28.12: Kinetic markers: pool sizes and turnover rates (24c.12)

Isotopic tracer studies in conjunction with a model-based com­partmental analysis have identified and measured a relatively small whole-body exchangeable pool of zinc (EZP). This pool com­prises the most meta­bolically active forms of zinc in the plasma, extra­cellular fluid, liver, pancreas, kidney, and intestine that make up about 10% of the whole-body zinc. The EZP provides zinc for zinc-dependent functions throughout the body and has a turnover rate of about 12.5 days. The size of EZP is estimated to contain 150–200mg zinc in adults, although varying markedly on a per kilogram body weight basis between adults and infants: 2.5mg Zn/kg in adults vs. 4.5mg Zn/kg in infants (King et al., 2001; Krebs et al., 2003).

Some but not all studies have shown a relation between dietary zinc and the size of the EZP. For example, the size of the EZP was significantly reduced in adults by severe dietary zinc restrictions (i.e, < 1mg Zn/d for 4–5 weeks) (King et al., 2001) or by chronically low habitual zinc intakes (i.e., average 5.2mg Zn/d) (Sian et al., 1996), but not by modest short-term changes in zinc intake (i.e., 4.6mg Zn/d for 10 weeks) (Pinna et al., 2001). Long-term (6 months) moderate zinc supple­mentation in male adults was shown to increase the size of EZP, which was reported to correlate positively with total zinc intake (Feillet-Coudray et al., 2005).

Of interest is the finding that during the study of severe restriction of dietary zinc (i.e., < 1mg Zn/d for 4–5 weeks) (King et al., 2001), the decline in EZP was nearly com­parable to that of plasma zinc (i.e., 60% vs. 65%). This finding suggests that the EZP is part of the vulnerable pool susceptible to zinc depletion, although not more sensitive than plasma zinc concen­trations. Whether the size of EZP is reduced by the meta­bolic redistribution of zinc due to inflam­mation and stress remains uncertain, although such a decrease is likely since plasma zinc is a com­ponent of the EZP (King, 2011). Other factors shown to influence the size of the EZP besides the level of dietary zinc include zinc absorp­tion, age, and sex, with men having a larger pool size than women (Pinna et al., 2001; Krebs et al., 2003; Ruz et al., 2011).

Use of the EZP size as a biomarker of zinc nutrition remains limited, in part because of uncertainties about age and sex-dependent cutoffs for zinc insufficiency, the limited sensitivity of EZP to small changes in dietary zinc intake, and the relationship between EZP size and zinc function. In addition, the measure­ment of EZP necessitates the use of stable isotopes and a mass spectrom­eter for analysis (King, 2011; King et al., 2015).

Isotopic tracer studies have also been used to investigate changes in plasma zinc turnover rates as a biomarker of zinc status. When the total body zinc content is reduced, plasma zinc turnover rates are increased to meet tissue needs. Normally, total plasma zinc turns over about 150 times per day to provide zinc for numerous functions throughout the body. Increases in the plasma turnover rate from about 150–200 times per day have been reported in healthy men as a result of acute, severe zinc depletion (i.e., 0.23mg Zn/d) (King et al., 2001), but not when zinc depletion was more modest (4.6mg Zn/d for 10 weeks) (Pinna et al., 2001). In a study in premenopausal women (n=33), lower intakes of beef, a good source of absorbable zinc, were associated with a reduction in the plasma zinc turnover rate and a reduction in taste acuity (Yokoi et al., 2003). More research is required to establish the validity of plasma zinc turnover rate as a biomarker of zinc status and to standardize the condi­tions for making the measure­ments.

The BOND Zinc Expert Group classified the kinetic markers based on pool sizes and plasma zinc turnover rates as “emerging” biomarkers as they require more research to establish their sensitivity and specificity to changes in zinc nutrition (King et al., 2015; Allan et al., 2000).