A short stature allele enhances tolerance to zinc deficiency and translocation of zinc in barley.

Background: Zinc (Zn) content is of great importance in healthy human diet, crop productivity and stress tolerance in soils with zinc deficiency. The genes used to increase yield per unit area such as semi-dwarf 1 (sdw1) is commonly considered to reduce mineral content of grain. Methods: In the present study, influence of sdw1.d, a widely used allele for short plant height in barley breeding, on zinc accumulation and tolerance to zinc deficiency were investigated. A near isogenic line of sdw1.d allele, its recurrent parent Tokak 157/37 and donor parent Triumph were grown in zinc-deficient and-sufficient hydroponic cultures. Two experiments were conducted until heading stage and physiological maturity. Results: In zinc-deficient conditions, sdw1.d allele increased shoot dry weight by 112.4 mg plant-1, shoot Zn concentration by 0.9 ppm, but decreased root Zn concentration by 6.6 ppm. It did not affect grain characteristics, but increased grain Zn content. In zinc-sufficient conditions, sdw1.d allele increased shoot Zn content, and decreased root Zn content. sdw1.d did not affect grain weight but increased grain Zn concentration by about 30% under zinc-sufficient conditions. The results showed that sdw1.d allele has no negative effect on tolerance to zinc deficiency, and even promotes tolerance to zinc deficiency by more Zn translocation. It was revealed that sdw1.d allele improves Zn accumulation under both zinc-deficient and zinc-sufficient condition. The sdw1.d allele could contribute to solving the problems in plant growth and development caused by zinc-deficiency via improving tolerance to zinc-deficiency. It could also provide a better Zn biofortification.

Causal association of micronutrients and supplements with pressure ulcer: A Mendelian randomization study.

BACKGROUND: Pressure ulcer (PU) is known to be associated with abnormalities of micronutrient status. However, to date, it is not clear whether a causal relationship exists between circulating levels of micronutrients and their supplementations and PU. METHODS: A two-sample Mendelian randomization (MR) study was conducted using summary statistics from Genome-Wide Association Studies (GWAS). Genetic instrumental variables (IVs) for 13 micronutrients were identified from a GWAS of 67 582 participants, IVs for supplement zinc were acquired from 18 826 cases and 44 255 880 controls, and IVs for PU were obtained from 663 PUs and 207 482 controls. The MR analysis was conducted using the MR base platform. The main analysis method was inverse variance weighted (IVW) analysis, supplemented by MR Egger, Weighted median, Weighted mode, and Simple mode analyses. Heterogeneity was assessed using Cochran's Q statistic for MR-IVW and Rucker's Q statistic for MR-Egger. Pleiotropy was determined by the MR-Egger regression. Sensitivity analysis was conducted using the leave-one-out method, and publication bias was evaluated using funnel plots. RESULTS: Genetically predicted lower circulating zinc levels were found to be causally linked to the development of PU (OR = 0.758, 95%CI 0.583-0.987, P = 0.040). However, there was no significant evidence of a causal relationship between supplemental zinc intake and PU development (P > 0.05). Additionally, no causal association was observed between the other circulating micronutrients and the occurrence of PU. Furthermore, there was no indication of horizontal pleiotropy or heterogeneity among genetic variants (P > 0.05), and the robustness of the findings was confirmed through leave-one-out tests and funnel plots. CONCLUSIONS: Our findings indicate a potential causal association between circulating zinc levels and decreased risk of PU. However, zinc supplementation did not demonstrate a significant reduction in the risk of PU. Further research is warranted to elucidate the underlying mechanisms through which zinc influences the pathogenesis of PU and evaluate the efficacy of zinc supplementation in the prevention and management of PU.

Zinc and Diabetes: A Connection between Micronutrient and Metabolism.

Diabetes mellitus is a global health problem and a major contributor to mortality and morbidity. The management of this condition typically involves using oral antidiabetic medication, insulin, and appropriate dietary modifications, with a focus on macronutrient intake. However, several human studies have indicated that a deficiency in micronutrients, such as zinc, can be associated with insulin resistance as well as greater glucose intolerance. Zinc serves as a chemical messenger, acts as a cofactor to increase enzyme activity, and is involved in insulin formation, release, and storage. These diverse functions make zinc an important trace element for the regulation of blood glucose levels. Adequate zinc levels have also been shown to reduce the risk of developing diabetic complications. This review article explains the role of zinc in glucose metabolism and the effects of its inadequacy on the development, progression, and complications of diabetes mellitus. Furthermore, it describes the impact of zinc supplementation on preventing diabetes mellitus. The available information suggests that zinc has beneficial effects on the management of diabetic patients. Although additional large-scale randomized clinical trials are needed to establish zinc's clinical utility further, efforts should be made to increase awareness of its potential benefits on human health and disease.

Extremely rare complication in high-risk newborn on long-term parenteral nutrition and large stool losses through ileostomy.

AIM: To analyse postnatal characteristics, clinical and laboratory findings, results of investigations in the newborn (25 gestational weeks; Apgar score: 6/9 points; born per caesarean section; birth weight: 600 g; birth length: 31 cm; head circumference: 21 cm) from the first high-risk pregnancy with acquired form of acrodermatitis enteropathica. RESULTS: After summarizing the clinical picture with laboratory findings, we analysed the components of parenteral nutrition with regard to the deficiency of trace elements and vitamins. The zinc depletion dominated. CONCLUSION: The diagnosis is clinical, based on the presence of a typical clinical picture together with a low serum zinc concentration. Standard preparations with elementary elements do not sufficiently cover the daily needs of children, other possibilities of supplementation in intravenous form are not available. It is necessary to supplement zinc in premature children, in children with high losses of zinc (with diarrhoea, in patients with a stoma, in patients with severe skin disease) (Fig. 4, Ref. 15).

Managing Micronutrient Deficiencies in High-Risk Patients: No Small Feat!

PURPOSE OF REVIEW: Micronutrients are vital dietary components for growth and development. Adequate intake of vitamins and minerals through diet is crucial for proper biomolecular and cellular functioning. Many developed countries supplement foods and micronutrient deficiencies are less common. However, many disease states impair micronutrient absorption, metabolism, and excretion. Thus, early recognition of the signs and symptoms of micronutrient deficiencies is critical for providers to improve quality of life and prevent complications in high-risk patients. This article reviews the basic function of micronutrients, recognizes the symptoms of each micronutrient deficiency, provides natural sources of intake, and discusses the diagnosis and supplementation of each micronutrient. High risk patients based on disease state for each micronutrient is discussed. In addition, Bariatric patients are a specific group at high risk of micronutrient deficiency and their management and supplementation for treatment is also covered. RECENT FINDINGS: Micronutrients play a vital role in antioxidant defense, especially in critically ill patients, due to an increase in oxidative stress. Early intervention with high-dose supplementation with vitamin C, vitamin E, zinc and selenium may have beneficial effects. Micronutrients deficiency remains an issue for patients in the developed world. Providers should recognize patients who are at high risk for micronutrients deficiencies and provide proper screening and prompt supplementation after diagnosis to prevent complications of micronutrient deficiencies.

Postnatal zinc deficiency due to giardiasis disrupts hippocampal and cerebellar development.

BACKGROUND: Giardiasis and zinc deficiency have been identified as serious health problems worldwide. Although Zn depletion is known to occur in giardiasis, no work has investigated whether changes occur in brain structures. METHODS: Three groups of gerbils were used: control (1), orogastrically inoculated on day 3 after birth with trophozoites of two isolates of Giardia intestinalis (HGINV/WB) group (2 and 3). Estimates were made at five ages covering: establishment of infection, Giardia population growth, natural parasite clearance and a post-infection age. QuantiChrome zinc assay kit, cresyl violet staining and TUNEL technique were used. RESULTS: A significant decrease (p<0.01) in tissue zinc was observed and persisted after infection. Cytoarchitectural changes were observed in 75% of gerbils in the HGINV or WB groups. Ectopic pyramidal neurons were found in the cornus ammonis (CA1-CA3). At 60 and 90 days of age loss of lamination was clearly visible in CA1. In the dentate gyrus (DG), thinning of the dorsal lamina and abnormal thickening of the ventral lamina were observed from 30 days of age. In the cerebellum, we found an increase (p<0.01) in the thickness of the external granular layer (EGL) at 14 days of age that persisted until day 21 (C 3 ± 0.3 µm; HGINV 37 ± 5 µm; WB 28 ± 3 µm); Purkinje cell population estimation showed a significant decrease; a large number of apoptotic somas were observed scattered in the molecular layer; in 60 and 90 days old gerbils we found granular cell heterotopia and Purkinje cell ectopia. The pattern of apoptosis was different in the cerebellum and hippocampus of parasitized gerbils. CONCLUSION: The morphological changes found suggest that neuronal migration is affected by zinc depletion caused by giardiasis in early postnatal life; for the first time, the link between giardiasis-zinc depletion and damaged brain structures is shown. This damage may explain the psychomotor/cognitive delay associated with giardiasis. These findings are alarming. Alterations in zinc metabolism and signalling are known to be involved in many brain disorders, including autism.

Trace Element Deficiency in Systemic Sclerosis-Too Much Effort for Some Traces?

Trace elements are essential for several physiological processes. To date, various data have suggested that inadequate levels of trace elements may be involved in the pathogenesis of different chronic diseases, including immune-mediated ones, or may develop during their course. Systemic sclerosis (SSc) is a complex autoimmune multisystemic disease, primarily characterized by microvascular dysregulation, the widespread activation of the immune system and tissue fibrosis. According to the latest reports regarding the pathogenesis of SSc, the main pathophysiological processes-inflammation, vasculopathy and fibrosis-may include various trace element derangements. The present literature review aims to update the available data regarding iron, zinc, copper and selenium status in SSc as well as to underline the possible implications of these trace elements in the complexity of the pathogenic process of the disease. We observe that the status of trace elements in SSc plays a crucial role in numerous pathogenic processes, emphasizing the necessity for proper monitoring and supplementation. The reported data are heterogenous and scarce, and future studies are needed in order to draw clearer conclusions about their complete spectrum.

The Hidden Hunger among Nepalese Non-Pregnant Women Aged 15-49 Years: The Role of Individual, Household, and Community-Level Factors.

Micronutrient deficiencies remain a public health burden among non-pregnant women in developing countries, including Nepal. Hence, this study examined micronutrient deficiencies among non-pregnant Nepalese women aged 15-49 using the 2016 Nepal National Micronutrient Status Survey (NNMSS). Data for 2143 non-pregnant women was extracted from the 2016 NNMSS. The study analysed the levels of ferritin, soluble transferrin receptor (sTfR), red blood cell (RBC) folate, and zinc of the participants. Multivariable logistic analysis was carried out to assess factors associated with micronutrient deficiencies. The prevalence of ferritin, sTfR, folate, and zinc was observed to be 19%, 13%, 16%, and 21%, respectively. Non-pregnant women from the Janajati region were significantly less prone to high levels of ferritin [adjusted odds ratio (AOR): 0.45; 95% confidence interval (CI): 0.25, 0.80], and those who had body mass index (BMI) of 25 kg/m2 or higher had significantly elevated ferritin levels [AOR: 2.69; 95% CI: 1.01, 7.17]. Non-pregnant women aged 35-49 years were significantly less predisposed to folate deficiency [AOR: 0.58; 95% CI: 0.40, 0.83], and the odds of zinc deficiency were significantly lower among non-pregnant women from wealthier households [AOR: 0.48; 95% CI: 0.31, 0.76]. This study provides further insight into screening high-risk subgroups and instituting public health interventions to address the prevailing micronutrient deficiencies among non-pregnant Nepalese women.

Zinc Deficiency and Zinc Supplementation in Allergic Diseases.

In recent decades, it has become clear that allergic diseases are on the rise in both Western and developing countries. The exact reason for the increase in prevalence has not been conclusively clarified yet. Multidimensional approaches are suspected in which diet and nutrition seem to play a particularly important role. Allergic diseases are characterized by a hyper-reactive immune system to usually harmless allergens, leading to chronic inflammatory diseases comprising respiratory diseases like asthma and allergic rhinitis (AR), allergic skin diseases like atopic dermatitis (AD), and food allergies. There is evidence that diet can have a positive or negative influence on both the development and severity of allergic diseases. In particular, the intake of the essential trace element zinc plays a very important role in modulating the immune response, which was first demonstrated around 60 years ago. The most prevalent type I allergies are mainly based on altered immunoglobulin (Ig)E and T helper (Th)2 cytokine production, leading to type 2 inflammation. This immune status can also be observed during zinc deficiency and can be positively influenced by zinc supplementation. The underlying immunological mechanisms are very complex and multidimensional. Since zinc supplements vary in dose and bioavailability, and clinical trials often differ in design and structure, different results can be observed. Therefore, different results are not surprising. However, the current literature suggests a link between zinc deficiency and the development of allergies, and shows positive effects of zinc supplementation on modulating the immune system and reducing allergic symptoms, which are discussed in more detail in this review.

Zinc Toxicity: Understanding the Limits.

Zinc, a vital trace element, holds significant importance in numerous physiological processes within the body. It participates in over 300 enzymatic reactions, metabolic functions, regulation of gene expression, apoptosis and immune modulation, thereby demonstrating its essential role in maintaining overall health and well-being. While zinc deficiency is associated with significant health risks, an excess of this trace element can also lead to harmful effects. According to the World Health Organization (WHO), 6.7 to 15 mg per day are referred to be the dietary reference value. An excess of the recommended daily intake may result in symptoms such as anemia, neutropenia and zinc-induced copper deficiency. The European Food Safety Authority (EFSA) defines the tolerable upper intake level (UL) as 25 mg per day, whereas the Food and Drug Administration (FDA) allows 40 mg per day. This review will summarize the current knowledge regarding the calculation of UL and other health risks associated with zinc. For example, zinc intake is not limited to oral consumption; other routes, such as inhalation or topical application, may also pose risks of zinc intoxication.

Differential effectiveness of dietary zinc supplementation with autism-related behaviours in Shank2 knockout mice.

The family of SHANK proteins have been shown to be critical in regulating glutamatergic synaptic structure, function and plasticity. SHANK variants are also prevalent in autism spectrum disorders (ASDs), where glutamatergic synaptopathology has been shown to occur in multiple ASD mouse models. Our previous work has shown that dietary zinc in Shank3-/- and Tbr1+/- ASD mouse models can reverse or prevent ASD behavioural and synaptic deficits. Here, we have examined whether dietary zinc can influence behavioural and synaptic function in Shank2-/- mice. Our data show that dietary zinc supplementation can reverse hyperactivity and social preference behaviour in Shank2-/- mice, but it does not alter deficits in working memory. Consistent with this, at the synaptic level, deficits in NMDA/AMPA receptor-mediated transmission are also not rescued by dietary zinc. In contrast to other ASD models examined, we observed that SHANK3 protein was highly expressed at the synapses of Shank2-/- mice and that dietary zinc returned these to wild-type levels. Overall, our data show that dietary zinc has differential effectiveness in altering ASD behaviours and synaptic function across ASD mouse models even within the Shank family. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.

Efficacy of Zinc Fortified and Fermented Wheat Flour (EZAFFAW): A randomized controlled trial protocol.

BACKGROUND: Zinc deficiency poses significant health risks, particularly in low-income settings. This study aims to evaluate the impact of agronomically zinc biofortified (fermented and non-fermented) and post-harvest wheat flour flatbread on zinc status and metabolic health in adolescents and adult women in rural Pakistan. METHODS: A four-arm triple-blind randomized controlled trial will be conducted in a rural district of Pakistan. Participants (adolescents aged 10-19 and adult women aged 20-40) will be assigned to receive fermented or unfermented high zinc agronomically biofortified wheat flour flatbread, post-harvest zinc-fortified wheat flour flatbread, or low zinc conventional whole wheat flour flatbread. The meal would be served once a day, six days a week for six months. The study aims to enroll 1000 participants and will be analyzed based on the intention-to-treat principle. The trial is registered with number NCT06092515. OUTCOMES: Primary outcomes will include serum zinc concentration and metabolic markers, while secondary outcomes include anthropometric measurements, blood pressure, and dietary intake. CONCLUSION: This trial will provide valuable insights into the efficacy of agronomically zinc biofortified wheat flour in improving zinc status and metabolic health. Findings may inform public health strategies to combat zinc deficiency in resource-limited settings.

Faecal microbiota of schoolchildren is associated with nutritional status and markers of inflammation: a double-blinded cluster-randomized controlled trial using multi-micronutrient fortified rice.

Faecal microbiota plays a critical role in human health, but its relationship with nutritional status among schoolchildren remains under-explored. Here, in a double-blinded cluster-randomized controlled trial on 380 Cambodian schoolchildren, we characterize the impact of six months consumption of two types of rice fortified with different levels of vitamins and minerals on pre-specified outcomes. We investigate the association between the faecal microbiota (16SrRNA sequencing) and age, sex, nutritional status (underweight, stunting), micronutrient status (iron, zinc and vitamin A deficiencies, anaemia, iron deficient anaemia, hemoglobinopathy), inflammation (systemic, gut), and parasitic infection. We show that the faecal microbiota is characterised by a surprisingly high proportion of Lactobacillaceae. We discover that deficiencies in specific micronutrients, such as iron and vitamin A, correlate with particular microbiota profiles, whereas zinc deficiency shows no such association. The nutritional intervention with the two rice treatments impacts both the composition and functions predicted from compositional analysis in different ways. (ClinicalTrials.gov (Identifier: NCT01706419)).

Marginal Zinc Deficiency Promotes Pancreatic Islet Enlargement While Zinc Supplementation Improves the Pancreatic Insulin Response in Zucker Diabetic Fatty Rats.

Zinc deficiency has been associated with the worsening of diabetes while zinc supplementation has been proposed to ameliorate diabetes. This study examined the effects of marginal zinc deficiency (MZD) and zinc supplementation (ZS) on obesity, glycemic control, pancreatic islets, hepatic steatosis and renal function of Zucker diabetic fatty (ZDF) rats. Male ZDF rats were fed an MZD, zinc control (ZC) or ZS diet (4, 30 and 300 mg Zn/kg diet, respectively), and lean Zucker rats were fed a ZC diet for 8 weeks. MZD and ZS did not alter body weight or whole-body composition in ZDF rats. MZD ZDF rats had reduced zinc concentrations in the femur and pancreas, a greater number of enlarged pancreatic islets and a diminished response to an oral glucose load based on a 1.8-fold greater incremental area-under-the-curve (AUC) for glucose compared to ZC ZDF. ZS ZDF rats had elevated serum, femur and pancreatic zinc concentrations, unchanged pancreatic parameters and a 50% reduction in the AUC for insulin compared to ZC ZDF rats, suggesting greater insulin sensitivity. Dietary zinc intake did not alter hepatic steatosis, creatinine clearance, or levels of proteins that contribute to insulin signaling, inflammation or zinc transport in epididymal fat. Potential adverse effects of ZS were suggested by reduced hepatic copper concentrations and elevated serum urea compared to ZC ZDF rats. In summary, ZS improved the pancreatic insulin response but not the glucose handling. In contrast, reduced zinc status in ZDF rats led to impaired glucose tolerance and a compensatory increase in the number and size of pancreatic islets which could lead to ß-cell exhaustion.

Mandatory large-scale food fortification programmes can reduce the estimated prevalence of inadequate zinc intake by up to 50% globally.

Large-scale food fortification (LSFF) can increase dietary micronutrient intake and improve micronutrient status. Here we used food balance sheet data from the Food and Agriculture Organization of the United Nations to estimate current country-specific prevalences of inadequate zinc intake. We assessed the potential effects of improving existing LSFF programmes for cereal grains or implementing new programmes in 40 countries where zinc deficiency is a potential public health problem. Accounting for LSFF programmes as currently implemented, 15% of the global population (1.13 billion individuals) is estimated to have inadequate zinc intake. In countries where zinc deficiency is a potential public health problem, the implementation of high-quality mandatory LSFF programmes that include zinc as a fortificant would substantially increase the availability of zinc in the national food supply, reducing the estimated prevalence of inadequate zinc intake by up to 50% globally. Investments in strong LSFF programmes could have a substantial impact on population zinc status.

MS785-MS27 Reactive Misfolded/Non-Native Zn-Deficient SOD1 Species Exhibit Cytotoxicity and Adopt Heterozygous Conformations in Motor Neurons.

Misfolding of superoxide dismutase-1 (SOD1) is a pathological hallmark of amyotrophic lateral sclerosis (ALS) with SOD1 mutations. The development of antibodies specific for misfolded SOD1 deepens our understanding of how the protein participates in ALS pathogenesis. Since the term "misfolding" refers to various disordered conformers other than the natively folded one, which misfolded species are recognized by specific antibodies should be determined. Here, we molecularly characterized the recognition by MS785-MS27, an antibody cocktail experimentally confirmed to recognize over 100 ALS-linked SOD1 mutants. Indirect ELISA revealed that the antibody cocktail recognized Zn-deficient wild-type and mutated SOD1 species. It also recognized conformation-disordered wild-type and mutated SOD1 species, such as unfolded and oligomeric forms, but had less affinity for the aggregated form. Antibody-reactive SOD1 exhibited cytotoxicity to a motor neuron cell model, which was blocked by Zn treatment with Zn-deficient SOD1. Immunohistochemistry revealed antibody-reactive SOD1 mainly in spinal motor neurons of SOD1G93A mice throughout the disease course, and the distribution after symptomatic stages differed from that of other misfolded SOD1 species. This suggests that misfolded/non-native SOD1 species exist as heterogeneous populations. In conclusion, MS785-MS27 recognizes various conformation-disordered SOD1 species lacking the Zn ion.

Effect of Enteral Zinc Supplementation on the Anthropometric Measurements of Preterm Infants at Discharge from the Neonatal Intensive Care Unit and Evaluation of Copper Deficiency.

Enteral zinc supplementation in preterm infants has been reported to improve short-term weight and height gain. This study aims to evaluate whether early enteral zinc supplementation in preterm infants admitted to the neonatal intensive care unit (NICU) affects their physical measurements at discharge, and to periodically test serum copper levels. Of the 221 patients admitted to the NICU, 102 were in the zinc group and 119 were in the no-zinc group. The zinc group was administered 3 mg/kg/day of zinc. Body weight, height, and head circumference at discharge (or on the expected delivery date) were evaluated, and the factors affecting these parameters were examined. Serum zinc and copper levels were also evaluated on admission and monthly thereafter. Multivariate analysis was performed and showed that the weeks of gestational age and small for gestational age (SGA) status affected the height and weight at discharge. SGA also affected the head circumference. Serum copper levels were within the reference range for all patients at 3 months of age. Enteral zinc supplementation of 3 mg/kg/day in preterm infants did not affect the weight, height, or head circumference at discharge, but was shown to be relatively safe.