zinc essay in english

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Occurrence, uses, and properties

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• National Center for Biotechnology Information - PubChem - Zinc
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• Table Of Contents

zinc (Zn) , chemical element , a low-melting metal of Group 12 (IIb, or zinc group ) of the periodic table , that is essential to life and is one of the most widely used metals . Zinc is of considerable commercial importance.

A little more abundant than copper , zinc makes up an average of 65 grams (2.3 ounces) of every ton of Earth ’s crust. The chief zinc mineral is the sulfide sphalerite (zinc blende), which, together with its oxidation products smithsonite and hemimorphite , constitute nearly all of the world’s zinc ore . Native zinc has been reported from Australia , New Zealand , and the United States , and the leading early 21st-century producers of zinc are China , Australia and Peru . For zinc’s mineralogical properties, see native element .

Zinc is an essential trace element in the human body , where it is found in high concentration in the red blood cells as an essential part of the enzyme carbonic anhydrase , which promotes many reactions relating to carbon dioxide metabolism . The zinc present in the pancreas may aid in the storage of insulin . Zinc is a component of some enzymes that digest protein in the gastrointestinal tract . Zinc deficiency in nut-bearing and fruit trees causes such diseases as pecan rosette, little leaf, and mottle leaf. Zinc functions in the hemosycotypsin of snails ’ blood to transport oxygen in a way analogous to iron in the hemoglobin of human blood.

Metallic zinc is produced by roasting the sulfide ores and then either leaching the oxidized product in sulfuric acid or smelting it in a blast furnace. Zinc is won from the leach solution by electrolysis or is condensed from the blast furnace gas and then distilled of impurities. For specific information on the mining, recovery, and refining of zinc, see zinc processing .

The major uses of zinc metal are in galvanizing iron and steel against corrosion and in making brasses and alloys for die-casting . Zinc itself forms an impervious coating of its oxide on exposure to the atmosphere, and hence the metal is more resistant to ordinary atmospheres than iron and corrodes at a much lower rate. In addition, because zinc tends to oxidize in preference to iron, some protection is afforded the steel surface even if some of it is exposed through cracks. The zinc coating is formed either by hot-dip galvanizing or electrogalvanizing.

Hot-dip galvanizing is the most common procedure for coating steel with zinc. This may be a batch process known as general galvanizing or a continuous coating of coils of steel strip. In general galvanizing, steel is pickled in acid , treated with fluxing agents, and then dipped in a bath of molten zinc at about 450 °C (840 °F). Layers of iron-zinc alloy are formed on the surface and are topped with an outer layer of zinc. Objects so treated range from small nuts and bolts to steel window frames and large girders used in construction. An ordinary grade of zinc containing up to 1.5 percent lead is normally used in this process.

In electrogalvanizing , zinc is deposited on a steel strop in as many as 20 consecutive electrolytic coating cells. There are several successful cell designs; the simple vertical cell is discussed here to explain the principle. The strip, connected to the negative side of a direct current through large-diameter conductor rolls located above and between two cells, is dipped into a tank of electrolyte by a submerged sink roll. Partially submerged anodes , opposing the strip, are connected to the positive side of the electric current by heavy bus bars. Zinc cations (i.e., positively charged zinc atoms ) present in the electrolyte are converted by the current into regular zinc atoms, which deposit on the strip. The bath is supplied with zinc cations either by zinc anodes, which are continuously dissolved by the direct current, or by zinc compounds continuously added to the electrolyte. In the latter case the anodes are made of insoluble materials, such as titanium coated with iridium oxide. The electrolyte is an acidic solution of zinc sulfide or zinc chloride with other bath additions to improve the quality of the coating and the current efficiency . Coating thickness is easier to control than in the hot-dip process because of the good relationship between electrical current and deposited zinc.

The negative electrode (outside can) in one common type of electric dry cell is composed of zinc. Another important series of alloys are those formed by the addition of 4 to 5 percent aluminum to zinc; these have a relatively low melting point but possess good mechanical properties and can be cast under pressure in steel dies. Considerable quantities of zinc in the rolled form are used for roofing, particularly in Europe; small additions of copper and titanium improve creep resistance —i.e., resistance to gradual deformation.

Freshly cast zinc has a bluish silver surface but slowly oxidizes in air to form a grayish protective oxide film. Highly pure zinc (99.99 percent) is ductile; the so-called prime western grade (99.8 percent pure) is brittle when cold but above 100 °C (212 °F) can be rolled into sheets that remain flexible. Zinc crystallizes in the hexagonal close-packed structure. When iron and zinc together are exposed to a corrosive medium, they constitute an electrolytic cell , and the zinc is attacked (oxidized to the Zn 2 + ion) preferentially because of its higher electrode potential. This so-called sacrificial protection, coupled with the much greater corrosion resistance of zinc under atmospheric conditions, is the basis for galvanizing .

Natural zinc is a mixture of five stable isotopes : 6 4 Zn (48.6 percent), 6 6 Zn (27.9 percent), 6 7 Zn (4.1 percent), 6 8 Zn (18.8 percent), and 7 0 Zn (0.6 percent).

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Role of zinc in health and disease

Lucy i. stiles.

1 Faculty of Life Sciences and Medicine, GKT School of Medical Education, King’s College London, London, UK

Kevin Ferrao

Kosha j. mehta.

2 Faculty of Life Sciences and Medicine, Centre for Education, King’s College London, London, UK

This review provides a concise overview of the cellular and clinical aspects of the role of zinc, an essential micronutrient, in human physiology and discusses zinc-related pathological states. Zinc cannot be stored in significant amounts, so regular dietary intake is essential. ZIP4 and/or ZnT5B transport dietary zinc ions from the duodenum into the enterocyte, ZnT1 transports zinc ions from the enterocyte into the circulation, and ZnT5B (bidirectional zinc transporter) facilitates endogenous zinc secretion into the intestinal lumen. Putative promoters of zinc absorption that increase its bioavailability include amino acids released from protein digestion and citrate, whereas dietary phytates, casein and calcium can reduce zinc bioavailability. In circulation, 70% of zinc is bound to albumin, and the majority in the body is found in skeletal muscle and bone. Zinc excretion is via faeces (predominantly), urine, sweat, menstrual flow and semen. Excessive zinc intake can inhibit the absorption of copper and iron, leading to copper deficiency and anaemia, respectively. Zinc toxicity can adversely affect the lipid profile and immune system, and its treatment depends on the mode of zinc acquisition. Acquired zinc deficiency usually presents later in life alongside risk factors like malabsorption syndromes, but medications like diuretics and angiotensin-receptor blockers can also cause zinc deficiency. Inherited zinc deficiency condition acrodermatitis enteropathica, which occurs due to mutation in the SLC39A4 gene (encoding ZIP4), presents from birth. Treatment involves zinc supplementation via zinc gluconate, zinc sulphate or zinc chloride. Notably, oral zinc supplementation may decrease the absorption of drugs like ciprofloxacin, doxycycline and risedronate.

Introduction

Significance of zinc in human health.

Zinc cannot be synthesised within the human body, so external intake of zinc is essential to maintain adequate levels in the body [ 1 ]. It is the second most abundant trace element in the body, after iron [ 2 ]. One in ten proteins found in the body is a zinc protein [ 3 ], and more than 300 enzymes and 1000 transcription factors depend on zinc for their activities [ 4 ]. Thus, zinc is an essential micronutrient involved in many cellular processes such as protein synthesis, nucleic acid metabolism including DNA synthesis, gene transcription [ 1 ], cell proliferation and differentiation, and mitosis [ 5 ].

These zinc-requiring cellular processes extend the significance of zinc to physiological level. For example, zinc is a structural component of the bone tissue and plays a role in collagen matrix synthesis, mineralisation, and bone turnover [ 6 ]. Also, zinc regulates intracellular signalling pathways of innate and adaptive immune cells [ 7 ], influences immune responses including antibody production, inflammatory signalling and lymphocyte differentiation [ 8 ], and thereby plays an essential role in the functionality of the immune system.

Zinc also plays a role in the endocrine system. For example, zinc is required in the formation and structural stability of insulin [ 9 ]. Essentially, insulin dimers form hexameric units, coordinated by two zinc ions in the central axis of the hexamer [ 10 ]. No wonder the beta cells of the pancreas contain significantly higher concentrations of zinc than other cells of the body. Furthermore, zinc ions act on the insulin signalling pathway and stimulate lipogenesis and glucose uptake into the adipocytes [ 9 ]. Zinc transporter (ZnT)-8 mediates signalling between the pancreas and liver to allow optimal insulin release, while zinc/iron-regulated-transporter-like-protein-(ZIP)7 is thought to play a role in glycaemic control within skeletal muscle. [ 9 ].

Thyroid hormones are involved in many physiological functions, such as the anabolism of proteins and increasing the basal metabolic rate and bone growth in children [ 11 ]. Zinc plays an important role in the metabolism of thyroid hormones. It regulates the synthesis of thyroid-releasing hormone (TRH) and thyroid-stimulating hormone (TSH). Zinc modulates their structure and thereby regulates the transcription factors which are essential for thyroid hormone synthesis [ 12 ]. Thus, in humans with zinc deficiency, levels of TSH, serum triiodothyronine (T3) and thyroxine (T4) also decrease [ 13 ], with several studies suggesting zinc deficiency as a cause of subclinical hypothyroidism [ 14 ]. Unsurprisingly, zinc supplementation appears to enhance thyroid hormone levels, particularly T3 [ 15 ].

Zinc is essential for male fertility. A zinc-sensing receptor, known as GPR39, has been found in the sperm tail and acrosome. When extracellular Zinc(II) binds to this receptor, it triggers an intracellular signalling pathway that ultimately results in increased sperm motility and acrosomal exocytosis [ 16 ]. Thus, zinc could have a role in the prevention, diagnosis and treatment of male infertility [ 17 ].

Additionally, zinc is important for the normal development and functioning of the central nervous system (CNS). Zinc balance is vital for neural tube formation and stem cell proliferation during development. Various zinc-dependent enzymes contribute to the function of the CNS, and ‘free’ zinc appears to modulate a variety of post-synaptic receptors. For example, zinc inhibits GABA-A receptors, which reduces their inhibitory actions. Alterations in zinc levels thereby affect the CNS and play a role in conditions such as Alzheimer’s disease and depression [ 18 ].

The human retina contains zinc in high concentrations [ 19 ]. Studies have suggested a link between higher anti-oxidant intake, including zinc (likely because zinc is a cofactor of superoxide dismutase, an anti-oxidant enzyme and also because zinc is an inhibitor of NADPH oxidase [ 20 ], which catalyses the production of reactive oxygen species [ 21 ]) and a decreased risk of age-related macular degeneration (AMD) [ 22 ], a leading cause of vision loss [ 23 ]. Studies have proposed the benefits of anti-oxidant supplementation, including zinc, in slowing the progression of AMD through the prevention of cellular damage in the retina [ 24 ].

Importantly, randomised trials in children six months to twelve years of age showed a positive effect of zinc supplementation in reducing all-cause and infectious disease mortality. It also showed a minor positive impact on linear growth [ 25 ].

Collectively, these examples highlight the significance of zinc in human health.

Micro-deficiencies and prevalence of zinc deficiency

It is estimated that 372 million (56%) preschool-aged children and 1.2 billion (69%) non-pregnant women of reproductive age across the globe have a deficiency in at least one of the micronutrients, namely zinc, folate, vitamin A and iron. Geographically, 75% of micronutrient-deficient preschool-aged children live in South Asia, sub-Saharan Africa, or East Asia and the Pacific. 57% of micronutrient-deficient non-pregnant women of reproductive age live in East Asia and the Pacific or South Asia [ 26 ]. An estimated 17% of the world’s population is at risk of insufficient zinc intake [ 1 , 27 ]. In Southeast Asia and sub-Saharan Africa, zinc deficiency is endemic, affecting up to 33% of the population. Zinc deficiency is also prevalent in Turkey, Egypt, and Iran due to high phytate intake in their diets, which decreases zinc absorption and, therefore, its bioavailability. Other countries have a markedly lower prevalence of zinc deficiency, notably China, where its incidence decreased from 17 to 8%, as recorded in 2005 [ 1 ].

Zinc uptake, absorption, and regulators of its bioavailability

Zinc: location, dietary sources, and intake recommendation.

Table ​ Table1 1 provides an overview of the level and proportion of zinc at physiological and cellular levels in the human body.

Table 1

Zinc levels in a healthy human

*Conversion performed using MediCalc available at https://www.scymed.com/en/smnxtb/tbcbpgh1.htm

Zinc cannot be stored in substantial amounts, and so, regular dietary intake is essential to ensure sufficient zinc availability [ 17 ]. Dietary sources of zinc include fish, oysters, meat, legumes, nuts, beans, whole grains, beef, eggs, and dairy. Oysters are the richest source of zinc, while fruits and vegetables are the poorest source. Although beans, nuts, and whole grains contain zinc, the bioavailability of zinc from these is lower than food from animal sources due to the presence of phytates [ 37 ].

There are differences in the dietary recommendations of zinc. Data around this include recommendations of 7.4 mg/day (approximately) [ 38 ]. In the US, recommendations include 15 mg/day [ 30 ], 11 mg/day [ 39 ] and 11 mg/day and 8 mg/day for adult men and women, respectively, who are age 19 and above [ 37 ]. In the UK, the recommendation is 9.5 mg/day for an adult man and 7 mg/day for an adult woman. The UK Department of Health recommends that zinc intake should not exceed 25 mg/day [ 40 ].

Zinc transporters: ZIPs and ZnTs

During digestion, zinc is released from food as free Zn 2+ ions. These ions need to be transported from the intestinal lumen to the enterocyte, then from here into the circulation and from circulation to the cells that require zinc for their activities. Also, within cells, there is intracellular zinc movement and compartmentalisation. These zinc transport processes are facilitated by two important types of zinc transporters: Zinc/iron-regulated-transporter-like-proteins (ZIPs) and Zinc transporters (ZnTs). ZIPs increase intracellular/cytoplasmic zinc levels by transporting zinc from the extracellular space and/or intracellular organelles into the cytoplasm. In general, ZnTs (the exception is ZnT5B, which is a bidirectional transporter) reduce intracellular/cytoplasmic zinc by transporting zinc from the cytoplasm to extracellular space (promoting zinc efflux from cells) or into an organelle for its compartmentalisation [ 38 ]. ZnTs and ZIPs are located in several different tissues/cells, on different regions of the cell surface, and on the surface of intracellular organelles (Tables  2 and ​ and3 3 ).

Table 2

ZnT transporters: location and regulation

Table 3

ZIP transporters: location and regulation

Process of zinc uptake, absorption, and circulation

Zinc absorption/uptake primarily occurs in the proximal part of the small intestine, in the distal duodenum and proximal jejunum [ 39 ]. Zn 2+ ion entry into the enterocyte is mediated via ZIP4 and/or ZnT5B in the duodenum and jejunum (Fig.  1 ). Another transmembrane ion transporter potentially involved in zinc uptake into the enterocyte is Divalent Metal Transporter-1 (DMT-1) [ 29 ]. Regardless of the transporter used, once Zn +2 ions are in the enterocyte, ZnT1 transports zinc from the enterocyte into the portal blood [ 45 ]. From here, these ions travel through the hepatic portal vein, mostly likely bound to ligands such as amino acids and citrate [ 96 ]. A previous study in rats found that most zinc travels to the liver in portal blood bound to transferrin [ 97 ]. At the liver, the portal vein branches, and the blood drains through sinusoids [ 98 ]. Some zinc enters hepatocytes, most likely via ZIP14 [ 99 ]. After the blood passes through the sinusoids, it is directed to the central vein, then hepatic veins and eventually the systemic circulation [ 98 ]. From the systemic circulation, zinc ions are transported to various body tissues such as the in brain, muscle, and bone [ 100 ] (Fig. 1 ).

Zinc uptake under physiological conditions. Zinc ions are transported from the intestinal lumen into the enterocyte by ZIP4. Other zinc transporters on the apical membrane include ZIP8 [ 101 ], ZnT10 [ 67 ] and ZnT5B [ 56 ]. ZnT5B has a bidirectional transport function [ 56 ]. Transporters located on the basolateral membrane of the enterocyte include ZnT1 [ 44 ], ZIP14 [ 102 ] and ZIP5 [ 103 ]. ZnT1 transports zinc ions from the enterocyte into the portal vein. Zinc ions travel in the portal blood to the liver, most likely bound to citrate, amino acids [ 96 ] and transferrin [ 97 ]. At the liver, portal blood drains through sinusoids, from where some zinc is taken up by hepatocytes. The rest of the zinc joins the systemic circulation from where it can reach distant tissues such as the brain, muscle, and bone via their respective ZIP transporters. Figure created with BioRender.com

There is a wide consensus that, in the systemic circulation, the majority of zinc is bound to albumin, a lesser amount bound to α 2 -macroglobulin, and a fraction bound to amino acids. There is a debate over whether transferrin has a role to play as a zinc carrier in the systemic circulation. Some studies suggest it may play a role [ 28 , 29 ], whilst others state that transferrin does not have a primary role in the distribution of zinc [ 104 ].

Variability in data regarding the proportion of zinc bound to albumin and α 2 -macroglobulin in systemic circulation

There have been various propositions regarding the proportions of these zinc carriers, particularly albumin. While some stated 80–85% of zinc is bound to albumin [ 105 ], others stated that this figure is 60% (with the remaining 30% bound to α 2 -macroglobulin and 10% to transferrin) [ 29 ], or 70% [ 38 ], or 80% (with the remaining 20% bound to α 2 -macroglobulin) [ 28 ], and yet others believe that approximately 98% zinc in the systemic circulation is bound to albumin [ 106 ].

Regardless of the exact percentage, conditions affecting albumin concentration, such as liver cirrhosis, may affect serum zinc levels [ 38 ]. For example, patients with liver cirrhosis and hepatic encephalopathy show decreased serum zinc levels [ 107 ].

Binding of Zn +2 ions to the different ligands could be the reason for the concentration of “free” Zn +2 ions in the circulation to be low (~ 0.1–1.0 nM) [ 96 ].

Regulators of zinc bioavailability

Bioavailability is the fraction of intake that can be absorbed into the blood and can be used for physiological processes in the body. Studies suggest that the typical range of zinc absorption from the intestinal lumen into the circulation is 16–50% [ 29 ], with an average of around 33% [ 38 ].

An important factor affecting zinc bioavailability is the solubility of zinc in the intestinal lumen. Previously, it was proposed that amino acids released from protein digestion enhanced zinc absorption by increasing its solubility [ 108 ]. Recent reviews have suggested that protein levels in the diet positively correlate with zinc uptake, and the presence of animal-based protein enhances zinc absorption more than the presence of plant-based protein. However, it is still uncertain whether amino acids can enhance zinc bioavailability due to a lack of consensus among studies. Citrate is a low molecular weight ligand found in milk which is thought to have a positive effect on zinc bioavailability by forming zinc-citrate complexes, thereby enhancing zinc uptake. These complexes are found in higher concentrations in human milk than in cow’s milk. Therefore, zinc absorption from human milk is higher than cow’s milk [ 29 ]. Also, food fermentation and germination enhance zinc absorption by reducing the phytate content of food [ 108 ]. Essentially, fermentation and germination both promote endogenous phytase activity [ 109 , 110 ]. Germination also facilitates de novo synthesis of phytases, enzymes which hydrolyse phytic acid [ 110 ].

On the other hand, several inhibitors decrease zinc solubility and, thereby, its bioavailability, for example, phytic acid/phytates found in food such as legumes, beans, and nuts. Phytates bind to zinc in the intestine, form insoluble complexes and thereby limit zinc absorption. Thus, zinc bioavailability from plant-based foods is lower than foods from animal sources [ 37 ]. Calcium and casein in cow’s milk may also reduce the bioavailability of zinc [ 25 ].

In addition, some medications may reduce serum zinc levels. For example, long-term use of distal-tube diuretics such as chlortalidone may result in significant zinc depletion due to increased urinary zinc excretion (hyperzincuria) [ 111 ]. Angiotensin-converting enzyme inhibitors (ACEis) or angiotensin-receptor blockers (ARBs), commonly used to treat heart failure, may cause zinc deficiency [ 112 ]. Also, when consuming or prescribing oral zinc supplements for zinc deficiency, interactions of medications must be carefully monitored. For example, orally consumed zinc may decrease the absorption of many orally taken drugs, such as alendronate and risedronate, which are used to prevent and treat osteoporosis. Similarly, zinc can inhibit the absorption of many antibiotics such as ciprofloxacin and doxycycline [ 113 ].

Zinc homeostasis at physiological level

At the physiological level, zinc homeostasis is primarily maintained by controlling zinc absorption and excretion. Of the zinc that is excreted from the body, ~ 50% is lost via faeces [ 38 ] (including zinc in sloughed epithelial cells) [ 28 ], and the rest is lost through urine, sweat, menstrual flow, semen, loss of hair and nails, and shedding of skin [ 29 ]. The zinc absorption mechanism adapts more slowly, while zinc excretion mechanisms can alter quickly [ 29 , 38 ]. During zinc deficiency, absorption of zinc can be increased up to 90% [ 28 ] and faecal and urinal excretion of zinc is rapidly reduced [ 29 ]. Certain tissues, such as the bone marrow, liver, and testes, secrete zinc into the circulation as a response to zinc deficiency. Other organs such as skin, skeletal muscle, heart, and kidney conserve their zinc levels even in zinc-deficient states [ 114 ].

Endogenous zinc secretion

The process of endogenous zinc secretion into the intestinal lumen may play a role in maintaining zinc homeostasis [ 115 ]. There are many ways of mediating zinc secretion into the intestinal lumen, for example, via biliary, pancreatic and gastroduodenal secretions and sloughing of mucosal cells [ 56 , 114 , 116 ]. Zinc transport from the portal circulation into the enterocyte is mediated by ZIP5 and ZIP14 on the basolateral membrane of enterocytes. ZnT5B transporter on the apical membrane of enterocytes is a bidirectional transporter that can transport enterocyte zinc ions into the intestinal lumen and vice versa, thereby mediating both, enterocyte uptake and endogenous secretion of zinc [ 29 , 117 ].

In the context of zinc secretion into intestinal lumen from the exocrine secretions of the pancreas, there are several zinc transporters that participate in this process. For example, zinc ions are transported into the pancreas from the plasma via ZIP5. These ions are then transported into zymogen granules via ZnT2 and excreted into the digestive tract as pancreatic secretions. Interestingly, zinc concentration in pancreatic tissues and secretions is influenced by dietary zinc intake. Excess dietary zinc leads to upregulation of ZnT2 in acinar cells, and restriction of dietary zinc leads to reduced zinc concentration in both pancreatic tissue and secretions. Thus, zinc homeostasis is regulated by adjusting zinc excretion through the entero-pancreatic axis.

Regardless of the pathway, some zinc in the lumen is reabsorbed into the circulation through uptake via enterocytes. Thus, the balance between the absorption of dietary zinc, and the excretion and reabsorption of endogenous zinc collectively maintain zinc levels in the body [ 29 ].

Zinc homeostasis at the cellular level

Zinc concentration at the physiological level is determined by zinc regulation at the cellular level, which is determined by zinc transporters (Tables  2 and ​ and3). 3 ). Zinc transporters are regulated through various mechanisms, including activation of transcription, stabilisation of mRNA, modification of protein, trafficking to specific organelles, and transporter degradation. Regulatory stimuli include zinc, cytokines, hormones, endoplasmic reticulum stress, oxidative stress, and hypoxia [ 28 ].

Effect of high and low zinc on ZnTs: how zinc regulates ZnT expression

ZnT transporters are differentially regulated by zinc levels but with some similarities in mechanisms. Table ​ Table2 2 presents a detailed view of ZnTs, their cellular and tissue distribution, and the stimuli and mechanisms involved in the upregulation or downregulation of the ZnTs. Essentially, high zinc levels increased ZnT1 and ZnT2 mRNA expressions [ 44 ] but decreased ZnT10 mRNA levels [ 68 ]. Interestingly, ZnT5 expression is unique and complex because high or low zinc levels have been shown to increase or decrease its expression [ 43 ]. This could be due to the B variant of ZnT5, which has a bidirectional functionality in zinc transport [ 29 ].

Effect of high and low zinc on ZIPs: how zinc regulates ZIP expression

Table ​ Table3 3 details the ZIPs, and their cellular and tissue distribution, along with the stimuli and mechanisms involved in their upregulation or downregulation.

Most ZIP transporters were confirmed to increase their expression in response to low zinc levels including ZIP2 [ 74 ], ZIP3 [ 70 , 76 ], ZIP4 [ 44 ], ZIP10 [ 86 ], and ZIP14 [ 92 ], while only ZIP5 expression was found to decrease [ 71 ]. There is some uncertainty regarding ZIP transporter regulation in response to high zinc levels. For example, ZIP7 levels inversely correlated with cellular zinc levels in CLN6 neurons [ 81 ] implying that higher cellular zinc would lead to lower ZIP7 levels. However, a causal link is yet to be confirmed because this finding could be confounded by the presence of CLN6 disease. In another example, dietary zinc restriction led to decreased ZIP11 expression in the mouse stomach. However, upon dietary zinc repletion, ZIP11 expression levels were not restored. This suggests that ZIP11 may be unaffected by zinc excess and possibly downregulated by zinc deficiency [ 89 ]. This unresponsiveness to zinc (in the form of dietary zinc repletion) [ 89 ] is unexpected, given the presence of multiple metal-response elements (MREs) upstream of the first exon of the ZIP11 gene [ 44 ].

Other regulators of ZnTs and ZIPs

Zinc transporters respond to various stimuli other than zinc (Tables  2 and ​ and3). 3 ). For example, in the immune system, T-cell stimulation by phytohaemagglutinin decreases the mRNA expressions of ZnT1, ZnT4, ZnT6 and ZnT7 [ 47 ]. These observations reiterate the importance of zinc in modulating the immune response. Moreover, in dendritic cells, lipopolysaccharide stimulation during toll-like receptor signalling increased the mRNA transcripts of ZnT1, ZnT4 and ZnT6 but decreased those of ZIP6 and ZIP10 [ 46 ].

Cytokines (namely IL-6) are known to increase ZIP14 levels [ 59 ] but decrease ZnT10 levels [ 44 ]. Hormones such as glucocorticoid and prolactin can increase ZnT2 levels [ 44 ], while thyroid hormone can increase ZIP10 levels [ 88 ]. In addition, glucose was found to increase ZIP14 levels [ 94 ].

Metals other than zinc, such as manganese [ 67 ] and iron [ 91 , 95 ], can also regulate zinc transporters, which reflects their role in assisting general metal homeostasis. Interestingly, high manganese intake upregulated liver ZIP14 expression in male and female mice but upregulated ZIP14 expression in the small intestine of only male mice. ZnT10 expression was upregulated in the same regions but only in male mice [ 67 ]. These observations indicate that there might be sex-based differences in the regulation of zinc transporters.

Metallothioneins (MTs): at the interface of physiological and cellular zinc regulation

MTs are a family of proteins, ubiquitously expressed (in most cells and tissues), which have a high affinity for d10 electron configuration metals, including zinc and copper [ 118 ]. MT1 and MT2 are the main isoforms expressed in most adult mammalian tissues. MT3 has been identified in the brain, kidney, breast, pancreas, intestine, and bladder. MT4 has been reported in stratified squamous epithelium around the body and plays an important role in cell differentiation [ 119 ].

MTs are thought to play a key role in the systemic regulation of trace elements, including that of zinc [ 35 , 118 ]. To execute this function, MTs within the enterocyte exhibit their regulatory effect at the absorption stage. Here, MTs can bind to zinc ions within the enterocyte cytoplasm and thereby reduce the availability of free intracellular zinc. Also, when zinc is needed by the cell, MTs can unbind zinc ions and make zinc available. So, if enterocyte zinc concentration is high, then MTs can bind to intracellular zinc and reduce free zinc ions [ 120 , 121 ]. Consequently, this would reduce the amount of zinc exported into the portal blood, which, in turn, would reduce the amount of zinc distributed around the body. MTs are also thought to mediate zinc trafficking within the cell and zinc transfer to zinc transporters. Thus, through their zinc buffering and muffling properties, MTs help in maintaining zinc homeostasis [ 29 ].

Acquired zinc deficiency: diagnosis and treatment

Acquired zinc deficiency could be due to insufficient intake (seen in anorexia nervosa), increased loss (seen in chronic diarrhoea or burns patients), increased requirement (seen in pregnant and breastfeeding individuals) or malabsorption (seen in Crohn’s disease [ 1 ] and coeliac disease [ 122 ]). It shows clinical features like diarrhoea, frequent infections, and skin lesions. However, these patients usually present the symptoms later in life alongside the aforementioned factors [ 123 ]. Due to overlap of symptoms, other differentials that should be considered whilst diagnosing zinc deficiency include: depression, hypothyroidism, vitamin (A, B12 and D) deficiencies, and iron deficiency [ 1 ].

Mild zinc deficiency can manifest clinically with serum values ranging from 40 to 60 µg/dL [ 124 ]. It has been suggested that acquired zinc deficiency can be diagnosed by a simple blood test showing fasting serum zinc < 70 µg /dL. Furthermore, since low albumin levels can cause low zinc levels, serum albumin levels should also be measured [ 125 ].

Some suggest that plasma zinc as a biomarker is non-specific, and it is difficult to develop a single biomarker of zinc status due to zinc’s diverse functions [ 25 ]. However, taking a fasting sample in the morning, separating plasma or serum from cells within 45 min and using zinc-free vacuum tubes can improve accuracy [ 1 ]. In general, urinary zinc levels are not a useful diagnostic parameter for zinc deficiency, whereas hair zinc levels are useful only in the context of chronic deficiency [ 1 , 126 ]. In addition to laboratory investigations, the clinical aspects comprising patient risk factors, geographical prevalence, and age of presentation, alongside physical examination and an appropriate history-taking, can help to establish the diagnosis [ 1 ].

Oral zinc supplementation, such as zinc gluconate for either short-term or long-term depending on the underlying aetiology, is usually used to cure the acquired deficiency [ 1 ]. Interestingly, zinc supplements can be formulated as zinc oxide or as salts with acetate, gluconate and sulphate [ 2 ]. A clinical trial reported that zinc oxide administered without food is less well absorbed than other zinc formulations as it is more insoluble [ 127 ]. Zinc citrate has a relatively higher zinc content, yet this is countered by the finding that zinc absorption in the form of citrate does not differ from that of zinc gluconate. However, the affordability of zinc citrate may make this an attractive alternative to zinc gluconate [ 127 ]. A potential complication of zinc deficiency treatment is overcorrection with zinc supplementation since this can cause acute zinc toxicity [ 1 ]

Other clinical conditions that may show low zinc levels are tabulated in Table  4 .

Table 4

Examples of clinical conditions that show low zinc levels

Inherited zinc deficiency acrodermatitis enteropathica: diagnosis and treatment

Many inherited defects of zinc deficiencies are known. Most cases are associated with mutations in the SLC39A4 gene on chromosome 8. This gene encodes the zinc transporter ZIP4 [ 134 – 136 ]. The pathological condition is referred to as acrodermatitis enteropathica, a rare autosomal recessive condition with the incidence of roughly 1 in 500,000 births [ 1 , 137 ]. It affects males and females equally [ 137 ]. Because ZIP4 mediates the transport of zinc ions from the intestinal lumen into the enterocyte, a mutation in the gene encoding ZIP4 does not allow zinc ions to be transported into the enterocyte through this transporter. Consequently, insufficient zinc ions reach the systemic circulation or distant tissues (Fig.  2 ) [ 29 ]. Although a small amount of zinc may be taken up via the passive paracellular route [ 138 ], the result is zinc deficiency.

Mechanisms/events underlying zinc deficiency due to mutation in ZIP4 (Acrodermatitis enteropathica). In acrodermatitis enteropathica, there is a mutation in the SLC39A4 gene which encodes the ZIP4 protein. Dysfunctionality in ZIP4 transporter causes limited zinc uptake by the enterocyte, and therefore, insufficient zinc transported into the portal vein via ZnT1. Insufficient zinc ions enter the liver and the systemic circulation, leading to less zinc reaching other tissues. The result is zinc deficiency, which can be life-threatening, if not treated promptly. Figure created with BioRender.com

Notably, while ZIP4 has two zinc-binding sites and thereby can show increased efficiency in capturing and delivering zinc to the enterocytes, how ZnT5B (another zinc importer on the enterocyte) transports zinc ions into the enterocyte is not known [ 139 ]. It is conceivable that ZnT5B may have a lower affinity to zinc ions than ZIP4, and therefore, although it can allow the entry of zinc ions into the enterocyte, it cannot compensate for ZIP4 dysfunction. Left untreated, acrodermatitis enteropathica is fatal within the first few years of life [ 125 ]

Acrodermatitis enteropathica patients usually manifest symptoms early in life [ 1 ] in the phase of weaning from breastfeeding [ 140 ]. Symptoms include a triad of alopecia, diarrhoea, and dermatitis [ 141 ]. Patients may also show growth impairment, psoriasiform lesions (well-defined scaly plaques most often found on the elbows) and frequent infections [ 1 ]. Alongside the consideration of clinical symptoms, serum zinc level < 70 µg/dL in fasting and low serum alkaline phosphatase may be suggestive of acrodermatitis enteropathica [ 125 ]. Note that alkaline phosphatase is a zinc-dependent enzyme [ 142 ]. Molecular genetic testing can identify SLC39A4 mutation and confirm acrodermatitis enteropathica.

Treatment involves zinc supplementation, but the formulation of zinc depends on the route of administration. For example, zinc gluconate and sulphate [ 1 ] are commonly used orally, while zinc chloride is preferred parenterally [ 125 ]. Treatment is lifelong with patient compliance being crucial [ 40 ].

Another genetic cause of acrodermatitis enteropathica is due to a mutation in the SLC30A2 gene of the breastfeeding mother. This gene encodes for ZnT2, a zinc transporter expressed in the mammary glands [ 143 ]. In secreting mammary epithelial cells, ZnT2 imports zinc into vesicles, mediating zinc secretion into the breast milk. A mutation in this gene results in decreased zinc secretion into the breast milk. This can lead to severe zinc deficiency in exclusively breastfed infants [ 44 ]. This can be treated by supplementation of zinc at 5 mg per day whilst breastfeeding. After weaning, no further action is needed [ 143 ]. Most paediatric patients with acrodermatitis enteropathica do not present with the classic triad of periorificial and acral dermatitis, diarrhoea, and alopecia. Less than one-third of paediatric patients present in this way. Common presentations in children include recurrent infections, irritability, behavioural changes, neurological disturbances, and failure to thrive [ 140 ].

ZIP8 mutations result in cortical atrophy and, consequently, intellectual disability in the affected patient. A mutation in the SLC39A14 gene (encoding ZIP14) can lead to parkinsonism-dystonia in children [ 144 ], whilst a mutated ZIP13 protein is responsible for the spondylocheirodysplastic form of Ehlers-Danlos syndrome [ 145 ]. In mice, ZIP7 knockout was lethal, whilst a morpholino knockdown of ZIP7 caused neurodevelopmental issues in zebrafish [ 144 ].

Zinc toxicity: diagnosis and treatment

To our knowledge, there have been no reports on zinc overload/toxicity due to mutations in zinc transporters. The reported cases of zinc toxicity are due to acquired causes rather than inherited ones. Causes include pesticide exposure and exposure to compounds used to make paints, rubber and dyes [ 40 ].

The tolerable upper intake level of zinc, according to the US Institute of Medicine, is as follows: 4 mg in youngest infants, 12 mg in children 4–8 years old, 34 mg in adolescents (14–18 years), and 40 mg for persons aged 19 or older [ 146 ]. Acute and chronic zinc toxicities are defined as zinc intake of more than 200 mg/day and 50–150 mg/day, respectively [ 40 ]. Acute zinc toxicity is likely due to excessive zinc supplementation as opposed to excessive dietary zinc intake. Longer-term causes of zinc toxicity include occupational exposure to zinc [ 147 ] and iatrogenic causes such as overprescribing of zinc-containing medication, zinc present in dental fixtures (though modern preparations in the UK and US are now zinc-free) and overconsumption of over-the-counter zinc supplements [ 148 ].

At zinc doses higher than 50 mg/day, symptoms such as nausea, diarrhoea and abdominal discomfort may occur, whilst doses higher than 150 mg/day can adversely affect the body’s lipid profile and immune system. On the other hand, it has been suggested that symptoms of zinc toxicity may not manifest until intake exceeds 1–2 g [ 30 ]. The most common cause of zinc excess is taking too many zinc supplements [ 149 ]. Chronic zinc toxicity can lead to disturbances in copper metabolism causing low copper status, which affects iron distribution and causes anaemia, red blood cell microcytosis, neutropenia and reduced immune function [ 150 , 151 ].

Zinc toxicity presents in different ways depending on the mode of zinc overload. For example, acute dietary ingestion presents as nausea, vomiting, diarrhoea, and muscle cramps. If toxicity is caused by inhalation of fumes, it presents with flu-like symptoms such as cough, fever, and chills. Chronic ingestion slowly leads to a syndrome of neuropathy, anaemia, fatigue, and spasticity. The 2017 Annual Report of the American Association of Poison Control Centres’ (AAPCC) National Poison Data System (NPDS) reported 1236 cases of exposure to zinc compounds, most of which were unintentional exposures in children less than five years of age. There were no deaths or major adverse health events as a consequence of this though [ 30 ].

An investigation to diagnose zinc poisoning includes several aspects like a thorough history to gain an understanding of the mode of overload, levels of serum zinc, copper and ceruloplasmin, liver function tests, platelet count, and chest X-ray. Treatment for acute ingestion involves anti-emetics, fluids and proton pump inhibitors [ 30 ]. Treatment for metal fume inhalation focuses on oral rehydration, anti-pyretics and supplemental oxygen with bronchodilators [ 152 ]. In chronic zinc toxicity, first the identification and then the removal of the source of zinc is essential. This can be followed by treatment with copper sulphate [ 30 ]. This treatment works because copper competes with zinc for absorption, so exogenous copper intake reduces zinc absorption [ 1 ]. Very severe cases may require zinc chelation with agents such as diethylenetriamine pentaacetate (DTPA) [ 30 ].

Zinc-induced copper deficiency (ZICD)

An important complication of chronic zinc toxicity is zinc-induced copper deficiency (ZICD). Excess zinc levels in the small intestine stimulate increased expression of MTs in the enterocytes. Since copper has a greater affinity for MTs compared to zinc, copper outcompetes zinc for MT binding sites, and consequently, the copper bound to MT is excreted via sloughing of enterocytes. This results in decreased absorption of copper and, therefore, copper deficiency [ 153 ]. The co-existence of hyperzincaemia (high zinc in serum) and hypocupraemia (low copper in serum) is suggestive of ZICD [ 154 ]. Measurements of urinary zinc can be useful in the diagnostics of ZICD because urinary zinc levels are usually high in this condition [ 155 ].

ZICD tends to develop slowly over many months or years, although this apparent slow onset may be due to delayed diagnosis [ 155 ]. Early manifestation includes neutropenia, leukopenia and anaemia [ 154 ]. This anaemia is likely due to the disruption of copper’s physiological role in the differentiation of haematopoietic stem cells as well as intestinal iron absorption [ 156 ].

Under physiological conditions, copper plays a vital role in the synthesis and stabilisation of myelin, and in several enzymatic pathways required for the functioning of the nervous system. Therefore, if ZICD is left undiagnosed, it can lead to severe and permanent neurological complications including gait disturbances, paraesthesia and myelopathy [ 156 ].

One study highlighted that the over-prescription of zinc was a significant cause of ZICD. This shows that zinc can have potentially serious side effects, and it is not a harmless agent that can be prescribed without a strong justification [ 155 ]. Removal of the source of excess zinc along with oral copper gluconate treatment is often sufficient to revert anaemia, neutropenia and leukopenia seen in ZICD. Neurological deficits may also improve with this treatment; however, many never fully recover and will be left with permanent neurological deficits [ 156 ].

Trace elements play an important role in human health and disease. For example, the role of iron in various diseases, including liver fibrosis, alcohol-related liver disease, and COVID-19, has been reviewed [ 157 – 160 ].

Zinc is an essential micronutrient which cannot be stored in significant amounts, so regular dietary intake is vital. There does not seem to be a clear consensus on the recommended zinc intake, where the recommendation ranges from 7.4 to 15 mg/day. Citrate and food processing such as fermentation and germination, can enhance zinc uptake. It is unclear whether amino acids enhance zinc uptake. Phytic acid, found in cereals, legumes, and nuts, is known to decrease zinc bioavailability.

Zinc absorption occurs primarily in the proximal small intestine, where ZIP4 mediates zinc entry into enterocytes. ZnT5B and DMT-1 are also thought to play a role in this process. ZnT1 transports zinc from the enterocyte into the portal vein, via which zinc travels to the liver. Here, some zinc may enter the hepatocytes via ZIP14, and the rest may eventually drain into the systemic circulation for distribution to various bodily tissues. In the circulation, most zinc is bound to albumin, and the majority in the body can be found in skeletal muscle and bone.

Zinc deficiency can be inherited or acquired. The acquired form is due to insufficient intake, malabsorption, increased requirement, or excessive loss of zinc. Inherited zinc deficiency is mostly associated with mutations in the SLC39A4 gene (which encodes for ZIP4), resulting in a triad of alopecia, diarrhoea and dermatitis in a condition known as acrodermatitis enteropathica. In both inherited and acquired deficiencies, oral zinc supplementation is the mainstay of treatment with an excellent prognosis.

Zinc toxicity is only known to be acquired, not inherited, and may be acute or chronic. Symptoms include nausea, diarrhoea and abdominal discomfort but may vary depending on the mode of overload. Treatment involves the chelation of excess zinc using drugs.

Recommendations for future work

This review helped us identify the knowledge gaps in the literature on zinc. For example, there is no clear consensus on the proportion of zinc that is bound to albumin in the systemic circulation. Albumin levels decrease in several conditions, including liver cirrhosis, and so, knowledge of the proportion of zinc bound to albumin may inform alternative or supplementary treatments for those with albumin-depletion-induced zinc deficiency. In such patients, only oral zinc supplementation may not be enough to resolve the deficiency because there is an insufficient level of the zinc carrier albumin to distribute zinc around the body. Should albumin be the predominant zinc carrier in the circulation, albumin supplementation may play an important role in treating zinc deficiency. There are some other uncertainties in the context of zinc carriers. For example, there are contrasting suggestions on whether transferrin has a role to play as a zinc carrier in the systemic circulation or not. Thus, the knowledge on zinc carriers will aid in our understanding of the pathogenesis of zinc-related conditions.

Another knowledge gap exists in the mechanisms by which the levels of certain zinc transporters increase or decrease in cells in response to a stimulus, as reflected in Tables  2 and ​ and3. 3 . Dedicated studies are required to elucidate these mechanisms as this might help devise ways of altering zinc levels within cells in a tissue-specific manner and thereby help ameliorate a zinc-related diseased state. Also, while our knowledge so far indicates that zinc toxicity is not caused by mutations in zinc transporters, examining genetics as a predisposing factor in the development of zinc toxicity might be helpful, as it has been in the case of zinc deficiency. Given the multi-faceted physiological role of zinc, such studies would improve the diagnostics and therapeutics of a range of conditions, positively impacting the health of the general population as well as of those with zinc-related diseases.

Acknowledgements

This article is made open access with the financial support of King’s College London, UK. Thanks to Najma Ali (GKT School of Medical Education, Faculty of Life Sciences and Medicine, King’s College London, UK) for providing some data that acted as a reference for writing a couple of paragraphs.

Author contributions

LIS contributed to primary investigation and writing-original draft; KF contributed to further literature search, analysis, and interpretation of data; and KJM contributed to conceptualisation, supervision, writing and editing.

No funding was accessed/obtained for writing this review.

Declarations

Authors declare that they have no competing or financial interests to disclose.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Zinc: Benefits, sources & deficiency

From immunity to skin health, we need zinc for a variety of bodily functions. Here are the best sources, as well as signs of deficiency

• Requirements

Bluish-silver zinc is a workhorse element, crucial to many industrial processes that often go unseen. Humans have used zinc for many centuries now, with archaeologists finding a handful of zinc artifacts that date back to 300 B.C. Today, the metal is used mostly as coating for steel and iron to prevent rusting. But even more importantly, zinc is essential to healthy nutrition. In fact, it is one of the most complex and versatile trace elements in our diet, and not getting enough of it can lead to many severe health problems. 

While zinc usage may be firmly rooted in ancient history, its importance to life sciences was, for a long time, overlooked. As scientists point out , only in 1961 was zinc recognised as essential for human health, and we are still learning what exact roles this nutrient plays in our bodies. 

Here, we’ll discuss what science says about zinc and its potential health benefits, as well as the best sources of zinc and signs of potential deficiency.  

Why do we need zinc?

Zinc was discovered before it was officially discovered. In 1746, German chemist Andreas Marggraf (also the inventor of a process to extract sugar from beets) figured out how to isolate zinc by heating carbon and calamine (the stuff in calamine lotion). Marggraf  reported the finding  in great detail, which earned him credit for the discovery, even though several European researchers had already completed the same feat. An English metallurgist, William Champion, had even patented the process years earlier. 

Zinc is crucial to the proper functioning of our immune system. According to the journal Advances in Nutrition , this trace mineral is essential to fighting off viruses, and zinc-deficient populations are often most at risk of acquiring infections like HIV or hepatitis C virus.

Zinc supplementation is also used as a complementary treatment for several infectious diseases, including malaria. According to the Molecules and Cells journal, that is because this nutrient helps with passing on the information within the immune system and regulating the activity of immune-boosting white blood cells. 

More recently, zinc has been shown to play a role in obesity, insulin resistance and fat metabolism. According to a review published in the Nutrients journal, researchers are particularly interested in the newly discovered zinc-related adipokine, zinc-α2-glycoprotein (ZAG). Adipokines are a type of cell signaling proteins released by fat tissue, many of which contribute to inflammation and chronic diseases. Studies suggest that excess body fat lowers blood concentrations of zinc and ZAG, leading not only to the development of obesity, but also to other components of the metabolic syndrome. Zinc itself appears to regulate ZAG levels in the body. 

Researchers have found that zinc supplementation in overweight individuals significantly reduced blood cholesterol and triglyceride levels. In addition, in vitro studies have shown that ZAG may inhibit the production of leptin, a hunger-regulating hormone. 

Cardiovascular health

According to a review published in the Cardiology in Review journal, zinc deficiency has been linked to heart failure, hardening of the veins, and heart attacks. It has been suggested that these effects are due to zinc involvement in regulating inflammation and blood pressure levels.  

What’s more, according to the Journal of Cardiac Failure , zinc supplementation may improve heart function in patients with heart failure. Increasing the intake of this micronutrient can also help significantly reduce systolic blood pressure, but not the diastolic blood pressure, as reported in the European Journal of Nutrition .  

Brain health

Zinc is important for proper brain function. According to the Neuroscience journal, it is abundant in many regions of the brain, and is heavily involved in neurotransmission and sensory processing. And as stated in the International Journal of Molecular Sciences , zinc deficiency has been linked to a host of pathological conditions with both acute and chronic effects on brain function, including age-related cognitive decline, depression and Alzheimer's disease.  

Zinc may be essential to gut health . According to the International Journal of Molecular Sciences , zinc may increase gut bacteria biodiversity and improve gut wall integrity. Moreover, alterations of gut microbiota caused by distubed zinc metabolism have been linked to systemic inflammation, acute pancreatitis, autism spectrum disorder , attention deficit hyperactivity disorder, fetal alcohol syndrome and obesity.

As reported in the Nutrients journal, zinc-fortified foods may help increase the populations of beneficial Lactobacillus and Ruminococcus bacteria strains, while decreasing the potentially pathogenic Streptococcus, Escherichia , and Enterobacter strains.

Skin health

According to the Nutrients journal, the skin is the third most zinc-abundant tissue in the body, and contains multiple zinc transporters. Mutations or dysregulation of these zinc transporters have been linked to skin diseases like acrodermatitis enteropathica (skin inflammation around mouth and/ or anus), Ehlers-Danlos syndrome (condition characterized by hypermobile joints and overstretched skin), and epidermodysplasia verruciformis (skin lesions). 

Moreover, zinc supplementation may help with certain skin problems. As described in the American Journal of Clinical Dermatology , studies suggest it may be used in the treatment of acne and eczema .

• Related: Vitamin E
• Related: Selenium

Bone health

Exercise recovery

Zinc levels appear to be related to exercise. According to a review published in the Sports Medicine journal, serum zinc levels increase immediately after exercise and decrease during exercise recovery. Scientists suggest that this trace mineral is linked to muscle repair mechanisms. 

Fertility 

The zinc fireworks could have real-world applications for women dealing with infertility, Woodruff told Live Science. 

Pregnancy 

Maintaining a good zinc status may be critical for healthy pregnancy. According to a review published in the Journal of Trace Elements in Medicine and Biology , zinc deficiency has been linked to numerous adverse effects on maternal health and pregnancy outcomes. That is because this trace mineral ensures proper expression of genetic material, and as such, healthy fetal development.  

How much zinc do you need?

The Daily Value (DV) for adults aged 19 and over is 11 mg per day for men and 8 mg per day for women. 

The Recommended Dietary Allowance (RDA) for pregnant and breastfeeding women is 11 mg per day and 12 mg per day, respectively.

The Tolerable Upper Intake Level (UL) for all adults aged 19 and over is 40 mg per day. Higher intakes may lead to harmful health effects, particularly in the case of zinc supplements.  

As listed by the Harvard School of Public Health , signs of zinc toxicity include:

• Nausea and vomiting
• Poor appetite
• Abdominal pain or cramping
• Diarrhea 

What are the best sources of zinc?

Zinc is mostly found in animal-based foods. Some plant foods are also good sources of this micronutrient, but they may also contain compounds called phytates. Phytates may bind to zinc and lower its absorption in the digestive tract.

The best sources of zinc included:

• Oysters: 52mg (472% DV) per 6 oysters / 61mg (555% DV) per 100g
• Beef steak: 15mg (140% DV) per 5oz serving / 11mg (99% DV) per 100g
• Chicken leg: 5mg (49% DV) per leg / 2mg (19% DV) per 100g 
• Firm tofu: 4mg (36% DV) per cup / 2mg (14% DV) per 100g 
• Lean pork chops: 4mg (32% DV) per 6oz serving / 2mg (19% DV) per 100g
• Squash and pumpkin seeds: 3mg (27% DV) per 1oz handful / 10mg (94% DV) per 100g
• Lentils: 3mg (23% DV) per cup / 1mg (12% DV) per 100g
• Low-fat yoghurt: 2mg (22% DV) per cup / 1mg (9% DV) per 100g   
• Oatmeal: 2mg (21% DV) per cup / 1mg (9% DV) per 100g 
• Cooked Shiitake mushrooms: 2mg (18% DV) per cup / 1mg (12% DV) per 100g 

Can you be deficient in zinc?

Zinc deficiency is relatively rare. It is mostly seen in people who do not absorb zinc properly due to digestive disorders, gastrointestinal surgery, or prolonged diarrhea. Severe conditions that increase zinc requirements, such as burns and sepsis, can also increase the risk of developing deficiency. 

According to the Harvard School of Public Health , the main symptoms of zinc deficiency include:

• Loss of taste and/or smell
• Depressed mood
• Decreased immunity 
• Delayed wound healing

This article is for informational purposes only and is not meant to offer medical advice.

Additional resources

• Jefferson Lab: The Element Zinc
• Los Alamos National Laboratory: Zinc
• Royal Society of Chemistry: Zinc

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Anna Gora is a health writer at Live Science, having previously worked across Coach, Fit&Well, T3, TechRadar and Tom's Guide. She is a certified personal trainer, nutritionist and health coach with nearly 10 years of professional experience. Anna holds a Bachelor's degree in Nutrition from the Warsaw University of Life Sciences, a Master’s degree in Nutrition, Physical Activity & Public Health from the University of Bristol, as well as various health coaching certificates. She is passionate about empowering people to live a healthy lifestyle and promoting the benefits of a plant-based diet.

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Zinc and its importance for human health: An integrative review

Affiliation.

• 1 Soil Protection, ETH Zurich, Institute of Terrestrial Ecosystem, Switzerland.
• PMID: 23914218
• PMCID: PMC3724376

Since its first discovery in an Iranian male in 1961, zinc deficiency in humans is now known to be an important malnutrition problem world-wide. It is more prevalent in areas of high cereal and low animal food consumption. The diet may not necessarily be low in zinc, but its bio-availability plays a major role in its absorption. Phytic acid is the main known inhibitor of zinc. Compared to adults, infants, children, adolescents, pregnant, and lactating women have increased requirements for zinc and thus, are at increased risk of zinc depletion. Zinc deficiency during growth periods results in growth failure. Epidermal, gastrointestinal, central nervous, immune, skeletal, and reproductive systems are the organs most affected clinically by zinc deficiency. Clinical diagnosis of marginal Zn deficiency in humans remains problematic. So far, blood plasma/serum zinc concentration, dietary intake, and stunting prevalence are the best known indicators of zinc deficiency. Four main intervention strategies for combating zinc deficiency include dietary modification/diversification, supplementation, fortification, and bio-fortification. The choice of each method depends on the availability of resources, technical feasibility, target group, and social acceptance. In this paper, we provide a review on zinc biochemical and physiological functions, metabolism including, absorption, excretion, and homeostasis, zinc bio-availability (inhibitors and enhancers), human requirement, groups at high-risk, consequences and causes of zinc deficiency, evaluation of zinc status, and prevention strategies of zinc deficiency.

Keywords: Zinc absorption; zinc bio-availability; zinc deficiency; zinc intervention; zinc nutrition; zinc requirement.

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Conflict of interest statement

Conflict of Interest: None declared.

Effect of various zinc application…

Effect of various zinc application methods on grain zinc concentration of wheat grown…

Effect of foliar applied zinc…

Effect of foliar applied zinc on growth of barley plants in Central Anatolia[106]

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