A moderate increase in dietary zinc reduces DNA strand breaks in leukocytes and alters plasma proteins without changing plasma zinc concentrations

Sarah J Zyba, Swapna V Shenvi, David W Killilea, Tai C Holland, Elijah Kim, Adrian Moy, Barbara Sutherland, Virginia Gildengorin, Mark K Shigenaga, Janet C King, Sarah J Zyba, Swapna V Shenvi, David W Killilea, Tai C Holland, Elijah Kim, Adrian Moy, Barbara Sutherland, Virginia Gildengorin, Mark K Shigenaga, Janet C King

Abstract

Background: Food fortification has been recommended to improve a population's micronutrient status. Biofortification techniques modestly elevate the zinc content of cereals, but few studies have reported a positive impact on functional indicators of zinc status.

Objective: We determined the impact of a modest increase in dietary zinc that was similar to that provided by biofortification programs on whole-body and cellular indicators of zinc status.

Design: Eighteen men participated in a 6-wk controlled consumption study of a low-zinc, rice-based diet. The diet contained 6 mg Zn/d for 2 wk and was followed by 10 mg Zn/d for 4 wk. To reduce zinc absorption, phytate was added to the diet during the initial period. Indicators of zinc homeostasis, including total absorbed zinc (TAZ), the exchangeable zinc pool (EZP), plasma and cellular zinc concentrations, zinc transporter gene expression, and other metabolic indicators (i.e., DNA damage, inflammation, and oxidative stress), were measured before and after each dietary-zinc period.

Results: TAZ increased with increased dietary zinc, but plasma zinc concentrations and EZP size were unchanged. Erythrocyte and leukocyte zinc concentrations and zinc transporter expressions were not altered. However, leukocyte DNA strand breaks decreased with increased dietary zinc, and the level of proteins involved in DNA repair and antioxidant and immune functions were restored after the dietary-zinc increase.

Conclusions: A moderate 4-mg/d increase in dietary zinc, similar to that which would be expected from zinc-biofortified crops, improves zinc absorption but does not alter plasma zinc. The repair of DNA strand breaks improves, as do serum protein concentrations that are associated with the DNA repair process. This trial was registered at clinicaltrials.gov as NCT02861352.

Keywords: DNA repair; antioxidant; inflammation; zinc biomarkers; zinc fortification.

© 2017 American Society for Nutrition.

Figures

FIGURE 1
FIGURE 1
Mean ± SD DNA strand breaks and oxidized lesions measured with the use of the alkaline comet and FPG comet assays. Olive tail moments (arbitrary units) from the alkaline comet assay are depicted with black bars; tail moments from FPG comets are depicted with gray bars. n = 18 for alkaline comets, and n = 13 for FPG comets. Significant differences between means were determined with the use of a repeated-measures ANOVA followed by Bonferroni’s multiple-comparisons test. Bars with the same letter or symbol represent means that are not significantly different from each other. DNA strand breaks increased from baseline (14.5% ± 4.7%) to the end of the low-zinc period (23.0% ± 6.3%; P < 0.001) and decreased by the end of the higher-zinc period (12.2% ± 3.7%; P < 0.001). Olive tail moments that were due to oxidation increased significantly from baseline (11.88% ± 4.17%) to the end of the low-zinc period (17.26% ± 7.83%; P = 0.01). FPG, formamidopyrimidine DNA-glycosylase.

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