Oral Zinc Supplementation May Improve Cognitive Function in Schoolchildren

Zinc is an important micronutrient for humans, and zinc deficiency among schoolchildren is deleterious to growth and development, immune competence, and cognitive function. However, the effect of zinc supplementation on cognitive function remains poorly understood. The purpose of our study was to evaluate the effect of oral zinc supplementation (5 mg Zn/day for 3 months) on the Full Scale Intelligence Quotient (FSIQ), Verbal Intelligence Quotient (VIQ), and Performance Intelligence Quotient (PIQ) using a Wechsler Intelligence Scale for Children (WISC-III). We studied 36 schoolchildren aged 6 to 9 years (7.8?±?1.1) using a nonprobability sampling method. The baseline serum zinc concentrations increased significantly after zinc supplementation (p?<?0.0001), with no difference between sexes. Tests were administered under basal conditions before and after zinc supplementation, and there was no difference in FSIQ according to gender or age. The results demonstrated that zinc improved the VIQ only in the Information Subtest (p?=?0.009), although the supplementation effects were more significant in relation to the PIQ, as these scores improved for the Picture Completion, Picture Arrangement, Block Design, and Object Assembly Subtests (p?=?0.0001, for all subtests). In conclusion, zinc supplementation improved specific cognitive abilities, thereby positively influencing the academic performance of schoolchildren, even those without marginal zinc deficiency.     

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.     

Long-term zinc and iron supplementation in children of short stature: effect of growth and on trace element content in tissues.

We evaluated the effect of one year of supplementation with iron plus zinc (12 mg/day of Fe+++ and 12.5 mg/day of Zn++), zinc alone (12.5 mg/day of Zn++) and placebo on growth and on the iron, zinc, copper and selenium tissue contents in 30 well-selected children of short stature (16 M and 14 F; 4-11 years old). Before and after supplementation, we measured the concentrations of iron, transferrin, ferritin, zinc and copper in serum, of zinc in erythrocytes and leukocytes, and of zinc, copper and selenium in hair, as well as glutathione peroxidase activity in erythrocytes. Before supplementation, ferritin and serum, erythrocyte and hair zinc contents were significantly lower than in age-matched controls, while the other measured indices were in the normal range. Iron plus zinc supplementation caused an improvement in growth rate in all subjects, i.e., the median Z-score increased from -2.22 +/- 0.45 to -0.64 +/- 0.55; (p < 0.01). In the zinc-supplemented group, only the subjects whose ferritin levels were higher than 20 ng/L before supplementation showed a similar improvement of growth rate. Iron plus zinc supplementation could be a reasonable treatment in short, prepubertal children affected by marginal zinc and iron deficiency.     

Vitamin D Supplementation Modulates Blood and Tissue Zinc, Liver Glutathione and Blood Biochemical Parameters in Diabetic Rats on a Zinc-Deficient Diet

Previous studies suggest a protective effect of vitamin D3 on zinc deficiency-induced insulin secretion and on pancreas β-cell function. The aim of this study was to investigate the effect of vitamin D on blood biochemical parameters, tissue zinc and liver glutathione in diabetic rats fed a zinc-deficient diet. For that purpose, Alloxan-induced diabetic rats were divided into four groups. The first group was fed a zinc-sufficient diet while the second group was fed a zinc-deficient diet. The third and fourth groups received zinc-sufficient or zinc-deficient diets plus oral vitamin D3 for 27 days. At the end of the experiment, blood, femur, pancreas, kidney and liver samples were taken from all rats. The serum, femur, pancreas, kidney and liver zinc concentrations, liver glutathione, serum alkaline phosphatase activity, daily body weight gain and food intake were lower in the zinc-deficient rats in comparison with those receiving adequate amounts of zinc. These values were increased in the zinc-deficient group that was supplemented with vitamin D3. The serum total cholesterol, triglycerides, total protein, urea, glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and blood glucose values were higher in rats fed a zinc adequate diet, but their concentrations were decreased by vitamin D3 supplementation. The serum total protein levels were not changed by zinc deficiency and vitamin D3 supplementation. These results suggest that vitamin D3 modulates tissue zinc, liver glutathione and blood biochemical values in diabetic rats fed a zinc-deficient diet.     

Effect of Zinc and Selenium Supplementation on Serum Testosterone and Plasma Lactate in Cyclist After an Exhaustive Exercise Bout

Zinc and selenium are essential minerals and have roles for more than 300 metabolic reactions in the body. The purpose of this study was to investigate how exhaustive exercise affects testosterone levels and plasma lactate in cyclists who were supplemented with oral zinc and selenium for 4?weeks. For this reason, 32 male road cyclists were selected equally to four groups: PL group, placebo; Zn group, zinc supplement (30?mg/day); Se group, selenium supplement (200?μg/day); and Zn-Se group, zinc-selenium supplement. After treatment, free, total testosterone, and lactate levels of subjects were determined before and after exhaustive exercise. Resting total, free testosterone, and lactate levels did not differ significantly between groups, and were increased by exercise (P?>?0.05). Serum total testosterone levels in Zn group were higher than in Se group after exercise (P??0.05). The results showed that 4-week simultaneous and separately zinc and selenium supplementation had no significant effect on resting testosterone and lactate levels of subjects who consume a zinc and selenium sufficient diet. It might be possible that the effect of zinc supplementation on free testosterone depends on exercise.     

Acute zinc deficiency and trabecular bone loss in rats with talc granulomatosis

Subcutaneous inflammation induced by magnesium silicate (talc) leads to the suppression of bone elongation, osteoblast insufficiency, and subsequent bone loss in rats. Since bone and immunological changes in talc granulomatosis are similar to those observed in zinc deficiency, we investigated the kinetics of zinc tissue distribution and the effects of zinc supplementation on the development of bone loss in rats with talc-induced inflammation. Decrease in serum zinc concentration was observed between 5 and 15 h in rats with talc granulomatosis. It was paralleled by the accumulation of zinc in the liver and rapid disappearance of osteoblasts from the trabecular bone surfaces. However, talc-injected rats supplemented parenterally and orally with zinc sulfate exhibited a decrease in osteoblast trabecular surface comparable to that of unsupplemented rats bearing granulomas despite normalized serum zinc concentrations. Zinc supplementation slightly increased osteoblast trabecular surface in all supplemented groups, but this effect was not significant. We conclude that zinc is the earliest indicator of the acute-phase response in rats with talc granulomatosis. Although zinc appears to be important for the normal function of bone cells, there is no causative relationship between acute zinc deficiency and decreased osteoblast number and activity in rats with talc granulomatosis.     

The immune system and the impact of zinc during aging

The trace element zinc is essential for the immune system, and zinc deficiency affects multiple aspects of innate and adaptive immunity. There are remarkable parallels in the immunological changes during aging and zinc deficiency, including a reduction in the activity of the thymus and thymic hormones, a shift of the T helper cell balance toward T helper type 2 cells, decreased response to vaccination, and impaired functions of innate immune cells. Many studies confirm a decline of zinc levels with age. Most of these studies do not classify the majority of elderly as zinc deficient, but even marginal zinc deprivation can affect immune function. Consequently, oral zinc supplementation demonstrates the potential to improve immunity and efficiently downregulates chronic inflammatory responses in the elderly. These data indicate that a wide prevalence of marginal zinc deficiency in elderly people may contribute to immunosenescence.     

Zinc homeostasis and immunosenescence

For more than 50 years, zinc is known to be an essential trace element, having a regulatory role in the immune system. Deficiency in zinc thus compromises proper immune function, like it is observed in the elderly population. Here mild zinc deficiency is a common condition, documented by a decline of serum or plasma zinc levels with age. This leads to a dysregulation mainly in the adaptive immunity that can result in an increased production of pro-inflammatory cytokines, known as a status called inflamm-aging. T cell activation as well as polarization of T helper (Th) cells into their different subpopulations (Th1, Th2, Th17, regulatory T cells (Treg)) is highly influenced by zinc homeostasis. In the elderly a shift of the Th cell balance towards Th2 response is observed, a non-specific pre-activation of T cells is displayed, as well as a decreased response to vaccination is seen. Moreover, an impaired function of innate immune cells indicate a predominance of zinc deficiency in the elderly that may contribute to immunosenescence. This review summarizes current findings about zinc deficiency and supplementation in elderly individuals.     

Zinc and immunity

Nutritional deficiency of zinc is widespread throughout the developing countries and a conditioned deficiency of zinc is known to occur in many diseased states. Zinc is known to play an important role in the immune system and zinc deficient subjects may experience increased susceptibility to a variety of pathogens. We have studied the effects of a mild deficiency of zinc on T cells in an experimental model of human zinc deficiency. We showed that T cell functions were affected adversely even when the deficiency of zinc was mild in humans. Characteristically during zinc deficiency, the serum thymulin activity (a thymic hormone) was decreased which was restored following zinc supplementation. Our studies also showed that zinc deficiency caused an imbalance between TH1 and TH2 functions. The production of IFN-g, IL-2, TNF-a (products of TH1 cells) were decreased, whereas the production of IL-4, IL-6 and IL-10 (products of TH2) were not affected during zinc deficiency. T cell subpopulation studies revealed that the CD4+ CD45RA+ to CD4+ CD45RO+ ratio was decreased as a result of zinc deficiency, suggesting that zinc may be required for the regeneration of new CD4+ T cells. We further documented that zinc deficiency decreased NK cell lytic activity and caused a decrease in the percentage of CD8+ CD73+ T cells which are known to be predominantly precursors of cytotoxic T cells. In a suitable cell culture model our studies revealed that the gene expression of a DNA synthesizing enzyme TK was affected adversely which resulted in delayed cell cycle and decreased cell growth. The above immunological consequences of zinc deficiency may be responsible for decreased cell mediated immune functions in zinc deficient subjects.     

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.     

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.     

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 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.     

Effects of zinc supplementation on serum zinc and leptin levels,BMI, and body composition in hemodialysis patients

ProjectThe aim of this study was to determine the effects of zinc supplementation on serum zinc and leptin levels as well as on anthropometric status and some biochemical parameters in hemodialysis (HD) patients.ProcedureIn this randomized, double-blind, and placebo-controlled trial, sixty HD patients were randomly divided into groups to receive a daily supplement of 100 mg elemental Zn (supplemented group) or placebo (control group) for 60 days. Anthropometric measurements were taken using standard calibrated instruments. Serum zinc and leptin levels were determined by atomic absorption and ELISA method respectively before and after intervention.ResultsZinc supplementation resulted in significant increase in the mean serum zinc level in the experimental group while changes observed in the placebo group were not significant. The mean serum leptin in women part of the experimental group was decreased significantly after supplementation. After adjusting for age, BMI, body fat (%), serum zinc and dietary Zn intake, a negative and significant association was observed between serum zinc and leptin levels in all subjects (β = −0.33, P = 0.03) as a result of Zn supplementation.ConclusionsMore studies are needed to clarify the mechanisms by which serum leptin level is influenced as a result of zinc supplementation in HD patients.     

Zinc serum level in human immunodeficiency virus-infected patients in relation to immunological status

In human immunodeficiency virus (HIV) infection, serum level of zinc, an important micronutrient for immune function, is frequently diminished. The aim of this study was to determine the zinc status in relation to immunological parameters and disease stage in 79 HIV-1 seropositive patients. The median serum level of zinc was within normal limits (12.5 micromol/L) but in 23% of patients, zinc deficiency was seen. Decreased serum zinc was associated with a low CD4 cell count, high viral load, and increased neopterin and IgA levels. According to current treatment recommendations, the majority of patients received antiretroviral triple therapy. Zinc levels in treated and untreated patients were comparable. Referring to disease stage (CDC classification, 1993), the mean zinc level was highest in stage C and lowest in stage A. In conclusion, even under antiretroviral triple therapy, zinc deficiency is still of great importance in HIV infection, and zinc substitution in zinc deficient individuals should be taken into account to optimize therapeutical success.     

Hormonal effects of zinc on growth in children

Zinc deficiency impairs the metabolism of thyroid hormones, androgens, and above all growth hormones. In view of their important role in growth, it is not surprising to find growth disorders associated with zinc deficiency. Stunted growth linked to zinc deficiency is found during gestation, and also in the newborn and children up to adolescence. Depending on the country, 5–30% of children suffer from moderate zinc deficiency, responsible for small-for-age height. Zinc supplementation has proven effective in many studies, mainly in children where zinc deficiency has first been found. Finally, zinc supplementation makes it possible in certain cases to overcome resistance to growth hormone treatment.     

Extracellular and immunological actions of zinc

Zinc is an essential trace element for the immune system, but also very important in other organ systems. Every highly proliferating cell system is dependent on sufficient availability of zinc. During the last decades the influence of zinc on various cell systems have been investigated. Multiple effects of exogenously added zinc have been described in in vitro culture systems and in in vivo systems. However, most of these effects are so far poorly understood, and the dosages used in the in vitro systems are not comparable and sometimes unphysiologically high. Especially in the immune system a number of effects were described and over the last ten years we have come to understand some molecular mechanisms of zinc in this cell system. A zinc deficiency is accompanied by an immunodeficiency, resulting in an increased number of infections. However, the immune function is delicately regulated by zinc, since both increased and decreased zinc levels result in a disturbed immune function. Therefore, zinc supplementation must be accurately supervised. In this review, we discuss the activity of extracellular zinc in four sections. 1. The effect of zinc on different in vitro cell systems, including keratinocytes, osteocytes and leukocytes, and the concentrations of zinc needed for a specific cell response. 2. The modulation of the innate immune system in vitro and in vivo. 3. The role of zinc in the B cell response and antibody production. 4. Effects of zinc on the development and function of T cells.     

Testosterone and zinc supplementation in castrated rats: Effects on plasma leptin levels and relation with LH, FSH and testosterone

The present study aims to examine how zinc and testosterone supplementation, in combination and separately, affect plasma LH, FSH and leptin levels in castrated rats. Eighty experimental animals used in the study were allocated to 8 groups, each containing an equal number of rats. Group 1, control group; Group 2, castration group; Group 3, testosterone group (5 mg/kg/day); Group 4, zinc-supplemented group (3 mg/kg/day); Group 5, testosterone and zinc-supplemented group; Group 6, zinc-supplemented castration group; Group 7, testosterone and castration group; and Group 8, zinc-supplemented, testosterone and castration group. Plasma zinc, leptin, LH, FSH and free and total testosterone levels were determined in the blood samples collected from the animals by decapitation. Group 2 had the highest leptin levels and together with group 6, it also showed the highest LH and FSH levels (p<0.01). The lowest leptin levels were observed in groups 3 and 7 (p<0.01). Leptin levels in groups 4 and 6 were higher than those in groups 1, 5 and 8 (p<0.01). LH levels in group 4 were lower than those in groups 2 and 6 and higher than those in all other groups (p<0.01). Free and total testosterone levels in groups 7 and 8 were lower than those in groups 3 and 5, but higher than those in all other groups (p<0.01). Plasma LH levels may be more effective than testosterone on plasma leptin and zinc may be an important mediator of the effect LH has on leptin.