Author : Sarah J. Zyba
Publisher :
ISBN 13 : 9780355967548
Total Pages : pages
Book Rating : 4.9/5 (675 download)
Book Synopsis Whole Body, Cellular, and Molecular Changes in Healthy Men Consuming Low, Moderate, Or Supplemental Zinc Intakes by : Sarah J. Zyba
Download or read book Whole Body, Cellular, and Molecular Changes in Healthy Men Consuming Low, Moderate, Or Supplemental Zinc Intakes written by Sarah J. Zyba and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Zinc deficiency is a leading global health concern and is a contributing factor to stunting and impaired immune function. The World Health Organization estimates that 1.4% of deaths worldwide can be attributed to zinc deficiency. However, due to the fact that zinc is required for many metabolic pathways in the human body and symptoms of zinc deficiency are non-specific, scientists have struggled to identify a sensitive and specific biomarker for zinc. To evaluate the effect changes in dietary zinc have on healthy individuals, a zinc depletion/ repletion study was conducted. In this study, eighteen healthy men, age 18-39, were provided a moderately low zinc (6 mg/day) diet with added phytic acid (1.5 g/d) for two weeks to facilitate zinc deficiency followed by a moderate zinc (10 mg/day) diet for four weeks. They then consumed an ad libitum diet while taking a 25mg zinc supplement for three weeks. The study diet was based on a traditional high-carbohydrate, low-animal source protein Bangladeshi diet. To determine what effect changing dietary zinc has on zinc absorption and whole-body zinc metabolism, fractional zinc absorption (FZA) and the size of the exchangeable zinc pool (EZP) were measured using a dual-tracer isotope method. Total absorbed zinc (TAZ) was then calculated from FZA. Blood samples were also collected throughout the study to look at cellular markers of zinc status and changes in the proteome. The results of this study are presented in three chapters. The first chapter evaluated the impact an increase of 4 mg dietary zinc per day had on the absorption and size of the exchangeable zinc pool of the participants. FZA decreased by 6.4% with the moderate zinc diet compared to the low-zinc diet, but TAZ increased by 0.7 mg with the moderate zinc diet. EZP did not change with any changes to the diet. These results indicate that neither an increase in 4 mg dietary zinc per day for four weeks, nor a 25 mg zinc supplement for three weeks was sufficient to affect the EZP of adult men. However, an increase in 4mg zinc per day increased absorbed zinc by 0.7 mg.The second chapter evaluated changes in cellular zinc markers including white blood cell (WBC), and red blood cell (RBC) zinc concentrations, WBC zinc transporters and metallothionein gene expression, in vitro WBC 65Zn uptake, and WBC DNA damage in the participants during the zinc depletion/repletion study. mRNA expression of zinc transporters, including ZIP1, ZIP4, ZIP8, ZNT1, and ZNT7, and a metallothionein gene (MT2a) was examined in isolated WBCs. ZNT1 and ZNT7 gene expression increased while ZIP4 gene expression decreased during the low zinc phase, although total plasma and WBC zinc concentrations did not change nor did in vitro WBC 65Zn uptake. Total DNA strand breaks and DNA strand breaks due to oxidative damage increased with a low zinc diet. Total DNA strand breaks then returned to baseline levels when the dietary zinc was increased to 10 mg/d during the moderate zinc phase, but strand breaks due to oxidative damage did not. These results show that a two-week, low zinc intake alters gene expression of ZNT1, ZNT7 and ZIP4 in WBCs, without any change in plasma zinc concentration. Also, DNA integrity is sensitive to changes in dietary zinc as small as 4 mg/d. Both WBC zinc transporter gene expression and DNA integrity may be useful to evaluate zinc deficiency and the effectiveness of zinc interventions even when plasma zinc concentrations remain unchanged.The fourth chapter evaluated changes in plasma proteins when healthy men consume a low zinc diet followed by moderate dietary zinc and when they consumed a zinc supplement. Of 1129 proteins that were measured, 19 proteins responded to changes in dietary zinc. These proteins either increased or decreased significantly with a 6 mg + phytate diet and then returned to the baseline after the participants consumed a 10 mg zinc diet for four weeks. The proteins that responded to the dietary zinc changes generally belonged to two metabolic categories: inflammation and apoptosis. The 6 mg zinc diet led to a pro-inflammatory and pro-apoptotic state that recovered when participants were fed a 10 mg zinc diet for four weeks. Forty-one proteins changed between baseline and the 3-week supplementation period with 25 mg zinc. These proteins varied in function and did no show a clear effect of zinc supplementation on a specific aspect of the proteome. Consuming a 6 mg zinc diet with added phytate induced a pro-inflammatory pro-apoptotic state in healthy men. Increasing dietary zinc to 10 mg /d and removing phytate permitted the plasma proteins to return to the baseline levels. Together these results show that even small changes in dietary zinc can have a significant impact on cellular function and zinc metabolism as well as the plasma proteome even when plasma zinc concentration is not affected. Some of the cellular and proteomic markers measured here may provide a sensitive and specific marker for diagnosing zinc deficiency or evaluating effectiveness of zinc dietary interventions.
