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Inositol and Bone Health

  • The first paper is an excellent review of phytates, which are inositol phosphates that are relatively indigestible by humans. Phytates in the undigested form interfere with the absorption of calcium, zinc, and other metals. This is not a big problem for people with good intake of calcium and iron, but worsens deficiencies in underdeveloped regions with low calcium/iron intake and high phytate diets. When phytate is completely digested, myo-inositol and phosphates are released and do not interfere with calcium absorption. However, some phytate is desirable to help protect from colon cancer and to provide other health benefits. This is another example where too much of a good thing, is not a good thing. Digestion of phytate is assisted by soaking beans overnight, germination of seeds and beans as sprouts, and heating to low temperatures. Current methods of food processing often disturb natural phytate digestion. Some probiotics contain enzymes that help digest phytates. Thus, the preparation of phytates and the availability of other nutrients seems to influence the beneficial or harmful effects of phytate consumption.
  • The second paper is an epidemiological study of Spanish women. This study reported that postmenopausal women who consumed a Mediterranean diet, but included phytate rich foods at least three times a week, had higher bone mineral density than those who consumed less phytate. This supports the opinion that phytates benefit bone health in the presence of an otherwise healthy diet.
  • The third paper correlates phytate consumption with improved bone mineral density and reports that the phosphate component has a mechanism of action similar to bisphosphonates (delays bone loss after it’s been formed).
  • The fourth paper reports that the myo-inositol component is essential for bone formation.
  • The fifth paper reports that supplementation with inositol increases the calcium in bone and this is further improved when inositol is combined with vitamin D supplementation. Thus, it is possible that the digestion of phytate is beneficial for bone because the myo-inositol component may promote bone formation while the phosphate component may inhibit bone resorption.
  • The sixth paper reports that the combination of arginine, inositol and silicon supplements improved the bone mineralization in quail.

1. Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.
Schlemmer U, Frølich W, Prieto RM, Grases F. Mol Nutr Food Res. 2009; 53 Suppl 2:S330-75.

Abstract: 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.

2. Phytate (myo-inositol hexaphosphate) and risk factors for osteoporosis.
López-González AA, Grases F, Roca P, Mari B, Vicente-Herrero MT, Costa-Bauzá A. J Med Food. 2008; 11(4):747-52.

Abstract: 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.

3. Phytate levels and bone parameters: a retrospective pilot clinical trial.
Lopez-Gonzalez AA, Grases F, Perello J, Tur F, Costa-Bauza A, Monroy N, Mari B, Vicente-Herrero T. Front Biosci (Elite Ed). 2010; 2:1093-8.

Abstract: 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.

4. Sodium/myo-inositol cotransporter 1 and myo-inositol are essential for osteogenesis and bone formation.
Dai Z. Chung SK. Miao D. Lau KS. Chan AW. Kung AW. Journal of Bone & Mineral Research. 2011; 26(3):582-90

Abstract: myo-Inositol (MI) plays an essential role in several important processes of cell physiology, is involved in the neural system, and provides an effective treatment for some psychiatric disorders. Its role in osteogenesis and bone formation nonetheless is unclear. Sodium/MI cotransporter 1 (SMIT1, the major cotransporter of MI) knockout (SMIT1(-/-)) mice with markedly reduced tissue MI levels were used to characterize the essential roles of MI and SMIT1 in osteogenesis. SMIT1(-/-) embryos had a dramatic delay in prenatal mineralization and died soon after birth owing to respiratory failure, but this could be rescued by maternal MI supplementation. The rescued SMIT1(-/-) mice had shorter limbs, decreased bone density, and abnormal bone architecture in adulthood. Deletion of SMIT1 resulted in retarded postnatal osteoblastic differentiation and bone formation in vivo and in vitro. Continuous MI supplementation partially restored the abnormal bone phenotypes in adult SMIT1(-/-) mice and strengthened bone structure in SMIT1(+/+) mice. Although MI content was much lower in SMIT1(-/-) mesenchymal cells (MSCs), the I(1,4,5)P(3) signaling pathway was excluded as the means by which SMIT1 and MI affected osteogenesis. PCR expression array revealed Fgf4, leptin, Sele, Selp, and Nos2 as novel target genes of SMIT1 and MI. SMIT1 was constitutively expressed in multipotential C3H10T1/2 and preosteoblastic MC3T3-E1 cells and could be upregulated during bone morphogenetic protein 2 (BMP-2)-induced osteogenesis. Collectively, this study demonstrated that deficiency in SMIT1 and MI has a detrimental impact on prenatal skeletal development and postnatal bone remodeling and confirmed their essential roles in osteogenesis, bone formation, and bone mineral density (BMD) determination. Copyright Copyright 2011 American Society for Bone and Mineral Research.

5. Effects of the hexahydroxyhexane myoinositol on bone uptake of radiocalcium in rats: Effect of inositol and vitamin D2 on bone uptake of 45Ca in rats.
Angeloff LG, Skoryna SC, Henderson IW. Acta Pharmacol Toxicol (Copenh). 1977; 40(2):209-15.

Abstract: The objective of this study was to investigate the effects of inositol and vitamin D2 on bone uptake of 45Ca in rats. The radioactive calcium was administered to young rats by orogastric intubation (2 muci/100 g body weight (b. wt)) with inositol (20 mg/100 g b. wt.) and/or vitamin D2 (5OO IU/100 g b. wt.) to normal rats. Bone uptake of 45Ca was measured after 24 hours by standard technique. Inositol alone produced a 48% increase in calcium uptake. It is concluded that inositol significantly increases bone uptake of radioactive calcium (P greater than 0.005). Simultaneous administration of vitamin D2 decreases the effect of inositol considerably, while vitamin D2 has no significant effect.

6. Dietary arginine silicate inositol complex improves bone mineralization in quail.
Sahin K, Onderci M, Sahin N, Balci TA, Gursu MF, Juturu V, Kucuk O. Poult Sci. 2006; 85(3):486-92.

Abstract: Skeletal abnormalities, low bone mass, bone deformities, and bone fractures increase the risk of osteoporosis and osteoarthritis, which are of concern from both a public standpoint and a cost-of-care burden standpoint. Arginine silicate inositol complex (ASI; Arg = 49.47%, silicone = 8.2%, inositol = 25%) is a novel, bioavailable source of Si and Arg and one that offers potential benefits for vascular and bone health. Skeletal abnormalities and architectural deterioration of bone tissue are common under hot climate conditions in the poultry industry. In this study, we evaluated the effects of ASI supplementation on performance and bone mineral density (BMD) in Japanese quail (Coturnix coturnix japonica) exposed to the high ambient temperature of 34 degrees C. The birds (n = 180; 10 d old) were randomly assigned to 6 treatment groups consisting of 10 replicates of 3 birds. Birds were kept in wire cages in a temperature-controlled room at either 22 degrees C (thermoneutral; TN) or 34 degrees C (heat stress; HS) for 8 h/d (0900 to 1700 h until the end of study) and were fed a basal (control) diet or the basal diet supplemented with either 500 or 1,000 mg of ASI/kg of diet. Heat exposure decreased performance and bone mineralization when the basal diet was fed (P = 0.001). The ASI supplement had no effect on feed intake, BW, feed efficiency, and carcass traits (P > 0.05) in quails reared under TN or HS conditions. The BMD was significantly improved by ASI supplementation in both TN and HS groups [0.72 (TN) vs. 0.60 (HS); P < or = 0.05]. Serum osteocalcin, dehydroepiandrosterone concentrations, and alkaline phosphatase activity increased, whereas tumor necrosis factor-alpha and Creactive protein concentrations decreased, as dietary ASI supplementation increased in quail reared under HS. This improvement was linear with increased doses of supplement (P = 0.001). In the ASI group, the amount of Ca, P, Mg, and Mn in the excreta decreased (P < or = 0.05), and the concentrations of these minerals in tibia ash increased in quail reared under HS conditions (P < or = 0.05). In conclusion, ASI supplementation to the basal diet significantly improved bone mineralization in quail and did not impact feed consumption, BW gain, or feed efficiency.