Zinc Metabolism and Homeostasis

Reference from the joint report of FAO/WHO expert consultation on Human Vitamins and Minerals verbatim.

3. Sandström, B. 1997. Bio-availability of zinc. Eur. J. Clin. Nutr., 51(suppl. 1): S17-S19

Zinc absorption is concentration dependent and occurs throughout the small intestine. Under normal physiologic conditions, transport processes of uptake are not saturated. Zinc administered in aqueous solutions to fasting subjects is absorbed efficiently (60–70 percent), whereas absorption from solid diets is less efficient and varies depending on zinc content and diet composition (3).

4. King, J.C. & Turnlund, J.R. 1989. Human zinc requirements. In: Zinc in human biology. Mills C.F. ed. p.335-350. Devon , U.K., Springer-Verlag. 

Zinc is lost from the body through the kidneys, skin, and intestine. The endogenous intestinal losses can vary from 7 μmol/day (0.5 mg/day) to more than 45 μmol/day (3 mg/day), depending on zinc intake (4). Urinary and skin losses are of the order of 7-10 μmol/day (0.5–0.7 mg/day) each and depend less on normal variations in zinc intake (4).

Starvation and muscle catabolism increase zinc losses in urine. Strenuous exercise and elevated ambient temperatures could lead to losses by perspiration. The body has no zinc stores in the conventional sense. In conditions of bone resorption and tissue catabolism, zinc is released and may be re-utilised to some extent.

5. Lukaski, H.C., Bolonchuk, W,W., Klevay, L.M., Milne, D.B. & Sandstead, H.H. 1984. Changes in plasma zinc content after exercise in men fed a low-zinc diet. Am. J.

Physiol., 247: E88-93.

6. Milne, D.B., Canfield, W.K., Gallagher, S.K., Hunt, J.R. & Klevay, L.M. 1987.

Ethanol metabolism in postmenopausal women fed a diet marginal in zinc. Am. J. Clin.

Nutr., 46: 688-93. 

Human experimental studies with low-zinc diets 2.6–3.6 mg/day (40-55 μmol/day) have shown that circulating zinc levels and activities of zinc-containing enzymes can be maintained within normal range over several months (5, 6), which highlights the efficiency of the zinc homeostasis mechanism.

7. Baer, M.J. & King, J.C. 1984. Tissue zinc levels and zinc excretion during experimental zinc depletion in young men. Am. J. Clin. Nutr., 39: 556-70.

8. Hess, F.M., King, J.C. & Margen, S. 1977. Zinc excretion in young women on low zinc intakes and oral contraceptive agents. J. Nutr., 107: 1610-20.

9. Milne, D.B., Canfield, W.K., Mahalko, J.R. & Sandstead, H.H. 1983. Effect of dietary zinc on whole body surface loss of zinc: impact on estimation of zinc retention by balance method. Am. J. Clin. Nutr., 38: 181-6.

10. Johnson, P.E., Hunt, C.D., Milne, D.B. & Mullen, L.K. 1993. Homeostatic control of zinc metabolism in men: zinc excretion and balance in men fed diets low in zinc. Am. J.

Clin. Nutr., 57: 557-565. 

Controlled depletion-repletion studies in humans have shown that changes in the endogenous excretion of zinc through the kidneys, intestine, and skin and changes in absorptive efficiency are how body zinc content is maintained (7-10).

11. Agett P.J. & Favier A. 1993. Zinc. Int. J. Vit. Nutr. Res., 63: 247-316.

The underlying mechanisms are poorly understood. Sensitive indexes for assessing zinc status are unknown at present. Static indexes, such as zinc concentration in plasma, blood cells, and hair, and urinary zinc excretion are decreased in severe zinc deficiency. A number of conditions that are unrelated to zinc status can affect all these indexes, especially zinc plasma levels. Infection, stress situations such as fever, food intake, and pregnancy lower plasma zinc concentrations whereas, for example, long-term fasting increases it (11).

12. Goldenberg, R.L., Tamura, T., Neggers, Y., Copper, R.L., Johnston, K.E., DuBard, M.B. & Hauth, J.C. 1995. The effect of zinc supplementation on pregnancy outcome. JAMA, 274: 463-468

13. Brown, K., Peerson, J.M. & Allen, L.H. 1998. Effects of zinc supplementation on children’s growth. In: Role of trace elements for health promotion and disease prevention. Sandström, B., Walter, P., eds. Bibliotheca Nutritio et Dieta, Basel: Karger; 54: 76-83.

14. Beck, F.W.J., Prasad, A.S. & Kaplan, J. 1997. Changes in cytokine production and T cell subpopulations in experimentally induced zinc-deficient Humans. Am. J. Physiol. 272: E1002-7.

However, on a population basis, reduced plasma zinc concentrations seem to be a marker for zinc-responsive growth reductions (12, 13). Experimental zinc depletion studies suggest that changes in immune response occur before reductions in plasmazinc concentrations are apparent (14).

 11. Agett P.J. & Favier A. 1993. Zinc. Int. J. Vit. Nutr. Res., 63: 247-316.

So far, it has not been possible to identify zinc dependent enzymes which could serve as early markers for zinc status. A number of functional indexes of zinc status have been suggested, for example, wound healing, taste acuity, and dark adaptation (11).

15. Sandström, B. Fairweather-Tait, S., Hurrell, R. & Van Dokkum, W. 1993. Methods for studying mineral and trace element absorption in Humans using stable isotopes. Nutr. Res. Revs., 6: 71-95.

Changes in these functions are,however, not specific to zinc and these indexes have so far not been proven useful for identifying marginal zinc deficiency in humans. The introduction of stable isotope techniques in zinc research (15) has created possibilities for evaluating the relationship between diet and zinc status and is likely to lead to a better understanding of the mechanisms underlying the homeostatic regulations of zinc.

16. Wastney, M.E., Gökmen, I.G., Aarmodt, R.L., Rumble, W.F., Gordon, G.E. & Henkin, R.I. 1991. Kinetic analysis of zinc metabolism in Humans and simultaneous administration of 65Zn and 70Zn. Am. J. Physiol., 260: R134-41.

17. Fairweather-Tait, S.J., Jackson, M.J., Fox, T.E., Wharf, S.G., Eagles, J. & Groghan, P.C. 1993. The measurement of exchangeable pools of zinc using the stable isotope 70Zn. Br. J. Nutr., 70: 221-34.

18. Miller, L.V., Hambidge, K.M., Naake, V.L., Hong, Z., Westcott, J.L. & Fennessey, P.V. 1994. 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., 124: 268-76.

19. Sian, L., Mingyan, X., Miller, L.V., Tong, L., Krebs, N.F. & Hambidge, K.M. 1996. Zinc absorption and intestinal losses of endogenous zinc in young Chinese women with marginal zinc intakes. Am. J. Clin. Nutr., 63: 348-53.

Estimations of turnover rates of administered isotopes in plasma or urine have revealed the existence of a relatively small rapidly exchangeable body pool of zinc of about 1.5-3 mmol (100-200 mg) (16-19). The size of the pool seems to be correlated to habitual dietary intake and it is reduced in controlled depletion studies (18). The exchangeable zinc pool was also found to be correlated to endogenous faecal excretion of zinc (19) and to total daily absorption of zinc. 

These data suggest that the size of the exchangeable pool depends on recently absorbed zinc and that a larger exchangeable pool results in larger endogenous excretion. Changes in endogenous intestinal excretion of zinc seem to be more important than changes in absorptive efficiency for maintenance of zinc homeostasis (19).