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

Effect of consuming hi-oleic peanuts on adiposity and cardiometabolic health

Assessment of Marginal Zinc Status in Humans

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

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.

Metallothionein and Zinc Transporter Expression in Circulating Human Blood Cells as Biomarkers of Zinc Status: a Systematic Review

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.

Vegetarian diets across the lifecycle: impact on zinc intake and status.

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

The associations among dietary zinc intakes and biomarkers of zinc status are unknown in apparently healthy children at high risk for zinc deficiency. To assess associations among zinc-related parameters in a sample of Guatemalan school-aged children. We assessed total dietary intakes and biomarkers of zinc status before and after receiving 6 months of zinc supplementation or placebo in 691 Guatemalan schoolchildren aged 6 to 11 years. Most of the children also received zinc-fortified milk from a government program that started shortly after the trial began. We assessed associations between zinc intakes and serum zinc, alkaline phosphatase (ALP), and albumin. At baseline, the prevalence of serum zinc < 65 microg/dL and dietary zinc intake below Estimated Average Requirements (EAR) (< 4 and < 7 mg/day for children < 9 and > or = 9 years, respectively) were 21.6% and 39.4%, respectively. Pearson correlations between serum zinc concentration and dietary zinc intake, serum ALP, and serum albumin were r = 0.07, 0.15, and 0.07, respectively. At the 6-month follow-up, low serum zinc and low total (diet plus fortified milk) zinc intakes were observed in 1.2% and 0.0% of children in the zinc-supplemented group and 4.0% and 34.1% in the placebo group, respectively. Pearson correlations between serum zinc concentration and total zinc intake, serum ALP, and serum albumin were 0.10, 0.06, and -0.11 in the zinc-supplemented group and -0.04, 0.05, and 0.01 in the placebo group, respectively. Zinc intake was inconsistently associated with markers of serum zinc concentration. Zinc fortification or supplementation attenuated the associations.

Proteomic analysis shows the upregulation of erythrocyte dematin in zinc-restricted human subjects

An initial evaluation of newly proposed biomarker of zinc status in humans - linoleic acid: dihomo-γ-linolenic acid (LA:DGLA) ratio

Portable X-ray fluorescence of zinc applied to human toenail clippings

Zinc deficiency has an estimated prevalence of 31% globally, and can lead to poor pregnancy outcomes, immune dysfunction, and increased risk for chronic disorders. A barrier to elucidating the exact role of zinc in human health is a lack of reliable clinical biomarkers for zinc status in humans. Currently used plasma zinc levels, lack both sensitivity and specificity to zinc status. To probe for novel biomarkers, metabolome profiles were studied in healthy, adult male subjects that underwent dietary zinc depletion and repletion. Plasma samples were analyzed following baseline (2 wk, 11mg Zn/d), zinc‐depletion (0.6mg Zn/d for 1 wk and 4mg Zn/d for 5 wk), and zinc‐repletion (4 wk, 11mg Zn/d) phases using untargeted, unbiased metabolomic LC‐MS/MS. Principle component analysis demonstrated metabolite clustering during each dietary phase of the study. A total of 12 different metabolites were significantly (P&lt;0.05) up or down regulated (log2 fold change) during dietary zinc depletion relative to baseline and were reversed with zinc repletion. Methylhistidine was identified as the most significantly altered metabolite (8.59‐fold change) and may indicate protein degradation to replenish plasma zinc. This research is a significant first step in utilizing metabolomics to establish novel consequences and biomarkers of zinc deficiency. Funding: USANA Health Sciences, T32 ES007060 &amp; P30 ES000210