Zinc - Toxicology of Metals - page 907

fasting concentrations are higher in the morning;
concentrations decrease after meals; men tend to have
higher concentrations than premenopausal women;
infants, children, and the aged (Hotz, 2003). The empir-
ical lower limit of normal for fasting plasma Zn is 10.7
µ

(Raz et al ., 1989; Cunningham et al ., 1994), or severe
catabolism (Cuthbertson et al ., 1972; Fell et al ., 1973).

6.2 Indirect Physiological
Indicators of Zn Status

g/L) (Pilch and Senti, 1985). However,
a study of 33 premenopausal women not taking oral
contraceptives found signifi cant correlations between
components of the three-compartment kinetics model
24 hours after administration of a stable Zn tracer; the
break points in the plasma Zn-Zn kinetics relation-
ship for different kinetic parameters ranged from 9.94
µ

mol/L (700 µ

6.2.1 Alkaline Phosphatase

Alkaline phosphatase requires Zn for structure and
function. If other infl uences on activity are absent,
plasma alkaline phosphatase tends to correlate with
plasma Zn concentration. Low activity of plasma alka-
line phosphatase is sometimes observed in association
with severe Zn defi ciency (Arakawa et al ., 1976).

mol/L (650 µ g/L) to 11.5 µ mol/L (750 µ g/L) (Yokoi

et al ., 2003).

6.1.3 White Blood Cell Zinc

Leukocyte and lymphocyte Zn concentrations are
more refl ective of Zn status than plasma Zn (Prasad
et al ., 1978; Meadows et al ., 1981). Unfortunately, isola-
tion and analysis of Zn in white blood cells and platelets
is technically demanding (Milne et al ., 1985).

6.2.2 Ecto 5'-Nucleotidase

Ecto 5'-nucleotidase is a cell membrane enzyme that
requires Zn (Zimmermann, 1992). Plasma activity of this
enzyme is more sensitive to decreases in Zn status than
plasma Zn concentration (Bales et al ., 1994). Lymphocyte
ecto 5'-nucleotidase activity is also a more sensitive index
of Zn status than plasma Zn (Meftah et al ., 1991). The
enzyme can be assessed by cell sorter and immunologi-
cal determination of the percentage of CD73+ cells in the
CD8+ T-lymphocyte population (Beck et al ., 1997).

6.1.4 Hair Zn

The fi nding of low concentrations of Zn in hair is
indicative of Zn defi ciency (Strain et al ., 1966). For
example, low hair Zn may be associated with growth
failure in children (Ferguson et al ., 1993; Cavan et al .,
1993; Gibson et al ., 1991). The lower limit of “normal” is
approximately 1.68 mmol/g. In contrast, hair Zn con-
centrations were not related to Zn status of 33 premeno-
pausal women who were not taking oral contraceptives
(Yokoi et al ., 2003) or dietary Zn or Zn bioavailability in
330 premenopausal New Zealand women aged 18-40
years (Gibson et al ., 2001).
Hair Zn is not commonly measured to ascertain
increased Zn exposure. However, it increases with
increased Zn intake in humans (Pekarek et al ., 1979)
and nonhuman primates (Marriott et al ., 1996) and,
therefore, should be considered a potential marker of
excess Zn exposure.

6.2.3 Immunity

Zinc is essential for immunity (Fraker et al ., 2000;
Fischer Walker and Black, 2004). The high sensitivity
of immunity to Zn status is illustrated by fi ndings in
mice. Mildly Zn-deprived mice that maintained thy-
mus weight and body weight displayed an increase
in the number of apothymulin-positive thymic epi-
thelial cells and the plasma concentration of apothy-
mulin, although plasma thymulin activity decreased
(Dardenne et al ., 1984). Thymulin is a nonapeptide
hormone whose active structure requires Zn (Bach and
Dardenne; 1989). Thymulin induces differentiation and
function of T cells.
The threshold at which limited Zn status impairs
immunity in humans is unknown. Human infants
recovering from protein-energy malnutrition dis-
played decreased thymus size and skin reactivity
to a common antigen. Zn treatment restored these
indices to normal (Golden et al ., 1977; Golden et al .,
1978). Consistent with these fi ndings, a Zn-deprived
man fed an otherwise adequate oral formula dis-
played low lymphocyte transformation after in vitro
stimulation by phytohemagglutinin. Zinc treatment
restored function (Pekarek et al ., 1979). More detailed
investigation in men subjected experimentally to
mild Zn deprivation revealed suppressed generation

6.1.5 Urine Zinc

Urinary Zn excretion is usually decreased in Zn
defi ciency (Prasad et al ., 1963) and increased by Zn excess
(Bonner et al ., 1981; Fuortes and Schenck, 2000; Main
et al ., 1982). Zinc-depleted men displayed urine Zn
concentrations <150

g/day, although at the same
time plasma Zn remained >700

µ

mol/L)
(Baer and King, 1984). However, large excretions of
Zn can occur in Zn-defi cient individuals affl icted by
hemolytic anemia (Prasad et al ., 1975), liver cirrhosis
and/or alcoholism (Sullivan and Heaney, 1970; Allan
et al ., 1975), noninsulin-dependent diabetes mellitus

µ g/L (10.7 µ