Julie M. Long of the University of Colorado, Denver discusses the exchangeable zinc pool (EZP) as a biomarker of zinc status and reviews the findings from a recently published sub-study of the Zinc in Powders Trial.
While a lot is known about dietary zinc requirements through the lifecycle and the necessity of this trace mineral for optimal growth, development, and immune function, identification of a ‘gold standard’ biomarker for zinc status remains elusive (1). Currently, serum or plasma zinc status or proxy indicators like dietary zinc intake or stunting rates, are used to estimate zinc status, but each has its limitations.
Small, observational studies suggest that the EZP may be a way to measure zinc status. The EZP is defined as the size of the combined pools, such as the liver, in the body that readily exchange with zinc in the plasma within 2–3 days. This rapidly exchanging zinc is estimated to include approximately 10% of total body zinc and is thought to reflect metabolically active zinc (2). Additionally, adult and pediatric studies suggest that EZP correlates well with dietary zinc intake and zinc absorption, and unlike serum or plasma zinc, EZP size may not decrease when systemic inflammation is present (3-5).
Recently a sub-study of the Zinc in Powders Trial (6) allowed researchers to test the usefulness of EZP as a marker of zinc status via a double blinded randomized controlled trial of zinc supplementation. The sub-study prospectively compared the change in EZP from study start to finish in children who were preventively supplemented with 10 mg of zinc for 6 months as part of a multiple micronutrient powder (MNP) consumed with food or as a zinc dispersible tablet versus a placebo powder.
The major findings of this study included:
· EZP increased for children who were given zinc supplements compared to no change for children that consumed a placebo powder
· Children who consumed the zinc dispersible tablet had the greatest increase in EZP, double the increase of children in the MNP group
· EZP of children experiencing systemic inflammation at baseline did not differ from EZP of children without inflammation
While these results are promising, the limitations of EZP as a biomarker include the requirement for use of stable isotope methodology, including careful urine collections and specialized analyses. Thus, it is less “field friendly” than serum zinc and presently may best be viewed as a useful addition to the zinc toolbox.
The implications of this study’s findings indicated that EZP was responsive to changes in zinc intake and was most responsive to the consumption of the more bioavailable zinc in a dispersible tablet. Additionally, unlike serum or plasma zinc, EZP appears to be resistant to changes when inflammation is present, suggesting it has potential to accurately and reliably measure zinc status!
References:
1. King, J.C.; Brown, K.H.; Gibson, R.S.; Krebs, N.F.; Lowe, N.M.; Siekmann, J.H.; Raiten, D.J. Biomarkers of Nutrition for Development (BOND)-zinc review. J. Nutr. 2016, 146, 858S–885S.
2. Miller, L.V.; Hambidge, K.M.; Naake, V.L.; Hong, Z.; Westcott, J.L.; Fennessey, P.V. Size of the zinc pools that exchange rapidly with plasma zinc in humans: Alternative techniques for measuring and relation to dietary zinc intake. J. Nutr. 1994, 124, 268–276.
3. Krebs, N.F.; Westcott, J.E.; Culbertson, D.L.; Sian, L.; Miller, L.V.; Hambidge, K.M. Comparison of complementary feeding strategies to meet zinc requirements of older breastfed infants. Am. J. Clin. Nutr. 2012, 96, 30–35.
4. Miller, L.; Long, J.; Mondal, P.; Westcott, J.; Islam, M.M.; Ahmed, M.; Ahmed, T.; Krebs, N. Exchangeable Zinc Pool (EZP) size in Bangladeshi toddlers at risk of environmental enteric dysfunction (EED) is not influenced by inflammation (OR07-03-19). Curr. Dev. Nutr. 2019, 3 (Suppl. 1), nzz034.OR07-03-19.
5. Miller, L.V.; Hambidge, K.M.; King, J.C.; Westcott, J.E.; Krebs, N.F. Predictors of the size of the exchangeable zinc pool differ between children and adults. J. Nutr. 2017, 147, 187–194.
6. Islam, M.M.; Black R.E.; Krebs N.F.; Westcott J.; Long J.; Islam K.M.; Peerson J.M.; Sthity R.A.; Khandaker A.M.; Hasan M.; El Arifeen S.; Ahmed T.; King J.C.; McDonald C.M. Different doses, forms, and frequencies of zinc supplementation for the prevention of diarrhea and promotion of linear growth among young Bangladeshi children: a six-arm, randomized, community-based efficacy trial. J Nutr. 2022, 152(5), 1306-1315.
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