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Open AccessArticle Chronic Zinc Deficiency Alters Chick Gut Microbiota Composition and Function

by Spenser Reed, Hadar Neuman, Sharon Moscovich, Raymond P. Glahn, Omry Koren and Elad Tako

Nutrients 2015, 7(12), 9768-9784; doi:10.3390/nu7125497

Received: 11 September 2015 / Revised: 10 November 2015 / Accepted: 12 November 2015 / Published: 27 November 2015

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Abstract

Zinc (Zn) deficiency is a prevalent micronutrient insufficiency. Although the gut is a vital organ for Zn utilization, and Zn deficiency is associated with impaired intestinal permeability and a global decrease in gastrointestinal health, alterations in the gut microbial ecology of the host

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Zinc (Zn) deficiency is a prevalent micronutrient insufficiency. Although the gut is a vital organ for Zn utilization, and Zn deficiency is associated with impaired intestinal permeability and a global decrease in gastrointestinal health, alterations in the gut microbial ecology of the host under conditions of Zn deficiency have yet to be studied. Using the broiler chicken (Gallus gallus) model, the aim of this study was to characterize distinct cecal microbiota shifts induced by chronic dietary Zn depletion. We demonstrate that Zn deficiency induces significant taxonomic alterations and decreases overall species richness and diversity, establishing a microbial profile resembling that of various other pathological states. Through metagenomic analysis, we show that predicted Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways responsible for macro- and micronutrient uptake are significantly depleted under Zn deficiency; along with concomitant decreases in beneficial short chain fatty acids, such depletions may further preclude optimal host Zn availability. We also identify several candidate microbes that may play a significant role in modulating the bioavailability and utilization of dietary Zn during prolonged deficiency. Our results are the first to characterize a unique and dysbiotic cecal microbiota during Zn deficiency, and provide evidence for such microbial perturbations as potential effectors of the Zn deficient phenotype. Full article

(This article belongs to the Special Issue Dietary Zinc and Human Health)

Open AccessArticle The Long Term Impact of Micronutrient Supplementation during Infancy on Cognition and Executive Function Performance in Pre-School Children

by Marisol Warthon-Medina, Pamela Qualter, Nelly Zavaleta, Stephanie Dillon, Fabiola Lazarte and Nicola M. Lowe

Nutrients 2015, 7(8), 6606-6627; doi:10.3390/nu7085302

Received: 2 May 2015 / Revised: 3 July 2015 / Accepted: 22 July 2015 / Published: 7 August 2015

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Abstract

Brain growth and development are critically dependent on several micronutrients. During early development cellular activity may be sensitive to micronutrient deficiencies, however the evidence from human studies is equivocal. The objective of this study was to examine the long-term cognitive and social-emotional effects

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Brain growth and development are critically dependent on several micronutrients. During early development cellular activity may be sensitive to micronutrient deficiencies, however the evidence from human studies is equivocal. The objective of this study was to examine the long-term cognitive and social-emotional effects of multiple micronutrient supplementation compared with iron supplementation alone, administered during infancy. This study was a follow-up to an initial randomized, double-blind controlled trial (RCT) in 2010 in which 902 infants, aged 6–17 months, from Lima, Peru, were given daily supplements of either iron (Fe) or multiple micronutrients (MMN) including zinc (451 in each group). The supplementation period for both groups was six months. In 2012, a subsample of 184 children from the original cohort (now aged 36–48 months) was randomly selected to participate in a follow-up trial and was assessed for intelligence, working memory, inhibition, and executive function. The tests showed no significant differences between the supplementation groups though there were some gender differences, with girls displaying higher scores than boys across both groups on the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) Verbal IQ sentences subtest, the Day-Night cognitive test and on the Brief Infant-Toddler Social Emotional Assessment (BITSEA) social competency, and boys scoring higher than girls in problem behaviour. The results indicate that MMN supplementation had no long term additional effects on cognitive function compared with iron supplementation alone. The timing of supplement administration for maximum impact on a child’s cognitive development requires further investigation. Full article

(This article belongs to the Special Issue Dietary Zinc and Human Health)

Open AccessArticle Associations between Blood Zinc Concentrations and Sleep Quality in Childhood: A Cohort Study

by Xiaopeng Ji and Jianghong Liu

Nutrients 2015, 7(7), 5684-5696; doi:10.3390/nu7075247

Received: 1 May 2015 / Revised: 17 June 2015 / Accepted: 23 June 2015 / Published: 13 July 2015

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Abstract

Little evidence is available regarding the relationship between zinc and sleep in school children. The present study aimed to examine the cross-sectional and longitudinal associations between blood zinc concentrations and sleep quality throughout childhood. A total of 1295 children from the Jintan Child

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Little evidence is available regarding the relationship between zinc and sleep in school children. The present study aimed to examine the cross-sectional and longitudinal associations between blood zinc concentrations and sleep quality throughout childhood. A total of 1295 children from the Jintan Child Cohort in China were included in this study. Venous blood sample of zinc and subjective sleep data were collected when the children were at preschool age (3–5 years old) and early adolescence (11–15 years old). Odds ratios (ORs) reflect the odds of the sleep quality/subdomain being at a greater impairment level associated with 1 unit increase in log zinc concentration. Cross-sectional analyses showed negative correlation of blood zinc concentrations with insufficient sleep duration (OR = 0.432, p = 0.002), sleep disturbances (OR = 0.454, p = 0.009) and poor sleep quality (OR = 0.559, p = 0.049) in adolescence, but no association at preschool age (p > 0.05). Longitudinal analyses indicated that blood zinc concentrations at preschool age predict poor sleep efficiency (OR = 0.186, p = 0.000) and poor sleep quality (OR = 0.358, p = 0.020) in adolescence. Our findings suggest that sufficient zinc concentration is associated with good sleep quality, dependent on the developmental stage in childhood. Future interventional research is warranted to examine the short and long-term effect of zinc status on sleep heath. Full article

(This article belongs to the Special Issue Dietary Zinc and Human Health)

Open AccessArticle Zinc Status of Vegetarians during Pregnancy: A Systematic Review of Observational Studies and Meta-Analysis of Zinc Intake

by Meika Foster, Ursula Nirmala Herulah, Ashlini Prasad, Peter Petocz and Samir Samman

Nutrients 2015, 7(6), 4512-4525; doi:10.3390/nu7064512

Received: 17 March 2015 / Revised: 14 May 2015 / Accepted: 18 May 2015 / Published: 5 June 2015

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Abstract

Pregnant women are vulnerable to a low zinc status due to the additional zinc demands associated with pregnancy and foetal development. The present systematic review explores the relationship between habitual vegetarian diets and dietary zinc intake/status during pregnancy. The association between vegetarian diets

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Pregnant women are vulnerable to a low zinc status due to the additional zinc demands associated with pregnancy and foetal development. The present systematic review explores the relationship between habitual vegetarian diets and dietary zinc intake/status during pregnancy. The association between vegetarian diets and functional pregnancy outcome also is considered. A literature search was conducted of MEDLINE; PubMed; Embase; the Cochrane Library; Web of Science; and Scopus electronic databases up to September 2014. Six English-language observational studies qualified for inclusion in the systematic review. A meta-analysis was conducted that compared the dietary zinc intake of pregnant vegetarian and non-vegetarian (NV) groups; the zinc intake of vegetarians was found to be lower than that of NV (−1.38 ± 0.35 mg/day; p < 0.001); and the exclusion of low meat eaters from the analysis revealed a greater difference (−1.53 ± 0.44 mg/day; p = 0.001). Neither vegetarian nor NV groups met the recommended dietary allowance (RDA) for zinc. In a qualitative synthesis; no differences were found between groups in serum/plasma zinc or in functional outcomes associated with pregnancy. In conclusion; pregnant vegetarian women have lower zinc intakes than NV control populations and both groups consume lower than recommended amounts. Further information is needed to determine whether physiologic adaptations in zinc metabolism are sufficient to meet maternal and foetal requirements during pregnancy on a low zinc diet. Full article

(This article belongs to the Special Issue Dietary Zinc and Human Health)

Open AccessArticle Zinc Status Affects Glucose Homeostasis and Insulin Secretion in Patients with Thalassemia

by Ellen B. Fung, Ginny Gildengorin, Siddhant Talwar, Leah Hagar and Ashutosh Lal

Nutrients 2015, 7(6), 4296-4307; doi:10.3390/nu7064296

Received: 10 February 2015 / Revised: 8 May 2015 / Accepted: 12 May 2015 / Published: 2 June 2015

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Abstract

Up to 20% of adult patients with Thalassemia major (Thal) live with diabetes, while 30% may be zinc deficient. The objective of this study was to explore the relationship between zinc status, impaired glucose tolerance and insulin sensitivity in Thal patients. Charts from

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Up to 20% of adult patients with Thalassemia major (Thal) live with diabetes, while 30% may be zinc deficient. The objective of this study was to explore the relationship between zinc status, impaired glucose tolerance and insulin sensitivity in Thal patients. Charts from thirty subjects (16 male, 27.8 ± 9.1 years) with Thal were reviewed. Patients with low serum zinc had significantly lower fasting insulin, insulinogenic and oral disposition indexes (all p < 0.05) and elevated glucose response curve, following a standard 75 g oral load of glucose compared to those with normal serum zinc after controlling for baseline (group × time interaction p = 0.048). Longitudinal data in five patients with a decline in serum zinc over a two year follow up period (−19.0 ± 9.6 μg/dL), showed consistent increases in fasting glucose (3.6 ± 3.2 mg/dL) and insulin to glucose ratios at 120 min post glucose dose (p = 0.05). Taken together, these data suggest that the frequently present zinc deficiency in Thal patients is associated with decreased insulin secretion and reduced glucose disposal. Future zinc trials will require modeling of oral glucose tolerance test data and not simply measurement of static indices in order to understand the complexities of pancreatic function in the Thal patient. Full article

(This article belongs to the Special Issue Dietary Zinc and Human Health)

Open AccessArticle Determination of Zinc Status in Humans: Which Indicator Should We Use?

by Frank T. Wieringa, Marjoleine A. Dijkhuizen, Marion Fiorentino, Arnauld Laillou and Jacques Berger

Nutrients 2015, 7(5), 3252-3263; doi:10.3390/nu7053252

Received: 17 February 2015 / Revised: 21 April 2015 / Accepted: 22 April 2015 / Published: 6 May 2015

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Abstract

Zinc deficiency has serious wide-ranging health consequences and is thought to be one of the most prevalent micronutrient deficiencies in the world. However, reliable indicators or biomarkers to assess zinc status are not available at present. Indirect indicators such as the prevalence of

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Zinc deficiency has serious wide-ranging health consequences and is thought to be one of the most prevalent micronutrient deficiencies in the world. However, reliable indicators or biomarkers to assess zinc status are not available at present. Indirect indicators such as the prevalence of stunting or anemia, iron deficiency, as well as more direct indicators such as plasma zinc concentrations are being used at present to estimate the prevalence of zinc deficiency in populations. However, as this paper shows by using data from a recent national micronutrient survey in Vietnam, the estimates of the prevalence of zinc deficiency using these different indicators can vary widely, leading to inconsistencies. In this paper, zinc deficiency among children is four times more prevalent than iron deficiency and 2.3 times more than stunting prevalence for example. This can lead not only to confusion concerning the real extent of the prevalence of zinc deficiency in populations, but also makes it hard to inform policy on whether action is needed or not. Moreover, evaluation of programs is hampered by the lack of a clear indicator. Efforts should be made to identify the most suitable indicator to evaluate the impact of programs aimed at improving zinc status and health of populations. Full article

(This article belongs to the Special Issue Dietary Zinc and Human Health)

Open AccessArticle Associations between Dietary Iron and Zinc Intakes, and between Biochemical Iron and Zinc Status in Women

by Karen Lim, Alison Booth, Ewa A. Szymlek-Gay, Rosalind S. Gibson, Karl B. Bailey, David Irving, Caryl Nowson and Lynn Riddell

Nutrients 2015, 7(4), 2983-2999; doi:10.3390/nu7042983

Received: 25 March 2015 / Revised: 10 April 2015 / Accepted: 14 April 2015 / Published: 20 April 2015

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Abstract

Iron and zinc are found in similar foods and absorption of both may be affected by food compounds, thus biochemical iron and zinc status may be related. This cross-sectional study aimed to: (1) describe dietary intakes and biochemical status of iron and zinc;

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Iron and zinc are found in similar foods and absorption of both may be affected by food compounds, thus biochemical iron and zinc status may be related. This cross-sectional study aimed to: (1) describe dietary intakes and biochemical status of iron and zinc; (2) investigate associations between dietary iron and zinc intakes; and (3) investigate associations between biochemical iron and zinc status in a sample of premenopausal women aged 18–50 years who were recruited in Melbourne and Sydney, Australia. Usual dietary intakes were assessed using a 154-item food frequency questionnaire (n = 379). Iron status was assessed using serum ferritin and hemoglobin, zinc status using serum zinc (standardized to 08:00 collection), and presence of infection/inflammation using C-reactive protein (n = 326). Associations were explored using multiple regression and logistic regression. Mean (SD) iron and zinc intakes were 10.5 (3.5) mg/day and 9.3 (3.8) mg/day, respectively. Median (interquartile range) serum ferritin was 22 (12–38) μg/L and mean serum zinc concentrations (SD) were 12.6 (1.7) μmol/L in fasting samples and 11.8 (2.0) μmol/L in nonfasting samples. For each 1 mg/day increase in dietary iron intake, zinc intake increased by 0.4 mg/day. Each 1 μmol/L increase in serum zinc corresponded to a 6% increase in serum ferritin, however women with low serum zinc concentration (AM fasting < 10.7 μmol/L; AM nonfasting < 10.1 μmol/L) were not at increased risk of depleted iron stores (serum ferritin <15 μg/L; p = 0.340). Positive associations were observed between dietary iron and zinc intakes, and between iron and zinc status, however interpreting serum ferritin concentrations was not a useful proxy for estimating the likelihood of low serum zinc concentrations and women with depleted iron stores were not at increased risk of impaired zinc status in this cohort. Full article

(This article belongs to the Special Issue Dietary Zinc and Human Health)

Open AccessArticle Height, Zinc and Soil-Transmitted Helminth Infections in Schoolchildren: A Study in Cuba and Cambodia

by Brechje de Gier, Liliane Mpabanzi, Kim Vereecken, Suzanne D. van der Werff, Patrick C. D'Haese, Marion Fiorentino, Kuong Khov, Marlene Perignon, Chhoun Chamnan, Jacques Berger, Megan E. Parker, Raquel Junco Díaz, Fidel Angel Núñez, Lázara Rojas Rivero, Mariano Bonet Gorbea, Colleen M. Doak, Maiza Campos Ponce, Frank T. Wieringa and Katja Polman

Nutrients 2015, 7(4), 3000-3010; doi:10.3390/nu7043000

Received: 6 February 2015 / Revised: 7 April 2015 / Accepted: 9 April 2015 / Published: 20 April 2015

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Abstract

Soil-transmitted helminth (STH) infections and zinc deficiency are often found in low- and middle-income countries and are both known to affect child growth. However, studies combining data on zinc and STH are lacking. In two studies in schoolchildren in Cuba and Cambodia, we

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Soil-transmitted helminth (STH) infections and zinc deficiency are often found in low- and middle-income countries and are both known to affect child growth. However, studies combining data on zinc and STH are lacking. In two studies in schoolchildren in Cuba and Cambodia, we collected data on height, STH infection and zinc concentration in either plasma (Cambodia) or hair (Cuba). We analyzed whether STH and/or zinc were associated with height for age z-scores and whether STH and zinc were associated. In Cuba, STH prevalence was 8.4%; these were mainly Ascaris lumbricoides and Trichuris trichiura infections. In Cambodia, STH prevalence was 16.8%, mostly caused by hookworm. In Cuban children, STH infection had a strong association with height for age (aB-0.438, p = 0.001), while hair zinc was significantly associated with height for age only in STH uninfected children. In Cambodian children, plasma zinc was associated with height for age (aB-0.033, p = 0.029), but STH infection was not. Only in Cambodia, STH infection showed an association with zinc concentration (aB-0.233, p = 0.051). Factors influencing child growth differ between populations and may depend on prevalences of STH species and zinc deficiency. Further research is needed to elucidate these relationships and their underlying mechanisms. Full article

(This article belongs to the Special Issue Dietary Zinc and Human Health)

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Open AccessReview Zinc in Early Life: A Key Element in the Fetus and Preterm Neonate

by Gianluca Terrin, Roberto Berni Canani, Maria Di Chiara, Andrea Pietravalle, Vincenzo Aleandri, Francesca Conte and Mario De Curtis

Nutrients 2015, 7(12), 10427-10446; doi:10.3390/nu7125542

Received: 8 August 2015 / Revised: 23 November 2015 / Accepted: 26 November 2015 / Published: 11 December 2015

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Abstract

Zinc is a key element for growth and development. In this narrative review, we focus on the role of dietary zinc in early life (including embryo, fetus and preterm neonate), analyzing consequences of zinc deficiency and adequacy of current recommendations on dietary zinc.

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Zinc is a key element for growth and development. In this narrative review, we focus on the role of dietary zinc in early life (including embryo, fetus and preterm neonate), analyzing consequences of zinc deficiency and adequacy of current recommendations on dietary zinc. We performed a systematic search of articles on the role of zinc in early life. We selected and analyzed 81 studies. Results of this analysis showed that preservation of zinc balance is of critical importance for the avoidance of possible consequences of low zinc levels on pre- and post-natal life. Insufficient quantities of zinc during embryogenesis may influence the final phenotype of all organs. Maternal zinc restriction during pregnancy influences fetal growth, while adequate zinc supplementation during pregnancy may result in a reduction of the risk of preterm birth. Preterm neonates are at particular risk to develop zinc deficiency due to a combination of different factors: (i) low body stores due to reduced time for placental transfer of zinc; (ii) increased endogenous losses; and (iii) marginal intake. Early diagnosis of zinc deficiency, through the measurement of serum zinc concentrations, may be essential to avoid severe prenatal and postnatal consequences in these patients. Typical clinical manifestations of zinc deficiency are growth impairment and dermatitis. Increasing data suggest that moderate zinc deficiency may have significant subclinical effects, increasing the risk of several complications typical of preterm neonates (i.e., necrotizing enterocolitis, chronic lung disease, and retinopathy), and that current recommended intakes should be revised to meet zinc requirements of extremely preterm neonates. Future studies evaluating the adequacy of current recommendations are advocated. Full article

(This article belongs to the Special Issue Dietary Zinc and Human Health)

Open AccessReview Crosstalk between Zinc Status and Giardia Infection: A New Approach

by Humberto Astiazarán-García, Gemma Iñigo-Figueroa, Luis Quihui-Cota and Iván Anduro-Corona

Nutrients 2015, 7(6), 4438-4452; doi:10.3390/nu7064438

Received: 30 March 2015 / Revised: 6 May 2015 / Accepted: 12 May 2015 / Published: 3 June 2015

Cited by 1 | PDF Full-text (112 KB) | HTML Full-text | XML Full-text

Abstract

Zinc supplementation has been shown to reduce the incidence and prevalence of diarrhea; however, its anti-diarrheal effect remains only partially understood. There is now growing evidence that zinc can have pathogen-specific protective effects. Giardiasis is a common yet neglected cause of acute-chronic diarrheal

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Zinc supplementation has been shown to reduce the incidence and prevalence of diarrhea; however, its anti-diarrheal effect remains only partially understood. There is now growing evidence that zinc can have pathogen-specific protective effects. Giardiasis is a common yet neglected cause of acute-chronic diarrheal illness worldwide which causes disturbances in zinc metabolism of infected children, representing a risk factor for zinc deficiency. How zinc metabolism is compromised by Giardia is not well understood; zinc status could be altered by intestinal malabsorption, organ redistribution or host-pathogen competition. The potential metal-binding properties of Giardia suggest unusual ways that the parasite may interact with its host. Zinc supplementation was recently found to reduce the rate of diarrhea caused by Giardia in children and to upregulate humoral immune response in Giardia-infected mice; in vitro and in vivo, zinc-salts enhanced the activity of bacitracin in a zinc-dose-dependent way, and this was not due to zinc toxicity. These findings reflect biological effect of zinc that may impact significantly public health in endemic areas of infection. In this paper, we shall explore one direction of this complex interaction, discussing recent information regarding zinc status and its possible contribution to the outcome of the encounter between the host and Giardia. Full article

(This article belongs to the Special Issue Dietary Zinc and Human Health)

Open AccessReview The Potential for Zinc Stable Isotope Techniques and Modelling to Determine Optimal Zinc Supplementation

by Cuong D. Tran, Geetha L. Gopalsamy, Elissa K. Mortimer and Graeme P. Young

Nutrients 2015, 7(6), 4271-4295; doi:10.3390/nu7064271

Received: 30 March 2015 / Accepted: 18 May 2015 / Published: 29 May 2015

Cited by 2 | PDF Full-text (300 KB) | HTML Full-text | XML Full-text

Abstract

It is well recognised that zinc deficiency is a major global public health issue, particularly in young children in low-income countries with diarrhoea and environmental enteropathy. Zinc supplementation is regarded as a powerful tool to correct zinc deficiency as well as to treat

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It is well recognised that zinc deficiency is a major global public health issue, particularly in young children in low-income countries with diarrhoea and environmental enteropathy. Zinc supplementation is regarded as a powerful tool to correct zinc deficiency as well as to treat a variety of physiologic and pathologic conditions. However, the dose and frequency of its use as well as the choice of zinc salt are not clearly defined regardless of whether it is used to treat a disease or correct a nutritional deficiency. We discuss the application of zinc stable isotope tracer techniques to assess zinc physiology, metabolism and homeostasis and how these can address knowledge gaps in zinc supplementation pharmacokinetics. This may help to resolve optimal dose, frequency, length of administration, timing of delivery to food intake and choice of zinc compound. It appears that long-term preventive supplementation can be administered much less frequently than daily but more research needs to be undertaken to better understand how best to intervene with zinc in children at risk of zinc deficiency. Stable isotope techniques, linked with saturation response and compartmental modelling, also have the potential to assist in the continued search for simple markers of zinc status in health, malnutrition and disease. Full article

(This article belongs to the Special Issue Dietary Zinc and Human Health)

Open AccessReview The Relevance of the Colon to Zinc Nutrition

by Geetha Lavaniya Gopalsamy, David H Alpers, Henry J Binder, Cuong D Tran, B S Ramakrishna, Ian Brown, Mark Manary, Elissa Mortimer and Graeme P Young

Nutrients 2015, 7(1), 572-583; doi:10.3390/nu7010572

Received: 7 November 2014 / Accepted: 31 December 2014 / Published: 14 January 2015

Cited by 3 | PDF Full-text (116 KB) | HTML Full-text | XML Full-text

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

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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. Full article

(This article belongs to the Special Issue Dietary Zinc and Human Health)

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