Plasma metabolome analysis during human zinc depletion and repletion

Abstract

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<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 & P30 ES000210