Diverse role of phytic acid in plants and approaches to develop low-phytate grains to enhance bioavailability of micronutrients.

Natural or synthetic compounds that interfere with the bioavailability of nutrients are called antinutrients. Phytic acid (PA) is one of the major antinutrients present in the grains and acts as a chelator of micronutrients. The presence of six reactive phosphate groups in PA hinders the absorption of micronutrients in the gut of non-ruminants. Consumption of PA-rich diet leads to deficiency of minerals such as iron and zinc among human population. On the contrary, PA is a natural antioxidant, and PA-derived molecules function in various signal transduction pathways. Therefore, optimal concentration of PA needs to be maintained in plants to avoid adverse pleiotropic effects, as well as to ensure micronutrient bioavailability in the diets. Given this, the chapter enumerates the structure, biosynthesis, and accumulation of PA in food grains followed by their roles in growth, development, and stress responses. Further, the chapter elaborates on the antinutritional properties of PA and explains the conventional breeding and transgene-based approaches deployed to develop low-PA varieties. Studies have shown that conventional breeding methods could develop low-PA lines; however, the pleiotropic effects of these methods viz. reduced yield, embryo abnormalities, and poor seed quality hinder the use of breeding strategies. Overexpression of phytase in the endosperm and RNAi-mediated silencing of genes involved in myo-inositol biosynthesis overcome these constraints. Next-generation genome editing approaches, including CRISPR-Cas9 enable the manipulation of more than one gene involved in PA biosynthesis pathway through multiplex editing, and scope exists to deploy such tools in developing varieties with optimal PA levels.

Considerations for improvising fortified extruded rice products.

Micronutrient fortification of rice by extrusion is an effective strategy to enhance micronutrient levels within rice-consuming individuals. The success of extrusion-based fortification is associated with micronutrient retention, enhanced bioavailability, low postprocessing losses, prolonged storage stability, and minimal sensory changes. The success of an optimally fortified product is primarily reliant upon the compositional considerations, but many attributes of extrudates can be indebted to the processing parameters too. Hence, an exhaustive investigation of this technology has been taken-up here, emphasizing on the compositional parameters in association with process parameters, which influence the final quality attributes like nutrient stability, bioavailability, and sensory properties. Based on these attributes of the end product, a collected data have been presented here to bring out the optimal compositional requirements. These together with cooking processes, extrusion process parameters, and storage conditions will enable formulate a product with enhanced sensory acceptance, better retention during cooking and storage, improved texture, and acceptable color. This review will thus help to optimize a need-based product, its quality, and enhance benefits of fortified extruded rice products.

Pharmaconutrition revisited for critically ill patients with coronavirus disease 2019 (COVID-19): Does selenium have a place?

Coronavirus disease 2019 (COVID-19) is a global pandemic causing one of the biggest challenges for critical care medicine. Mortality from COVID-19 is much greater in elderly men, many of whom succumb to acute respiratory distress syndrome (ARDS) triggered by the viral infection. Because there is no specific antiviral treatment against COVID-19, new strategies are urgently needed. Selenium is an essential trace element with antioxidant and immunomodulatory effects. Poor nutritional status increases the pathogenicity of viruses and low selenium in particular can be a determinant of viral virulence. In the past decade, selenium pharmaconutrition studies have demonstrated some reduction in overall mortality, including how reduced incidence of ventilator-associated pneumonia and infectious complications such as ARDS in the critically ill. Consequently, we postulate that intravenous selenium therapy, could be part of the therapeutic fight against COVID-19 in intensive care unit patients with ARDS and that outcomes could be affected by age, sex, and body weight. Our working hypothesis addresses the question: Could high-dose selenite pharmaconutrition, as an early pharmacologic intervention, be effective at reducing the incidence and the progression from type 1 respiratory failure (non-ARDS) to severe ARDS, multiorgan failure, and new infectious complications in patients with COVID-19 patients?

Folic Acid Affects Iron Status in Female Rats with Deficiency of These Micronutrients.

Although simultaneous supplementation with iron and folic acid is justified, the potential interactions between these micronutrients are unknown. The aim of this study was to determine the effects of oral iron and folic acid, administered together or separately, on iron concentration in tissues in rats with a deficiency of both these micronutrients. In the first stage of the experiment (28 days), 150 8-week-old female Wistar rats were randomly assigned to a control group (C; n = 30) fed the standard diet and to a study group (n = 120) fed a diet deficit in iron and folate. The study group was then randomly divided to four groups: D group fed a deficit diet, FE group fed a deficit diet with iron gluconate, the FOL group fed a deficit diet with folate acid, and the FEFOL group fed a deficit diet with iron gluconate and folate acid. After 2, 10, and 21 days of supplementation, ten animals from each group were killed. Morphological parameters were measured in whole blood. Iron concentration was assayed in serum, liver, spleen, pancreas, heart, and kidneys. Folic acid supplementation more significantly decreased iron concentrations in the pancreas and spleen than in the D group after 10 and 21 days of supplementation. Moreover, the combination of iron with folic acid markedly decreased iron levels in the liver and spleen, in comparison with iron alone, after 10 and 21 days of the experiment. In conclusion, folic acid affects iron status in female rats deficient in these micronutrients in moderate and long-term supplementation.

Cerebral Microvascular Injury: A Potentially Treatable Endophenotype of Traumatic Brain Injury-Induced Neurodegeneration.

Traumatic brain injury (TBI) is one the most common human afflictions, contributing to long-term disability in survivors. Emerging data indicate that functional improvement or deterioration can occur years after TBI. In this regard, TBI is recognized as risk factor for late-life neurodegenerative disorders. TBI encompasses a heterogeneous disease process in which diverse injury subtypes and multiple molecular mechanisms overlap. To develop precision medicine approaches where specific pathobiological processes are targeted by mechanistically appropriate therapies, techniques to identify and measure these subtypes are needed. Traumatic microvascular injury is a common but relatively understudied TBI endophenotype. In this review, we describe evidence of microvascular dysfunction in human and animal TBI, explore the role of vascular dysfunction in neurodegenerative disease, and discuss potential opportunities for vascular-directed therapies in ameliorating TBI-related neurodegeneration. We discuss the therapeutic potential of vascular-directed therapies in TBI and the use and limitations of preclinical models to explore these therapies.

[Are vegetarian diets nutritionally adequate? A revision of the scientific evidence]. / ¿Son las dietas vegetarianas nutricionalmente adecuadas? Una revisión de la evidencia científica.

INTRODUCTION: Vegetarian diets are booming and, although these diets have been linked to some health benefits, the low bioavailability of some micronutrients in plant foods may result in risk of nutritional deficiencies, which makes necessary adequate planning of these diets. In this regard, vitamin B12 deficiency in vegetarians has been evidenced and there is a consensus on the need of supplementation of this vitamin. Vitamin D deficiency may be more frequent than in omnivores, particularly during the winter, when skin synthesis is minimal. The low bioavailability of iron, zinc and selenium in vegetables can also affect nutritional status of vegetarians. Furthermore, vegetarian diets are usually deficient in polyunsaturated fatty acids of the omega-3 family, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. On the other hand, these diets appear to provide adequate quantities of other vitamins, such as ascorbic acid, folic acid and the fat-soluble vitamins A and E. In this review, the characteristics of the intake of macro- and micronutrients of vegetarian diets and the diet and health relationships are presented. In addition, data on nutritional status of this population are also shown and suggestions on nutritional recommendations to prevent deficiencies are given. Finally, the possible clinical application of controlled interventions with vegetarian diets is presented.

INTRODUCCIÓN: El seguimiento de dietas vegetarianas está en auge y, aunque estas se han relacionado con algunos beneficios para la salud, la baja biodisponibilidad de determinados micronutrientes en los alimentos vegetales puede resultar en riesgo de déficit nutricional, por lo que se hace necesaria una adecuada planificación de dichas dietas. En este sentido, se ha evidenciado el déficit de vitamina B12 en vegetarianos y está consensuada la necesidad de ingerir complementos de esta vitamina. La deficiencia de vitamina D puede ser más frecuente que en omnívoros, particularmente durante el invierno, cuando la síntesis cutánea es mínima. La baja biodisponibilidad del hierro, el zinc y el selenio en los alimentos vegetales puede afectar también al estado nutricional de vegetarianos. Además, las dietas vegetarianas suelen ser deficitarias en ácidos grasos poliinsaturados de la serie omega-3, eicosapentaenoico (EPA) y docosahexaenoico (DHA). Por otro lado, estas dietas sí parecen aportar cantidades adecuadas de otras vitaminas, como el ácido ascórbico, el ácido fólico y las vitaminas liposolubles A y E. En esta revisión se presentan las características de la ingesta de macro- y micronutrientes procedentes de las dietas vegetarianas y la relación dieta-salud. Se exponen, además, datos sobre el estado nutricional de adultos que consumen dichas dietas, proponiendo recomendaciones nutricionales primordiales para prevenir deficiencias. Finalmente, se presenta la posible aplicación clínica de intervenciones controladas con dietas vegetarianas.

Effect of iron and folic acid fortification on in vitro bioavailability and starch hydrolysis in ready-to-eat parboiled rice.

Iron (Fe) and folic acid (FA) fortified parboiled rice was produced by applying 'brown rice parboiling' method. The effect of milling and the effectiveness of fortification were tested in relation to the amount of bioaccessible and bioavailable form of Fe and FA. An in vitro starch hydrolysis assay was employed to assess the effect on simulated glycaemic index (GI). The % bioaccessiblity of Fe and FA in the unmilled fortified rice were in the range of 57.6-65.8%, and 55.1-91.9%, respectively. The % bioavailability in the unfortified parboiled rice was negligible as compared to Fe (14.7-32.1%) and FA (13.5-27.5%) fortified rice. The GI of unfortified and fortified parboiled rice samples was in the range of 56-69, which was lower than the raw rice. The results demonstrated that this approach can be a novel and rapid method to produce micronutrient enhanced ready-to-eat rice.

Micronutrient-fortified rice can be a significant source of dietary bioavailable iron in schoolchildren from rural Ghana.

Iron deficiency and anemia are prominent contributors to the preventable disease burden worldwide. A substantial proportion of people with inadequate dietary iron rely on rice as a staple food, but fortification efforts are limited by low iron bioavailability. Furthermore, using high iron fortification dosages may not always be prudent in tropical regions. To identify alternative fortification formulations with enhanced absorption, we screened different iron compounds for their suitability as rice fortificants, measured in vitro gastric solubility, and assessed dietary iron bioavailability using stable isotopic labels in rural Ghanaian children. Isotopic incorporation in red blood cells indicates that in the two age groups of children investigated (4 to 6 and 7 to 10 years), formulations provided 36 and 51% of the median daily requirement in absorbed iron, respectively. We describe approaches to enhancing iron bioavailability from fortified rice, which can substantially contribute to the prevention of iron deficiency in rice-eating populations.

Studying the real-time interplay between triglyceride digestion and lipophilic micronutrient bioaccessibility using droplet microfluidics. 1 lab on a chip method.

This article is the first part of a series reporting on real-time digestion kinetics of triglyceride droplets containing different lipophilic micronutrients. This part focuses on the design, fabrication, and operation of a polydimethylsiloxane microfluidic device which enables the generation and digestion of oil droplets. The micro-channels were made hydrophilic to obtain oil droplets in an aqueous continuous phase. Optimized chip design and outlet control were implemented to provide efficient oil droplet generation, manipulation, and immobilization on a single chip. Highly monodisperse oil droplets were generated, immobilized in an array of traps and monitored in real time by fluorescence using a confocal microscopy method. The device was used to study the kinetics of beta-carotene release during tricaprylin digestion (intestinal lipolysis and micellar solubilization). The effect of the gastric phase on beta-carotene degradation was also investigated using the same method.

Fatty acids and elemental composition as biomarkers of Octopus vulgaris populations: Does origin matter?

The present study describes the novel use of fatty acids (FAs) and element profiles of Octopus vulgaris inhabiting three coastal areas in the W-Mediterranean Sea. These populations are exposed to different anthropogenic activities, and were compared at different geographical scales. The FA composition in the mantle of O. vulgaris exhibited significant differences in 22:6 n-3 (DHA) and 22:5 n-3 (EPA) among the sampled populations. The essential microelements Fe, Cu, Zn and Ni, and the non-essential microelements As, Sr, Al and Cd were the main contributors of variability among sampled octopus populations, with some notable differences among tissues. The variations in the FAs and elemental composition in octopus tissues were detected with other populations throughout the species distribution range, which might reflect differences in natural habitats and foraging strategies. Therefore, these may be considered biomarkers as a proxy to distinguish the origin of octopus specimens at different scales.

A comprehensive review on environmental transformation of selenium: recent advances and research perspectives.

Selenium (Se) is an important micronutrient and essential trace element for both humans and animals, which exist in the environment ubiquitously. Selenium deficiency is an important issue worldwide, with various reported cases of its deficiency. Low selenium contents in some specific terrestrial environments have resulted in its deficiency in humans. However, high levels of selenium in the geochemical environment may have harmful influences and can cause a severe toxicity to living things. Due to its extremely narrow deficiency and toxicity limits, selenium is becoming a serious matter of discussion for the scientists who deals with selenium-related environmental and health issues. Based on available relevant literature, this review provides a comprehensive data about Se sources, levels, production and factors affecting selenium bioavailability/speciation in soil, characteristics of Se, biogeochemical cycling, deficiency and toxicity, and its environmental transformation to know the Se distribution in the environment. Further research should focus on thoroughly understanding the concentration, speciation, Se cycling in the environment and food chain to effectively utilize Se resources, remediate Se deficiency/toxicity, and evaluate the Se states and eco-effects on human health.

Peripheral neuropathy and gastroenterologic disorders: an overview on an underrecognized association.

BACKGROUND AND AIM OF THE WORK: Although peripheral neuropathies in children are often of genetic origin, acquired causes should be carefully looked for and ruled out also in the pediatric age. Gastroenterological disorders can be complicated by peripheral neuropathy as a result of micronutrients deficiency, drug toxicity or because of shared pathophysiological mechanisms. METHODS: In this descriptive review we sought to give an overview on the most relevant clinical conditions in which peripheral neuropathies are associated with gastro-intestinal disorders or symptoms. RESULTS: We describe the clinical, demographic, and electrophysiological features of peripheral neuropathy in three main clinical scenarios: in the context of common gastroenterological disorders (inflammatory bowel and celiac disease), in the context of micronutrients deficiencies arising from malabsorption irrespective of etiology, and in a rare degenerative mitochondrial disorder, mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) disorder. CONCLUSIONS: The association between gastrointestinal and peripheral nervous system symptoms is probably still underrecognized but has to be actively sought, in order to provide prompt diagnosis resulting in optimal care and long-term management with the aim to improve quality of life and, at least in some conditions, try to impact on prognosis.

Use of Stable Isotopes to Evaluate Bioefficacy of Provitamin A Carotenoids, Vitamin A Status, and Bioavailability of Iron and Zinc.

The ability of nutrition scientists to measure the status, bioavailability, and bioefficacy of micronutrients is affected by lack of access to the parts of the body through which a nutrient may travel before appearing in accessible body compartments (typically blood or urine). Stable isotope-labeled tracers function as safe, nonradioactive tools to follow micronutrients in a quantitative manner because the absorption, distribution, metabolism, and excretion of the tracer are assumed to be similar to the unlabeled vitamin or mineral. The International Atomic Energy Agency (IAEA) supports research on the safe use of stable isotopes in global health and nutrition. This review focuses on IAEA's contributions to vitamin A, iron, and zinc research. These micronutrients are specifically targeted by the WHO because of their importance in health and worldwide prevalence of deficiency. These 3 micronutrients are included in food fortification and biofortification efforts in low- and middle-income regions of the world. Vitamin A isotopic techniques can be used to evaluate the efficacy and effectiveness of interventions. For example, total body retinol stores were estimated by using 13C2-retinol isotope dilution before and after feeding Zambian children maize biofortified with ß-carotene to determine if vitamin A reserves were improved by the intervention. Stable isotopes of iron and zinc have been used to determine mineral bioavailability. In Thailand, ferrous sulfate was better absorbed from fish sauce than was ferrous lactate or ferric ammonium citrate, determined with the use of different iron isotopes in each compound. Comparisons of one zinc isotope injected intravenously with another isotope taken orally from a micronutrient powder proved that the powder increased total absorbed zinc from a meal in Pakistani infants. Capacity building by the IAEA with appropriate collaborations in low- and middle-income countries to use stable isotopes has resulted in many advancements in human nutrition.

Clinically Relevant Herb-Micronutrient Interactions: When Botanicals, Minerals, and Vitamins Collide.

The ability of certain foods to impair or augment the absorption of various vitamins and minerals has been recognized for many years. However, the contribution of botanical dietary supplements (BDSs) to altered micronutrient disposition has received little attention. Almost half of the US population uses some type of dietary supplement on a regular basis, with vitamin and mineral supplements constituting the majority of these products. BDS usage has also risen considerably over the last 2 decades, and a number of clinically relevant herb-drug interactions have been identified during this time. BDSs are formulated as concentrated plant extracts containing a plethora of unique phytochemicals not commonly found in the normal diet. Many of these uncommon phytochemicals can modulate various xenobiotic enzymes and transporters present in both the intestine and liver. Therefore, it is likely that the mechanisms underlying many herb-drug interactions can also affect micronutrient absorption, distribution, metabolism, and excretion. To date, very few prospective studies have attempted to characterize the prevalence and clinical relevance of herb-micronutrient interactions. Current research indicates that certain BDSs can reduce iron, folate, and ascorbate absorption, and others contribute to heavy metal intoxication. Researchers in the field of nutrition may not appreciate many of the idiosyncrasies of BDSs regarding product quality and dosage form performance. Failure to account for these eccentricities can adversely affect the outcome and interpretation of any prospective herb-micronutrient interaction study. This review highlights several clinically relevant herb-micronutrient interactions and describes several common pitfalls that often beset clinical research with BDSs.

The ultrasound assisted hydration as an opportunity to incorporate nutrients into grains.

Hydration is an important but long step in processing beans. Consequently, any ways of taking advantage of this processing time are desirable. One possibility is to fortify the beans during the hydration process, especially with water-soluble nutrients. This work studied the incorporation of iron into beans during hydration with and without ultrasound, describing the kinetics of water and iron uptake, the entrance pathway and its effect on germination and the cooking process. For that, carioca beans were soaked in ferrous sulfate solution (0.271% w/v) with and without ultrasound (91 W/L; 25 kHz) at 25 °C. It was demonstrated that iron could be incorporated during the hydration process, describing a similar kinetics behavior to the water uptake. In addition, ultrasound accelerated this process, achieving 60.1 mg Fe/100 g w.b. after 510 min of process, in contrast to 34.4 mg Fe/100 g w.b. when the beans were hydrated without ultrasound. Finally, by hydrating the beans with ferrous sulfate, the cooking process was accelerated, which is desirable. However, the capacity for germination of the beans was reduced. In conclusion, the hydration process time can be used to fortify the beans with iron (and, possibly, other water-soluble nutrients). Nevertheless, future studies must be performed to determine if the incorporated iron is bioavailable and bioaccessible, as well as how relevant this approach is as a nutritional policy.

Maternal and neonatal micronutrient levels in newborns with CHD.

OBJECTIVE: It is suggested that folic acid and/or multivitamins, taken periconceptionally, have a role in the prevention of many congenital anomalies. The aim of this study was to determine the serum micronutrient levels in mother-infant pairs with CHD compared with those with healthy newborns and their mothers. METHODS: Serum levels of folic acid, homocysteine, zinc, vitamin A, vitamin D, and vitamin B12 were measured from 108 newborns with CHD (study group) and 103 healthy newborns (control group). The mothers' micronutrient levels were also measured simultaneously. RESULTS: When compared with healthy newborns, for both maternal and neonatal data, homocysteine and zinc levels were higher and vitamin D levels were lower in the study group. In multivariate analysis, only maternal high zinc levels were associated with CHD in the newborns (p=0.02, OR: 0.9, 95% CI 0.8-0.9). The results did not change when analysed for truncal anomalies including truncus arteriosus, tetralogy of Fallot, and d-transposition of great arteries. There were positive correlations between maternal and neonatal levels of micronutrients, except vitamin B12. CONCLUSION: We thought that high homocysteine and zinc levels and low vitamin D levels in mother-infant pairs might have a role in the aetiopathogenesis of CHD. Large-scale, prospective studies are needed to clarify the role of micronutrients in CHDs.

Agronomic Approach of Zinc Biofortification Can Increase Zinc Bioavailability in Wheat Flour and thereby Reduce Zinc Deficiency in Humans.

Zinc (Zn) deficiency is a common disorder of humans in developing countries. The effect of Zn biofortification (via application of six rates of Zn fertilizer to soil) on Zn bioavailability in wheat grain and flour and its impacts on human health was evaluated. Zn bioavailability was estimated with a trivariate model that included Zn homeostasis in the human intestine. As the rate of Zn fertilization increased, the Zn concentration increased in all flour fractions, but the percentages of Zn in standard flour (25%) and bran (75%) relative to total grain Zn were constant. Phytic acid (PA) concentrations in grain and flours were unaffected by Zn biofortification. Zn bioavailability and the health impact, as indicated by disability-adjusted life years (DALYs) saved, increased with the Zn application rate and were greater in standard and refined flour than in whole grain and coarse flour. The biofortified standard and refined flour obtained with application of 50 kg/ha ZnSO4·7H2O met the health requirement (3 mg of Zn obtained from 300 g of wheat flour) and reduced DALYs by >20%. Although Zn biofortification increased Zn bioavailability in standard and refined flour, it did not reduce the bioavailability of iron, manganese, or copper in wheat flour.

Instant noodles made with fortified wheat flour to improve micronutrient intake in Asia: a review of simulation, nutrient retention and sensory studies.

BACKGROUND AND OBJECTIVES: Consumption of foods made with wheat flour, particularly instant noodles, is increasing in Asia. Given this trend, fortifying wheat flour with vitamins and minerals may improve micronutrient intake in the region. The objective of this review was to understand what is known about fortifying wheat flour used to make instant noodles. METHODS AND STUDY DESIGN: A literature review of seven databases was performed using the search terms "noodle" and ("Asian" or "instant"). Grey literature was requested through a food fortification listserv. Articles were title screened first for relevance and duplicity, with exclusion criteria applied during the second round of abstract-level screening. This review considered studies examining simulation, retention, sensory, bioavailability, efficacy, and effectiveness of instant noodles made with fortified wheat flour. RESULTS: Fourteen relevant documents were reviewed for simulation (n=1), retention (n=11), and sensory studies (n=3). The documents revealed that instant noodles produced from fortified wheat flour have potential to improve nutrient intakes, have high retention of most nutrients, and provoke no or minimal changes in sensory characteristics. CONCLUSIONS: The available literature indicates that using fortified wheat flour for instant noodle production results in retention of the added nutrients, except thiamin, with no significant sensory change to the final product. Given the rising consumption of instant noodles, production of this item with fortified wheat flour has potential to improve nutrient intakes in Asia. This review provides a resource for the design of a wheat flour fortification program in countries where a large proportion of wheat flour is consumed as instant noodles.

Bioavailability of Nutrients and Micronutrients: Advances in Modeling and In Vitro Approaches.

The bioavailability of food nutrients and microconstituents is recognized as a determinant factor for optimal health status. However, human and animal studies are expensive and limited by the large amount of potential food bioactive compounds. The search for alternatives is very active and raises many questions. On one hand, in vitro digestion systems are good candidates, but to date only bioaccessibility has been correctly assessed. To go further, to what degree should natural processes be reproduced? What techniques can be used to measure the changes in food properties and structures in situ in a noninvasive way? On the other hand, modeling approaches have good potential, but their development is time-consuming. What compromises should be done between food and physiology realism and computational ease? This review addresses these questions by identifying highly resolved analytical methods, detailed computer models and simulations, and the most promising dynamic in vitro systems.