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Dietary Zn and Human Health

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A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (15 December 2017) | Viewed by 177521

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Dr. Elad Tako

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USDA-ARS, Robert W. Holley Center for Agriculture and Health, Cornell University, Ithaca, NY 14853, USA
Interests: dietary micronutrients; Fe and Zn deficiencies; anemia; Zn status biomarkers; bioactive compounds; prebiotics; microbiome; nutrigenomics; intestinal functionality and development; polyphenols; in vivo models of human nutrition
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Dear Colleagues,

Zinc is an essential micronutrient that contributes to the proper functioning of over 300 enzymes and multiple biochemical and structural processes in the body. Zinc functions in the regulation of an extensive variety of genes, such as those involved in nucleic acid metabolism, cell signalling, apoptosis, and play an integral role in immune system functioning. Even a mild Zn deficiency can profoundly affect growth and development, as well as impede immune differentiation and maturation. Zinc is widely distributed in foods, however, it was demonstrated that dietary constituents, such as phytate, polyphenols, and the intestinal microbiome, affect its dietary bioavailability and intestinal absorption. Regulation of zinc metabolism is achieved through a balance of absorption and excretion and involves adaptive mechanisms. The aim of this Special Issue is to explore dietary approaches that aim to improve Zn bioavailability and absorption, biomarkers of status, and the effect of Zn status on the intestinal microbiome.

Assis. Prof. Elad Tako
Guest Editor

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Keywords

Zinc
Bioavailability
Absorption
Transport
In vivo model
Brush Border Membrane functionality
Biomarkers
Prebiotics
Intestinal Microbial Population

Published Papers (14 papers)

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15 pages, 1080 KiB

Open AccessArticle

Modifiable “Predictors” of Zinc Status in Toddlers

by Lisa Daniels, Sheila M. Williams, Rosalind S. Gibson, Rachael W. Taylor, Samir Samman and Anne-Louise M. Heath

Nutrients 2018, 10(3), 306; https://doi.org/10.3390/nu10030306 - 05 Mar 2018

Cited by 6 | Viewed by 4862

Abstract

Suboptimal zinc status is common in very young children and likely associated with increased risk of infection and detrimental effects on growth. No studies have determined potentially modifiable “predictors” of zinc status in toddlers from high-income countries. This cross-sectional analysis of 115 toddlers from the Baby-Led Introduction to SolidS (BLISS) study used weighed diet records (three non-consecutive days) to assess dietary intake, and a venous blood sample (trace-element free techniques) to assess plasma zinc, at 12 months of age. “Predictors” of plasma zinc were determined by univariate analysis and multiple regression. Mean (SD) plasma zinc was 9.7 (1.5) μmol/L, 60% were below the IZiNCG reference limit of <9.9 μmol/L. Median (25th, 75th percentiles) intake of zinc was 4.4 (3.7, 5.4) mg/day. Red meat intake (p = 0.004), consumption of zinc-fortified infant formula (3–6 mg zinc/100 g) (p = 0.026), and food fussiness (p = 0.028) were statistically significant “predictors” of plasma zinc at 12 months. Although higher intakes of red meat, and consumption of infant formula, are potentially achievable, it is important to consider possible barriers, particularly impact on breastfeeding, cost, and the challenges of behavior modification. Of interest is the association with food fussiness—further research should investigate the direction of this association. Full article

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

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15 pages, 916 KiB

Open AccessArticle

Assessment of Validity and Reproducibility of the Zinc-Specific Dietary Intake Questionnaire Conducted for Young Polish Female Respondents

by Dominika Głąbska, Aleksandra Staniec and Dominika Guzek

Nutrients 2018, 10(1), 104; https://doi.org/10.3390/nu10010104 - 19 Jan 2018

Cited by 8 | Viewed by 4807

Abstract

One of the brief methods enabling the assessment of the zinc intake and identification of individuals characterized by insufficient zinc intake, is zinc-specific food frequency questionnaire. The aim of the study was to assess the validity and reproducibility of the elaborated zinc-specific food frequency questionnaire ZINC-FFQ (Zinc INtake Calculation—Food Frequency Questionnaire) in a group of young Polish female respondents. The validity was assessed in comparison with 3-day dietary records, while reproducibility was assessed for the ZINC-FFQ filled in twice (FFQ1 and FFQ2—six weeks apart). Bland–Altman indexes in the assessment of validity were 5.5% (FFQ1) and 6.7% (FFQ2), while in assessment of reproducibility it was 3.3%. In the assessment of reproducibility, 83% of respondents were classified into the same category of zinc intake adequacy and 72% of respondents were classified into the same tertile, that contributed to weighted κ statistic of 0.65 (substantial agreement). It may be concluded, that ZINC-FFQ is characterized by a validity on a satisfactory and reproducibility on a very good level, in a group of young Polish female respondents, and may be applied to indicate individuals characterized by the risk of insufficient intake. Full article

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

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10 pages, 230 KiB

Open AccessArticle

Prospective Study of Dietary Zinc Intake and Risk of Cardiovascular Disease in Women

by Abul Hasnat Milton, Khanrin P. Vashum, Mark McEvoy, Sumaira Hussain, Patrick McElduff, Julie Byles and John Attia

Nutrients 2018, 10(1), 38; https://doi.org/10.3390/nu10010038 - 04 Jan 2018

Cited by 26 | Viewed by 5109

Abstract

Several animal and human studies have shown that zinc is associated with cellular damage and cardiac dysfunction. This study aims to investigate dietary zinc and the zinc-iron ratio, as predictors of incident cardiovascular disease (CVD) in a large longitudinal study of mid-age Australian women (aged 50–61 years). Data was self-reported and validated food frequency questionnaires were used to assess dietary intake. Energy-adjusted zinc was ranked using quintiles and predictors of incident CVD were examined using stepwise logistic regression. After six years of follow-up, 320 incident CVD cases were established. A positive association between dietary zinc intake, zinc-iron ratio and risk of CVD was observed even after adjusting for potential dietary and non-dietary confounders. Compared to those with the lowest quintile of zinc, those in the highest quintile (Odds Ratio (OR) = 1.67, 95% Confidence Interval (CI) = 1.08–2.62) and zinc-iron ratio (OR = 1.72, 95% CI = 1.05–2.81) had almost twice the odds of developing CVD (p trend = 0.007). This study shows that high dietary zinc intake and zinc-iron ratio is associated with a greater incidence of CVD in women. Further studies are required detailing the source of zinc and iron in diet and their precise roles when compared to other essential nutrients. Full article

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

6256 KiB

Open AccessArticle

Zinc Supplementation Improves Glucose Homeostasis in High Fat-Fed Mice by Enhancing Pancreatic β-Cell Function

by Vinícius Cooper-Capetini, Diogo Antonio Alves De Vasconcelos, Amanda Roque Martins, Sandro Massao Hirabara, José Donato Jr., Angelo Rafael Carpinelli and Fernando Abdulkader

Nutrients 2017, 9(10), 1150; https://doi.org/10.3390/nu9101150 - 20 Oct 2017

Cited by 36 | Viewed by 7337

Abstract

Zinc is an essential component of the insulin granule and it possibly modulates insulin secretion and signaling. Since insulin resistance is a hallmark in the development of type 2 diabetes mellitus, this study aimed at investigating if zinc supplementation is able to improve glucose tolerance and β-cell function in a model of insulin resistance. Male C57BL/6 mice were distributed in four groups according to the diet: normal fat (NF); normal fat supplemented with ZnCl₂ (NFZ); high-fat (HF); and, high-fat chow supplemented with ZnCl₂ (HFZ). Intraperitoneal glucose (ipGTT) and insulin (ipITT) tolerance, glycemia, insulinemia, HOMA-IR, and HOMA-β were determined after 15 weeks in each diet. Glucose-stimulated insulin secretion (GSIS) was investigated in isolated islets. The insulin effect on glucose uptake, metabolism, and signaling was investigated in soleus muscle. ZnCl₂ did not affect body mass or insulin sensitivity as assessed by ipITT, HOMA-IR, muscle glucose metabolism, and Akt and GSK3-β phosphorylation. However, glucose tolerance, HOMA-β, and GSIS were significantly improved by ZnCl₂ supplementation. Therefore, ZnCl₂ supplementation improves glucose homeostasis in high fat-fed mice by a mechanism that enhances β-cell function, rather than whole-body or muscle insulin sensitivity. Full article

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

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596 KiB

Open AccessArticle

Intrauterine Zn Deficiency Favors Thyrotropin-Releasing Hormone-Increasing Effects on Thyrotropin Serum Levels and Induces Subclinical Hypothyroidism in Weaned Rats

by Viridiana Alcántara-Alonso, Elena Alvarez-Salas, Gilberto Matamoros-Trejo and Patricia De Gortari

Nutrients 2017, 9(10), 1139; https://doi.org/10.3390/nu9101139 - 18 Oct 2017

Cited by 4 | Viewed by 5035

Abstract

Individuals who consume a diet deficient in zinc (Zn-deficient) develop alterations in hypothalamic-pituitary-thyroid axis function, i.e., a low metabolic rate and cold insensitivity. Although those disturbances are related to primary hypothyroidism, intrauterine or postnatal Zn-deficient adults have an increased thyrotropin (TSH) concentration, but unchanged thyroid hormone (TH) levels and decreased body weight. This does not support the view that the hypothyroidism develops due to a low Zn intake. In addition, intrauterine or postnatal Zn-deficiency in weaned and adult rats reduces the activity of pyroglutamyl aminopeptidase II (PPII) in the medial-basal hypothalamus (MBH). PPII is an enzyme that degrades thyrotropin-releasing hormone (TRH). This hypothalamic peptide stimulates its receptor in adenohypophysis, thereby increasing TSH release. We analyzed whether earlier low TH is responsible for the high TSH levels reported in adults, or if TRH release is enhanced by Zn deficiency at weaning. Dams were fed a 2 ppm Zn-deficient diet in the period from one week prior to gestation and up to three weeks after delivery. We found a high release of hypothalamic TRH, which along with reduced MBH PPII activity, increased TSH levels in Zn-deficient pups independently of changes in TH concentration. We found that primary hypothyroidism did not develop in intrauterine Zn-deficient weaned rats and we confirmed that metal deficiency enhances TSH levels since early-life, favoring subclinical hypothyroidism development which remains into adulthood. Full article

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

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7155 KiB

Open AccessArticle

Chronic High Dose Zinc Supplementation Induces Visceral Adipose Tissue Hypertrophy without Altering Body Weight in Mice

by Xiaohua Huang, Dandan Jiang, Yingguo Zhu, Zhengfeng Fang, Lianqiang Che, Yan Lin, Shengyu Xu, Jian Li, Chao Huang, Yuanfeng Zou, Lixia Li, De Wu and Bin Feng

Nutrients 2017, 9(10), 1138; https://doi.org/10.3390/nu9101138 - 18 Oct 2017

Cited by 27 | Viewed by 7205

Abstract

The trace element zinc plays an important role in human life. Zinc deficiency impairs growth, reproduction, metabolism and immunity in both human and animals. Thus, zinc supplementation is recommended in daily life. However, the effect of long-term chronic zinc supplementation on adipose homeostasis has not been well elucidated. In the current study, mice were supplemented with zinc sulfate in the drinking water for 20 weeks. The results suggested that chronic zinc supplementation impaired systemic glucose clearance after exogenous insulin or glucose challenges, as compared to the control mice. Further study revealed that chronic zinc supplementation made no difference to body weight, but increased visceral adipose tissue weight and adipocyte size. In addition, gene expression of leptin and IL6 in the visceral adipose tissue of zinc-supplemented mice were higher than those of control mice. Moreover, serum level of leptin of the zinc-supplemented mice was twice as high as that of the control mice. Besides, phosphorylation level of AKT T308 was attenuated in the perirenal adipose tissue of zinc-supplemented mice. In comparison, the expression of macrophage marker genes and lipogenic genes were not affected by chronic zinc supplementation, but the protein levels of FAS and SCD1 decreased or tended to decrease in the perirenal adipose tissue of zinc-supplemented mice, as compared to the control mice. Our findings suggest that chronic high dose zinc supplementation induces visceral adipose tissue hypertrophy and impairs AKT signaling in perirenal adipose tissue. Full article

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

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Review

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19 pages, 300 KiB

Open AccessReview

Zinc, Magnesium, Selenium and Depression: A Review of the Evidence, Potential Mechanisms and Implications

by Jessica Wang, Phoebe Um, Barbra A. Dickerman and Jianghong Liu

Nutrients 2018, 10(5), 584; https://doi.org/10.3390/nu10050584 - 09 May 2018

Cited by 192 | Viewed by 27183

Abstract

Micronutrient deficiency and depression are major global health problems. Here, we first review recent empirical evidence of the association between several micronutrients—zinc, magnesium, selenium—and depression. We then present potential mechanisms of action and discuss the clinical implications for each micronutrient. Collectively, empirical evidence most strongly supports a positive association between zinc deficiency and the risk of depression and an inverse association between zinc supplementation and depressive symptoms. Less evidence is available regarding the relationship between magnesium and selenium deficiency and depression, and studies have been inconclusive. Potential mechanisms of action involve the HPA axis, glutamate homeostasis and inflammatory pathways. Findings support the importance of adequate consumption of micronutrients in the promotion of mental health, and the most common dietary sources for zinc and other micronutrients are provided. Future research is needed to prospectively investigate the association between micronutrient levels and depression as well as the safety and efficacy of micronutrient supplementation as an adjunct treatment for depression. Full article

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

14 pages, 4144 KiB

Open AccessReview

The Role of the Slc39a Family of Zinc Transporters in Zinc Homeostasis in Skin

by Bum-Ho Bin, Shintaro Hojyo, Juyeon Seo, Takafumi Hara, Teruhisa Takagishi, Kenji Mishima and Toshiyuki Fukada

Nutrients 2018, 10(2), 219; https://doi.org/10.3390/nu10020219 - 16 Feb 2018

Cited by 21 | Viewed by 6931

Abstract

The first manifestations that appear under zinc deficiency are skin defects such as dermatitis, alopecia, acne, eczema, dry, and scaling skin. Several genetic disorders including acrodermatitis enteropathica (also known as Danbolt-Closs syndrome) and Brandt’s syndrome are highly related to zinc deficiency. However, the zinc-related molecular mechanisms underlying normal skin development and homeostasis, as well as the mechanism by which disturbed zinc homeostasis causes such skin disorders, are unknown. Recent genomic approaches have revealed the physiological importance of zinc transporters in skin formation and clarified their functional impairment in cutaneous pathogenesis. In this review, we provide an overview of the relationships between zinc deficiency and skin disorders, focusing on the roles of zinc transporters in the skin. We also discuss therapeutic outlooks and advantages of controlling zinc levels via zinc transporters to prevent cutaneous disorganization. Full article

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

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19 pages, 1777 KiB

Open AccessReview

Zinc and Skin Disorders

by Youichi Ogawa, Manao Kinoshita, Shinji Shimada and Tatsuyoshi Kawamura

Nutrients 2018, 10(2), 199; https://doi.org/10.3390/nu10020199 - 11 Feb 2018

Cited by 124 | Viewed by 20079

Abstract

The skin is the third most zinc (Zn)-abundant tissue in the body. The skin consists of the epidermis, dermis, and subcutaneous tissue, and each fraction is composed of various types of cells. Firstly, we review the physiological functions of Zn and Zn transporters in these cells. Several human disorders accompanied with skin manifestations are caused by mutations or dysregulation in Zn transporters; acrodermatitis enteropathica (Zrt-, Irt-like protein (ZIP)4 in the intestinal epithelium and possibly epidermal basal keratinocytes), the spondylocheiro dysplastic form of Ehlers-Danlos syndrome (ZIP13 in the dermal fibroblasts), transient neonatal Zn deficiency (Zn transporter (ZnT)2 in the secretory vesicles of mammary glands), and epidermodysplasia verruciformis (ZnT1 in the epidermal keratinocytes). Additionally, acquired Zn deficiency is deeply involved in the development of some diseases related to nutritional deficiencies (acquired acrodermatitis enteropathica, necrolytic migratory erythema, pellagra, and biotin deficiency), alopecia, and delayed wound healing. Therefore, it is important to associate the existence of mutations or dysregulation in Zn transporters and Zn deficiency with skin manifestations. Full article

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

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20 pages, 2504 KiB

Open AccessReview

Zinc, Carnosine, and Neurodegenerative Diseases

by Masahiro Kawahara, Ken-ichiro Tanaka and Midori Kato-Negishi

Nutrients 2018, 10(2), 147; https://doi.org/10.3390/nu10020147 - 29 Jan 2018

Cited by 83 | Viewed by 12769

Abstract

Zinc (Zn) is abundantly present in the brain, and accumulates in the synaptic vesicles. Synaptic Zn is released with neuronal excitation, and plays essential roles in learning and memory. Increasing evidence suggests that the disruption of Zn homeostasis is involved in various neurodegenerative diseases including Alzheimer’s disease, a vascular type of dementia, and prion diseases. Our and other numerous studies suggest that carnosine (β-alanyl histidine) is protective against these neurodegenerative diseases. Carnosine is an endogenous dipeptide abundantly present in the skeletal muscles and in the brain, and has numerous beneficial effects such as antioxidant, metal chelating, anti-crosslinking, and anti-glycation activities. The complex of carnosine and Zn, termed polaprezinc, is widely used for Zn supplementation therapy and for the treatment of ulcers. Here, we review the link between Zn and these neurodegenerative diseases, and focus on the neuroprotective effects of carnosine. We also discuss the carnosine level in various foodstuffs and beneficial effects of dietary supplementation of carnosine. Full article

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

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17 pages, 703 KiB

Open AccessReview

Associations between Zinc Deficiency and Metabolic Abnormalities in Patients with Chronic Liver Disease

by Takashi Himoto and Tsutomu Masaki

Nutrients 2018, 10(1), 88; https://doi.org/10.3390/nu10010088 - 14 Jan 2018

Cited by 117 | Viewed by 11344

Abstract

Zinc (Zn) is an essential trace element which has favorable antioxidant, anti-inflammatory, and apoptotic effects. The liver mainly plays a crucial role in maintaining systemic Zn homeostasis. Therefore, the occurrence of chronic liver diseases, such as chronic hepatitis, liver cirrhosis, or fatty liver, results in the impairment of Zn metabolism, and subsequently Zn deficiency. Zn deficiency causes plenty of metabolic abnormalities, including insulin resistance, hepatic steatosis and hepatic encephalopathy. Inversely, metabolic abnormalities like hypoalbuminemia in patients with liver cirrhosis often result in Zn deficiency. Recent studies have revealed the putative mechanisms by which Zn deficiency evokes a variety of metabolic abnormalities in chronic liver disease. Zn supplementation has shown beneficial effects on such metabolic abnormalities in experimental models and actual patients with chronic liver disease. This review summarizes the pathogenesis of metabolic abnormalities deriving from Zn deficiency and the favorable effects of Zn administration in patients with chronic liver disease. In addition, we also highlight the interactions between Zn and other trace elements, vitamins, amino acids, or hormones in such patients. Full article

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

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839 KiB

Open AccessReview

Zinc in Wound Healing Modulation

by Pei-Hui Lin, Matthew Sermersheim, Haichang Li, Peter H. U. Lee, Steven M. Steinberg and Jianjie Ma

Nutrients 2018, 10(1), 16; https://doi.org/10.3390/nu10010016 - 24 Dec 2017

Cited by 249 | Viewed by 47894

Abstract

Wound care is a major healthcare expenditure. Treatment of burns, surgical and trauma wounds, diabetic lower limb ulcers and skin wounds is a major medical challenge with current therapies largely focused on supportive care measures. Successful wound repair requires a series of tightly coordinated steps including coagulation, inflammation, angiogenesis, new tissue formation and extracellular matrix remodelling. Zinc is an essential trace element (micronutrient) which plays important roles in human physiology. Zinc is a cofactor for many metalloenzymes required for cell membrane repair, cell proliferation, growth and immune system function. The pathological effects of zinc deficiency include the occurrence of skin lesions, growth retardation, impaired immune function and compromised would healing. Here, we discuss investigations on the cellular and molecular mechanisms of zinc in modulating the wound healing process. Knowledge gained from this body of research will help to translate these findings into future clinical management of wound healing. Full article

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

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915 KiB

Open AccessReview

The Linoleic Acid: Dihomo-γ-Linolenic Acid Ratio (LA:DGLA)—An Emerging Biomarker of Zn Status

by Marija Knez, James C. R. Stangoulis, Maria Glibetic and Elad Tako

Nutrients 2017, 9(8), 825; https://doi.org/10.3390/nu9080825 - 01 Aug 2017

Cited by 35 | Viewed by 6618

Abstract

Zinc (Zn) deficiency is a common aliment predicted to affect 17% of the world’s population. Zinc is a vital micronutrient used for over 300 enzymatic reactions and multiple biochemical and structural processes in the body. Although whole blood, plasma, and urine zinc decrease in severe zinc deficiency, accurate assessment of zinc status, especially in mild to moderate deficiency, is difficult as studies with these biomarkers are often contradictory and inconsistent. Hence, as suggested by the World Health Organization, sensitive and specific biological markers of zinc status are still needed. In this review, we provide evidence to demonstrate that the LA:DGLA ratio (linoleic acid:dihomo-γ-linolenic acid ratio) may be a useful additional indicator for assessing Zn status more precisely. However, this biomarker needs to be tested further in order to determine its full potential. Full article

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

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16 pages, 385 KiB

Open AccessProtocol

Study Protocol for a Randomized, Double-Blind, Community-Based Efficacy Trial of Various Doses of Zinc in Micronutrient Powders or Tablets in Young Bangladeshi Children

by M. Munirul Islam, Christine M. McDonald, Nancy F. Krebs, Jamie Westcott, Ahmed Ehsanur Rahman, Shams El Arifeen, Tahmeed Ahmed, Janet C. King and Robert E. Black

Nutrients 2018, 10(2), 132; https://doi.org/10.3390/nu10020132 - 26 Jan 2018

Cited by 11 | Viewed by 7086

Abstract

Zinc is essential to supporting growth in young children especially for tissues undergoing rapid cellular differentiation and turnover, such as those in the immune system and gastrointestinal tract. Therapeutic zinc supplementation has been initiated in low-income countries as part of diarrhea treatment programs to support these needs for young children, but the effects of preventive supplemental zinc as a tablet or as a multiple micronutrient powder (MNP) on child growth and diarrheal disease are mixed and pose programmatic uncertainties. Thus, a randomized, double-blind community-based efficacy trial of five different doses, forms, and frequencies of preventive zinc supplementation vs. a placebo was designed for a study in children aged 9–11 months in an urban community in Dhaka, Bangladesh. The primary outcomes of this 24-week study are incidence of diarrheal disease and linear growth. Study workers will conduct in-home morbidity checks twice weekly; anthropometry will be measured at baseline, 12 weeks and 24 weeks. Serum zinc and other related biomarkers will be measured in a subsample along with an estimate of the exchangeable zinc pool size using stable isotope techniques in a subgroup. Therapeutic zinc will be provided as part of diarrhea treatment, in accordance with Bangladesh’s national policy. Therefore, the proposed study will determine the additional benefit of a preventive zinc supplementation intervention. The protocol has been approved by the Institutional Review Boards (IRBs) of icddr,b and Children’s Hospital Oakland Research Institute (CHORI). The IRB review process is underway at the University of Colorado Denver as well. Full article

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

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