This study was carried out to determine whether a short-term zinc supplementation contributes to beneficial changes in glycemic control among type 2 diabetic patients. Seventy-six diabetic subjects and 72 normal adults participated in this study. Subjects were divided into supplemented and control groups. Forty-four diabetic patients and 34 normal subjects were supplemented with 50 mg zinc daily as zinc gluconate for 4 weeks. Zinc status was assessed from fasting plasma levels and urinary excretion. The effects of zinc supplementation on fasting blood glucose, HbA1c, insulin, and C-peptide were measured at the beginning of the study and after 4 weeks of supplementation. The changes in glycemic control indicators were compared between diabetic groups, classified by baseline HbA1c levels, and by diabetic duration. At baseline, the incidence of marginal zinc deficiency in the diabetic group, as determined by plasma zinc level, was approximately twice as high as in the normal adult group. The changes of HbA1c concentration, and fasting blood glucose following supplementation were not statistically significant in diabetic subjects. In normal subjects, a significant decrease of HbA1c occurred only in the zinc supplemented group. No significant changes were observed for serum insulin and C-peptide in diabetic as well as normal subjects. However, when the changes were compared by baseline HbA1c level, we found that diabetic subjects with HbA1c ≥ 7.5% showed significantly improved levels of HbA1c and fasting glucose after Zn supplementation. While such improvement in fasting blood glucose was significant among diabetics with shorter diabetic duration, significant levels of increase in serum insulin and C-peptide were observed in zinc supplemented subjects with longer diabetic duration. Fasting blood glucose was significantly decreased, whereas serum insulin and C-peptide were increased in diabetics with marginal zinc status. Therefore, we suggest that Zn supplementation for a short-term period may improve glycemic control in diabetic patients with higher HbA1c levels and marginal zinc status.

Changes in dietary zinc and copper affect zinc-status indicators of postmenopausal women, notably, extracellular superoxide dismutase and amyloid precursor proteins

Investigation of Lymphocyte Gene Expression for Use as Biomarkers for Zinc Status in Humans

Zinc and copper bioavailability in monkeys and rats with psyllium consumption

Diminished taste acuity (hypogeusia) has been linked to zinc deficiency in humans and animals. This phenomenon has been exploited in the Zinc Taste Test (ZTT), a taste acuity test commonly employed by Australian naturopaths. However, its validity has not yet been firmly established. A systematic search of several key databases was conducted. Only studies in which there were full reports of clinical trials comparing the ZTT to at least one other zinc test within the same sample population were included. Three (3) studies matched the criteria for inclusion. Study I compared the ZTT with sweat zinc in patients with food intolerance, reporting moderate correlation. Study II recruited pregnant women using the ZTT and serum zinc to assess zinc status, with above 70% congruence between the two tests at the start of the trial and 100% congruence at the end. Study III also recruited pregnant women at three stages during gestation, assessing ZTT and leukocyte zinc initially, later adding dietary zinc intake and at delivery cord blood zinc. No significant correlation was found between the results of these different methods; however, statistically significant differences in the ZTT responders (tasters and nontasters) were found for pregnancy outcomes. The methodology of the three studies is critically discussed. Although depletion of zinc leads to decreased taste acuity, it does not explain all cases of hypogeusia. Various other influences on taste perception are discussed in relation to the validity of the ZTT. Stringent exclusion criteria are therefore mandatory to increase specificity. Large variations from the original test design have been identified. The laboratory assays of zinc in these studies are also lacking sensitivity to accurately assess zinc status. To date, there are no tests that are both sensitive and specific that accurately assess marginal zinc status in humans. The ZTT, albeit widely used, does not fill this void, and further research is needed.

Marginal Zinc Status Does Not Exacerbate Pancreatic Carcinogenesis Associated with Dietary Soybean Trypsin Inhibitor Concentrate in Rats

Competitive Reverse Transcriptase–Polymerase Chain Reaction Shows That Dietary Zinc Supplementation in Humans Increases Monocyte Metallothionein mRNA Levels1–3

Background: Zinc is essential for maintaining immune health, and its deficiency is prevalent in older populations, contributing to weakened defenses against infections. Prior research indicates that targeted zinc intake can help normalize levels and support T-lymphocyte activity in those with suboptimal status. Objective: We evaluated whether a 3-month course of 30 mg/day zinc supplementation could elevate serum zinc in adults over 65 years with initial levels below 70 μg/dL and explored its potential to enhance T-cell responses. Methods: This pilot trial randomized 30 participants to receive either 30 mg/day zinc (as zinc sulfate; n=15) or a low-dose control (5 mg/day zinc; n=15). The main focus was the shift in serum zinc from baseline to 3 months, with additional assessments of T-cell proliferation and select biomarkers. Results: Serum zinc rose significantly more in the zinc group (mean change: +18.1 μg/dL) than the control (±2.3 μg/dL; adjusted β=20.91 ± 2.35 μg/dL, P<0.001). Proliferation in response to anti-CD3/CD28 and phytohemagglutinin also improved (β=8.73 ± 3.15 ×1000 cpm, P=0.010; β=14.99 ± 3.70 ×1000 cpm, P<0.001, respectively), linked to higher T-cell counts (β=219.75 ± 40.67 cells/μL, P<0.001). Adjustments for T-cell numbers eliminated proliferation differences, suggesting benefits from expanded cell populations. Conclusion: Moderate-dose zinc supplementation effectively addresses marginal deficiency in older adults, with associated gains in T-cell numbers that may bolster immunity. Larger trials are needed to confirm infection-related outcomes

There is need for a reliable index of zinc status in humans. Considering the importance of zinc in membrane function, activities of erythrocyte membrane enzymes have been measured in animals of low and normal zinc status as possible indices. Immature rats and neonatal pigs were fed low and adequate zinc diets; the latter was fed both ad libitum and restricted so as to control for food intake effects. Low rates of gain and plasma zinc concentrations demonstrated that animals fed the low zinc diets were of low zinc status. Erythrocyte membranes were prepared and assayed for Na,K-ATPase, 5'-nucleotidase, and calcium-ATPase activities. Na,K-ATPase activity was not affected by zinc status, but 5'-nucleotidase was significantly lower in deficient animals of both species than in controls, whose food intake was restricted to maintain comparable weight (2.76 vs 3.94 nmol/hr/mg of protein in rats and 60.5 vs 119 in pigs). The basal calcium-ATPase activities were also decreased by low zinc status in both species. Addition of calmodulin in vitro stimulated activity two-fold to four-fold and resulted in the same maximal activities for all treatments. The results show that erythrocyte membrane 5'-nucleotidase activity is an index of zinc status in these species. It is suggested that the decreased membrane calcium-ATPase activity in zinc deficiency is caused by a defect in calmodulin metabolism.

Aging impacts immunity, zinc status, and overall health, with these factors being closely interconnected. Zinc is known to modulate protein expression and cytokine production, with new molecular mechanisms continuing to be identified. ZIP8 facilitates IFN-γ production by increasing the intracellular zinc levels; how zinc status in humans affects ZIP8 expression remains unclear. We assessed serum zinc, dietary zinc intake, proton pump inhibitor (PPI) use, phytohemagglutinin (PHA)-stimulated IFN-γ production, and ZIP8 protein expression in elderly hospitalized patients and young healthy controls. Compared to young adults, elderly participants exhibited lower zinc status and IFN-γ levels, with PPI use among the elderly correlating with zinc deficiency. Zinc-deficient elderly participants received zinc aspartate supplementation for approximately 7 days, resulting in increased serum zinc levels, IFN-γ production, and a trend toward increased ZIP8 expression; in participants taking PPIs, this increase reached statistical significance. Although we found no clear correlation between ZIP8 expression and zinc status, the observed response to supplementation warrants further investigation. These findings reinforce the relevance of zinc supplementation in the elderly, although further studies are needed to elucidate the precise mechanisms linking zinc status to IFN-γ production, particularly regarding the role of ZIP8 expression levels.

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

Metallothionein concentrations in erythrocyte lysates derived from human subjects were measured by an ELISA procedure. IgG obtained from serum of sheep injected with human metallothionein 1 was used in this competitive assay. Subjects were fed a semipurified zinc-deficient diet (0.7 mg of zinc per kg of diet) for an 8-day depletion period after 3 days of acclimation. Fasting plasma zinc concentrations were reduced approximately 7%. Metallothionein in the erythrocyte lysates was significantly decreased to 59% of the initial level by the end of the depletion period. Supplementation of these depleted subjects with zinc (50 mg) did not increase erythrocyte metallothionein levels within 24 hr. Daily supplementation of control subjects with zinc (50 mg/day) increased erythrocyte metallothionein to a 7-fold maximum within 7 days. These levels were reduced by 61% within 14 days after zinc supplementation was terminated. Incubation of rat [35S]metallothionein with human erythrocyte lysate showed a time-dependent increase in 35S soluble in 20% trichloroacetic acid, indicating degradation of the labeled protein, presumably via protease activity in the lysate. It is proposed that zinc supplementation induces erythrocyte metallothionein during erythropoiesis and that low zinc intake decreases synthesis and/or accelerates degradation of the protein in reticulocytes/erythrocytes. Metallothionein levels in erythrocytes may provide a useful index upon which to assess zinc status in humans.

Zinc deficiency limits the yield of soybeans (Glycine max (L.) Merrill) on black earth soils (vertisols) in south eastern Queensland but may be prevented by using zinc fertilizers. The use of cultivars less sensitive to zinc deficiency on those soils of marginal zinc status may be a preferable alternative. Variability in genotypic response (symptom expression, seed yield) to zinc deficiency has been recognized in soybeans but no screening technique has been developed to utilize this knowledge for breeding purposes. This thesis reports an attempt to develop such a screening technique.Soil collected from a known zinc-deficient site was used as the culture medium in a series of glasshouse pot experiments. The influences of soil temperature, nitrogen supply and soil moisture on the development of zinc deficiency in soybean lines were examined.Control of soil temperature was a necessity. Each 1oC rise in soil temperature above 20oC had the same effect on soybean growth in the zinc-deficient black earth soil as a soil application of 1.0 µg g-1 (1.8 kg ha-1) zinc. Inadequate nitrogen supply reduced the dry matter yield response to zinc, whereas excessive amounts of nitrogen stimulated soybean growth in the zinc-deficient soil thereby masking dry matter responses to zinc. A nitrogen concentration of 80 mg 1-1 in the water supply was necessary to achieve maximal shoot dry weight responses to zinc (≈ 100%).The effects of two watering techniques on dry matter responses to zinc were determined. The constant water table (CWT) technique increased responsiveness to zinc over the watering-to-weight (WTW) technique, not by intensifying zinc deficiency but by stimulating growth in soil treated with zinc. The CWT also allowed the satisfactory use of small masses of soil (375 g) normally not practical with WTW procedures because of -limitations in water-holding capacity.The constant water table was supplied from a centrally placed inverted bottle that partially occupied a central glass well within the pot. This well was surrounded by soil. The self-contained reservoir of 370 ml capacity substantially decreased the labour required in WTW procedures, since weighing was avoided and the refilling operation was less frequent. In addition, the water supply was maintained and reproduced precisely in the CWT technique.Studies on the size of the test unit led to the adoption of a single plant in 375 g of soil. The use of single plant units would be necessary in screening segregating breeding populations in which each plant is considered to be genetically unique.Changes in soil pH over time and throughout the profile were observed in CWT and WTW pots. Localized decreases in soil pH were attributed to root activity and were of sufficient magnitude to increase substantially the concentration of zinc in the soil solution. The observed recovery from zinc deficiency was attributed to this effect. Despite such recovery, two-fold responses in shoot dry weights to zinc fertilization still were obtained. The CWT technique was used to study the zinc uptake and dry matter response of eight soybean lines to seven rates of zinc applied to the zincdificient black earth soil. More than 97% of the variation due to zinc fertilization in whole plant dry matter was accounted for in each line by Mitscherlich relationships. The concentration of zinc in node 5 laminae of three soybean lines accounted for more than 70% of the variation in shoot weight in contrast to only 48% that could be accounted for by the concentration of zinc in the lamina of the youngest fully expanded leaf. The node 5 lamina is thus the preferred index tissue for assessing the zinc status of soybeans, and a critical zinc concentration of 18 µg g-1 (mean of four lines) associated with 90% maximum shoot dry weight is proposed for this tissue.The CWT cultural technique fulfilled many of the criteria considered important in a practical screening procedure. However, while differences in dry matter production and zinc uptake among the lines were expressed clearly in zinc treated soil, such differences were small under maximum zinc stress. Thus, further investigations,on the role of zinc in the seed in the development of zinc deficiency, should be completed before the CWT procedure is adopted as a routine tool for screening soybean genotypes for sensitivity to zinc-deficient soil.

The negative health impact of zinc deficiency overlaps significantly with arsenic exposure, and is associated with increased risk for chronic diseases. Arsenic contamination in the groundwater often co-exists in regions of the world that are prone to zinc deficiency. Notably, low zinc status shares many hallmarks of arsenic exposure, including increased oxidative stress and inflammation. Despite their common targets and frequent co-distribution in the population, little is known regarding the interaction between zinc deficiency and arsenic exposure. In this study, we tested the effect of arsenic exposure at environmentally relevant doses in combination with a physiologically relevant level of zinc deficiency (marginal zinc deficiency) on zinc status, oxidative damage, and inflammation. In cell culture, zinc-deficient THP-1 monocytes co-exposed with arsenic resulted in further reduction in intracellular zinc, as well as further increase in oxidative stress and inflammatory markers. In ananimal study, zinc-deficient mice had further decrease in zinc status when co-exposed to arsenic. Zinc deficiency, but not arsenic exposure, resulted in an increase in baseline transcript abundance of inflammatory markers in the liver. Upon lipopolysaccharide challenge to elicit an acute inflammatory response, arsenic exposure, but not zinc deficiency, resulted in an increase in proinflammatory response. In summary, zinc deficiency and arsenic exposure can function independently or cooperatively to affect zinc status, oxidant stress, and proinflammatory response. The results highlight the need to consider both nutritional status and arsenic exposures together when considering their impact on health outcomes in susceptible populations.

Trace element concentrations in serum and breast milk were studied longitudinally in 197 Nigerian women from 6 months of gestation to 6 months postpartum; 99 of them received a daily iron supplement of 100 mg from 6 months of gestation to delivery. During the last 3 months of pregnancy, serum selenium declined, whereas serum zinc remained unchanged and serum copper increased. After delivery, copper concentration in maternal serum decreased, whereas serum zinc increased from delivery to 3 months postpartum and then reached a plateau. Serum selenium increased from delivery to 6 months postpartum. In breast milk, selenium and zinc decreased from 5 days to 6 months postpartum. Copper in breast milk also declined during the course of lactation but reached a plateau by 3 months postpartum. Iron concentration in breast milk remained unchanged during the study. Iron supplementation had no significant effect upon the concentrations of copper, selenium and zinc in mother serum and breast milk. In umbilical serum, iron status, copper and zinc levels were similar in the two groups, whereas, unexpectedly, selenium concentration was significantly decreased (p < 0.03) in the iron-supplemented group. Taken together, our results suggest that the beneficial effect of iron supplementation on iron deficiency was not associated with an adverse effect on copper and zinc status. On the other hand, our results suggest that Nigerian women had a marginal zinc status but an adequate selenium status.