, as it uses a mechanism of action similar to some bisphosphonates.

Lopez-Gonzalez AA, Grases F, Perello J, Tur F…
Front Biosci (Elite Ed) 2010
PMID: 20515779