Human Bioavailability Research Articles

Iron from nanostructured ferric phosphate: absorption and biodistribution in mice and bioavailability in iron deficient anemic women

Food fortification with iron nanoparticles (NPs) could help prevent iron deficiency anemia, but the absorption pathway and biodistribution of iron-NPs and their bioavailability in humans is unclear. Dietary non-heme iron is physiologically absorbed via the divalent metal transporter-1 (DMT1) pathway. Using radio- iron isotope labelling in mice with a partial knockdown of intestine-specific DMT1, we assessed oral absorption and tissue biodistribution of nanostructured ferric phosphate (FePO4-NP; specific surface area [SSA] 98 m2g-1) compared to to ferrous sulfate (FeSO4), the reference compound. We show that absorption of iron from FePO4-NP appears to be largely DMT1 dependent and that its biodistribution after absorption is similar to that from FeSO4, without abnormal deposition of iron in the reticuloendothelial system. Furthermore, we demonstrate high bioavailability from iron NPs in iron deficient anemic women in a randomized, cross-over study using stable-isotope labelling: absorption and subsequent erythrocyte iron utilization from two 57Fe-labeled FePO4-NP with SSAs of 98 m2g−1 and 188 m2g−1 was 2.8-fold and 5.4-fold higher than from bulk FePO4 with an SSA of 25 m2g−1 (P < 0.001) when added to a rice and vegetable meal consumed by iron deficient anemic women. The FePO4-NP 188 m2g-1 achieved 72% relative bioavailability compared to FeSO4. These data suggest FePO4-NPs may be useful for nutritional applications.

Uptake and time-dependent subcellular localization of native and micellar curcumin in intestinal cells.

Uptake into intestinal cells and intracellular distribution into metabolically competent organelles, such as the endoplasmic reticulum, are important processes potentially limiting the bioavailability of xenobiotics. The incorporation of curcumin into polysorbate 80 micelles improves its naturally low oral bioavailability in humans. Here, we investigated uptake and time-dependent localization of curcumin in intestinal cells when administered as native or micellar formulation. Differentiated Caco-2 cells were incubated with 200 μmol/L native or micellar curcumin for up to 180 min and cellular uptake was quantified. Intracellular curcumin was detected already after 30 min and did not differ significantly between formulations or over time. Subcellular localization of native and micellar curcumin in Caco-2 cells was studied by density gradient centrifugation. After 30 min, curcumin from both formulations was mainly associated with mitochondria and lysosomes, after 180 min native curcumin was associated with mitochondria and peroxisomes, micellar curcumin with peroxisomes only. Uptake and localization of native and micellar curcumin in intestinal cells do not differ significantly and consequently do not explain differences in bioavailability in humans. The temporary co-localization with lysosomes is in agreement with the previously proposed role of endocytosis in cellular uptake of curcumin and warrants further investigation.

Technological and Biotechnological Processes To Enhance the Bioavailability of Dietary (Poly)phenols in Humans.

The health effects of (poly)phenols (PPs) depend upon their bioavailability that, in general, is very low and shows a high interindividual variability. The low bioavailability of PPs is mainly attributed to their low absorption in the upper gastrointestinal tract as a result of their low water solubility, their presence in foods as polymers or in glycosylated forms, and their tight bond to food matrices. Although many studies have investigated how technological and biotechnological processes affect the phenolic composition of fruits and vegetables, limited information exists regarding their effects on PP bioavailability in humans. In the present review, the effect of food processing (mechanical, thermal, and non-thermal treatments), oral-delivery nanoformulations, enzymatic hydrolysis, fermentation, co-administration with probiotics, and generation of postbiotics in PP bioavailability have been overviewed, focusing in the evidence provided in humans.

Bioavailability Study of Isothiocyanates and Other Bioactive Compounds of Brassica oleracea L. var. Italica Boiled or Steamed: Functional Food or Dietary Supplement?

The levels of bioactive compounds in broccoli and their bioavailability following broccoli intake can be affected by the cooking procedures used for vegetable preparation. In the present pilot study, we compared the human plasma bioavailability of antioxidant compounds (β-carotene, lutein and isothiocyanate) and of phylloquinone (vitamin K) on seven volunteers before and after the administration of boiled and steamed broccoli. Moreover, plasma isothiocyanate (ITCs) levels were also evaluated after the administration of a single dose of BroccoMax®, a dietary supplement containing GLSs with active myrosinase. Steam-cooking has been demonstrated to promote higher plasma bioavailability in ITCs than boiling (AUCSTEAMED = 417.4; AUCBOILED = 175.3) and is comparable to that reached following the intake of BroccoMax®, a supplement containing glucoraphanin and active myrosinase (AUC = 450.1). However, the impact of boiling and steaming treatment on plasma bioavailability of lipophilic antioxidants (lutein and β-carotene) and of phylloquinone was comparable. The lutein and β-carotene plasma levels did not change after administration of steamed or boiled broccoli. Conversely, both treatments led to a similar increase of phylloquinone plasma levels. Considering the antioxidant action and the potential chemopreventive activity of ITCs, steaming treatments can be considered the most suitable cooking method to promote the health benefits of broccoli in the diet.

HobPre: accurate prediction of human oral bioavailability for small molecules

Human oral bioavailability (HOB) is a key factor in determining the fate of new drugs in clinical trials. HOB is conventionally measured using expensive and time-consuming experimental tests. The use of computational models to evaluate HOB before the synthesis of new drugs will be beneficial to the drug development process. In this study, a total of 1588 drug molecules with HOB data were collected from the literature for the development of a classifying model that uses the consensus predictions of five random forest models. The consensus model shows excellent prediction accuracies on two independent test sets with two cutoffs of 20% and 50% for classification of molecules. The analysis of the importance of the input variables allowed the identification of the main molecular descriptors that affect the HOB class value. The model is available as a web server at www.icdrug.com/ICDrug/ADMET for quick assessment of oral bioavailability for small molecules. The results from this study provide an accurate and easy-to-use tool for screening of drug candidates based on HOB, which may be used to reduce the risk of failure in late stage of drug development.Graphical

Safety and Efficacy of Novasil Clay (Calcium Montmorillonite) in Children Exposed to Aflatoxin in Ejura-Sekyedumase District in Ghana

Background. Aflatoxin levels are very high in animals and humans in places where cereals are poorly stored. In this study, Novasil was evaluated for safety and efficacy in children. Methods. Children (200) aged between 2 and 9 years were put into Novasil and placebo group. Participants received either 1.5 g of Novasil or calcium carbonate in their food. Urine samples were analyzed for AFM1 by HPLC, blood samples were assayed for complete blood count and chemistries. Results. Aflatoxin M1 levels in the Novasil treated group, significantly reduced to 60% compared to an increase of urine AFM1 in the placebo group. Hematological parameters did not change except for an increase in hemoglobin level in the Novasil group. Biochemical parameters remained unchanged except calcium ions. Glutathione levels in the Novasil increased, compared group to the placebo group. Conclusion. Novasil is safe, reduce aflatoxin bioavailability in humans while improving GSH antioxidant capacity as well.The trial has been registered with Pan African Clinical Trial Registry (www.pactr.org). A WHO registry for clinical trials with a unique identification number PACTR202202797930675.

The Effect of Food Thickeners on the Bitterness and Dissolution of Amlodipine Besilate Powder When Co-Administered with Thickeners to Patients with Dysphagia

Purpose: The present research was performed to evaluate the effect of food thickeners on the bitterness and dissolution of bitter drugs when co-administered to patients with dysphagia. Methods: Amlodipine besilate (AMPB) powder was used as a model drug. Starch- and xanthan gum-based food thickeners were examined, with swallowing-aid jelly as a reference. The line-spread test (LST), texture prolife analysis (TPA) were done firstly. In related to AMPB powder mixed with food thickeners solution, a conventional dissolution test simulating the oral cavity was performed, the amlodipine (AMP) concentration and taste sensor output for dissolved medium versus time profiles were developed. The dissolution test at pH 1.2 and 4.5, representing typical gastric conditions for younger or elderly people, was performed in two kinds of thickener solution and swallowing-aid jelly those were mixed with AMPB powder. Results: LST demonstrated that xanthan gum-based food thickeners fulfilled the requirements for patients with dysphagia but that starch-based food thickeners did not. In TPA, hardness and adhesiveness decreased proportionally as the concentration increased for both kinds of food thickener. Conventional dissolution test simulating oral cavity demonstrated the following bitterness ranking: xanthan gum-based food thickener < starch-based food thickener < swallowing-aid jelly. In dissolution test at pH 1.2 and 4.5, starch-based thickener and swallowing-aid jelly mixed with AMPB powder showed complete AMP dissolution. However, xanthan gum-based food thickeners mixed with AMPB powder showed about only 60% AMP dissolution after 120 minutes. Conclusion: Although xanthan gum-based food thickeners were successful in masking the bitterness of AMP, they may reduce its bioavailability in humans. The 7.1 and 4.7 (w/v) % starch-based thickener show bitterness inhibition under simulated oral cavity conditions and complete dissolution of AMP under simulated gastric conditions.

Results from a Validated in vitro Gastrointestinal Model (TIM) used as input Data for in silico Modeling Give Highly Predictive Information for the Human Situation

The aim of this review paper is to evaluate the predictive quality of a combination of in vitro dynamic gastrointestinal models, mucosal transit models and in silico kinetic modeling. The TNO gastro-Intestinal Model (TIM) is a computer-controlled system, mimicking essential gastrointestinal parameters of the stomach, small intestine and large intestine. The systems have dialysis or filtration units connected to the intestinal compartments. TIM settings are adapted to the condition that has to be simulated, such as fasted and fed state, age, and co-medication. In this way the transit and digestibility of food, release, dissolution, and bioaccessibility of nutrients, drugs, and metabolites can be studied. The TIM Systems have been validated in comparison to human studies for various food products and oral drugs, published in peer-reviewed journals. The results show the potential availability for absorption, called 'bioaccessibility'. Combining TIM with mucosal transit assays, it is possible to also analyze the intestinal absorption. But for predicting bioavailability and plasma concentrations in time it needs additional kinetic data, such as distribution, metabolism, and excretion. TIM bioaccessibility data and (published) kinetic data can be used as input in commercial in silico models or specifically developed in silico modeling. Validation studies show a high predictive quality for human nutrient and drug bioavailability and plasma concentrations. Maybe not (yet) in all cases the predictions will cover for 100% the human data, so there is room for improvement. However, the reviewed studies clearly show the strength of combining a validated gastrointestinal model with physiological kinetic data in in silico modeling. It certainly will replace animal experiments and will strongly increase the success rate of follow-up human studies, saving time and costs.

Microphysiological endothelial models to characterize subcutaneous drug absorption.

The high variability in subcutaneous bioavailability of protein therapeutics is poorly understood, contributing to critical delays in patient access to new therapies. Preclinical animal and in vitro models fail to provide a physiologically relevant testbed to parse potential contributors to human bioavailability, therefore new strategies are necessary. Here, we present a microphysiological model of the human hypodermal vasculature at the injection site to study the interactions of administered protein therapeutics within the microenvironment that influence subcutaneous bioavailability. Our model combines human dermal endothelial cells, fibroblasts, and adipocytes, self-assembled into three-dimensional, perfusable microvessels that express relevant extracellular matrix. We demonstrate the utility of the model for measurement of biophysical parameters within the hypodermal microenvironment that putatively impact protein kinetics and distribution at the injection site. We propose that microphysiological models of the subcutaneous space have applications in preclinical development of protein therapeutics intended for subcutaneous administration with optimal bioavailability.

Installation of Pargyline, a LSD1 Inhibitor, in the HDAC Inhibitory Template Culminated in the Identification of a Tractable Antiprostate Cancer Agent.

Pragmatic insertion of pargyline, a LSD1 inhibitor, as a surface recognition part in the HDAC inhibitory pharmacophore was planned in pursuit of furnishing potent antiprostate cancer agents. Resultantly, compound 14 elicited magnificent cell growth inhibitory effects against the PC-3 and DU-145 cell lines and led to remarkable suppression of tumor growth in human prostate PC-3 and DU-145 xenograft nude mouse models. The outcome of the enzymatic assays ascertained that the substantial antiproliferative effects of compound 14 were mediated through HDAC6 isoform inhibition as well as selective MAO-A and LSD1 inhibition. Moreover, the signatory feature of LSD1 inhibition by 14 in the context of H3K4ME2 accumulation was clearly evident from the results of western blot analysis. Gratifyingly, hydroxamic acid 14 demonstrates good human hepatocytic stability and good oral bioavailability in rats and exhibits enough promise to emerge as a therapeutic for the treatment of prostate cancer in the near future.

Effects of Low Doses of L-Carnitine Tartrate and Lipid Multi-Particulate Formulated Creatine Monohydrate on Muscle Protein Synthesis in Myoblasts and Bioavailability in Humans and Rodents.

The primary objective of this study was to investigate the potential synergy between low doses of L-carnitine tartrate and creatine monohydrate to induce muscle protein synthesis and anabolic pathway activation in primary human myoblasts. In addition, the effects of Lipid multi-particulates (LMP) formulation on creatine stability and bioavailability were assessed in rodents and healthy human subjects. When used individually, L-carnitine tartrate at 50 µM and creatine monohydrate at 0.5 µM did not affect myoblast protein synthesis and signaling. However, when combined, they led to a significant increase in protein synthesis. Increased AKT and RPS6 phosphorylation were observed with 50 µM L-carnitine tartrate 5 µM creatine in combination in primary human myoblasts. When Wistar rats were administered creatine with LMP formulation at either 21 or 51 mg/kg, bioavailability was increased by 27% based on the increase in the area under the curve (AUC) at a 51 mg/kg dose compared to without LMP formulation. Tmax and Cmax were unchanged. Finally, in human subjects, a combination of LMP formulated L-carnitine at 500 mg (from L-carnitine tartrate) with LMP formulated creatine at 100, 200, or 500 mg revealed a significant and dose-dependent increase in plasma creatine concentrations. Serum total L-carnitine levels rose in a similar manner in the three combinations. These results suggest that a combination of low doses of L-carnitine tartrate and creatine monohydrate may lead to a significant and synergistic enhancement of muscle protein synthesis and activation of anabolic signaling. In addition, the LMP formulation of creatine improved its bioavailability. L-carnitine at 500 mg and LMP-formulated creatine at 200 or 500 mg may be useful for future clinical trials to evaluate the effects on muscle protein synthesis.

Iron Bioavailability from Multiple Biofortified Foods Using an In Vitro Digestion, Caco-2 Assay for Optimizing a Cyclical Menu for a Randomized Efficacy Trial.

ABSTRACTBackgroundInadequate nutritional status contributes to substantial losses in human health and productivity globally. A multiple biofortified food crop trial targeting iron, zinc, and vitamin A deficiencies among young children and their breastfeeding mothers is being conducted in India.ObjectiveWe sought to determine the relative iron bioavailability from biofortified and conventional crops and crop combinations representative of a cyclical menu using crops targeted for inclusion in the feeding trial.MethodsCrops were procured from India, cooked, freeze-dried, and analyzed with an established in vitro digestion/Caco-2 iron bioavailability assay using a fixed sample weight. Crop proportions representative of meals planned for the human study were determined and combined such that samples included either all biofortified or all control crops. Crops were analyzed as single crops (n = 4) or crop combinations (n = 7) by variety (biofortified or control) in triplicate. The primary outcome was iron uptake measured by Caco-2 ferritin production normalized to total Caco-2 protein (nanograms of ferritin/milligrams of cell protein) analyzed for effects of crop variety and crop proportion using generalized linear models.ResultsBiofortified pearl millet alone demonstrated higher iron uptake than conventional varieties (5.01 ± 1.66 vs. 2.17 ± 0.96; P = 0.036). Addition of sweet potato or sweet potato + pulse improved iron uptake for all proportions tested in control varieties and select proportions for biofortified varieties (P ≤ 0.05). Two multiple crop combinations demonstrated modestly higher iron uptake from biofortified crops.ConclusionsOptimizing total iron delivery should consider matrix effects, processing, and promoters/inhibitors of iron absorption in addition to total iron concentration. Future directions include evaluating recipes as prepared for consumption and comparison against human iron bioavailability studies.

Microplastics as a Trojan horse for trace metals

Due to an assumed lack of anionic binding sites (most plastics are non-polar), scientists long considered virgin particulate plastics inert towards metal ions. However, we proved significant metal sorption to microplastics at neutral pH and release in a solution mimicking gastrointestinal chemistry serving as a proof-of-principle for environmental and human bioavailability. Competitive ion-exchange incubation experiments comprised 55 metals and metalloids. Fast kinetics were observed with 45 %–75 % of As, Be, Bi, Cr, Fe, In, Pb, Th, Sn and the rare-earth element ions being sorbed after 1 h. The investigated metal and metalloid cations showed significant differences in the extent of sorption, based upon which a distinct categorization was possible. Microplastics are not only a potential danger for aquatic and human life, but - as demonstrated in this paper - also serve as a Trojan Horse for dissolved metal cations. The corresponding effects on aquatic and human health will gain higher importance in the near future due to the predicted increases of marine plastic litter and microplastic sorbents.

Oxaliplatin, an Anticancer Agent, Causes Erectile Dysfunction in Rats due to Endothelial Dysfunction

Chemotherapeutics, one of the standard treatment options for cancer worldwide, have various adverse effects, including erectile dysfunction (ED). To investigate erectile function in an animal model after administration of the anticancer agent oxaliplatin (L-OHP). Male Wistar/ST rats were divided into 2 groups: L-OHP rats (n = 21), which were intravenously administered L-OHP (4 mg/kg; twice a week for 4 weeks), and Control rats (n = 21), which were injected with the same volume of 5% glucose solution, using the same dosing schedule. At the end of the study period, erectile function was evaluated by measuring intracavernous pressure (ICP) and mean arterial pressure (MAP) after cavernous nerve stimulation (n = 9-10). Endothelial function was evaluated with an isometric tension study using corpus cavernosum strips (n = 11). Western blot analysis was used to assess neuronal nitric oxide (nNOS) and endothelial NO synthase (eNOS) protein levels (n = 7). Real-time quantitative polymerase chain reaction (qRT-PCR) was used to assess the expression of inflammation- and oxidative stress-related markers (nicotinamide adenine dinucleotide phosphate oxidase-1, p22phox, interleukin [IL]-6, and nuclear factor-kappa B) (n = 6). Statistical significance was determined using the Student's t-test. The L-OHP group had a significantly lower ICP:MAP ratio than the control group (P < .05). Compared to the Control group, the L-OHP group exhibited significantly lower responses to ACh and eNOS protein levels and significantly higher inflammatory biomarker levels. The results based on this animal model indicate that use of the anticancer agent L-OHP should be considered as a risk factor for ED occurring via reduction of NO bioavailability in humans; our results provide possible treatment strategies for maintaining the erectile function of cancer survivors. Our study showed that the anticancer agent L-OHP has the propensity to cause ED in rats. A major limitation of this study is the lack of an established cure for ED associated with L-OHP and the lack of clinical evidence. L-OHP causes ED in rats via reduction of NO bioavailability caused by endothelial dysfunction.

Combination of a biopharmaceutic classification system and physiologically based pharmacokinetic models to predict absorption properties of baicalein in vitro and in vivo

To determine the in vitro and in vivo absorption properties of active ingredients of the Chinese medicine, baicalein, to enrich mechanistic understanding of oral drug absorption. The Biopharmaceutic Classification System (BCS) category was determined using equilibrium solubility, intrinsic dissolution rate, and intestinal permeability to evaluate intestinal absorption mechanisms of baicalein in rats in vitro . Physiologically based pharmacokinetic (PBPK) model commercial software GastroPlus™ was used to predict oral absorption of baicalein in vivo . Based on equilibrium solubility, intrinsic dissolution rate, and permeability values of main absorptive segments in the duodenum, jejunum, and ileum, baicalein was classified as a drug with low solubility and high permeability. Intestinal perfusion with venous sampling (IPVS) revealed that baicalein was extensively metabolized in the body, which corresponded to the low bioavailability predicted by the PBPK model. Further, the PBPK model predicted the key indicators of BCS, leading to reclassification as BCS-II. Predicted values of peak plasma concentration of the drug (C max ) and area under the curve (AUC) fell within two times of the error of the measured results, highlighting the superior prediction of absorption of baicalein in rats, beagles, and humans. The PBPK model supported in vitro and in vivo evidence and provided excellent prediction for this BCS class II drug. BCS and PBPK are complementary methods that enable comprehensive research of BCS parameters, intestinal absorption rate, metabolism, prediction of human absorption fraction and bioavailability, simulation of PK, and drug absorption in various intestinal segments across species. This combined approach may facilitate a more comprehensive and accurate analysis of the absorption characteristics of active ingredients of Chinese medicine from in vitro and in vivo perspectives.

An Untargeted Metabolomics Approach for Correlating Pulse Crop Seed Coat Polyphenol Profiles with Antioxidant Capacity and Iron Chelation Ability

Pulse crop seed coats are a sustainable source of antioxidant polyphenols, but are typically treated as low-value products, partly because some polyphenols reduce iron bioavailability in humans. This study correlates antioxidant/iron chelation capabilities of diverse seed coat types from five major pulse crops (common bean, lentil, pea, chickpea and faba bean) with polyphenol composition using mass spectrometry. Untargeted metabolomics was used to identify key differences and a hierarchical analysis revealed that common beans had the most diverse polyphenol profiles among these pulse crops. The highest antioxidant capacities were found in seed coats of black bean and all tannin lentils, followed by maple pea, however, tannin lentils showed much lower iron chelation among these seed coats. Thus, tannin lentils are more desirable sources as natural antioxidants in food applications, whereas black bean and maple pea are more suitable sources for industrial applications. Regardless of pulse crop, proanthocyanidins were primary contributors to antioxidant capacity, and to a lesser extent, anthocyanins and flavan-3-ols, whereas glycosylated flavonols contributed minimally. Higher iron chelation was primarily attributed to proanthocyanidin composition, and also myricetin 3-O-glucoside in black bean. Seed coats having proanthocyanidins that are primarily prodelphinidins show higher iron chelation compared with those containing procyanidins and/or propelargonidins.

Tocopherols and Tocotrienols-Bioactive Dietary Compounds; What Is Certain, What Is Doubt?

Tocopherols and tocotrienols are natural compounds of plant origin, available in the nature. They are supplied in various amounts in a diet, mainly from vegetable oils, some oilseeds, and nuts. The main forms in the diet are α- and γ-tocopherol, due to the highest content in food products. Nevertheless, α-tocopherol is the main form of vitamin E with the highest tissue concentration. The α- forms of both tocopherols and tocotrienols are considered as the most metabolically active. Currently, research results indicate also a greater antioxidant potential of tocotrienols than tocopherols. Moreover, the biological role of vitamin E metabolites have received increasing interest. The aim of this review is to update the knowledge of tocopherol and tocotrienol bioactivity, with a particular focus on their bioavailability, distribution, and metabolism determinants in humans. Almost one hundred years after the start of research on α-tocopherol, its biological properties are still under investigation. For several decades, researchers’ interest in the biological importance of other forms of vitamin E has also been growing. Some of the functions, for instance the antioxidant functions of α- and γ-tocopherols, have been confirmed in humans, while others, such as the relationship with metabolic disorders, are still under investigation. Some studies, which analyzed the biological role and mechanisms of tocopherols and tocotrienols over the past few years described new and even unexpected cellular and molecular properties that will be the subject of future research.

Understanding micronutrient bioavailability and the impact on micronutrient malnutrition

Jayashree Arcot received her Bachelor's degree in Nutrition and Dietetics from the University of Madras, India and a Master's degree in Food Science and Nutrition. She received her PhD in Foods and Nutrition from the Andhra Pradesh Agricultural University in Hyderabad, India in 1988 while being a recipient of the prestigious Senior Research Fellowship from the Indian Council of Agricultural Research. While in Hyderabad she had the opportunity to collaborate with several leading scientists in the field of nutrition at the National Institute of Nutrition, a premier organization under the auspices of the Indian Council of Medical Research in India and the International Crops Research Institute for Semi-arid Tropics (ICRISAT). She mastered the analysis of vitamins in foods using the microbiological assay during her PhD. When she arrived in Australia in the early 1990s, as an academic at the University of New South Wales, Sydney, she had the opportunity to establish a research group in the field of food science and nutrition. She pursued several projects funded by government and industry with her food-based approaches to solve nutrition problems particularly micronutrient malnutrition. Fascinated by the complexity of vitamins in foods and their matrix effects, she established a laboratory for vitamin methodology for foods using the microbiological assay, high-end chromatography (LC-MS/MS), to measure different forms of vitamins, for example, folates; studying vitamin bioavailability in humans. Her lab was the first in the Oceania region capable of measuring vitamins in foods using the microbiological assay. She has conducted several international workshops and short courses in food composition and vitamin assays for researchers. She has pursued her interest in vitamins through several fortification projects and bioavailability of folate-fortified foods in humans and in vitro cell culture techniques. Her other interests are in developing accurate methods for the bioactive compounds in foods and studying their bioactivity using cell culture techniques. She has several publications in the field of 2D culture models for the bioaccessibility and bioavailability of compounds such as phenolic acids, flavonoids, and carotenes from foods. Her publications in this field are related to interactions between these bioactive compounds in foods and their health properties such as cellular anti-inflammatory and anti-oxidant effects. More recently, she has focused on food and health security with a particular focus on complementary feeding in infants, and malnutrition in middle-income and lower income countries. In this context, she has been studying ways of recovering nutrients (protein) from food manufacturing stream wastes and collaborated with industry on several projects. She has over 100 research publications and has graduated several research students in the last 20 years. She is a professional member of the Australian Institute of Food Science and Technology, Nutrition Society of Australia, and the American Society of Nutrition. She is an Associate Professor of Food and Health at the School of Chemical Engineering, UNSW, Sydney, Australia.

Measuring Dietary Iron Absorption From Edible Tenebrio molitor and Assessing the Effect of Chitin on Iron Bioavailability: A Stable Iron Isotope Study in Young Women

Abstract Objectives Iron deficiency is estimated to affect up to 1.5–2 billion people worldwide. Edible insects can be a rich source of iron and may have a smaller environmental food print than other animal source foods. Mealworm (Tenebrio molitor) larvae are recognized as an edible insect, but iron bioavailability in humans has not been investigated. Chitin, a major component of insect biomass, is a known iron binder. Our primary objective was to measure fractional iron absorption (FIA) from T.molitor with and without chitin in young women. Secondly, we aimed to assess the effect of the presence of mealworm biomass on iron absorption from iron present in low-phytate maize porridge. Methods Non-anemic females (18–45 years, body weight &amp;lt; 65 kg) were recruited and FIA was measured as erythrocyte incorporation of stable isotopes tracers in red blood cells 14 days after test meal administration. Using a randomized cross over design, three different meals were administered to each subject, consisting of A) a low phytate refined maize porridge with 54FeSO4; B) intrinsically labelled (57Fe) T.molitor with native chitin and extrinsic 58FeSO4; C) intrinsically labelled (57Fe) T.molitor with reduced chitin and extrinsic 58FeSO4. Results Median serum ferritin concentration in the participating subjects (n = 21) was 22.7 µg/L. Iron content in T.molitor larvae was FIA from meals B (58Fe, 5.28%) and C (58Fe, 4.55%) in which mealworm biomass was given in combination with maize porridge did not significantly differ to FIA from maize porridge fed alone (5.84%). In case of intrinsic labelling, FIA from meals B (57Fe, 4.11%) and C (57Fe, 4.03%) were significantly lower compared to maize meal A (P &amp;lt; 0.001). Conclusions FIA from T.molitor was similar to low-phytate containing maize. Presence of mealworm biomass did not enhance or inhibit the FIA of iron present in the maize meal. Furthermore, a chitin reduction process did not show any discernible effect on FIA. T.molitor larvae could be a viable source of iron in the human diet, but iron absorption may be similar to plant-based foods. The study was registered at clinicaltrials.gov as NCT04510831. Funding Sources Coop Research Program, World Food System Center, ETH Zurich, Switzerland.

P037 Nonclinical pharmacokinetics and absorption, distribution, metabolism, and excretion properties of MORF-057 support its clinical development as an oral selective α4β7 integrin inhibitor

Abstract Background MORF-057 is a potent and selective small molecule inhibitor of the α 4β 7 integrin. Using a receptor occupancy (RO) assay under physiologically relevant conditions, MORF-057 achieves 90% α 4β 7 RO at approximately 10 nM in human whole blood. The current studies evaluate nonclinical pharmacokinetics (PK) and properties of absorption, distribution, metabolism, and excretion (ADME) to enable dose/exposure projection to humans. Methods PK studies were conducted in mouse, rat, dog, and monkey following intravenous (IV) and oral administration. ADME studies were conducted in vitro and in rats using carbon-14 [14C] labeled MORF-057. MORF-057 levels were quantified using liquid chromatography coupled with tandem mass spectrometry. Human PK was predicted based on body weight allometry, well-stirred and semi-physiological models. Results MORF-057 exhibited low to moderate clearance (CL) in animals with species dependent volume of distribution (Vdss) resulting in half-lives of 1.1 to 2.7 hours (Table 1). Following an oral dose, absorption was high with bioavailability ranging from 15% to 49%. MORF-057 is highly protein bound and distribution of [14C]MORF-057 derived radioactivity in rat was predominantly in the small intestine wall, liver, and stomach wall. Rifampin, an inhibitor of organic anion transporting polypeptides, decreased MORF-057 clearance by 3-fold in monkeys suggesting MORF-057 elimination involves hepatic uptake transport. MORF-057 is further cleared via CYP3A metabolism followed by biliary/fecal elimination of metabolites. MORF-057 is predicted to have moderate bioavailability (40%) and CL (6.5 mL/min/kg) in humans. Wajima transformation shows good agreement of the normalized PK across animal species, with a predicted human concentration-time profile supporting &amp;gt;90% α 4β 7 RO at trough following 200 mg twice daily dose (Figure 1). Conclusion These data demonstrate that MORF-057 is well absorbed and PK properties in animals support the potential for achieving high α4β7 RO following oral administration in humans. These nonclinical results provided a basis for the progression of MORF-057 into a first-in-human Phase 1 clinical study assessing safety, pharmacokinetics, and receptor occupancy (results being reported separately).