Zinc is an essential nutrient for humans; however, a sensitive biomarker to assess zinc status has not been identified. The objective of this systematic review was to compile and assess studies that determined zinc transporter and/or metallothionein expression in various blood cell types and to determine their reliability and sensitivity to changes in dietary zinc. Sixteen studies were identified that determined the expression of zrt-, irt-like protein (ZIP) 1 [solute carrier family (SLC) 39A1], ZIP3 (SLC39A3), ZIP5 (SLC39A5), ZIP6 (SLC39A6), ZIP7 (SLC39A7), ZIP8 (SLC39A8), ZIP10 (SLC39A10), ZIP14 (SLC39A14), zinc transporter (ZnT)1 (SLC30A1), ZnT2 (SLC30A2), ZnT4 (SLC30A4), ZnT5 (SLC30A5), ZnT6 (SLC30A6), ZnT7 (SLC30A7), ZnT9 (SLC30A9), and/or metallothionein in various blood cells isolated from healthy adult men and women in response to zinc supplementation or depletion. Cell types included leukocytes, peripheral blood mononuclear cells, T lymphocytes, monocytes, and erythrocytes. ZIP1, ZnT1, and metallothionein were the most commonly measured proteins. Changes in ZIP1 and ZnT1 in response to zinc supplementation or depletion were not consistent across studies. Leukocyte metallothionein decreased with zinc depletion (-39% change from baseline, <5 mg Zn/d, n = 2 studies) and increased with zinc supplementation in a dose-dependent manner (35%, 15-22 mg Zn/d, n = 7 studies; 267%, 50 mg Zn/d, n = 2 studies) and at the earliest time points measured; however, no change or delayed response was observed in metallothionein in erythrocytes. A greater percentage of studies demonstrated that metallothionein in leukocyte subtypes was a more reliable (100%, n = 12; 69%, n = 16) and responsive (92%, n = 12; 82%, n = 11) indicator of zinc exposure than was plasma zinc, respectively. In conclusion, current evidence indicates that metallothionein in leukocyte subtypes may be a component in determining zinc status.

Zinc is an essential nutrient for humans; however, a sensitive biomarker to assess zinc status has not been identified. The objective of this study was to determine the reliability and sensitivity of zinc transporter and metallothionein (MT) genes in peripheral blood mononuclear cells (PBMCs) to zinc exposure ex vivo and to habitual zinc intake in human subjects. In study 1, human PBMCs were cultured for 24 h with 0-50 µM ZnSO4 with or without 5 µM N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) and mRNA expression of SLC30A1-10, SLC39A1-14, MT1 subtypes (A, B, E, F, G, H, L, M, and X), MT2A, MT3, and MT4 mRNA was determined. In study 2, 54 healthy male and female volunteers (31.9 ± 13.8 y, BMI 25.7 ± 2.9 kg/m2) completed a Food Frequency Questionnaire, blood was collected, PBMCs were isolated, and mRNA expression of selected zinc transporters and metallothionein isoforms was determined. Study 1: MT1E, MT1F, MT1G, MT1H, MT1L, MT1M, MT1X, MT2A, and SLC30A1 increased with increased with increasing concentrations of zinc and declined with the addition of TPEN. Study 2: Average daily zinc intake was 16.0 ± 5.3 mg/d (range: 9–31 mg/d) and plasma zinc concentrations were 101.4 ± 18.0 μg/dL (range: 68-153 μg/dL). PBMC MT2A was positively correlated with dietary zinc intake (r=0.306, P=0.03) and total zinc intake (r=0.382, P<0.01), whereas plasma zinc was not (P>0.05 for both). Findings suggest that MT2A mRNA in PBMCs reflects dietary zinc intake in healthy adults and may be a component in determining zinc status.

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