Zinc bioavailability and homeostasis

Abstract

Zinc has earned recognition recently as a micronutrient of outstanding and diverse biological, clinical, and global public health importance. Regulation of absorption by zinc transporters in the enterocyte, together with saturation kinetics of the absorption process into and across the enterocyte, are the principal means by which whole-body zinc homeostasis is maintained. Several physiologic factors, most notably the quantity of zinc ingested, determine the quantity of zinc absorbed and the efficiency of absorption. Other factors are age and the time over which zinc is ingested. Zinc from supplements has not been shown to be absorbed differently from that taken with meals that lack inhibitors of zinc absorption. The principal dietary factor known to impair zinc bioavailability is inositol hexa- (and penta-) phosphate or phytate. Modeling of zinc absorption as a function of dietary zinc and phytate accounts for >80% of the variability in the quantity of zinc absorbed. Fitting the model to new data has resulted in continual improvement in parameter estimates, which currently indicate a maximal absorption in adults of approximately 6 mg Zn/d and that the average estimated dietary requirement doubles with 1000 mg dietary phytate/d. Intestinal excretion of endogenous zinc is regulated in response to recent absorption and to zinc status. The quantitative relation of intestinal excretion of endogenous zinc to zinc absorption is currently considered to be of major importance in the determination of zinc requirements. The effects of phytate on intestinal losses of endogenous zinc merit further investigation but are probably not of the same magnitude as its inhibitory effects on absorption of exogenous zinc.

FIGURE 1

Saturation response model of total absorbed zinc per day as a function of total ingested zinc. Data modeled are the means of the 10 sets of healthy young adults used in the estimation of Dietary Reference Intakes for zinc by the Institute of Medicine (2). Also depicted is the line of equality for absorbed zinc compared with ingested zinc. Arrows depict theoretic up- and down-regulation of zinc transporters in the enterocytes. PR, physiologic requirement for men estimated by the Institute of Medicine (2); DR, average dietary zinc requirement estimated from this model, an estimate that is essentially identical to the Estimated Average Requirement (2).

FIGURE 2

Trivariate model of absorbed zinc as a function of dietary zinc and phytate. A 3-dimensional surface of the model is shown. Each black dot represents the mean for one set of data from all identified research projects that include measurements of quantity of zinc absorbed, dietary zinc, and dietary phytate. Lines associated with each dot represent residuals.

FIGURE 3

Comparison of current and original model parameters. Saturation response curves for selected phytate concentrations are shown as dashed lines for the original model (18) and as continuous lines for the current model.

FIGURE 4

Regression residuals relative to quantities of dietary zinc and phytate and predicted quantities of zinc absorbed.

FIGURE 5

Estimates of endogenous fecal zinc (EFZ) at amounts of absorbed zinc required to meet physiologic requirements by the Institute of Medicine (IOM) compared with those of the World Health Organization (WHO). Shown are estimated quantities of total endogenous zinc excretion (TEZ) and EFZ as a function of absorbed zinc at amounts of absorbed zinc below and up to quantities estimated to be necessary to meet physiologic requirements of men. WHO “normative” (unadapted) (17) and IOM calculations used in the estimation of Dietary Reference Intakes (DRIs) are compared (2). The intercept of TEZ excretion lines with the line of equality shows the estimated physiologic requirement. Continuous vertical lines indicate EFZ at amounts of absorption estimated to be necessary to just meet physiologic requirements. Dotted vertical lines indicate endogenous excretion by other routes.

FIGURE 6

Relation of endogenous fecal zinc to absorbed zinc by sex. Linear regressions of sex-specific data for endogenous fecal zinc compared with absorbed zinc. Female and male regression lines are are shown. y-int, y-intercept.

FIGURE 7

Linear regression slopes for endogenous fecal zinc compared with absorbed zinc in combined sexes and men only. y-int, y-intercept.

FIGURE 8

Linear regression for endogenous fecal zinc compared with absorbed zinc in 2 individual data sets: young Chinese women (A) (29) and young American women (B).

FIGURE 9

Estimated total endogenous zinc losses compared with absorbed zinc in women and combined sexes. Note similarity in intercepts with the line of equality (- - -), which gives an estimate of physiologic requirements.

FIGURE 10

Residuals from linear regression of endogenous fecal zinc (EFZ) on absorbed zinc, plotted against dietary phytate.