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Consales A, Agostoni C, Cazzola R, Ottria R, Giannì ML. Tracing Zinc's Role in Preterm Infants' Health: A Narrative Review. Adv Nutr 2024; 15:100295. [PMID: 39675840 PMCID: PMC11705620 DOI: 10.1016/j.advnut.2024.100295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 08/30/2024] [Accepted: 09/03/2024] [Indexed: 12/17/2024] Open
Abstract
Zinc (Zn) is a trace element involved in numerous physiological processes, including enzyme function, gene transcription, and cell signaling. Its importance is especially pronounced in preterm infants, who are at high risk of Zn deficiency due to disrupted transplacental transfer, high nutrient demands, and medical complications. The inherent risk of Zn deficiency in this population is further increased by poor Zn dietary intake. Human milk from preterm mothers contains low concentrations of Zn, although it is highly bioavailable. Additionally, the Zn content steadily declines from colostrum (first few days postpartum) to mature milk (>10-14 d postpartum). Formula milk contains higher Zn concentrations to compensate for nutrient losses during production and storage, and lower bioavailability compared with human milk, which is further decreased in case of high phytate content, such as in soy milk-based formulas. Zn supplements may prove useful in meeting the preterm infant's needs, although caution is warranted regarding potential interactions with other nutrients within multinutrient supplements. Early detection of Zn deficiency is challenging due to the lack of reliable Zn status biomarkers, necessitating a high index of suspicion. Clinical signs of Zn deficiency can range from mild, nonspecific symptoms to severe, multisystem involvement. Chronic deficiency may lead to failure to thrive. Zn supplementation can support growth and mitigate comorbidities in preterm infants, although variability across studies complicates efforts to establish optimal dosing, and define safety and long-term effects. Although rare, Zn toxicity in preterm infants should not be overlooked, especially in infants on long-term parenteral nutrition. This narrative review aimed to consolidate existing knowledge and identify research gaps, highlighting the critical role of Zn in supporting preterm infants' health. Further research is needed to establish evidence-based practices to improve health outcomes in this vulnerable population.
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Affiliation(s)
- Alessandra Consales
- Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023-2027, University of Milan, Milan, Italy
| | - Carlo Agostoni
- Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023-2027, University of Milan, Milan, Italy; Pediatric Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
| | - Roberta Cazzola
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
| | - Roberta Ottria
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
| | - Maria Lorella Giannì
- Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023-2027, University of Milan, Milan, Italy; NICU, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
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2
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Cirovic A, Cirovic A, Yimthiang S, Vesey DA, Satarug S. Modulation of Adverse Health Effects of Environmental Cadmium Exposure by Zinc and Its Transporters. Biomolecules 2024; 14:650. [PMID: 38927054 PMCID: PMC11202194 DOI: 10.3390/biom14060650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Revised: 05/22/2024] [Accepted: 05/30/2024] [Indexed: 06/28/2024] Open
Abstract
Zinc (Zn) is the second most abundant metal in the human body and is essential for the function of 10% of all proteins. As metals cannot be synthesized or degraded, they must be assimilated from the diet by specialized transport proteins, which unfortunately also provide an entry route for the toxic metal pollutant cadmium (Cd). The intestinal absorption of Zn depends on the composition of food that is consumed, firstly the amount of Zn itself and then the quantity of other food constituents such as phytate, protein, and calcium (Ca). In cells, Zn is involved in the regulation of intermediary metabolism, gene expression, cell growth, differentiation, apoptosis, and antioxidant defense mechanisms. The cellular influx, efflux, subcellular compartmentalization, and trafficking of Zn are coordinated by transporter proteins, solute-linked carriers 30A and 39A (SLC30A and SLC39A), known as the ZnT and Zrt/Irt-like protein (ZIP). Because of its chemical similarity with Zn and Ca, Cd disrupts the physiological functions of both. The concurrent induction of a Zn efflux transporter ZnT1 (SLC30A1) and metallothionein by Cd disrupts the homeostasis and reduces the bioavailability of Zn. The present review highlights the increased mortality and the severity of various diseases among Cd-exposed persons and the roles of Zn and other transport proteins in the manifestation of Cd cytotoxicity. Special emphasis is given to Zn intake levels that may lower the risk of vision loss and bone fracture associated with Cd exposure. The difficult challenge of determining a permissible intake level of Cd is discussed in relation to the recommended dietary Zn intake levels.
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Affiliation(s)
- Ana Cirovic
- Institute of Anatomy, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (A.C.); (A.C.)
| | - Aleksandar Cirovic
- Institute of Anatomy, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (A.C.); (A.C.)
| | - Supabhorn Yimthiang
- Environmental Safety Technology and Health, School of Public Health, Walailak University, Nakhon Si Thammarat 80160, Thailand;
| | - David A. Vesey
- Centre for Kidney Disease Research, Translational Research Institute, Brisbane, QLD 4102, Australia;
- Department of Kidney and Transplant Services, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia
| | - Soisungwan Satarug
- Centre for Kidney Disease Research, Translational Research Institute, Brisbane, QLD 4102, Australia;
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3
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Weaver CM, Wastney M, Fletcher A, Lividini K. An Algorithm to Assess Calcium Bioavailability from Foods. J Nutr 2024; 154:921-927. [PMID: 38072154 DOI: 10.1016/j.tjnut.2023.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 11/30/2023] [Accepted: 12/06/2023] [Indexed: 12/28/2023] Open
Abstract
BACKGROUND The recommended calcium intakes to meet calcium requirements at various ages are based on average population absorption values. Absorption is altered by physiology, the calcium load, and type of food. The calcium intake necessary, therefore, to meet requirements depends upon diet composition, through bioavailability. OBJECTIVE The objectives of this study was to improve predictions of calcium bioavailability on the basis of the food matrix. METHODS We modeled calcium absorption data from individual foods, beverages, and fortified foods that were determined with calcium isotopic tracers and compared with milk as a referent to adjust for physiologic differences of the host. RESULTS Data from 496 observations were modeled to develop a predictive algorithm for calcium bioavailability in adults on the basis of calcium load and oxalate and phytate loads, which represent the 2 main inhibitors of calcium absorption. CONCLUSIONS This algorithm will be helpful in assessing calcium availability from the food supply, for developing diets for individuals and research cohorts, and for designing policies and interventions to address inadequate calcium intake for populations.
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Affiliation(s)
- Connie M Weaver
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, CA, United States.
| | - Meryl Wastney
- Metabolic Modeling Services, West Lafayette, IN, United States
| | - Andrew Fletcher
- Sustainable Nutrition Initiative®, Riddet Institute, Massey University, Palmerston North, New Zealand; Fonterra Research and Development Centre, Palmerston North, New Zealand
| | - Keith Lividini
- Research Delivery & Impact Division/International Food Policy Research Institute (IFPRI), Washington DC, United States; Friedman School of Nutrition Science and Policy, Tufts University, Boston MA, United States
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4
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Noor RA, Abioye AI, Darling AM, Hertzmark E, Aboud S, Premji Z, Mugusi FM, Duggan C, Sudfeld CR, Spiegelman D, Fawzi W. Prenatal Zinc and Vitamin A Reduce the Benefit of Iron on Maternal Hematologic and Micronutrient Status at Delivery in Tanzania. J Nutr 2020; 150:240-248. [PMID: 31618430 PMCID: PMC7373818 DOI: 10.1093/jn/nxz242] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 05/28/2019] [Accepted: 09/11/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Zinc and vitamin A supplementation have both been shown to affect iron status, hemoglobin (Hb) concentration, and anemia in animal and human studies. However, evidence on their combined use in pregnancy, in the context of iron-folic acid (IFA) supplementation, remains limited. OBJECTIVE This study determined the effects of prenatal zinc, vitamin A, and iron supplementation on maternal hematologic and micronutrient status at delivery in Tanzania. METHODS We analyzed 2 large randomized controlled trials, using generalized estimating equations, and examined the effect of daily zinc (25 mg) and vitamin A (2500 IU) supplementation starting in the first trimester of pregnancy compared with placebo (n = 2500), and separately evaluated the safety and efficacy of daily iron (60 mg) supplementation among iron-replete pregnant women (n = 1500). Blood samples from baseline and delivery were tested for Hb, serum ferritin, soluble transferrin receptor, plasma zinc, and zinc protoporphyrin. RESULTS Zinc and vitamin A supplementation were associated with lower Hb concentrations at delivery of -0.26 g/dL (95% CI: -0.50, -0.02 g/dL) and -0.25 g/dL (95% CI: -0.49, -0.01 g/dL), respectively. Vitamin A increased mean ferritin concentrations at delivery (14.3 μg/L, 95% CI: 1.84, 29.11 μg/L), but was associated with increased risk of severe anemia (RR: 1.41; 95% CI: 1.06, 1.88). Among women who were iron replete at baseline, iron supplementation reduced the risk of iron depletion at delivery by 47% (RR: 0.53; 95% CI: 0.43, 0.65). There was no effect of zinc or iron supplements on plasma zinc concentrations. CONCLUSIONS Our findings support existing WHO guidelines on prenatal iron, vitamin A, and zinc supplementation among pregnant women. In this setting, scaling uptake of prenatal iron supplements is warranted, but prenatal zinc and vitamin A supplementation did not benefit maternal hematologic status at delivery. In settings where vitamin A deficiency is endemic, the efficacy and safety of the WHO recommended prenatal vitamin A supplementation require further evaluation.
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Affiliation(s)
- Ramadhani A Noor
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
| | - Ajibola I Abioye
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
| | - Anne Marie Darling
- Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, MA, USA
| | - Ellen Hertzmark
- Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, MA, USA
| | - Said Aboud
- Department of Microbiology and Immunology, School of Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | - Zulfiqarali Premji
- Department of Parasitology/Medical Entomology, School of Public Health and Social Sciences, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | - Ferdinand M Mugusi
- Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | - Christopher Duggan
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
- Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, MA, USA
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Christopher R Sudfeld
- Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, MA, USA
| | - Donna Spiegelman
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
- Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, MA, USA
- Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA
- Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, MA, USA
- Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA
| | - Wafaie Fawzi
- Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA
- Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, MA, USA
- Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA
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5
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Knez M, Graham RD, Welch RM, Stangoulis JCR. New perspectives on the regulation of iron absorption via cellular zinc concentrations in humans. Crit Rev Food Sci Nutr 2017; 57:2128-2143. [PMID: 26177050 DOI: 10.1080/10408398.2015.1050483] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Iron deficiency is the most prevalent nutritional deficiency, affecting more than 30% of the total world's population. It is a major public health problem in many countries around the world. Over the years various methods have been used with an effort to try and control iron-deficiency anemia. However, there has only been a marginal reduction in the global prevalence of anemia. Why is this so? Iron and zinc are essential trace elements for humans. These metals influence the transport and absorption of one another across the enterocytes and hepatocytes, due to similar ionic properties. This paper describes the structure and roles of major iron and zinc transport proteins, clarifies iron-zinc interactions at these sites, and provides a model for the mechanism of these interactions both at the local and systemic level. This review provides evidence that much of the massive extent of iron deficiency anemia in the world may be due to an underlying deficiency of zinc. It explains the reasons for predominance of cellular zinc status in determination of iron/zinc interactions and for the first time thoroughly explains mechanisms by which zinc brings about these changes.
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Affiliation(s)
- Marija Knez
- a School of Biological Sciences, Flinders University , Adelaide , South Australia , Australia
| | - Robin D Graham
- a School of Biological Sciences, Flinders University , Adelaide , South Australia , Australia
| | - Ross M Welch
- b USDA/ARS, Robert W. Holley Centre for Agriculture and Health, Cornell University , Ithaca , New York , USA
| | - James C R Stangoulis
- a School of Biological Sciences, Flinders University , Adelaide , South Australia , Australia
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Kordas K. The "Lead Diet": Can Dietary Approaches Prevent or Treat Lead Exposure? J Pediatr 2017; 185:224-231.e1. [PMID: 28283259 DOI: 10.1016/j.jpeds.2017.01.069] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Revised: 12/29/2016] [Accepted: 01/27/2017] [Indexed: 10/20/2022]
Affiliation(s)
- Katarzyna Kordas
- Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY.
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7
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Ribeiro SMDF, Moya AMTM, Braga CBM, Domenici FA, Feitosa MR, Feres O, Rocha JJRD, Cunha SFDCD. Copper-Zinc ratio and nutritional status in colorectal cancer patients during the perioperative period. Acta Cir Bras 2017; 31 Suppl 1:24-8. [PMID: 27142901 DOI: 10.1590/s0102-86502016001300006] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2024] Open
Abstract
PURPOSE This study aimed to determine Cu/Zn ratio, nutritional and inflammatory status in patients during the perioperative period for colorectal cancer. METHODS The study included patients with histological diagnosis of colorectal adenocarcinoma (Cancer Group, n=46) and healthy volunteers (Control Group, n=28). We determined habitual food intake, body composition, laboratory data of nutritional status, serum calprotectin and plasma Cu and Zn concentrations. Mann-Whitney U-test was performed between-group comparisons and Spearman correlation test for correlations between the variables. RESULTS Individuals in the Cancer Group presented significantly lower BMI, fat mass, plasma hemoglobin, total protein and albumin as compared with the Control Group. Serum calprotectin[70.1 ng/mL (CI95% 55.8-84.5) vs.53.3 ng/mL (40.3-66.4), p=0.05], plasma Cu concentrations [120 µg/dL(CI95% 114-126) vs. 106 µg/dL(CI95% 98-114), p<0.01] and the Cu/Zn ratio [1.59 (CI95% 1.48-1.71)vs. 1.35 (CI95% 1.23-1.46), p=0.01]were higher in patients with colorectal cancer than in controls. Additionally, the Cancer Group showed negative correlations between the Cu/Zn ratio and Zn intake, hemoglobin, serum albumin, and positive correlation between the Cu/Zn ratio and serum calprotectin. CONCLUSION These results indicate that an increased plasma Cu/Zn ratio and serum calprotectin, and decreased protein values may be a result of the systemic inflammatory response to the tumor process.
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Affiliation(s)
| | | | | | | | - Marley Ribeiro Feitosa
- Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Brazil
| | - Omar Feres
- Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Brazil
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8
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Brnić M, Hurrell RF, Songré-Ouattara LT, Diawara B, Kalmogho-Zan A, Tapsoba C, Zeder C, Wegmüller R. Effect of phytase on zinc absorption from a millet-based porridge fed to young Burkinabe children. Eur J Clin Nutr 2016; 71:137-141. [DOI: 10.1038/ejcn.2016.199] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2016] [Revised: 08/21/2016] [Accepted: 09/01/2016] [Indexed: 11/09/2022]
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9
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Alves CX, de Brito NJN, Vermeulen KM, Dantas Lopes MMG, França MC, Bruno SS, Almeida MDG, Brandão-Neto J. Serum zinc reference intervals and its relationship with dietary, functional, and biochemical indicators in 6- to 9-year-old healthy children. Food Nutr Res 2016; 60:30157. [PMID: 27053632 PMCID: PMC4823628 DOI: 10.3402/fnr.v60.30157] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2015] [Revised: 02/24/2016] [Accepted: 02/25/2016] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND Zinc is an important cause of morbidity, particularly among young children. The dietary, functional, and biochemical indicators should be used to assess zinc status and to indicate the need for zinc interventions. OBJECTIVE The purpose of this study was to determine the zinc status and reference intervals for serum zinc concentration considering dietary, functional, and biochemical indicators in apparently healthy children in the Northeast Region of Brazil. DESIGN The cross-sectional study included 131 healthy children: 72 girls and 59 boys, aged between 6 and 9 years. Anthropometric assessment was made by body mass index (BMI) and age; dietary assessment by prospective 3-day food register, and an evaluation of total proteins was performed. Zinc in the serum samples was analyzed in triplicate in the same assay flame, using atomic absorption spectrophotometry. RESULTS With respect to dietary assessment, only the intake of fiber and calcium was below the recommendations by age and gender. All subjects were eutrophic according to BMI and age classification. Zinc intake correlated with energy (p=0.0019), protein (p=0.0054), fat (p<0.0001), carbohydrate (p=0.0305), fiber (p=0.0465), calcium (p=0.0006), and iron (p=0.0003) intakes. Serum zinc correlated with protein intake (p=0.0145) and serum albumin (p=0.0141), globulin (p=0.0041), and albumin/globulin ratio (p=0.0043). Biochemical parameters were all within the normal reference range. Reference intervals for basal serum zinc concentration were 0.70-1.14 µg/mL in boys, 0.73-1.17 µg/mL in girls, and 0.72-1.15 µg/mL in the total population. CONCLUSIONS This study presents pediatric reference intervals for serum zinc concentration, considering dietary, functional, and biochemical indicators, which are useful to establish the zinc status in specific groups. In this regard, there are few studies in the literature conducted under these conditions, which make it an innovative methodology.
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Affiliation(s)
- Camila Xavier Alves
- Department of Internal Medicine, Postgraduate Program in Health Sciences, Federal University of Rio Grande do Norte, Natal, RN, Brazil
| | - Naira Josele Neves de Brito
- Department of Internal Medicine, Postgraduate Program in Health Sciences, Federal University of Rio Grande do Norte, Natal, RN, Brazil
| | - Karina Marques Vermeulen
- Department of Internal Medicine, Postgraduate Program in Health Sciences, Federal University of Rio Grande do Norte, Natal, RN, Brazil
| | - Márcia Marília Gomes Dantas Lopes
- Department of Internal Medicine, Postgraduate Program in Health Sciences, Federal University of Rio Grande do Norte, Natal, RN, Brazil
| | | | - Selma Sousa Bruno
- Department of Physiotherapy, Federal University of Rio Grande do Norte, Natal, RN, Brazil
| | - Maria das Graças Almeida
- Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, RN, Brazil
| | - José Brandão-Neto
- Department of Internal Medicine, Federal University of Rio Grande do Norte, Natal, Brazil;
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Raiten DJ, Sakr Ashour FA, Ross AC, Meydani SN, Dawson HD, Stephensen CB, Brabin BJ, Suchdev PS, van Ommen B. Inflammation and Nutritional Science for Programs/Policies and Interpretation of Research Evidence (INSPIRE). J Nutr 2015; 145:1039S-1108S. [PMID: 25833893 PMCID: PMC4448820 DOI: 10.3945/jn.114.194571] [Citation(s) in RCA: 168] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Revised: 06/08/2014] [Accepted: 10/29/2014] [Indexed: 02/06/2023] Open
Abstract
An increasing recognition has emerged of the complexities of the global health agenda—specifically, the collision of infections and noncommunicable diseases and the dual burden of over- and undernutrition. Of particular practical concern are both 1) the need for a better understanding of the bidirectional relations between nutritional status and the development and function of the immune and inflammatory response and 2) the specific impact of the inflammatory response on the selection, use, and interpretation of nutrient biomarkers. The goal of the Inflammation and Nutritional Science for Programs/Policies and Interpretation of Research Evidence (INSPIRE) is to provide guidance for those users represented by the global food and nutrition enterprise. These include researchers (bench and clinical), clinicians providing care/treatment, those developing and evaluating programs/interventions at scale, and those responsible for generating evidence-based policy. The INSPIRE process included convening 5 thematic working groups (WGs) charged with developing summary reports around the following issues: 1) basic overview of the interactions between nutrition, immune function, and the inflammatory response; 2) examination of the evidence regarding the impact of nutrition on immune function and inflammation; 3) evaluation of the impact of inflammation and clinical conditions (acute and chronic) on nutrition; 4) examination of existing and potential new approaches to account for the impact of inflammation on biomarker interpretation and use; and 5) the presentation of new approaches to the study of these relations. Each WG was tasked with synthesizing a summary of the evidence for each of these topics and delineating the remaining gaps in our knowledge. This review consists of a summary of the INSPIRE workshop and the WG deliberations.
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Affiliation(s)
- Daniel J Raiten
- Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD;
| | - Fayrouz A Sakr Ashour
- Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD
| | - A Catharine Ross
- Departments of Nutritional Sciences and Veterinary and Biomedical Science and Center for Molecular Immunology and Infectious Disease, Pennsylvania State University, University Park, PA
| | - Simin N Meydani
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA
| | - Harry D Dawson
- USDA-Agricultural Research Service, Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, Beltsville, MD
| | - Charles B Stephensen
- Agricultural Research Service, Western Human Nutrition Research Center, USDA, Davis, CA
| | - Bernard J Brabin
- Child and Reproductive Health Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Global Child Health Group, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - Parminder S Suchdev
- Department of Pediatrics and Global Health, Emory University, Atlanta, GA; and
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11
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Mertens K, Lowes DA, Webster NR, Talib J, Hall L, Davies MJ, Beattie JH, Galley HF. Low zinc and selenium concentrations in sepsis are associated with oxidative damage and inflammation. Br J Anaesth 2015; 114:990-9. [PMID: 25833826 DOI: 10.1093/bja/aev073] [Citation(s) in RCA: 93] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/06/2015] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND Oxidative stress with dysregulated inflammation are hallmarks of sepsis. Zinc and selenium have important antioxidant functions, such that they could be important in patients with sepsis. We used an in vitro approach to assess the effect of zinc and selenium on oxidative stress, mitochondrial function, and inflammatory responses in conditions mimicking sepsis and related the findings to plasma concentrations and biomarkers in patients with and without sepsis. METHODS Human endothelial cells were exposed to a range of zinc and selenium concentrations in conditions mimicking sepsis. Zinc, selenium, and a series of biomarkers of oxidative stress and inflammation were measured in plasma from critically ill patients with and without sepsis. RESULTS Culturing cells with different concentrations of zinc caused altered zinc transporter protein expression and cellular zinc content, and selenium affected glutathione peroxidase 3 activity. Although zinc or selenium at physiological concentrations had no effect on interleukin-6 release in vitro, higher concentrations of the trace elements were associated with improved mitochondrial function. Plasma zinc and selenium concentrations were low in patients [zinc: median (range) 4.6 (2.1-6.5) μM in control patients without sepsis and 3.1 (1.5-5.4) μM in patients with sepsis, P=0.002; and selenium: 0.78 (0.19-1.32) μM in control patients and 0.42 (0.22-0.91) μM in sepsis patients, P=0.0009]. Plasma concentrations of interleukin-6, other biomarkers of inflammation, and markers of oxidative damage to proteins and lipids were elevated, particularly in patients with sepsis, and were inversely related to plasma zinc and selenium concentrations. CONCLUSIONS Zinc and selenium concentrations were reduced in critically ill patients, with increased oxidative stress and inflammatory biomarkers, particularly in patients with sepsis. Oxidative stress as a result of suboptimal selenium and zinc concentrations might contribute to damage of key proteins. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov: registration number NCT01328509.
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Affiliation(s)
- K Mertens
- Academic Unit of Anaesthesia and Intensive Care, School of Medicine & Dentistry and
| | - D A Lowes
- Academic Unit of Anaesthesia and Intensive Care, School of Medicine & Dentistry and
| | - N R Webster
- Academic Unit of Anaesthesia and Intensive Care, School of Medicine & Dentistry and
| | - J Talib
- The Heart Research Institute and Faculty of Medicine, University of Sydney, Sydney, NSW, Australia
| | - L Hall
- The Heart Research Institute and Faculty of Medicine, University of Sydney, Sydney, NSW, Australia
| | - M J Davies
- The Heart Research Institute and Faculty of Medicine, University of Sydney, Sydney, NSW, Australia Present address: Panum Institute, Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, Copenhagen N DK-2200, Denmark
| | - J H Beattie
- Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK
| | - H F Galley
- Academic Unit of Anaesthesia and Intensive Care, School of Medicine & Dentistry and
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12
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The relevance of the colon to zinc nutrition. Nutrients 2015; 7:572-83. [PMID: 25594440 PMCID: PMC4303854 DOI: 10.3390/nu7010572] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2014] [Accepted: 12/31/2014] [Indexed: 02/07/2023] Open
Abstract
Globally, zinc deficiency is widespread, despite decades of research highlighting its negative effects on health, and in particular upon child health in low-income countries. Apart from inadequate dietary intake of bioavailable zinc, other significant contributors to zinc deficiency include the excessive intestinal loss of endogenously secreted zinc and impairment in small intestinal absorptive function. Such changes are likely to occur in children suffering from environmental (or tropical) enteropathy (EE)—an almost universal condition among inhabitants of developing countries characterized by morphologic and functional changes in the small intestine. Changes to the proximal gut in environmental enteropathy will likely influence the nature and amount of zinc delivered into the large intestine. Consequently, we reviewed the current literature to determine if colonic absorption of endogenous or exogenous (dietary) zinc could contribute to overall zinc nutriture. Whilst we found evidence that significant zinc absorption occurs in the rodent colon, and is favoured when microbially-fermentable carbohydrates (specifically resistant starch) are consumed, it is unclear whether this process occur in humans and/or to what degree. Constraints in study design in the few available studies may well have masked a possible colonic contribution to zinc nutrition. Furthermore these few available human studies have failed to include the actual target population that would benefit, namely infants affected by EE where zinc delivery to the colon may be increased and who are also at risk of zinc deficiency. In conducting this review we have not been able to confirm a colonic contribution to zinc absorption in humans. However, given the observations in rodents and that feeding resistant starch to children is feasible, definitive studies utilising the dual stable isotope method in children with EE should be undertaken.
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Reid MA, Marsh KA, Zeuschner CL, Saunders AV, Baines SK. Meeting the nutrient reference values on a vegetarian diet. Med J Aust 2015; 199:S33-40. [PMID: 25369927 DOI: 10.5694/mja11.11510] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2011] [Accepted: 04/20/2012] [Indexed: 11/17/2022]
Abstract
Surveys over the past 10 years have shown that Australians are increasingly consuming more plant-based vegetarian meals. Many studies demonstrate the health benefits of vegetarian diets. As with any type of eating plan, vegetarian diets must be well planned to ensure nutritional needs are being met. This clinical focus project shows that well planned vegetarian diets can meet almost all the nutritional needs of children and adults of all ages. Sample single-day lacto-ovo-vegetarian meal plans were developed to comply with the nutrient reference values - including the increased requirements for iron and zinc at 180% and 150%, respectively, for vegetarians - for both sexes and all age groups set by Australia's National Health and Medical Research Council and the New Zealand Ministry of Health. With the exception of vitamin D, long-chain omega-3 fatty acids and extended iron requirements in pregnancy for vegetarians, the meal plans meet key requirements with respect to energy; protein; carbohydrate; total fat; saturated, poly- and monounsaturated fats; α-linolenic acid; fibre; iron; zinc; calcium; folate; and vitamins A, C, E and B₁₂.
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Affiliation(s)
- Michelle A Reid
- Corporate Nutrition, Sanitarium Health and Wellbeing, Berkeley Vale, NSW, Australia.
| | - Kate A Marsh
- Northside Nutrition and Dietetics, Sydney, NSW, Australia
| | | | - Angela V Saunders
- Corporate Nutrition, Sanitarium Health and Wellbeing, Berkeley Vale, NSW, Australia
| | - Surinder K Baines
- School of Health Sciences, University of Newcastle, Newcastle, NSW, Australia
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14
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Skrovanek S, DiGuilio K, Bailey R, Huntington W, Urbas R, Mayilvaganan B, Mercogliano G, Mullin JM. Zinc and gastrointestinal disease. World J Gastrointest Pathophysiol 2014; 5:496-513. [PMID: 25400994 PMCID: PMC4231515 DOI: 10.4291/wjgp.v5.i4.496] [Citation(s) in RCA: 91] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2014] [Revised: 09/18/2014] [Accepted: 10/01/2014] [Indexed: 02/06/2023] Open
Abstract
This review is a current summary of the role that both zinc deficiency and zinc supplementation can play in the etiology and therapy of a wide range of gastrointestinal diseases. The recent literature describing zinc action on gastrointestinal epithelial tight junctions and epithelial barrier function is described. Zinc enhancement of gastrointestinal epithelial barrier function may figure prominently in its potential therapeutic action in several gastrointestinal diseases.
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15
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Young GP, Mortimer EK, Gopalsamy GL, Alpers DH, Binder HJ, Manary MJ, Ramakrishna BS, Brown IL, Brewer TG. Zinc deficiency in children with environmental enteropathy-development of new strategies: report from an expert workshop. Am J Clin Nutr 2014; 100:1198-207. [PMID: 25240082 PMCID: PMC4163797 DOI: 10.3945/ajcn.113.075036] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2013] [Accepted: 07/17/2014] [Indexed: 12/31/2022] Open
Abstract
Zinc deficiency is a major cause of childhood morbidity and mortality. The WHO/UNICEF strategy for zinc supplementation as adjunctive therapy for diarrhea is poorly implemented. A conference of experts in zinc nutrition and gastrointestinal disorders was convened to consider approaches that might complement the current recommendation and what research was needed to develop these approaches. Several key points were identified. The design of novel zinc interventions would be facilitated by a better understanding of how disturbed gut function, such as environmental (or tropical) enteropathy, affects zinc absorption, losses, and homeostasis. Because only 10% of zinc stores are able to be rapidly turned over, and appear to be rapidly depleted by acute intestinal illness, they are probably best maintained by complementary regular supplementation in a primary prevention strategy rather than secondary prevention triggered by acute diarrhea. The assessment of zinc status is challenging and complex without simple, validated measures to facilitate field testing of novel interventions. Zinc bioavailability may be a crucial factor in the success of primary prevention strategies, and a range of options, all still inadequately explored, might be valuable in improving zinc nutrition. Some therapeutic actions of zinc on diarrhea seem attributable to pharmacologic effects, whereas others are related to the reversal of deficiency (ie, nutritional). The distinction between these 2 mechanisms cannot be clarified given the insensitivity of serum zinc to identify subclinical deficiency states. Why zinc seems to be less effective than expected at all ages, and ineffective for secondary prevention of diarrhea in children <12 mo of age, remains unclear. It was concluded that a reframing of the current recommendation is warranted with consideration of how to better optimize and deliver zinc and whether to provide a complementary public health primary prevention zinc strategy. This requires careful consideration of the zinc product to be used as well as strategies for its delivery.
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Affiliation(s)
- Graeme P Young
- From the School of Medicine, Flinders University of South Australia, Adelaide, Australia (GPY, EKM, GLG, and ILB); Washington University School of Medicine, St Louis, MO (DHA and MJM); Yale University School of Medicine, New Haven, CT (HJB); the Department of Medical Gastroenterology, Christian Medical College Vellore, Vellore, India (BSR); and Enteric and Diarrheal Diseases, the Bill & Melinda Gates Foundation, Seattle, WA (TGB)
| | - Elissa K Mortimer
- From the School of Medicine, Flinders University of South Australia, Adelaide, Australia (GPY, EKM, GLG, and ILB); Washington University School of Medicine, St Louis, MO (DHA and MJM); Yale University School of Medicine, New Haven, CT (HJB); the Department of Medical Gastroenterology, Christian Medical College Vellore, Vellore, India (BSR); and Enteric and Diarrheal Diseases, the Bill & Melinda Gates Foundation, Seattle, WA (TGB)
| | - Geetha L Gopalsamy
- From the School of Medicine, Flinders University of South Australia, Adelaide, Australia (GPY, EKM, GLG, and ILB); Washington University School of Medicine, St Louis, MO (DHA and MJM); Yale University School of Medicine, New Haven, CT (HJB); the Department of Medical Gastroenterology, Christian Medical College Vellore, Vellore, India (BSR); and Enteric and Diarrheal Diseases, the Bill & Melinda Gates Foundation, Seattle, WA (TGB)
| | - David H Alpers
- From the School of Medicine, Flinders University of South Australia, Adelaide, Australia (GPY, EKM, GLG, and ILB); Washington University School of Medicine, St Louis, MO (DHA and MJM); Yale University School of Medicine, New Haven, CT (HJB); the Department of Medical Gastroenterology, Christian Medical College Vellore, Vellore, India (BSR); and Enteric and Diarrheal Diseases, the Bill & Melinda Gates Foundation, Seattle, WA (TGB)
| | - Henry J Binder
- From the School of Medicine, Flinders University of South Australia, Adelaide, Australia (GPY, EKM, GLG, and ILB); Washington University School of Medicine, St Louis, MO (DHA and MJM); Yale University School of Medicine, New Haven, CT (HJB); the Department of Medical Gastroenterology, Christian Medical College Vellore, Vellore, India (BSR); and Enteric and Diarrheal Diseases, the Bill & Melinda Gates Foundation, Seattle, WA (TGB)
| | - Mark J Manary
- From the School of Medicine, Flinders University of South Australia, Adelaide, Australia (GPY, EKM, GLG, and ILB); Washington University School of Medicine, St Louis, MO (DHA and MJM); Yale University School of Medicine, New Haven, CT (HJB); the Department of Medical Gastroenterology, Christian Medical College Vellore, Vellore, India (BSR); and Enteric and Diarrheal Diseases, the Bill & Melinda Gates Foundation, Seattle, WA (TGB)
| | - Balakrishnan S Ramakrishna
- From the School of Medicine, Flinders University of South Australia, Adelaide, Australia (GPY, EKM, GLG, and ILB); Washington University School of Medicine, St Louis, MO (DHA and MJM); Yale University School of Medicine, New Haven, CT (HJB); the Department of Medical Gastroenterology, Christian Medical College Vellore, Vellore, India (BSR); and Enteric and Diarrheal Diseases, the Bill & Melinda Gates Foundation, Seattle, WA (TGB)
| | - Ian L Brown
- From the School of Medicine, Flinders University of South Australia, Adelaide, Australia (GPY, EKM, GLG, and ILB); Washington University School of Medicine, St Louis, MO (DHA and MJM); Yale University School of Medicine, New Haven, CT (HJB); the Department of Medical Gastroenterology, Christian Medical College Vellore, Vellore, India (BSR); and Enteric and Diarrheal Diseases, the Bill & Melinda Gates Foundation, Seattle, WA (TGB)
| | - Thomas G Brewer
- From the School of Medicine, Flinders University of South Australia, Adelaide, Australia (GPY, EKM, GLG, and ILB); Washington University School of Medicine, St Louis, MO (DHA and MJM); Yale University School of Medicine, New Haven, CT (HJB); the Department of Medical Gastroenterology, Christian Medical College Vellore, Vellore, India (BSR); and Enteric and Diarrheal Diseases, the Bill & Melinda Gates Foundation, Seattle, WA (TGB)
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16
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Lebel A, Matte JJ, Guay F. Effect of mineral source and mannan oligosaccharide supplements on zinc and copper digestibility in growing pigs. Arch Anim Nutr 2014; 68:370-84. [PMID: 25179553 DOI: 10.1080/1745039x.2014.954357] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
This study aimed to compare the effects of organic (proteinate) and inorganic (sulphate) copper (Cu) and zinc (Zn) supplements, in presence or absence of a mannan oligosaccharide (MOS) supplement, on mineral solubility and digestibility in pigs. Twenty-eight barrows (25 ± 4 kg) assigned randomly to four treatment groups were fed a corn-wheat-soya bean meal diet with 10 mg/kg of Cu and 100 mg/kg of Zn supplied as organic or inorganic supplement, and supplemented or not with 0.1% MOS. After an adaptation period, total faeces and urine were collected for a period of 6-7 days. Pigs were then euthanatised and digesta from ileum and caecum were collected. Apparent digestibility was calculated in ileum and caecum using titanium dioxide. The organic mineral supplement improved total (faecal) digestibility and retained/ingested ratio of Cu (p < 0.05) while reducing apparent digestibility of Zn in the ileum (p < 0.05) without effect on total digestibility of Zn. Solubilities of Cu and Zn in liquid fraction of ileum and caecum were not affected by mineral sources. Although MOS supplement increased Cu solubility in the ileum (p < 0.05), it had no effect on digestibility of Zn and Cu in ileum, caecum and faeces, retained/ingested ratio of Zn and Cu, or pH and volatile fatty acid concentration in ileal and caecal digesta. In conclusion, organic mineral supplement improved total digestibility and retained/ingested ratio of Cu in pigs but this cannot be attributed to its solubility in ileal and caecal digesta. The MOS supplement did not interfere with digestibility or dietary utilisation of Zn and Cu in pigs fed above the Zn and Cu requirements.
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Affiliation(s)
- Alexandre Lebel
- a Département des sciences animals , Université Laval Québec , Québec , Canada G1V 0A6
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17
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Elmadfa I, Meyer AL. Developing suitable methods of nutritional status assessment: a continuous challenge. Adv Nutr 2014; 5:590S-598S. [PMID: 25469404 PMCID: PMC4188242 DOI: 10.3945/an.113.005330] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Reliable information about the nutritional status is essential to identify potential critical nutrients and the population groups at risk of deficiency, as well as to develop effective public health policies to counteract unfavorable nutrition patterns that contribute to morbidity and mortality. In this review, the important role of biomarkers in the assessment of nutritional status is outlined, major strengths and limitations of established and new biomarkers are described, and important criteria for biomarker selection and development are discussed. Indeed, biomarkers offer a more objective assessment tool than pure dietary approaches that suffer from inadequate data reporting in particular, although biomarkers are often only measured in subsamples because of the higher costs and proband burden they entail. However, biomarkers are subject to individual variability and influences from other factors besides the nutrient of interest. Rapid turnover or tight control of nutrient concentrations in blood (homeostasis) limits their sensitivity as biomarkers, as in the case of many trace elements. The existence of different forms of a micronutrient in the body adds additional complexity. Functional biomarkers, such as enzyme activities, mirror long-term status better but are subject to confounding factors, and some are influenced by several micronutrients, not specific for only 1, so using a combination of biomarkers is advisable. Additionally, the applicability of a biomarker also depends on the existence of adequate reference values and cutoff points for the target population. Therefore, a careful selection is warranted, especially when biomarkers are to be used in larger samples.
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Affiliation(s)
- Ibrahim Elmadfa
- Department of Nutritional Sciences, University of Vienna, Vienna,
Austria
| | - Alexa L. Meyer
- Department of Nutritional Sciences, University of Vienna, Vienna,
Austria
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18
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Qin Q, Wang X, Zhou B. Functional studies of Drosophila zinc transporters reveal the mechanism for dietary zinc absorption and regulation. BMC Biol 2013; 11:101. [PMID: 24063361 PMCID: PMC4015762 DOI: 10.1186/1741-7007-11-101] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2013] [Accepted: 09/23/2013] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Zinc is key to the function of many proteins, but the process of dietary zinc absorption is not well clarified. Current knowledge about dietary zinc absorption is fragmented, and mostly derives from incomplete mammalian studies. To gain a comprehensive picture of this process, we systematically characterized all zinc transporters (that is, the Zip and ZnT family members) for their possible roles in dietary zinc absorption in a genetically amenable model organism, Drosophila melanogaster. RESULTS A set of plasma membrane-resident zinc transporters was identified to be responsible for absorbing zinc from the lumen into the enterocyte and the subsequent exit of zinc to the circulation. dZip1 and dZip2, two functionally overlapping zinc importers, are responsible for absorbing zinc from the lumen into the enterocyte. Exit of zinc to the circulation is mediated through another two functionally overlapping zinc exporters, dZnT1, and its homolog CG5130 (dZnT77C). Somewhat surprisingly, it appears that the array of intracellular ZnT proteins, including the Golgi-resident dZnT7, is not directly involved in dietary zinc absorption. By modulating zinc status in different parts of the body, we found that regulation of dietary zinc absorption, in contrast to that of iron, is unresponsive to bodily needs or zinc status outside the gut. The zinc transporters that are involved in dietary zinc absorption, including the importers dZip1 and dZip2, and the exporter dZnT1, are respectively regulated at the RNA and protein levels by zinc in the enterocyte. CONCLUSIONS Our study using the model organism Drosophila thus starts to reveal a comprehensive sketch of dietary zinc absorption and its regulatory control, a process that is still incompletely understood in mammalian organisms. The knowledge gained will act as a reference for future mammalian studies, and also enable an appreciation of this important process from an evolutionary perspective.
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Affiliation(s)
- Qiuhong Qin
- State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China
| | - Xiaoxi Wang
- State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China
| | - Bing Zhou
- State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China
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19
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Ou O, Allen‐Redpath K, Urgast D, Gordon M, Campbell G, Feldmann J, Nixon GF, Mayer C, Kwun I, Beattie JH. Plasma zinc's alter ego is a low‐molecular‐weight humoral factor. FASEB J 2013; 27:3672-82. [DOI: 10.1096/fj.13-228791] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- Ou Ou
- Rowett Institute of Nutrition and HealthUniversity of AberdeenAberdeenUK
| | | | - Dagmar Urgast
- Trace Element Speciation LaboratoryUniversity of AberdeenAberdeenUK
| | | | - Gill Campbell
- Rowett Institute of Nutrition and HealthUniversity of AberdeenAberdeenUK
| | - Jörg Feldmann
- Trace Element Speciation LaboratoryUniversity of AberdeenAberdeenUK
| | | | | | - In‐Sook Kwun
- Department of Food Science and NutritionAndong National UniversityAndongKyungbookSouth Korea
| | - John H. Beattie
- Rowett Institute of Nutrition and HealthUniversity of AberdeenAberdeenUK
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