An Evaluation of Zinc Status Biomarkers

The purpose of this study is to determine the effect of a moderate decrease in dietary zinc on DNA strand breaks and other cellular zinc biomarkers.

Assessing the zinc status of humans has proven to be difficult because of the unique physiological features of zinc homeostasis. Animal and human studies show that a small, vulnerable pool of cellular zinc is sensitive to changes in dietary zinc. The protein, Metallothionein (MT), is made within cells to stabilize this transient zinc pool and to provide a means to 'park' a small zinc reserve. The overall goal is to develop a new method for measuring MT in cells and to assess other cellular responses to changes in small changes in dietary zinc. Culture models of zinc deficiency and excess have been developed and used to test the response of cellular MT levels and mineralization to changes in zinc availability. In Phase II, the changes in the expression of leukocytic zinc transporters and the cellular in vitro uptake of isotopic zinc will be measured. Healthy men will be recruited to participate in a 6-week feeding trial to be followed by a 3-week recovery period. The results of this study will determine if potential new cellular zinc biomarkers respond to changes in zinc status when the men are fed an additional 4 mg zinc/d incorporated into a rice-based meal. These findings will provide essential, new information for designing an efficacy trial of biofortified rice and the zinc status of infants and young children.

4 mg zinc, as zinc sulfate, was added to a controlled diet; 25 mg supplemental zinc was given during the final recovery period when an ad lib diet was consumed

Baseline measurements were made upon entry into the study. Subsequent measurements were made after 2 weeks on a low zinc diet (6 mg/d), 4 weeks on a moderate zinc intake (10 mg/d) and after 3 weeks of consuming a 25 mg zinc supplement.

Change in DNA strand breaks measured at baseline, 2, 4, and 3 week intervals with changes in diet zinc

Specific measurements included the gene expression of zinc transporters, the in vitro uptake of leukocytic radioactive Zn, and a comprehensive serum metabolomic and proteomic analysis.

Inclusion Criteria: willing to limit food and beverage intake to that provided by the study willing to discontinue consumption of alcoholic beverages during the study has an operative understanding of English no plans to move from the area during the study period Exclusion Criteria: chronic or acute metabolic disease (i.e., diabetes or asthma) taking medications for a metabolic disorder evidence of alcohol abuse or use of illicit drugs

Zyba SJ, Shenvi SV, Killilea DW, Holland TC, Kim E, Moy A, Sutherland B, Gildengorin V, Shigenaga MK, King JC. A moderate increase in dietary zinc reduces DNA strand breaks in leukocytes and alters plasma proteins without changing plasma zinc concentrations. Am J Clin Nutr. 2017 Feb;105(2):343-351. doi: 10.3945/ajcn.116.135327. Epub 2016 Dec 21. Erratum In: Am J Clin Nutr. 2017 Dec;106(6):1539.