The role of zinc in reproduction

Zinc is a very important element in the reproductive cycle of species. In humans, it is necessary for the formation and maturation of spermatozoa, for ovulation, and for fertilization. During pregnancy, zinc deficiency causes a number of anomalies: spontaneous abortion, pregnancy-related toxemia, extended pregnancy or prematurity, malformations, and retarded growth. Delivery is adversely affected by deficiency. These different effects of zinc can be explained by its multiple action on the metabolism of androgen hormones, estrogen and progesterone, together with the prostaglandins. Nuclear receptors for steroids are all zinc finger proteins. Zinc supplementation has already proven beneficial in male sterility and in reducing complications during pregnancy. However, it would be worth conducting larger-scale trials to confirm these beneficial effects.     

Leptin,NPY, Melatonin and Zinc Levels in Experimental Hypothyroidism and Hyperthyroidism: The Relation to Zinc

Since zinc mediates the effects of many hormones or is found in the structure of numerous hormone receptors, zinc deficiency leads to various functional impairments in the hormone balance. And also thyroid hormones have important activity on metabolism and feeding. NPY and leptin are affective on food intake and regulation of appetite. The present study is conducted to determine how zinc supplementation and deficiency affect thyroid hormones (free and total T3 and T4), melatonin, leptin, and NPY levels in thyroid dysfunction in rats. The experiment groups in the study were formed as follows: Control (C); Hypothyroidism (PTU); Hypothyroidism+Zinc (PTU+Zn); Hypothyroidism+Zinc deficient; Hyperthyroidism (H); Hyperthyroidism+Zinc (H+Zn); and Hyperthyroidism+Zinc deficient. Thyroid hormone parameters (FT₃, FT₄, TT₃, and TT₄) were found to be reduced in hypothyroidism groups and elevated in the hyperthyroidism groups. Melatonin values increased in hyperthyroidism and decreased in hypothyroidism. Leptin and NPY levels both increased in hypo- and hyperthyroidism. Zinc levels, on the other hand, decreased in hypothyroidism and increased in hyperthyroidism. Zinc supplementation, particularly when thyroid function is impaired, has been demonstrated to markedly prevent these changes.     

Correlation between serum zinc and testosterone: A systematic review

Zinc is a vital trace element for normal function of the living system. In male, zinc is involved in various biological processes, an important function of which is as a balancer of hormones such as testosterone. For this purpose, studies related to the influence of zinc on serum testosterone were selected and summarized, including the effect of dietary zinc deficiency and zinc supplementation on testosterone concentrations. After preliminary searching of papers on databases, 38 papers including 8 clinical and 30 animal studies were included in this review. We concluded that zinc deficiency reduces testosterone levels and zinc supplementation improves testosterone levels. Furthermore, the effect degree of zinc on serum testosterone may vary depending on basal zinc and testosterone levels, zinc dosage form, elementary zinc dose, and duration. In conclusion, serum zinc was positively correlated with total testosterone, and moderate supplementation plays an important role in improving androgen.     

Serum zinc levels and goiter in Iranian school children

Iodine deficiency has been shown to have high prevalence in Iran despite sufficient iodine supplementation. Zinc deficiency may also contribute to the pathogenesis of endemic goiter. The aim of this study was to compare serum zinc level in Iranian school children with and without goiter. A cross-sectional study was performed among urban children aged 8-12 years in city of Kerman, Iran. A multistage proportional to size cluster sampling method was used to screen 5500 subjects out of 29,787 students. After the screening phase, serum and urine specimens of randomly selected 165 students were evaluated for serum zinc levels and urinary iodine excretion and compared in goiterous and non-goiterous children. Serum zinc level was 149.5±29.4 μg/l in goiterous children and 141.2±52 μg/l in non-goiterous children but no significant difference was found between the groups (p=0.37). But urinary iodine excretion was significantly (p<0.001) lower in goiterous children (207.5 μg/l in goiterous children and 262.5 μg/l in non-goiterous children). This study showed that serum zinc level in goiterous and non-goiterus children is not different and zinc deficiency is not a risk factor for endemic goiter in this population.     

Bioavailability, antioxidant and immune-enhancing properties of zinc methionine

Although a large number of transition metals and cations remarkably induce oxidative deterioration of biological macromolecules including lipids, proteins and DNA, the trace element zinc acts as a novel dietary supplement and an essential micronutrient, and serves a wide range of biological functions in human and animal health. Zinc promotes antioxidant and immune functions, stabilizes and maintains the structural integrity of biological membranes, and plays a pivotal role in skin and connective tissue metabolism and repair. Zinc is an integral constituent of a large number of enzymes including antioxidant enzymes, and hormones including glucagon, insulin, growth hormone, and sex hormones. High concentrations of zinc are found in the prostate gland and choroids of the eye. Zinc deficiency leads to biochemical abnormalities including the impairments of growth, dermal, gastrointestinal, neurologic and immunologic systems. Given its superior bioavailability, antioxidant and immune-enhancing properties, zinc methionine may serve as a novel dietary supplement to promote health benefits in humans and animals.     

Serum zinc concentrations in the maintenance hemodialysis patients

Zinc is necessary for growth and cells' division. Its deficiency may seriously affect antioxidant defense system and is usually related to renal failure, gastrointestinal diseases and alcoholism. It is very important to know zinc status in dialyzed patients and to prevent hypo- or hyperzincemia. Serum samples from 89 patients with chronic terminal renal failure on regular hemodialysis were withdrawn for the estimation of zinc concentrations immediately before and after dialysis. Serum zinc concentrations showed to be highly dependent on hemodialysis. In 57 (64%) patients, serum zinc concentrations decreased, sometimes from very high to normal values. In remaining 32 (36%) patients serum zinc concentrations tended to increase, but remained within normal range. Zinc supplementation may be recommended only in the patients with proven zinc deficiency, but for all chronic renal failure patients it is questionable.     

Assessment of Zinc Status in School-Age Children from Rural Areas in China Nutrition and Health Survey 2002 and 2012

Zinc is an essential trace element for growth and development in children, but zinc deficiency is a serious nutritional problem worldwide. Our study aimed to assess the zinc status of school-age children living in rural areas of China and to examine the change of zinc status based on the China Nutrition and Health Survey 2002 and 2012. We used the probability proportional to size sampling method for subject selection, and a total of 3407 school-age children were included in this study. Zinc status was assessed by three items of indicators recommended by the World Health Organization (WHO), the United Nations Children’s Fund (UNICEF), the International Atomic Energy Agency (IAEA), and the International Zinc Nutrition Consultative Group (IZiNCG). The concentration of serum zinc was 718.2 μg/L, and 44.4% of children being zinc deficiency in 2002, while 846.8 μg/L and 10.4% in 2012. Zinc intake was 7.8 mg/day with a 7.6% inadequate zinc intake in 2002, together with 6.9 mg/day and 38.2% in 2012. Height-for-age Z score was ?1.06 and 19.1% of children being stunting in 2002, as well as ?0.15 and 6.8% in 2012. In conclusion, the zinc status of school-age children living in rural areas of China has been significantly improved in addition to zinc intake over the past 10 years. However, the zinc deficiency still observed in poor rural areas of China in 2012. In addition, we suggested that the zinc bioavailability should be taken into account when assessing zinc status in population.     

Mutagenicity, carcinogenicity and teratogenicity of zinc

Zinc is a common element in the human environment and constitutes an important trace element intervening in many biological processes. Toxicity of zinc is low; zinc deficiency represents, however, a hazard for human health. Zinc is not mutagenic and has little, if any, clastogenic properties. Zinc can induce tumours but only following local application, and does not represent a carcinogenic risk to man. It is still uncertain whether zinc can cause malignant transformation but zinc is needed for cellular proliferation of existing tumours and tumour growth is retarded by zinc deficiency. Zinc is not teratogenic; it can, in fact, avert teratogenicity of other agents. Conversely, zinc deficiency may be harmful to the developing organism.     

Both zinc deficiency and supplementation affect plasma melatonin levels in rats

At physiological levels, zinc and various hormones affect each other reciprocally. Reduction in zinc levels in pinealectomized rats suggests the relation between zinc and melatonin. The effect of both zinc deficiency and supplementation on plasma melatonin levels in rats were investigated in this study. The study was done in Sel?uk University, Experimental Medicine Research and Application Center. Twenty-four adult male Sprague Dawley rats were divided into 3 groups. Eight rats were fed with zinc-deficient diet. Zinc supplementation was administered intaperitoneally to 8 rats. The remaining 8 rats were used as controls. All rats sacrificed 3 weeks later. Plasma melatonin and zinc levels were determined. The plasma zinc levels of the zinc-supplemented group were higher than those of the other groups as expected (P<0.01). Similarly, the melatonin levels in the zinc-supplemented group were higher than those in the other groups. A significant decrease was observed in melatonin levels of the zinc-deficient group compared to the control and zinc-supplemented group (P<0.01). The results of this study suggest that zinc deficiency decreases the melatonin levels and zinc supplementation may increase the plasma melatonin levels in rats.     

Effect of zinc supplementation on type 2 diabetes parameters and liver metallothionein expressions in Wistar rats

Zinc is a trace metal and acts as an active component of various enzymes. Zinc deficiency has been suggested to be associated with the development of diabetes. The present study investigated the role of zinc supplementation on prevention of diabetic conditions. A double-disease model mimicking hyperlipidemia and type 2 diabetes was created by applying high-fat diet and streptozotocin (STZ) to Wistar rats. We demonstrated that zinc supplementation improved symptoms of diabetes such as polydipsia and increased serum level of high-density lipoprotein cholesterol, indicating that zinc supplementation has a potential beneficial effect on diabetic conditions. The level of maldondialdehyde (MDA), an oxidative stress marker, was reduced in liver by zinc supplementation in high fat-fed rats with or without STZ injection. Meanwhile, we observed an increase in the expression of metallothioneins (MTs) in liver of rats treated with zinc. This suggests that the induction of MTs in liver, which has been shown to be important in scavenging free radicals, could be one of the underlying mechanisms of zinc supplementation on reducing MDA levels in liver. Finally, we found that zinc levels in liver were increased while there was no change in serum zinc levels, indicating that local zinc level might be a critical factor for the induction of MTs. Also, the level of MTs could potentially be an index of zinc bioavailability. Taken together, these results suggest that both zinc and MT could play an important role in balancing nutrition and metabolism to prevent diabetic development.     

Is zinc deficiency a cause of subclinical hypothyroidism in Down syndrome?

In Down syndrome there is a high incidence of overt or subclinical hypothyroidism as well as some immunological defects, early thymic involution associated to low serum zinc levels. Zinc supplementation to the diet has been reported to transiently improve thymic function; moreover thymic function has been shown to be in relation with the pituitary-thyroid axis. The aim of this study was to evaluate if, in Down patients, zinc therapy could improve also thyroid function, by determining serum levels of total and free thyroid hormones and basal TSH levels. In 52 patients studied, we found a high incidence of subclinical hypothyroidism (30%); in 17 patients treated with zinc sulphate we showed a reduction of FT3. More significantly, we detected 9 patients with low zinc levels in which zinc supplementation improved thyroid function, thus reducing the incidence of subclinical hypothyroidism.     

Iron-loaded cardiac myocytes stimulate cardiac myofibroblast DNA synthesis

Zinc is an essential nutrient with a wide range of functions and closely involved in a variety of enzymatic processes of importance in glucose, protein and lipid metabolism. Ghrelin is the endogenous ligand of the G protein coupled growth hormone secretagogue receptor. The regulatory mechanism that explain the biosynthesis and secretion of ghrelin in the gastrointestinal tract has not been clarified. This study was undertaken to examine the effect of zinc supplementation on the streptozotocin (STZ)-induced diabetic rats, which exhibits ghrelin production and secretion, and lipid metabolism on the gastrointestinal tract. The animals were divided into four groups. Group I: Non-diabetic untreated animals. Group II: Zinc-treated non-diabetic rats. Group III: STZ-induced diabetic untreated animals. Group IV: Zinc-treated diabetic animals. Zinc sulfate was given to some of the experimental animals by gavage at a dose of 100 mg/kg body weight every day for 60 days. In the zinc-treated diabetic group, the blood glucose levels decreased and body weight increased as compared to the diabetic untreated group. Zinc supplementation to STZ-diabetic rats revealed the protective effect of zinc on lipids parameters such as total lipid, cholesterol, HDL-cholesterol and atherogenic index. There is no statistically change in ghrelin-immunoreactive cells in gastrointestinal tissue. But, it has found that zinc supplementation caused a significant reduction in densities of ghrelin-producing cells of fundic mucosa of zinc-treated diabetic animals as compared to untreated, non-diabetic controls. Zinc supplementation may contribute to prevent some complications of diabetic rats, biochemically.     

Zinc sulfate supplementation improves thyroid function in hypozincemic down children

In subjects affected by trisomy 21 (Down syndrome), hypothyroidism is the most common endocrinological deficit. Plasma zinc levels, which are commonly detected below the normal range in Down patients, are related to some endocrinological and immunological functions; in fact, zinc deficiency has been shown to impair immune response and growth rate. Aims of this study were to evaluate (1) the role of zinc deficiency in subclinical hypothyroidism and (2) thyroid function changes in Down children cyclically supplemented with zinc sulfate. Inverse correlations have been observed between age and triiodotironine (T3) and between zinc and thyroid-stimulating hormone (TSH); higher TSH levels have been found in hypozincemic patients at the beginning of the study. After 6 mo of supplementation, an improvement of thyroid function (TSH levels: 3.96 ± 1.84 vs 2.64 ± 1.33 mUI/mL basally and after 6 mo, respectively) was observed in hypozincemic patients. In the second cycle of supplementation, a similar trend of TSH was observed. At the end of the study, TSH significantly decreased in treated hypozincemic subjects (4.48 ± 1.93 vs 2.96 ± 1.20 mUI/mL) and it was no longer different in comparison to normozincemic patients. We suggest zinc supplementation to the diet in hypozincemic Down children as a simple and useful therapeutic tool.     

Therapeutic Value of Zinc Supplementation in Acute and Persistent Diarrhea: A Systematic Review

Background

For over a decade, the importance of zinc in the treatment of acute and persistent diarrhea has been recognized. In spite of recently published reviews, there remain several unanswered questions about the role of zinc supplementation in childhood diarrhea in the developing countries. Our study aimed to assess the therapeutic benefits of zinc supplementation in the treatment of acute or persistent diarrhea in children, and to examine the causes of any heterogeneity of response to zinc supplementation.

Methods and Findings

EMBASE®, MEDLINE ® and CINAHL® databases were searched for published reviews and meta-analyses on the use of zinc supplementation for the prevention and treatment of childhood diarrhea. Additional RCTs published following the meta-analyses were also sought. The reviews and published RCTs were qualitatively mapped followed by updated random-effects meta-analyses, subgroup meta-analyses and meta-regression to quantify and characterize the role of zinc supplementation with diarrhea-related outcomes. We found that although there was evidence to support the use of zinc to treat diarrhea in children, there was significant unexplained heterogeneity across the studies for the effect of zinc supplementation in reducing important diarrhea outcomes. Zinc supplementation reduced the mean duration of diarrhea by 19.7% but had no effect on stool frequency or stool output, and increased the risk of vomiting. Our subgroup meta-analyses and meta-regression showed that age, stunting, breast-feeding and baseline zinc levels could not explain the heterogeneity associated with differential reduction in the mean diarrheal duration. However, the baseline zinc levels may not be representative of the existing zinc deficiency state.

Conclusions

Understanding the predictors of zinc efficacy including the role of diarrheal disease etiology on the response to zinc would help to identify the populations most likely to benefit from supplementation. To improve the programmatic use of zinc, further evaluations of the zinc salts used, the dose, the frequency and duration of supplementation, and its acceptability are required. The significant heterogeneity of responses to zinc suggests the need to revisit the strategy of universal zinc supplementation in the treatment children with acute diarrhea in developing countries.     

Zinc aspartate suppresses T cell activation in vitro and relapsing experimental autoimmune encephalomyelitis in SJL/J mice

Zinc is an essential trace element with a critical role in normal growth and development and in immune homeostasis. Zinc deficiency impairs both the innate and the adaptive immune system and can be normalized by zinc supplementation. On the other end of the spectrum, high dosages of zinc diminish immune cell functions similar to zinc deficiency. Here, we investigated the influence of zinc aspartate on proliferation and cytokine production of stimulated human T cells and mouse splenocytes in vitro. Furthermore, the effect of zinc aspartate was examined in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of Multiple Sclerosis (MS) with a Th1/Th17 T cell-mediated immunopathogenesis. Zinc aspartate suppressed proliferation as well as IL-2, IL-10 and IL-17 production in stimulated human T cells and mouse splenocytes. Importantly, administration of a medium range dose of 30 μg/day zinc aspartate [1.5 mg/kg body weight (BW)] in a therapeutic manner led to a significant reduction of the clinical severity of the EAE during the first relapse of the disease. A lower zinc aspartate dose (6 μg/day, 0.3 mg/kg BW) had no significant therapeutic effect on the severity of the EAE, while administration of higher zinc aspartate amounts (120 μg/day, 6 mg/kg BW) led to more severe disease. Taken together, our data suggest that zinc aspartate can modulate activation, proliferation and cytokine production of effector T cells in vitro and in vivo and that activated autoreactive T cells may be potential therapeutic targets of tightly controlled zinc supplementation in autoimmune diseases like MS.     

Effects of Zinc Supplementation on Physical Growth in 2–5-Year-Old Children

Physical growth disorders in under 5-year-old children are a common health problem in many countries including Iran. The aim of this study was to determine effects of supplemental zinc on physical growth in preschool children with retarded linear growth. This study was a community-based randomized controlled trial on 2–5-year-old children with height-for-age below 25th percentile of National Center for Health Statistics growth chart. Ninety children were randomly assigned in zinc group (ZG) or placebo group (PG). After 6 months of zinc or placebo supplementation, we followed up the children for another 6 months. Anthropometric indicators were measured before the intervention and then monthly for 11 months. Forty children in ZG and 45 in PG concluded the study. Zinc supplementation increased weight gain in boys (P = 0.04) and girls (P = 0.05) compared to placebo but had no significant effect on mid-upper arm circumference increment in either sexes. The most significant (P = 0.001) effect of Zinc supplementation was seen in boys’ height increment at the end of follow-up period. Stunted growth rate in ZG changed significantly (P = 0.01) from 26.7% to 2.5% throughout the study. This study showed that daily supplementation of 5 mg elemental zinc for 6 months improves physical growth in terms of height increment and weight gain in children with undesirable linear growth, especially in boys.     

Clioquinol Synergistically Augments Rescue by Zinc Supplementation in a Mouse Model of Acrodermatitis Enteropathica

Background

Zinc deficiency due to poor nutrition or genetic mutations in zinc transporters is a global health problem and approaches to providing effective dietary zinc supplementation while avoiding potential toxic side effects are needed.

Methods/Principal Findings

Conditional knockout of the intestinal zinc transporter Zip4 (Slc39a4) in mice creates a model of the lethal human genetic disease acrodermatitis enteropathica (AE). This knockout leads to acute zinc deficiency resulting in rapid weight loss, disrupted intestine integrity and eventually lethality, and therefore provides a model system in which to examine novel approaches to zinc supplementation. We examined the efficacy of dietary clioquinol (CQ), a well characterized zinc chelator/ionophore, in rescuing the Zip4 ^{intest KO} phenotype. By 8 days after initiation of the knockout neither dietary CQ nor zinc supplementation in the drinking water was found to be effective at improving this phenotype. In contrast, dietary CQ in conjunction with zinc supplementation was highly effective. Dietary CQ with zinc supplementation rapidly restored intestine stem cell division and differentiation of secretory and the absorptive cells. These changes were accompanied by rapid growth and dramatically increased longevity in the majority of mice, as well as the apparent restoration of the homeostasis of several essential metals in the liver.

Conclusions

These studies suggest that oral CQ (or other 8-hydroxyquinolines) coupled with zinc supplementation could provide a facile approach toward treating zinc deficiency in humans by stimulating stem cell proliferation and differentiation of intestinal epithelial cells.     

User and researcher collaborations in mental health in low and middle income countries: a case study of the EMPOWER project

Background

Zinc deficiency is a major public health problem in many developing countries including Nepal. The present study was designed to assess the prevalence of zinc deficiency and to study the association of zinc deficiency with anthropometric and socio-demographic variables, in school children of eastern Nepal.

Methods

This cross-sectional study included total 125 school children of age group 6–12 years from Sunsari and Dhankuta districts of eastern Nepal. Plasma zinc level was estimated by Flame Atomic Absorption Spectroscopy.

Results

The Median interquartile range (IQR) values of zinc in the two districts Sunsari and Dhankuta were 5.9 (4.4, 7.9) μmol/L and 5.8 (4.3, 8.4) μmol/L respectively. A total of 55 children (87.3%) in Sunsari and 52 (83.9%) in Dhankuta had zinc deficiency, no significant difference was observed in the Median (IQR) plasma zinc levels (p = 0.9) and zinc deficiency patterns (p = 0.3) of the two districts. Significant differences were observed in the plasma zinc levels (p = 0.02) and zinc deficiency patterns (p = 0.001), of the school children having age groups 6–8 years than in 9–10 and 11–12 years of age, and zinc deficiency patterns between male and female school children (p = 0.04) respectively.

Conclusions

The present study showed higher prevalence of zinc deficiency among school children in eastern Nepal. In our study, zinc deficiency was associated with both sex and age. The findings from the present study will help to populate data for policy implementation regarding consumption and supplementation of zinc.