Dietary zinc restriction and repletion affects DNA integrity in healthy men

Abstract

Background:Zinc plays an important role in antioxidant defense and the maintenance of cellular DNA integrity. However, no experimental human studies have been performed to examine the role of zinc status on DNA damage. Objective:We evaluated the effects of dietary zinc depletion and repletion on DNA strand breaks, oxidative stress, and antioxidant defenses in healthy men. Design:Nine healthy men with reported mean daily zinc intakes >11 mg/d were recruited. Subjects completed 3 consecutive dietary periods: baseline (days 1 to 13; 11 mg Zn/d), zinc depletion (days 14 to 55; 0.6 mg Zn/d for 1 wk and 4 mg Zn/d for 5 wk), and zinc repletion (days 56 to 83; 11 mg Zn/d for 4 wk with 20 mg supplemental Zn for first 7 d). Blood samples were collected on days 1, 13, 35, 55, and 83. DNA damage in peripheral blood cells, plasma oxidative stress, and antioxidant defense biomarkers were assessed. Results:Dietary zinc depletion (6 wk) was associated with increased DNA strand breaks in peripheral blood cells (day 13 compared with day 55;P < 0.05), changes that were ameliorated by zinc repletion (day 55 compared with day 83;P < 0.05). Plasma zinc concentrations were negatively correlated with DNA strand breaks (r = −0.60,P = 0.006) during the zinc-depletion period. Plasmaα- and γ-tocopherol concentrations, plasma total antioxidant capacity, and erythrocyte superoxide dismutase activity did not change significantly, and plasma F2-isoprostanes were unaffected by dietary period. Conclusions:Changes in dietary zinc intake affected DNA single-strand breaks. Zinc appears to be a critical factor for maintaining DNA integrity in humans.