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Pulmonary fibrosis, a disabling lung disease, results from the fibrotic transformation of lung tissue. This fibrotic transformation leads to a deterioration of lung capacity, resulting in significant respiratory distress and a reduction in overall quality of life. Currently, the frontline treatment of pulmonary fibrosis remains limited, focusing primarily on symptom relief and slowing disease progression. Bacterial infections with Pseudomonas aeruginosa are contributing to a severe progression of idiopathic pulmonary fibrosis. Phytic acid, a natural chelator of zinc, which is essential for the activation of metalloproteinase enzymes involved in pulmonary fibrosis, shows potential inhibition of LasB, a virulence factor in P. aeruginosa, and mammalian metalloproteases (MMPs). In addition, phytic acid has anti-inflammatory properties believed to result from its ability to capture free radicals, inhibit certain inflammatory enzymes and proteins, and reduce the production of inflammatory cytokines, key signaling molecules that promote inflammation. To achieve higher local concentrations in the deep lung, phytic acid was spray dried into an inhalable powder. Challenges due to its hygroscopic and low melting (25 °C) nature were mitigated by converting it to sodium phytate to improve crystallinity and powder characteristics. The addition of leucine improved aerodynamic properties and reduced agglomeration, while mannitol served as carrier matrix. Size variation was achieved by modifying process parameters and were evaluated by tools such as the Next Generation Impactor (NGI), light diffraction methods, and scanning electron microscopy (SEM). An inhibition assay for human MMP-1 (collagenase-1) and MMP-2 (gelatinase A) allowed estimation of the biological effect on tissue remodeling enzymes. The activity was also assessed with respect to inhibition of bacterial LasB. The formulated phytic acid demonstrated an IC50 of 109.7 µg/mL for LasB with viabilities > 80 % up to 188 µg/mL on A549 cells. Therefore, inhalation therapy with phytic acid-based powder shows promise as a treatment for early-stage Pseudomonas-induced pulmonary fibrosis., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Poor bioavailability may contribute to iron deficiency among children in high-resource countries, but iron bioavailability of Australian pre-schooler diets is unknown. This study aimed to estimate the bioavailability of Australian pre-schooler iron intakes across the day and by eating occasions to identify optimal timing for intervention, by using five previously developed algorithms, and to estimate the proportion of children with intakes of absorbable iron below the requirements., Methods: Dietary data of children aged 2 to < 6 y (n = 812) from the 2011-12 National Nutrition and Physical Activity Survey were collected via two 24-h recalls. Usual food and nutrient intakes were estimated via Multiple Source Method. Phytate, polyphenol, and heme iron values were sourced from international databases or the literature. Five previously published algorithms were applied to observed dietary data to estimate iron bioavailability and calculate the prevalence of children with intakes of absorbable iron below requirements., Results: Pre-schooler daily iron bioavailability was low (2.7-10.5%) and corresponded to intakes of 0.18-0.75 mg/d of absorbable iron. The proportion of children with inadequate intakes of absorbable iron ranged between 32 and 98%. For all eating occasions, dinner offered iron of the greatest bioavailability (4.2-16.4%), while iron consumed at breakfast was of the lowest bioavailability (1.2-5.6%)., Conclusion: Future strategies are required to improve intakes of bioavailable iron for pre-schoolers to prevent the risk of deficiency. These strategies could include the encouragement of concomitant consumption of enhancers of iron absorption with iron-rich sources, particularly at breakfast., (© 2024. The Author(s).)

Phytic acid (PA) is a natural antioxidant with various biological activities, providing protective effects in multiple animals. Ochratoxin A (OTA) is a mold toxin commonly found in feed, which induces multi-organ damage, with kidney being the target organ of its toxicity. This study investigates the protective effects of PA on OTA-induced renal damage and its potential mechanisms in chicks. The results demonstrates that PA treatment restores OTA-induced renal pathological injuries, reverses the diminished activities of antioxidant enzymes, reduces the accumulation of malondialdehyde, and normalizes the expression of pro-inflammatory cytokines, which confirms that PA can alleviate OTA-induced renal damage. Further investigations reveal that OTA-induced renal injury accompanied by an increase in tissue iron content and the transcription levels of ferroptosis-related genes (TFR, ACSL4, and HO-1), and a decrease in the levels of SLC7A11 and GPX4. PA treatment reverses all these effects, indicating that PA mitigates OTA-induced renal ferroptosis. Moreover, PA supplementation improves intestinal morphology and mucosal function, corrects OTA-induced changes in the intestinal microbiota. Besides, PA microbiota transplantation alleviates renal inflammation and oxidative stress caused by OTA. In conclusion, PA plays a protective role against renal damage through the regulation of ferroptosis and the intestinal microbiota, possibly providing novel insights into the control and prevention of OTA-related nephrotoxicity., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

1. This study determined the effect of dietary Zn concentration and source in phytase-supplemented diets on bone mineralisation, gastrointestinal phytate breakdown, mRNA -level gene expression (in jejunum, liver and Pectoralis major muscle) and growth performance in broiler chickens.2. Male Cobb 500 broilers were housed in floor pens (d 0-d 21) to test seven treatments with six replicate pens (12 birds per pen). Diets were arranged in a 2 × 3 + 1-factorial arrangement. The experimental factors were Zn source (Zn-oxide (ZnO) or Zn-glycinate (ZnGly) and Zn supplementation level (10, 30 or 50 mg/kg of diet). A maize-soybean meal-based diet without supplementation and formulated to contain 28 mg Zn/kg (analysed to be 35 mg Zn/kg), served as a control.3. Zinc source and level did not influence ( p  > 0.05) bone ash concentration and quantity or mineral concentrations in bone ash. Tibia thickness was greater in the treatment ZnO10 than in the treatments ZnO30 and ZnGly50 (Zn level × Zn source: p  = 0.036), but width and breaking strength were not affected.4. Pre-caecal P digestibility and concentrations of phytate breakdown products in the ileum, except for InsP 5 , were not affected by Zn source or level. Only the expression of EIF4EBP1 (eukaryotic translation initiation factor 4E-binding protein 1) and FBXO32 (F-box only protein 32) in Pectoralis major muscle was affected by source, where expression was increased in ZnO compared to ZnGly diets ( p  < 0.05).5. In conclusion, Zn level and source did not affect gastrointestinal phytate degradation and bone mineralisation in phytase-supplemented diets. The intrinsic Zn concentration appeared to be sufficient for maximum bone Zn deposition under the conditions of the present study but requires validation in longer-term trials.

Type 2 diabetes mellitus has a worldwide prevalence of 10.5% in the adult population (20-79 years), and by 2045, the prevalence is expected to keep rising to one in eight adults living with diabetes. Mild cognitive impairment has a global prevalence of 19.7% in adults aged 50 years. Both conditions have shown a concerning increase in prevalence rates over the past 10 years, highlighting a growing public health challenge. Future forecasts indicate that the prevalence of dementia (no estimations done for individuals with mild cognitive impairment) is expected to nearly triple by 2050. Type 2 diabetes mellitus is a risk factor for the development of cognitive impairment, and such impairment increase the likelihood of poor glycemic/metabolic control. High phytate intake has been shown to be a protective factor against the development of cognitive impairment in observational studies. Diary phytate intake might reduce the micro- and macrovascular complications of patients with type 2 diabetes mellitus through different mechanisms. We describe the protocol of the first trial (the PHYND trial) that evaluate the effect of daily phytate supplementation over 56 weeks with a two-arm double-blind placebo-controlled study on the progression of mild cognitive impairment, cerebral iron deposition, and retinal involvement in patients with type 2 diabetes mellitus. Our hypothesis proposes that phytate, by inhibiting advanced glycation end product formation and chelating transition metals, will improve cognitive function and attenuate the progression from Mild Cognitive Impairment to dementia in individuals with type 2 diabetes mellitus and mild cognitive impairment. Additionally, we predict that phytate will reduce iron accumulation in the central nervous system, mitigate neurodegenerative changes in both the central nervous system and retina, and induce alterations in biochemical markers associated with neurodegeneration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pujol, Sanchis, Tamayo, Nicolau, Grases, Espino, Estremera, Rigo, Amengual, Rodríguez, Ribes, Gomila, Simó-Servat and Masmiquel.)

Dental caries is a widespread oral disease that poses a significant medical challenge. Traditional caries prevention methods, primarily the application of fluoride, often fall short in effectively destroying biofilms and preventing enamel demineralization, thereby providing limited efficacy in halting the progression of caries over time. To address this issue, we have developed a green and cost-effective synergistic strategy for the prevention of dental caries. By combining natural sodium phytate and chitosan, we have created chitosan-sodium phytate nanoparticles that offer both the antimicrobial properties of chitosan and the enamel demineralization-inhibiting capabilities of sodium phytate. In an ex vivo biofilm model of human teeth, we found that these nanoparticles effectively prevent biofilm buildup and acid damage to the mineralized tissue. Additionally, topical treatment of dental caries in rodent models has shown that these nanoparticles effectively suppress disease progression without negatively impacting oral microbiota diversity or causing harm to the gingival-mucosal tissues, unlike traditional prevention methods.

There is a gap in the understanding of the relationship between dietary phytate levels and the relative efficacy of phytase to improve amino acid (AA) digestibility in pigs and chickens. Two experiments were conducted to investigate the effect of exogenous phytase on standardized ileal digestibility (SID) of AA and the apparent ileal digestibility (AID) of P in both standard- (SP) and high-phytate (HP) diets for broilers and swine. There were either 40 cages of Cobb 500 male broilers or 10 crossbred barrows (35 kg) fitted with ileal T-cannulas. Both studies were allotted to five dietary treatments (8 replicates). Treatments consisted of four corn-soybean meal-based diets arranged in a 2 × 2 factorial of standard or high phytate and exogenous phytase at 0 or 1 000 phytase units (FYT)/kg; and one N-free diet. Birds were fed a common starter diet from d 0 to 20 and fed experimental diets from d 20 to 25. Birds were euthanized on d 25 via CO 2 asphyxiation, and digesta were collected from the terminal ileum. Pigs were fed for a total of four 7-d periods, where digesta were collected on d 6 and 7 of each period. Diet and digesta samples were analyzed for DM, N, Ti, AA, and P to determine AA and P digestibility. The SID of AA was determined by correcting the AID of AA for the basal endogenous losses estimated using the N-free diet. Main effects of the diet type (standard or HP) and phytase (0 or 1 000 FYT/kg), and the interaction of diet type and phytase were evaluated. For both experiments, the HP diets produced lower SID of AA compared to the SP (P < 0.001). For broilers, there was a phytase effect (P < 0.001) for the SID of all AAs evaluated regardless of the diet type. For pigs, phytase improved (P < 0.05) the SID of Met, Lys, Cys, Glu and Ser and tended to improve (P < 0.10) Arg, Leu, Thr, and Tyr. There were no significant interactions for either experiment. For both experiments, AID of P was lower for the HP diets (P < 0.01), and phytase produced greater AID of P for both diet types (P < 0.01). These data indicate that phytase greatly improves the digestibility of P for broilers and pigs and has the ability to significantly increase the digestibility of amino acids for these animals, regardless of the dietary phytate P., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The main objective of this work was to explore the association of dietary phytate intake with bone mineral density (BMD) in a Mediterranean population of postmenopausal women. For this purpose, a cross-sectional analysis of 561 women aged 55-75 years with overweight/obesity and metabolic syndrome from a Mediterranean area and with data on dual-energy X-ray absorptiometry (DXA) scans in femur and lumbar spine was performed. Estimated phytate intake was calculated using a validated food frequency questionnaire. Our results indicated that phytate intake was associated with BMD [β(95%CI) per each 25 mg/100 kcal] in femoral neck [0.023(0.060-0.040) g/cm 2 ], femoral Ward's triangle [0.033(0.013-0.054) g/cm 2 ], total femur [0.018(0.001-0.035) g/cm 2 ], and all the analyzed lumbar spine sites [L1-L4: 0.033(0.007-0.059) g/cm 2 ] after adjusting for potential confounders. The sensitivity analysis showed that phytate intake was directly associated with lumbar spine BMD in women younger than 66 years, with a body mass index higher than 32.6 kg/cm 2 and without type 2 diabetes (all p -for interactions < 0.05). The overall results indicated that phytate, a substance present in food as cereals, legumes and nuts, was positively associated with BMD in Mediterranean postmenopausal women. Phytate may have a protective effect on bone resorption by adsorbing on the surfaces of HAP. Nevertheless, large, long-term, and randomized prospective clinical studies must be performed to assess the possible benefits of phytate consumption on BMD in postmenopausal women.

Phytate (PA) serves as a phosphate storage molecule in cereals and other plant foods. In food and in the human body, PA has a high affinity to chelate Zn 2+ and Fe 2+ , Mg 2+ , Ca 2+ , K + , Mn 2+ and Cu 2+ . As a consequence, minerals chelated in PA are not bio-available, which is a concern for public health in conditions of poor food availability and low mineral intakes, ultimately leading to an impaired micronutrient status, growth, development and increased mortality. For low-income countries this has resulted in communications on how to reduce the content of PA in food, by appropriate at home food processing. However, claims that a reduction in PA in food by processing per definition leads to a measurable improvement in mineral status and that the consumption of grains rich in PA impairs mineral status requires nuance. Frequently observed decreases of PA and increases in soluble minerals in in vitro food digestion (increased bio-accessibility) are used to promote food benefits. However, these do not necessarily translate into an increased bioavailability and mineral status in vivo. In vitro essays have limitations, such as the absence of blood flow, hormonal responses, neural regulation, gut epithelium associated factors and the presence of microbiota, which mutually influence the in vivo effects and should be considered. In Western countries, increased consumption of whole grain foods is associated with improved health outcomes, which does not justify advice to refrain from grain-based foods because they contain PA. The present commentary aims to clarify these seemingly controversial aspects.

Myo-inositol hexaphosphate (phytate; IP6) is a natural compound that is abundant in cereals, legumes, and nuts, and it can bind to crystal surfaces and disturb crystal development, acting as crystallization inhibitor. The adsorption of such inhibitors to crystal faces can also inhibit crystal dissolution. The binding of phytate to metal cofactors suggests that it could be used for treatment of osteoporosis. Our in-vitro study showed that phytate inhibits dissolution of hydroxyapatite (HAP). The effect of phytate was similar to that of alendronate and greater than that of etidronate. This led us to perform a cross-sectional study to investigate the impact of consumption of IP6 on bone mineral density (BMD) in post-menopausal women. Our data indicate that BMD and t-score of lumbar spine increased with increasing phytate consumption, and a phytate consumption higher than 307 mg/day was associated with a normal BMD (t-score > -1). These data suggest that phytate may have a protective effect in bone decalcification by adsorbing on the surfaces of HAP, and a daily consumption of phytate-rich foods (at least one serving/day of legumes or nuts) may help to prevent or minimize bone-loss disorders, such as osteoporosis. However, further studies are needed to gain a better understanding about the mechanism of inhibition of phytate in bone-related diseases (see graphical abstract).

Pseudoxanthoma elasticum (PXE), a prototype of heritable ectopic calcification disorders, affects the skin, eyes and the cardiovascular system due to inactivating mutations in the ABCC6 gene. There is no effective treatment for the systemic manifestations of PXE. In this study, the efficacy of INS-3001, an analogue of phytic acid, was tested for inhibition of ectopic calcification in an Abcc6 -/- mouse model of PXE. In prevention study, Abcc6 -/- mice, at 6 weeks of age, the time of onset of ectopic calcification, were treated with INS-3001 with 0.16, 0.8, 4, 20 or 100 mg/kg/day administered by subcutaneous implantation of osmotic pumps, as well as 4 mg/kg/day by subcutaneous injection thrice weekly or 14, 4 and 0.8 mg/kg/day once weekly subcutaneous injection. Mice were necropsied at 12 weeks of age. Histologic examination and quantitative calcium assay revealed that mice receiving 6 weeks of continuous INS-3001 administration via osmotic pumps showed dose-dependent inhibition of muzzle skin calcification with complete response at 4 mg/kg/day and a minimum effective dose at 0.8 mg/kg/day. INS-3001 plasma concentrations were dose-dependent and largely consistent during treatment for each dose. thrice weekly and once weekly subcutaneous injections of INS-3001 also prevented calcification. In established disease study, 12-week-old Abcc6 -/- mice with extensive calcification were continuously administered INS-3001 at 4 mg/kg/day for a follow-up of 12 weeks. INS-3001 treatment was found to stabilize existing calcification that had developed at start of treatment. These results suggest that INS-3001 may provide a promising preventive treatment strategy for PXE, a currently intractable ectopic calcification disorder., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: In the current study, we reported our experience on sentinel node mapping of breast cancer patients during the extreme shortage of Mo99-Tc99m generators using Tc-99m phytate. Methods and Results: During the period from March 7, 2019, to April 18, 2020, due to disruption of molybdenum supply chain, we used low specific activity Tc-99m pertechnetate elute (0.5-2 mCi of 99m TcO 4 in 5 mL) for each kit preparation. Two or three intradermal periareolar injections were done for each patient (0.02-0.1 mCi/0.2 mL for each injection). Immediately following injection, dynamic lymphoscintigraphy was done. Surgery was done the same day of injection and the axillary sentinel node was sought using a gamma probe. Overall, 35 patients were included in the study. The specific activity of the Tc-99m elute (in 5 mL) used for kit preparation was 2 mCi/10 mg in four, 1.5 mCi/10 mg in eight, 1.25 mCi/10 mg in eight, 1 mCi/10 mg in three, 0.75 mCi/10 mg in five, and 0.5 mCi/10 mg of 99m Tc-Phytate in seven patients. For the first four groups of patients, we used two 0.2 mL injections, while in the latter two groups, three 0.2 mL injections were used. At least one sentinel node was detected in all patients but three in whom axilla was involved. Conclusion: Sentinel node biopsy can be achieved with low specific activity of Tc-99m elute at the time of Mo99-Tc-99m generator shortage. If special personal protection is used, sentinel node mapping can be done in nuclear medicine departments with excellent results despite the COVID-19 pandemic and disruption of generator shipment.

Plant-based diets are associated with reduced risk of lifestyle-induced chronic diseases. The thousands of phytochemicals they contain are implicated in cellular-based mechanisms to promote antioxidant defense and reduce inflammation. While recommendations encourage the intake of fruits and vegetables, most people fall short of their target daily intake. Despite the need to increase plant-food consumption, there have been some concerns raised about whether they are beneficial because of the various 'anti-nutrient' compounds they contain. Some of these anti-nutrients that have been called into question included lectins, oxalates, goitrogens, phytoestrogens, phytates, and tannins. As a result, there may be select individuals with specific health conditions who elect to decrease their plant food intake despite potential benefits. The purpose of this narrative review is to examine the science of these 'anti-nutrients' and weigh the evidence of whether these compounds pose an actual health threat.

Objective: Dietary phytate (IP6) enjoys a reputation as an inhibitor of calcium renal stone formation, although there are very few human studies to support this notion. In South Africa, urolithiasis occurs in the white (W) but is rare in the black (B) population. We undertook this unique human model to further investigate the IP6 theory., Methods: Healthy W and B males completed baseline food-frequency recall questionnaires. Dietary intake of IP6 was restricted for 18 days. An IP6 dietary supplement was ingested on days 15-18. Twenty-four-hour urinary phytate and other urinary components were determined. Relative supersaturations of calcium salts were calculated. The urinary metastable limit (MSL) of calcium oxalate (CaOx) and its crystallisation kinetics were determined experimentally., Results: Habitual dietary intake of IP6 and its urinary excretion were significantly higher in B than in W (1650 ± 202 vs. 640 ± 134 mg/d, P = .0002 and 1.13 ± 0.12 vs. 0.75 ± 0.13 μM, P <.05, respectively). In B, urinary phytate decreased significantly after 15 days of IP6 restriction, but in W, its excretion remained constant. After supplementation, urinary IP6 increased significantly in both groups reaching levels commensurate with the baseline value in B. No significant differences occurred in B in any of the routine urinary risk factors throughout the trial. However, in W, urinary citrate excretion increased on day 18 relative to day 0. There were no significant intragroup or intergroup changes in relative supersaturation, metastable limit, or crystallization kinetics., Conclusions: Despite notable differences in the renal handling of ingested IP6, there were no changes in any of the well-established urinary risk factors for calcium renal stone formation in either of our uniquely different test groups. We conclude that, in the absence of hard evidence, claims that IP6 is a stone inhibitor remain unproven., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The present study aimed to explore the effects of phytic acid (PA) on the antimicrobial activity and inflammatory response in three immune organs (head kidney, spleen and skin) of on-growing grass carp (Ctenopharyngodon idella). To achieve this goal, we first conducted a 60-day growth trial by feeding fish with graded levels of PA (0, 0.8, 1.6, 2.4, 3.2 and 4.0%). Then, the fish were challenged with Aeromonas hydrophila for 6 days. Compared with the control group, the following results were obtained regarding supplementation with certain levels of PA in the diet. (1) There was an increase in skin haemorrhage and lesion morbidity in fish. (2) There was a decrease in activities or contents of immune factors, including lysozyme (LZ), complement 3 (C3), C4 and immunoglobulin M (IgM), and there was downregulation of gene expression levels of hepcidin, liver-expressed antimicrobial peptide 2A (LEAP-2A), LEAP-2B, and β-defensin-1 in immune organs. (3) There was upregulation in the gene expression of the following pro-inflammatory cytokines: tumour necrosis factor α (TNF-α), interleukin 1β (IL-1β) (except in the spleen), interferon γ2 (IFN-γ2), IL-6 (except in the spleen), IL-8, IL-12p40, IL-15 and IL-17D. These changes were partly related to the nuclear factor kappa B (NF-κB) signalling pathway, but downregulation of mRNA levels of anti-inflammatory cytokines (transforming growth factor β1 (TGF-β1), TGF-β2, IL-413/A, IL-413/B, IL-10 (except in the skin) and IL-11) occurred in a manner partially related to the target of rapamycin (TOR) signalling pathway. Finally, based on the broken-line analysis of skin haemorrhage and lesion morbidity and IgM content in the head kidney, the maximum tolerance levels of PA for on-growing grass carp (120.56-452.00 g) were estimated to be 1.79 and 1.31% of the diet, respectively., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Osteoporosis commonly affects postmenopausal women and accounts for 300,000 hip fractures in the United States each year. More women are deferring or discontinuing pharmacologic treatment because of intolerable adverse reactions or fear of long-term safety. Supplementing dietary intake of certain vitamins and minerals can have positive effects on bone parameters. Calcium is frequently recommended for osteoporotic patients but many not confer much benefit toward bone density. Certain forms of vitamins A and K have been shown to increase bone density. Isoflavones and phytates are phytochemicals found in soy foods that are comparable to bisphosphonates when consumed at certain levels. Lastly, increasing certain daily fruit and vegetable servings can improve bone health. Nutritional interventions are typically safe alternatives that should be considered for postmenopausal women who are seeking nonpharmacologic treatment options for osteoporosis.

Background: Encrustation of ureteral double J stents is a common complication that may affect its removal. The aim of the proposed study is to evaluate the efficacy and safety of a new oral composition to prevent double J stent encrustation in indwelling times up to 8 weeks., Methods: A double-blinded, multicenter, placebo-controlled trial was conducted with 105 patients with indwelling double J stents enrolled across 9 public hospitals in Spain. The patients were randomly assigned (1:1) into intervention (53 patients) or placebo (52 patients) groups for 3 to 8 weeks and both groups self-monitored daily their morning urine pH levels. The primary outcome of analysis was the degree of stent ends encrustation, defined by a 4-point score (0 - none; 3 - global encrustation) using macroscopic and electron microscopy analysis of crystals, after 3 to 8-w indwelling period. Score was exponentially transformed according to calcium levels. Secondary endpoints included urine pH decrease, stent removal, and incidence of adverse events., Results: The intervention group benefits from a lower global encrustation rate of stent ends than placebo group (1% vs 8.2%; p < 0.018). Mean encrustation score was 85.12 (274.5) in the placebo group and 18.91 (102.27) in the intervention group (p < 0.025). Considering the secondary end points, treated patients reported greater urine pH decreases (p = 0.002). No differences in the incidence of adverse events were identified between the groups., Conclusions: Our data suggest that the use of this new oral composition is beneficial in the context of ureteral double J indwelling by decreasing mean, as well as global encrustation., Trial Registration: This trial was registered at www.clinicaltrials.gov under the name "Combined Use of a Medical Device and a Dietary Complement in Patient Urinary pH Control in Patients With an Implanted Double J Stent" with date 2nd November 2017, code NCT03343275, and URL.

Background: The high cardiovascular morbidity and mortality in patients with end-stage kidney disease could be partially caused by extensive cardiovascular calcification. SNF472, intravenous myo-inositol hexaphosphate, selectively inhibits the formation and growth of hydroxyapatite., Methods: This double-blind, placebo-controlled phase 2b trial compared progression of coronary artery calcium volume score and other measurements of cardiovascular calcification by computed tomography scan during 52 weeks of treatment with SNF472 or placebo, in addition to standard therapy, in adult patients with end-stage kidney disease receiving hemodialysis. Patients were randomized 1:1:1 to SNF472 300 mg (n=92), SNF472 600 mg (n=91), or placebo (n=91) by infusion in the hemodialysis lines thrice weekly during hemodialysis sessions. The primary end point was change in log coronary artery calcium volume score from baseline to week 52. The primary efficacy analysis combined the SNF472 treatment groups and included all patients who received at least 1 dose of SNF472 or placebo and had an evaluable computed tomography scan after randomization., Results: The mean change in coronary artery calcium volume score was 11% (95% CI, 7-15) for the combined SNF472 dose group and 20% (95% CI, 14-26) for the placebo group ( P =0.016). SNF472 compared with placebo attenuated progression of calcium volume score in the aortic valve (14% [95% CI, 5-24] versus 98% [95% CI, 77-123]; P <0.001) but not in the thoracic aorta (23% [95% CI, 16-30] versus 28% [95% CI, 19-38]; P =0.40). Death occurred in 7 patients (4%) who received SNF472 and 5 patients (6%) who received placebo. At least 1 treatment-emergent adverse event occurred in 86%, 92%, and 87% of patients treated with SNF472 300 mg, SNF472 600 mg, and placebo, respectively. Most adverse events were mild. Adverse events resulted in discontinuation of SNF472 300 mg, SNF472 600 mg, and placebo for 14%, 29%, and 20% of patients, respectively., Conclusions: Compared with placebo, SNF472 significantly attenuated the progression of coronary artery calcium and aortic valve calcification in patients with end-stage kidney disease receiving hemodialysis in addition to standard care. Future studies are needed to determine the effects of SNF472 on cardiovascular events. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02966028.

Objective: To evaluate the relationship between pelvic/para-aortic sentinel lymph node status and two different injection sites of 99m-technetium ( 99m Tc)-labeled phytate in patients with endometrial cancer., Methods: This was a randomized controlled trial involving 81 patients with endometrial cancer. In the cervical group (n=40), injections of 99m Tc were performed at the 3 and 9 o'clock positions of the uterine cervix. In the endometrial group (n=41), 99m Tc was injected into the fundal endometrium using a transcervical catheter. Sentinel lymph nodes were detected through pre-operative lymphoscintigraphy and intra-operatively using a handheld gamma probe. All patients underwent complete pelvic and para-aortic lymphadenectomy procedures. Pathologic ultra-staging was performed with immunostaining for cytokeratin in sentinel lymph nodes after routine hematoxylin and eosin histological examinations. The primary endpoint was the estimation of detection rates, sensitivity, false-negative rates, negative predictive value, and analysis of the distribution of pelvic and para-aortic sentinel lymph nodes., Results: The rate of detection of at least one sentinel lymph node, sensitivity, and the negative predictive value was 80%, 66.6%, 96.6% for the cervical group and 85%, 66.6%, 96.9% for the endometrial group, respectively. False-negative sentinel lymph nodes were detected in one patient from each group . There was no significant difference between the groups in terms of total sentinel lymph node count, sentinel pelvic lymph node count, and pelvic bilaterality, but the para-aortic sentinel lymph node count was significantly higher in the endometrial group (p<0.001). Ultra-staging examination of the pelvic sentinel lymph nodes revealed isolated tumor cells in one patient from each group., Conclusion: Transcervical endometrial tracer injection in endometrial cancer revealed similar pelvic but significantly higher para-aortic sentinel lymph node detection., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Phytic acid (PA) or myoinositol intake was recently reported by our group to suppress hepatic lipogenic gene expression and modulate gut microbiota in rats fed a high-sucrose diet (HSC). The aim of this study was to investigate the effect of PA and dietary fat level on fatty liver and gut microbiota in rats fed an HSC diet. Male Sprague-Dawley rats were fed a high-fat (HF), HSC diet or a low-fat (LF), HSC diet with or without 1.02% sodium PA for 12 days. Hepatic lipid levels, hepatic enzyme activity, and expression of the enzymes and transcriptional factors related to lipid metabolism, cecal organic acids, and fecal microbiota were evaluated. PA intake depressed hepatic total lipid and triglyceride levels; reduced hepatic activity and expression of lipogenic enzymes; elevated fecal proportion of Lactobacillus spp; and increased cecal succinate level in rats fed the LF diet. The HF diet, when compared with the LF diet, depressed hepatic total lipid and triglyceride levels; reduced hepatic activity and expression of lipogenic enzymes; increased hepatic expression of carnitine palmitoyl-transferase 1a and cAMP-responsive element binding protein 3-like 3; and elevated fecal proportions of Lactobacillus spp and Bifidobacterium spp. In the HF diet groups, PA intake did not affect the factors associated with hepatic lipid metabolism and gut microbiota. In conclusion, dietary fat level could change the effect of PA on hepatic lipid metabolism and gut microbiota and, in turn, could alter the degree of nutritional importance of PA in rats fed an HSC diet., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cobb 400, male broilers (n=4,752) were fed one of 12 diets, with 12 pens/diet and 33 birds/pen. Treatments consisted of 3 levels of phytate P (0.24, 0.345, or 0.45%) and 4 doses of phytase (0, 500, 1,000, or 2,000 phytase units (FTU)/kg). Diets were formulated with reduced Ca (0.22%), available P (0.20%), energy (80 to 120 kcal/kg), and amino acids (1 to 5%) when compared with breed requirements. Prediction equations suggested feeding dietary phytate P > 0.275, 0.295, or 0.319% reduced feed intake (FI) and body weight gain (BWG) and increased feed conversion ratio, respectively, from day 0 to 21. Supplementing phytase at 561, 1,285, or >2,000 FTU/kg resulted in the maximum FI, BWG, or feed efficiency, respectively. From day 0 to 42, maximum BWG or feed efficiency were achieved at phytate P concentrations <0.281 or 0.25%, respectively. Supplementing phytase at 449 or 2,000 FTU/kg maximized BWG or feed efficiency, respectively. Tibia ash weight, percent or Ca concentration were maximized at phytate P concentrations <0.24, 0.296, or 0.24%, respectively and phytase supplementation at 822 or >2,000 FTU/kg maximized tibia ash weight or percent respectively. In the absence of phytase, phytate (IP6) concentration in the gizzard was greatest in birds fed 0.45% phytate P and phytase supplementation between 1,132 to 1,285 FTU/kg resulted in the lowest IP6 concentration in the gizzard. There was no effect of dietary phytate P on the concentration of phytate esters (IP5 or IP4) in the gizzard, which were minimized at 1,208 FTU/kg of phytase. In the absence of phytase, the concentration of phytate ester (IP3) or inositol in the gizzard was greatest in birds fed 0.345% phytate P and phytase supplementation at ∼500 FTU/kg minimized IP3, whereas 2,000 FTU/kg maximized inositol, except in birds fed 0.45% phytate P, which was maximized at 202 FTU/kg of phytase. Prediction equations can be useful to determine the influence of phytase and phytate P on broiler performance, phytate degradation and bone ash., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Cobb 400, male broilers (n = 4,752) were housed in 12 pens/diet and 33 birds/pen. There were 3 levels of phytate P (0.24, 0.345, or 0.45%) and 4 phytase doses (0, 500, 1,000 or 2,000 phytase units (FTU)/kg) to evaluate the influence of phytate and phytase dose on apparent ileal digestibility (AID) and digestible nutrient intake. Diets were formulated with reduced Ca (0.22%), available P (0.20%), energy (80 to 120 kcal/kg) and amino acids (1 to 5%). On day 21, digesta was collected from 8 birds/pen. Prediction equations determined the linear or non-linear influence of phytate P, log phytase dose, and the interaction. The AID of amino acids, Ca or P and digestible amino acid or Ca intake were influenced by linear or non-linear phytate P × log phytase dose (P < 0.0001). Increasing the dietary phytate P from 0.24 to 0.345 or 0.45% was predicted to reduce the AID of amino acids in a non-linear manner by an average of 6 to 7 percentage points, respectively. This corresponded to a non-linear decrease in digestible amino acid intake of an average of 80 to 90 mg/D. The negative effect of increasing dietary phytate P from 0.24 to 0.45% on AID was greatest for cysteine (-14 percentage points), aspartic acid or glycine (-9 percentage points) and lowest for methionine, tryptophan, serine, or glutamic acid (-5 percentage points). The predicted digestible intake of lysine (-120 mg/D), aspartic acid (-180 mg/D), or glutamic acid (-290 mg/D) were reduced in birds fed diets containing 0.345% vs. 0.24% phytate P. Phytase supplementation was predicted to increase the AID of amino acids, Ca, or P in a non-linear-log or log-linear manner at all levels of phytate P, with the greatest response at higher doses of phytase in diets containing 0.345 or 0.45% phytate P. The effect of phytase on digestible nutrient intake was less clear. Prediction equations can be useful to determine the influence of phytase and phytate P on AID and digestible nutrient intake in broilers., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Phytic acid, a constituent of various plants, has been related to health benefits. Phytic acid has been shown to inhibit purine nucleotide metabolism in vitro and suppress elevation of plasma uric acid levels after purine administration in animal models. This study investigated the effect of phytic acid on postprandial serum uric acid (SUA) in humans. This randomized, double-blind, crossover design study included 48 healthy subjects with normal fasting SUA. Subjects consumed a control drink and a phytic acid drink with purine-rich food, and serum and urine uric acid levels were measured for 360 min after purine loading. Phytic acid lowered the incremental area under the curve (0-360 min) and incremental maximum concentration of SUA after purine loading ( p  < 0.05); tended to lower cumulative urinary uric acid excretion (0-360 min) after purine loading ( p  < 0.10); and suppressed postprandial SUA in this clinical study. Altogether, our findings suggest that phytic acid may play a beneficial role in controlling postprandial SUA.

Phytate (myo-inositol hexaphosphate, InsP6) is an important component of seeds, legumes, nuts, and whole cereals. Although this molecule was discovered in 1855, its biological effects as an antinutrient was first described in 1940. The antinutrient effect of phytate results because it can decrease the bioavailability of important minerals under certain circumstances. However, during the past 30 years, researchers have identified many important health benefits of phytate. Thus, 150 years have elapsed since the discovery of phytate to the first descriptions of its beneficial effects. This long delay may be due to the difficulty in determining phytate in biological media, and because phytate dephosphorylation generates many derivatives (InsPs) that also have important biological functions. This paper describes the role of InsP6 in blocking the development of pathological calcifications. Thus, in vitro studies have shown that InsP6 and its hydrolysates (InsPs), as well as pyrophosphate, bisphosphonates, and other polyphosphates, have high capacity to inhibit calcium salt crystallization. Oral or topical administration of phytate in vivo significantly decreases the development of pathological calcifications, although the details of the underlying mechanism are uncertain. Moreover, oral or topical administration of InsP6 also leads to increased urinary excretion of mixtures of different InsPs; in the absence of InsP6 administration, only InsP2 occurs at detectable levels in urine.

Objective: To evaluate the urinary levels of inositol phosphates (InsPs) in rats that received different salts of myo-inositol hexaphosphate (InsP6) by gavage or by oral administration., Methods: Thirty rats received AIN-76A diet (in which InsPs are undetectable) for 15 days. Then, 12 rats received InsP6 by gavage as a Na salt or a Ca/Mg salt; after 4 days, the Na or Ca/Mg InsP6 was administered with water containing 15 g/L sucrose and urine samples were collected. The other 18 rats received oral InsP6, in which 0.5 g of sugar was combined with InsP6 as a Na salt, a Ca/Mg salt, or a Na salt with CaCO3; daily urine samples were collected. Urine levels of InsPs were determined using a nonspecific method and a specific method (polyacrylamide gel electrophoresis, PAGE), and different InsPs were identified by mass spectroscopy (MS)., Results: After 15 days of the InsP6-free diet, the non-specific method detected no urinary InsPs, and MS detected only InsP2. After administration of Na-InsP6 by gavage, the non-specific method indicated more urinary InsPs than the amount of InsP6 determined by PAGE. MS indicated the presence of urinary InsP2, InsP3, InsP4, InsP5, and InsP6 in these rats, with notable variations among animals. Use of the same treatment to administer Ca/Mg-InsP6 led to a lower overall content of urinary InsPs and a lower level of InsP6. Oral administration of InsP6 as a sugar pill led to lower urinary levels of InsPs than administration of InsP6 by gavage, and administration as a Ca/Mg pill or a Ca/Mg pill with CaCO3 led to lower levels than administration as a Na pill., Conclusion: Administration of InsP6 to rats leads to the excretion of a mixture of different InsPs. Rats more effectively absorb InsP6 when supplied without dietary components that interfere with its uptake, such as the Ca ion and sugar., Competing Interests: The authors have declared that no competing interests exist.

Among the 10 leading causes of death in developed countries are chronic non-communicable diseases (NCDs). The effect of these multifactorial diseases on public health has stimulated considerable research aimed at investigating their primary risk factors (genetic factors, stress, food intake, and amount of physical exercise). Thus, healthful foods (e.g., fruits, vegetables, oils, grains, and seeds) are sources of bioactive compounds that promote good health and disease prevention. Among their components are non-caloric substances identified as non-nutrients (polyphenols, phytosterols, saponins, and phytates), which have been found to have a role in modulating metabolic pathways, maintaining health, and preventing NCDs. The aim of this study is to demonstrate and review the performance of some non-nutrients, such as their antioxidant and anti-inflammatory action, modulation of the antiatherogenic lipid profile (higher high-density lipoprotein cholesterol, lower oxidized low-density lipoprotein, and triacylglycerols), reduction of glucose and fat intestinal absorption, increase in insulin sensitivity, and stimulation of nitic oxide synthesis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Calciphylaxis in end-stage renal disease is characterized by painful necrotic skin ulcers and high mortality. There are no approved therapies. SNF472, an intravenous formulation of myo-inositol hexaphosphate, inhibits the formation and growth of hydroxyapatite crystals, the final common pathway in the pathogenesis of vascular calcification., Methods: In this open-label, single-arm study, calciphylaxis patients on thrice-weekly hemodialysis and standard care, received intravenous SNF472 3 times per week for 12 weeks. The primary endpoint was wound healing assessed using the quantitative Bates-Jensen Wound Assessment Tool (BWAT). Pain visual analog scale (VAS), quality of life (wound-QoL), and qualitative wound image review were secondary endpoints. Quantitative changes from baseline were analyzed by paired t-tests using multiple imputation to account for missing observations., Results: Fourteen patients received SNF472. Improvements from baseline to week 12 were observed for mean BWAT score (- 8.1; P < 0.001), pain VAS (- 23.6 mm; P = 0.015) and wound-QoL global score (- 0.90; P = 0.003). Of the 9 patients with ulcerated lesions at baseline who completed treatment, wound image review showed improvement for 7. SNF472 was well tolerated with no serious treatment-related adverse events. The most common adverse events were infections which occur frequently in patients on hemodialysis. None of these were considered as treatment-related., Conclusions: SNF472 was well-tolerated and improvements from baseline to week 12 in wound healing, pain, and quality of life were observed. A randomized, double-blind, placebo-controlled trial is planned to evaluate SNF472 in patients with calciphylaxis.

Phytic acid (PA) is one of the most common anti-nutritional factors in plant-derived protein feeds, and it poses considerable threats to aquaculture production. However, little is known about the effects of PA on fish intestinal health. This study aimed to investigate the impacts of PA on intestinal immune function in on-growing grass carp. To achieve this goal, a growth trial was conducted for 60 days by feeding 540 fish (120.56 ± 0.51 g) with six semi-purified diets containing graded levels of PA (0, 0.8, 1.6, 2.4, 3.2 and 4.0%). Then fish were challenged with Aeromonas hydrophila for 6 days. The results indicated that, compared with the control group (0% PA), PA did the following: (1) suppressed fish growth performance (percentage weight gain and feed efficiency) and reduced their ability to resist enteritis; (2) decreased fish intestinal antimicrobial ability by reducing intestinal lysozyme (LZ) activities, the contents of complement 3 (C3), C4 and immunoglobulin M (IgM), and downregulating the mRNA levels of hepcidin, liver-expressed antimicrobial peptide 2A (LEAP-2A), LEAP-2B, and β-defensin-1; and (3) aggravated fish intestinal inflammation responses by upregulating the mRNA levels of pro-inflammatory cytokines including tumour necrosis factor α (TNF-α), interleukin 1β (IL-1β) (except in the DI), interferon γ2 (IFN-γ2), IL-8, IL-12p40, IL-15 (except in the DI) and IL-17D, which is partly related to the nuclear factor kappa B (NF-κB) signalling pathway, whereas downregulating the mRNA levels of anti-inflammatory cytokines including transforming growth factor β1 (TGF-β1), IL-4/13A, IL-4/13B, IL-10 and IL-11, which is partially associated with the target of rapamycin (TOR) signalling pathway. The possible reasons for some distinctive gene expression patterns in fish three intestinal segments were discussed. Finally, based on the percent weight gain, enteritis morbidity, IgM content and LZ activity in the PI, the maximum tolerance levels of PA for on-growing grass carp were estimated to be 2.17, 1.68, 1.47 and 1.18% of the diet, respectively., (Copyright © 2019. Published by Elsevier Ltd.)

A nanocomposite, phytic acid-chitosan-magnetic iron oxide nanoparticles (IP 6 -CS-MNPs) has been used to treat colon cancer in vitro, previously. However, its potential toxicity in vivo has yet to be elucidated. Hence, the present study aimed to evaluate the acute effects of oral administration of IP 6 -CS-MNPs in mice. In this study, 1000 and 2000 mg/kg body weight (b.w) of IP 6 -CS-MNPs were orally administered to two different groups of BALB/c mice, once. Additionally, the mice in the control group were given only deionized water. After 14 days of post-IP 6 -CS-MNPs administration, in a similar way to the untreated mice, the treated mice showed no sign of mortality and abnormalities. However, the serum urea level of mice receiving 2000 mg/kg b.w of IP 6 -CS-MNPs was significantly higher than the control group ( p < 0.05). The mice that received 1000 mg/kg IP 6 -CS-MNPs showed a significantly higher level of serum alkaline phosphatase (ALP) compared to the control group. However, there were no significant histopathological changes seen in the liver and kidneys of treated mice compared to the untreated group.

Phytic acid has anti-oxidant properties, which are useful in addressing inflammation. This study investigated the relationship between dietary phytate intake and C-reactive protein (CRP) levels among individuals that are overweight or obese. The study used cross-sectional data from the 2009/2010 National Health and Nutrition Examination Survey (NHANES) for 3152 subjects. Phytate intake was estimated using phytate content of foods reported by the International Zinc Nutrition Consultative Group (IZiNCG). Logistic regression was used to determine the associations between phytate intake and odds of elevated CRP concentration (CRP >3 mg/L), adjusting for confounders. Medians (and 95% CIs) for phytate intake and CRP concentration were 0.66 (0.64, 0.68) g/d and 1.4 (1.2, 1.5) mg/L, respectively. Phytate intake was higher in males than females, higher in non-Hispanic Whites than non-Hispanic Blacks and Mexican Americans, and lower in current smokers than former smokers and nonsmokers. Higher phytate intake was associated with lower odds of elevated CRP (OR = 0.66; 95% CI = 0.52, 0.84). Women, as well as current and former smokers with overweight or obesity, had higher odds of elevated CRP concentration. These results imply that individuals with high phytate intake, particularly among those with overweight or obesity, have lower risk for inflammation-related chronic diseases such as cardiovascular diseases.

Many mechanistic studies have been performed to analyze the cellular functions of the highly phosphorylated molecule inositol hexakisphosphate (InsP 6 ) in health and disease. While the physiological intracellular functions are well described, the mechanism of potential pharmacological effects on cancer cell proliferation is still controversial. There are numerous studies demonstrating that a high InsP 6 concentration (≥75 µM) inhibits growth of cancer cells in vitro and in vivo. Thus, there is no doubt that InsP 6 exhibits anticancer activity but the mechanism underlying the cellular effects of extracellular InsP 6 on cancer cells is far from being understood. In addition, studies on the inhibitory effect of InsP 6 on cancer progression in animal models ignore aspects of its bioavailability. Here, we review and critically discuss the uptake mechanism and the intracellular involvement in signaling pathways of InsP 6 in cancer cells. We take into account the controversial findings on InsP 6 plasma concentration, which is a critical aspect of pharmacological accessibility of InsP 6 for cancer treatment. Further, we discuss novel findings with respect to the effect of InsP 6 on normal and immune cells as well as on platelet aggregate size. Our goal is to stimulate further mechanistic studies into novel directions considering previously disregarded aspects of InsP 6 . Only when we fully understand the mechanism underlying the anticancer activity of InsP 6 novel and more efficient treatment options can be developed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To investigate the effects of eating wholegrain rye bread with high or low amounts of phytate on iron status in women under free-living conditions., Methods: In this 12-week, randomized, parallel-design intervention study, 102 females were allocated into two groups, a high-phytate-bread group or a low-phytate-bread group. These two groups were administered: 200 g of blanched wholegrain rye bread/day, or 200 g dephytinized wholegrain rye bread/day. The bread was administered in addition to their habitual daily diet. Iron status biomarkers and plasma alkylresorcinols were analyzed at baseline and post-intervention., Results: Fifty-five females completed the study. There was a significant difference in change over time in total body iron stores between the two groups (p < 0.035). In the low-phytate bread group (n = 24) there were significant within-group decreases in both ferritin (mean 12%; from 32 ± 7 to 27 ± 6 μg/L, geometric mean ± SEM, p < 0.018) and total body iron (mean 12%; from 6.9 ± 1.4 to 5.4 ± 1.1 mg/kg, p < 0.035). Plasma alkylresorcinols indicated that most subjects complied with the intervention, Conclusions: In Swedish females of reproductive age, no statistically significant difference in iron status was detected after 12 weeks of high-phytate wholegrain bread consumption. However, consumption of low-phytate wholegrain bread for 12 weeks resulted in a reduction of markers of iron status. Although single-meal studies clearly show an increase in iron bioavailability from dephytinization of cereals, medium-term consumption of reduced phytate bread under free-living conditions suggests that this strategy does not work to improve iron status in healthy women of reproductive age.

Phytic acid (PA) has momentous chemotherapeutic potential. Due to the chelate formation and rapid elimination, it is not popular in cancer treatment. The present work was inquested to develop a surface-modified nanoformulation of PA which prevents its speedy elimination and maximizes chemotherapeutic action. Chloroauric acid was reduced with pectin to produce pectin-gold nanoparticles (PGNPs). PGNPs were incubated with PA and jacalin for drug loading and surface modifications, respectively, to form PA-loaded jacalin-pectin-gold nanoparticles (PA-J-PGNPs). Formulation(s) were assessed for various pharmaceutical/pharmacological parameters. To validate the efficacy against colon carcinogenesis, formulation(s) were assessed in 1,2-dimethylhydrazine (DMH)-treated Wistar rats. DMH treatment distorted colonic architecture, oxidative, and hemodynamic parameters, which were favorably restored by PA-J-PGNP administration. To further confirm our deliberations, formulation(s) were also examined against DMH-altered metabolic changes and expression of markers pertaining to cellular proliferation, which was reinstated by PA-J-PGNPs. Our findings establish PA formulation(s) as a promising approach for suppression of colon carcinogenesis.

Clostridium difficile causes increasing numbers of life-threatening intestinal infections. Symptoms associated with C. difficile infection (CDI) are mediated by secreted protein toxins, whose virulence is modulated by intracellular auto-proteolysis following allosteric activation of their protease domains by inositol hexakisphosphate (IP6). Here, we explore the possibility of inactivating the C. difficile toxin B (TcdB) by triggering its auto-proteolysis in the gut lumen prior to cell uptake using gain-of-function small molecules. We anticipated that high calcium concentrations typically found in the gut would strongly chelate IP6, precluding it from pre-emptively inducing toxin auto-proteolysis if administered exogenously. We therefore designed IP6 analogs with reduced susceptibility to complexation by calcium, which maintained allosteric activity at physiological calcium concentrations. We found that oral administration of IP6 analogs attenuated inflammation and promoted survival in mouse models of CDI. Our data provide impetus to further develop small-molecule allosteric triggers of toxin auto-proteolysis as a therapeutic strategy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The study was conducted to distinguish the effect of dietary non-phytate phosphorus (NPP) levels on the community diversity and structure of the cecal microbiota in meat duck based on 16S rDNA high-throughput sequencing. In total, 525 1-d-old ducklings were fed diets (105 ducklings, 7 pens of 15 ducklings, on each diet) containing five levels of NPP (0.22, 0.34, 0.40, 0.46, and 0.58%) for 21 days. The results showed that dietary NPP levels linearly and quadratically increased (P < 0.05) 21 d body weight, 1 to 21 d feed intake and NPP intake, and contrarily, linearly decreased (P < 0.05) β-diversity of cecal microbial population in ducks. ß-diversity analyses showed that microbiota clustering based on dietary NPP levels occured, with 0.22% NPP groups distinctly different from the 0.46% and 0.58% NPP group samples. Moreover, dietary NPP levels could change the relative abundance of the phylum Proteobacteria (linear, P < 0.05), genera Eubacterium coprostanoligenes (quadratic, P < 0.05), Ruminococcaceae UCG-014 (quadratic, P < 0.05) and Subdoligrannulum (linear, P < 0.05), and Lachnospiraceae family (quadratic, P < 0.05) in cecal microbiota of ducks. Increasing the dietary NPP level influenced the cecal microbiota and positively affected the growth of meat ducks.

Background: Cardiovascular calcification (CVC) is a major concern in hemodialysis (HD) and the loss of endogenous modulators of calcification seems involved in the process. Phytate is an endogenous crystallization inhibitor and its low molecular mass and high water solubility make it potentially dialyzable. SNF472 (the hexasodium salt of phytate) is being developed for the treatment of calciphylaxis and CVC in HD patients. We aimed to verify if phytate is lost during dialysis, and evaluate SNF472's behaviour during dialysis., Methods: Dialyzability was assessed in vitro using online-hemodiafiltration and high-flux HD systems in blood and saline. SNF472 was infused for 20 min and quantified at different time points., Results: Phytate completely dialyzed in 1 h at low concentrations (10 mg/l) but not when added at 30 or 66.67 mg/l SNF472. In bypass conditions, calcium was slightly chelated during SNF472 infusion but when the system was switched to dialysis mode the calcium in the bath compensated this chelation., Conclusion: Phytate dialyses with a low clearance. The administration of SNF472 as an exogenous source of phytate allows to attain supra-physiological levels required for its potential therapeutic properties. As SNF472 is infused during the whole dialysis session, the low clearance would not affect the drug's systemic exposure.

Aims: Previous studies demonstrated a remarkable increase of urinary InsP 6 by topical administration. However, the methodology used for InsP 6 analysis was not specific. The aim of this paper is to measure urinary inositol phosphates InsPs using more advanced methodologies and to compare the results with those obtained by the non-specific method., Materials and Methods: We fed 12 female rats with a diet without InsP 6 for 16days. Then, we administered a topical InsP 6 gel at high doses for 7days (50mgInsP 6 /day) or at low doses for 28days (20mgInsP 6 /day). We measured urine levels InsPs using a nonspecific method (based on the ability of InsPs to complex Al 3+ ) and levels of InsP 6 by a specific method (using polyacrylamide gel electrophoresis). Identification of different InsPs was performed by MS., Key Findings: At baseline, after dietary deprivation of InsP 6 , rats only excreted InsP 2 in their urine, and there was no detectable InsP 6 or other InsPs. Rats given the high dose treatment for 7days had abundant urinary InsP 6 , but also had other InsPs in their urine; cessation of InsP 6 administration led to decreased levels of urinary InsPs. Rats given the low dose treatment for 28days had increasing levels of urinary InsPs over time. The maximum urinary InsP 6 was at 21days, after which InsPs excretion decreased., Significance: We conclude that the skin can absorb InsP 6 from a topical gel, and that InsP 6 is excreted in the urine, along with other InsPs (InsP 5 , InsP 4 , InsP 3 , and InsP 2 )., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Diabetes mellitus, as a result of microvascular and macrovascular injury, causes organ dysfunction in a wide variety of tissues. The objective of this study was to investigate the effect of combined inositol hexakisphosphate and inositol supplement on renal and pancreatic integrity in type 2 diabetic rats. Thirty male Sprague-Dawley rats were divided into five groups (n=6 per group). Type 2 diabetes was induced in three groups using high-fat diet combined with a single dose of streptozotocin (35mg/kg body weight, intraperitoneally). Two of the diabetic groups were treated with combined IP6 and inositol or glibenclamide. Serum biochemical markers of kidney damage kidney, antioxidant status (superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) and lipid peroxidation were measured. Histomorphological and morphometric examinations of the H&E stained pancreas were also carried out. The administration of combined IP6 and inositol supplement resulted in 64% and 27% increase in CAT activities and GSH levels respectively and a 25% decrease in lipid peroxidation level compared to the diabetic control. Serum uric acid, creatinine and BUN levels in the combination treated group was comparable to the normal control. Examination of H&E stained pancreatic sections showed a significant increase (107%) in the number of islets in the combined IP6 and inositol treated group compared to the untreated diabetic group. Overall, the treatment of type 2 diabetic rats with combined IP6 and inositol supplement resulted in the improvement of renal and pancreatic function., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Purpose: Zinc is essential for normal growth and metabolism. We aimed to characterise the total and bioavailable dietary zinc intake and plasma zinc concentrations in healthy children, longitudinally, and to examine the association between plasma zinc concentrations, dietary zinc intake and cardiometabolic markers in the same cohort., Methods: A secondary data analysis of a prospective cohort study, the Nepean Longitudinal Study, which followed an Australian birth cohort at ages 8 (n = 436) and 15 years (n = 290) collecting dietary, anthropometry and biochemistry data (plasma zinc, fasting glucose, insulin and lipid profile). Diet was assessed by a 3-day food record and a food frequency questionnaire at 8 and 15 years, respectively. Zinc bioavailability was determined by the phytate/zinc molar ratio., Results: At 8 years, the median zinc intake was 7.84 mg (interquartile range 6.57-9.35) for boys and 7.06 mg (5.98-8.30) for girls. Three of 345 children reported inadequate absorbable zinc intake, and none reported inadequate total zinc intake. At 15 years, median zinc intake was 11.8 mg (9.41-14.8) for boys and 8.54 mg (6.76-10.7) for girls. The prevalence of inadequate intakes of absorbable zinc and total zinc was 19 and 29 %, respectively. Plasma zinc concentration was not correlated with dietary zinc intake, adiposity nor lipids at either time point, but it was inversely correlated with fasting glucose at 8 year and with insulin at 15 years., Conclusions: Australian children had an overall adequate zinc status. However, adolescents who reported suboptimal dietary zinc intakes were more likely to have raised insulin concentrations.

Background: Milk has been suggested to increase zinc absorption. The effect of processing and the ability of milk to enhance zinc absorption from other foods has not been measured directly in humans. Objective: We aimed to assess zinc absorption from 1 ) milk undergoing various processing and preparatory steps and 2 ) from intrinsically labeled high-phytate rice consumed with milk or water. Methods: Two randomized crossover studies were conducted in healthy young women [age:18-25 y; body mass index (in kg/m 2 ): 20-25]: 1 ) a milk study ( n = 19) comparing the consumption of 800 mL full-fat ultra-high temperature (UHT) milk [heat-treated milk (HTM)], full-fat UHT milk diluted 1:1 with water [heat-treated milk and water (MW)], water, or unprocessed (raw) milk (UM), each extrinsically labeled with 67 Zn, and 2 ) a rice study ( n = 18) comparing the consumption of 90 g intrinsically 67 Zn-labeled rice with 600 mL of water [rice and water (RW)] or full-fat UHT milk [rice and milk (RM)]. The fractional absorption of zinc (FAZ) was measured with the double-isotope tracer ratio method. In vitro, we assessed zinc extraction from rice blended into water, UM, or HTM with or without phytate. Results: FAZ from HTM was 25.5% (95% CI: 21.6%, 29.4%) and was not different from UM (27.8%; 95% CI: 24.2%, 31.4%). FAZ from water was higher (72.3%; 95% CI: 68.7%, 75.9%), whereas FAZ from MW was lower (19.7%; 95% CI: 17.5%, 21.9%) than HTM and UM (both P < 0.01). FAZ from RM (20.7%; 95% CI: 18.8%, 22.7%) was significantly higher than from RW (12.8%; 95% CI: 10.8%, 14.6%; P < 0.01). In vitro, HTM and UM showed several orders of magnitude higher extraction of zinc from rice with HTM than from rice with water at various phytate concentrations. Conclusions: Milk enhanced human FAZ from high-phytate rice by 62% compared with water. Diluting milk with water decreases its absorption-enhancing proprieties, whereas UHT processing does not. This trial was registered at the Dutch trial registry as NTR4267 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4267)., Competing Interests: 2: Author disclosures: EF Talsma, D Moretti, SC Ly, E Boelsma, TJ Stomph, C Zeder, and A Melse-Boonstra, no conflicts of interest. R Dekkers and EGHM van den Heuvel are employees at Friesland-Campina. A Fitri conducted the in vitro studies as an internship student at Friesland-Campina., (© 2017 American Society for Nutrition.)

Objective: Oral treatment with inositol hexaphosphate (InsP6) has shown to be efficient in decreasing adverse effects in patients with breast cancer under chemotherapy. This study was aimed at evaluating and comparing the efficacy of topical InsP6 in improving quality of life in women treated with anticancer drugs., Patients and Methods: The study was a double-blind, randomized controlled trial (RCT) with allocation concealment of 20 patients in two groups, one (experimental) applied 4% topical formulation of InsP6 once a day, whereas the second one (control) a gel containing hyaluronic acid. InsP6 therapy started 6 weeks after lumpectomy. Blood tests were monitored in both groups and quality of life was assessed using standardized QLQ-C30 and QLQ-BR23., Results: Patients who applied InsP6 on the breast significantly improved their quality of life and functional status reducing side effects compared to control group; moreover, after treatment, a significant difference between the two groups was observed in the white blood cells and platelets count values., Conclusions: Topical InsP6 treatment has demonstrated to be effective and safe in preventing and/or mitigating chemotherapy-induced side effects as well as the preserving quality of life in women with ductal breast cancer.

Background: Estimated physiologic requirements (PRs) for zinc increase in late pregnancy and early lactation, but the effect on dietary zinc requirements is uncertain. Objective: The aim of this study was to determine changes in daily fractional absorbed zinc and total absorbed zinc (TAZ) from ad libitum diets of differing phytate contents in relation to physiologic zinc requirements during pregnancy and lactation. Methods: This was a prospective observational study of zinc absorption at 8 (phase 1) and 34 (phase 2) wk of gestation and 2 (phase 3) and 6 (phase 4) mo of lactation. Participants were indigenous Guatemalan women of childbearing age whose major food staple was maize and who had been randomly assigned in a larger study to either of 2 ad libitum feeding groups: low-phytate maize (LP; 1.6 mg/g; n = 14) or control maize (C; 7.1 mg/g; n = 8). Total dietary zinc (milligrams per day, TDZ) and phytate (milligrams per day) were determined from duplicate diets and fractional absorption (FAZ) by dual isotope ratio technique (TAZ = TDZ × FAZ). All variables were examined longitudinally and by group and compared with PRs. TAZ values at later phases were compared with phase 1. Measured TAZ was compared with predicted TAZ for nonpregnant, nonlactating (NPNL) women. Results: TAZ was greater in the LP group than in the C group at all phases. All variables increased from phase 1 to phases 2 and 3 and declined at phase 4. TAZ increased by 1.25 mg/d ( P = 0.045) in the C group and by 0.81 mg/d ( P = 0.058) in the LP group at phase 2. At phase 3, the increases were 2.66 mg/d ( P = 0.002) in the C group and 2.28 mg/d ( P = 0.0004) in the LP group, compared with a 1.37-mg/d increase in PR. Measured TAZ was greater than predicted values in phases 2-4. Conclusions: Upregulation of zinc absorption in late pregnancy and early lactation matches increases in PRs of pregnant and lactating women, regardless of dietary phytate, which has implications for dietary zinc requirements of pregnant and lactating women., Competing Interests: 2: Author disclosures: KM Hambidge, LV Miller, M Mazariegos, J Westcott, NW Solomons, V Raboy, JF Kemp, A Das, N Goco, T Hartwell, L Wright, and NF Krebs, no conflicts of interest., (© 2017 American Society for Nutrition.)

Chitosan (CS) iron oxide magnetic nanoparticles (MNPs) were coated with phytic acid (PTA) to form phytic acid-chitosan-iron oxide nanocomposite (PTA-CS-MNP). The obtained nanocomposite and nanocarrier were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, vibrating sample magnetometry, transmission electron microscopy, and thermogravimetric and differential thermogravimetric analyses. Fourier transform infrared spectra and thermal analysis of MNPs and PTA-CS-MNP nanocomposite confirmed the binding of CS on the surface of MNPs and the loading of PTA in the PTA-CS-MNP nanocomposite. The coating process enhanced the thermal stability of the anticancer nanocomposite obtained. X-ray diffraction results showed that the MNPs and PTA-CS-MNP nanocomposite are pure magnetite. Drug loading was estimated using ultraviolet-visible spectroscopy and showing a 12.9% in the designed nanocomposite. Magnetization curves demonstrated that the synthesized MNPs and nanocomposite were superparamagnetic with saturation magnetizations of 53.25 emu/g and 42.15 emu/g, respectively. The release study showed that around 86% and 93% of PTA from PTA-CS-MNP nanocomposite could be released within 127 and 56 hours by a phosphate buffer solution at pH 7.4 and 4.8, respectively, in a sustained manner and governed by pseudo-second order kinetic model. The cytotoxicity of the compounds on HT-29 colon cancer cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The HT-29 cell line was more sensitive against PTA-CS-MNP nanocomposite than PTA alone. No cytotoxic effect was observed on normal cells (3T3 fibroblast cells). This result indicates that PTA-CS-MNP nanocomposite can inhibit the proliferation of colon cancer cells without causing any harm to normal cell., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Food fortification has been recommended to improve a population's micronutrient status. Biofortification techniques modestly elevate the zinc content of cereals, but few studies have reported a positive impact on functional indicators of zinc status., Objective: We determined the impact of a modest increase in dietary zinc that was similar to that provided by biofortification programs on whole-body and cellular indicators of zinc status., Design: Eighteen men participated in a 6-wk controlled consumption study of a low-zinc, rice-based diet. The diet contained 6 mg Zn/d for 2 wk and was followed by 10 mg Zn/d for 4 wk. To reduce zinc absorption, phytate was added to the diet during the initial period. Indicators of zinc homeostasis, including total absorbed zinc (TAZ), the exchangeable zinc pool (EZP), plasma and cellular zinc concentrations, zinc transporter gene expression, and other metabolic indicators (i.e., DNA damage, inflammation, and oxidative stress), were measured before and after each dietary-zinc period., Results: TAZ increased with increased dietary zinc, but plasma zinc concentrations and EZP size were unchanged. Erythrocyte and leukocyte zinc concentrations and zinc transporter expressions were not altered. However, leukocyte DNA strand breaks decreased with increased dietary zinc, and the level of proteins involved in DNA repair and antioxidant and immune functions were restored after the dietary-zinc increase., Conclusions: A moderate 4-mg/d increase in dietary zinc, similar to that which would be expected from zinc-biofortified crops, improves zinc absorption but does not alter plasma zinc. The repair of DNA strand breaks improves, as do serum protein concentrations that are associated with the DNA repair process. This trial was registered at clinicaltrials.gov as NCT02861352., (© 2017 American Society for Nutrition.)

Radioactive nuclides leak into the surrounding environment after nuclear power plant disasters, such as the Chernobyl accident and the Fukushima Daiichi Nuclear Power Plant disaster. Cesium-137 ( 137 Cs) (t 1/2 =30.1 year), a water-soluble radionuclide with a long physical half-life, contaminates aquatic ecosystems and food products. In humans, 137 Cs concentrates in muscle tissue and has a long biological half-life, indicating it may be harmful. myo-Inositol-hexakisphosphate (IP6) is a compound found in grain, beans, and oil seeds. IP6 has the ability to form insoluble complexes with metals, including lanthanum (La) and zinc (Zn). We hypothesized that La-IP6 and Zn-IP6 may promote the elimination of 137 Cs from the body through the adsorption of La-IP6 and Zn-IP6 to 137 Cs in the gastrointestinal tract. Therefore, in this study, we evaluated the adsorptive capacity of La-IP6 and Zn-IP6 complexes with 137 Cs in vitro and in vivo. La-IP6 and Zn-IP6 complexes were stable in acidic solution (pH 1.2) at 37°C. In vitro binding assays indicated that La-IP6 and Zn-IP6 complexes adsorbed 137 Cs, with the adsorption capacity of Zn-IP6 to 137 Cs greater than that of La-IP6. To evaluate the usefulness of La-IP6 and Zn-IP6 in vivo, La-IP6 or Zn-IP6 was administrated to mice after intravenous injection of 137 Cs. However, the biodistribution of 137 Cs in the La-IP6 treated group and the Zn-IP6 treated group was nearly identical to the non-treated control group, indicating that La-IP6 and Zn-IP6 were not effective at promoting the elimination of 137 Cs in vivo.

1. Five hundred and seventy six-d old Ross 308 broiler chicks (6 cages per diet, 8 birds per cage in 3 × 2 × 2 factorial arrangement) were fed on maize-soybean meal-based diets containing three concentrations of Ca (6, 8 or 10 g/kg), two concentrations of non-phytate phosphorus (NPP) (3 or 4 g/kg) and two levels of exogenous microbial phytase (0 or 500 FTU/kg) from d 0 to 35. 2. Body weight (BW), feed intake (FI) and mortality records were collected. Two birds per replicate were killed at 24 d of age to obtain tibia samples. 3. Increasing Ca level significantly reduced the FI and body weight gain (BWG) between hatch and 10 and 24 d, especially with the phytase-supplemented diets. However, phytase supplementation of the diet containing 4 g NPP/kg improved the FI and BWG at d 10 and 24. At d 24, phytase supplementation improved feed conversion ratio (FCR) of birds that consumed diets containing high NPP. The overall FCR was better in birds offered the phytase-supplemented, medium-Ca diet. 4. There was a significant reduction in length, width and breaking strength of the tibia bone in birds fed on a diet with high Ca and low NPP. Phytase supplementation improved the tibia ash content and bone breaking strength of chicks fed on the diet containing 8 and 4 g/kg Ca and NPP, respectively. The Ca content of the tibia bone was low in birds fed on diets with 6 and 4 g/kg Ca and NPP, respectively, but this was counteracted by phytase supplementation. 5. Birds fed on diets with 4 g/kg NPP had the best carcass percentage and parts yield. Phytase supplementation to high-Ca diets significantly reduced the carcass yield of birds. 6. These results confirmed the detrimental effect of high dietary Ca on phytase activity and subsequent growth and bone development of birds, especially when NPP is in short supply.

Background: Experience on sentinel node mapping in ovarian tumors is very limited. We evaluated the sentinel node concept in ovarian tumors using intra-operativeTc-99m-Phytate injection and lymphoscintigraphy imaging., Methods: Thirty-five patients with a pelvic mass due to an ovarian pathology were included in the study. The radiotracer was injected just after laparotomy and before removal of the tumor either beneath the normal cortex (10 patients) or in the utero-ovarian and suspensory ligaments of the ovary just beneath the peritoneum two injections of the radiotracer (25 patients). For malignant masses, the sentinel nodes were identified using a hand held gamma probe. Then standard pelvic and para-aortic lymphadenectomy was performed. In case of benign pathologies or borderline ovarian tumors on frozen section, lymphadenectomy was not performed. The morning after surgery, all patients were sent for lymphoscintigraphy imaging of the abdomen and pelvis., Results: Sentinel node was identified only in 4 patients of the cortical injection group. At least one sentinel node could be identified in 21 patients of the sub-peritoneal group. Sentinel nodes were identified only in the para-aortic area in 21, pelvic/para-aortic areas in 2, and pelvic only area in 2 patients. Three patients had lymph node involvement and all had involved sentinel nodes (no false negative case)., Conclusion: Sentinel node mapping using intra-operative injection of the radiotracer (in the utero-ovarian and suspensory ligaments of the ovary just beneath the peritoneum) is feasible in ovarian tumors. Technical aspects of this method should be explored in larger multicenter studies in the future.

Objective: The aim of this study was to evaluate the relationship between physiological levels of myo-inositol hexaphosphate (phytate) and cardiovascular (CV) calcification in patients with chronic kidney disease (CKD)., Design and Methods: This was a prospective cross-sectional study conducted from December 2012 to June 2013., Subjects: Sixty-nine consecutive patients with CKD who were not undergoing renal replacement therapy., Intervention: All subjects were given lateral lumbar X-rays to quantify abdominal aortic calcification (AAC). Clinical laboratory analyses and phytate food frequency questionnaires were also performed., Main Outcome Measure: Phytate urinary excretion, estimated phytate consumption (based on food frequency questionnaire) and AAC score. Patients were divided into two groups based on median abdominal aortic calcification (AAC) score: no/mild AAC (AAC ≤ 6, n = 35) and moderate/severe AAC (AAC > 6, n = 34)., Results: Patients with no/mild AAC were younger, had lower pulse pressure, greater dietary intake of phytate, greater urinary phytate and the prevalence of prior CV disease was significantly lower compared to patients with moderate/severe AAC. Among the top 10 phytate-rich foods, lentil consumption was significantly greater in patients with no/mild AAC than in those with moderate/severe AAC. Multivariate logistic regression analysis indicated that age, prior CV disease, urinary phytate (or lentil consumption) were independently associated to AAC., Conclusion: Our results suggest that adequate consumption of phytate can prevent AAC in patients with CKD. Further prospective studies must be performed to elucidate the benefits of a phytate-rich diet and the associated risk of phosphorus bioavailability in these patients., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The fractional zinc absorption values used in the current Dietary Reference Intakes (DRIs) for zinc were based on data from published studies. However, the inhibitory effect of phytate was underestimated because of the low phytate content of the diets in the studies used., Objective: The objective of this study was to estimate the fractional absorption of dietary zinc from the US diet by using 2 published algorithms., Methods: Nutrient intake data were obtained from the NHANES 2009-2010 and the corresponding Food Patterns Equivalents Database. Data were analyzed with the use of R software by taking into account the complex survey design. The International Zinc Nutrition Consultative Group (IZiNCG; Brown et al. Food Nutr Bull 2004;25:S99-203) and Miller et al. (Br J Nutr 2013;109:695-700) models were used to estimate zinc absorption., Results: Geometric means (95% CIs) of zinc absorption for all subjects were 30.1% (29.9%, 30.2%) or 31.3% (30.9%, 31.6%) with the use of the IZiNCG model and Miller et al. model, respectively. For men, women, and adolescents, absorption values obtained in this study with the use of the 2 models were 27.2%, 31.4%, and 30.1%, respectively, for the IZiNCG model and 28.0%, 33.0%, and 31.6%, respectively, for the Miller et al. model, compared with the 41%, 48%, and 40%, respectively, used in the current DRIs. For preadolescents, estimated absorption values (31.1% and 32.8% for the IZiNCG model and Miller et al. model, respectively) compare well with the conservative estimate of 30% used in the DRIs. When the new estimates of zinc absorption were applied to the current DRI values for men and women, the results suggest that the Estimated Average Requirement (EAR) and RDA for these groups need to be increased by nearly one-half of the current values in order to meet their requirements for absorbed zinc., Conclusions: These data suggest that zinc absorption is overestimated for men, women, and adolescents in the current DRI. Upward adjustments of the DRI for these groups are recommended., (© 2016 American Society for Nutrition.)