Chemistry Reference
In-Depth Information
Zn defi ciency (McClain, 1985). The risk of Zn defi ciency is
increased, by excretion of Zn released from erythrocytes
by hemolysis, in patients with sickle cell disease (Prasad,
2002) and thalassemia (Prasad
et al
., 1965). Chronic
bleeding, from hookworm and other parasites (Farid,
Patwardhan, and Darby, 1969), also causes loss of Zn
(Prasad
et al
., 1963), as does menorrhagia (Yokoi
et al
.,
1994; Yokoi
et al
., 2003). Increased Zn excretion in urine
occurs in some renal diseases (Lindeman, 1989), cirrhosis
of the liver and alcoholism (McClain
et al
., 1986), stress
(McClain
et al
., 1993), catabolism (Fell
et al
., 1973), and
chronic infl ammatory diseases that increase interleukin-
1 (IL-1) (Goldblum
et al
., 1987). Pharmacological intakes
of ferrous Fe (Solomons 1986), Ca (Wood and Zheng,
1997), and folic acid (Milne
et al
., 1984; Simmer
et al
.,
1987) can inhibit Zn absorption.
High oral intakes of Zn typically impair Cu nutri-
ture (Magee and Matrone, 1960). The putative mecha-
nism involves Zn induction of thionein synthesis in
enterocytes, which binds Zn and Cu to become metal-
lothionein (MT). Redox conditions affect release of Zn
and Cu from MT. Binding of Cu by MT is many times
stronger than binding of Zn. It is unknown whether Zn
competes with Cu for binding to proteins that medi-
ate the exit of Cu from enterocytes into the body. In
any case, Cu retained in the enterocytes is excreted in
feces, which in some instances results in Cu defi ciency
(Sandstead, 1995).
Copper defi ciency causes many abnormalities (e.g.,
decreased iron use, low serum ferritin (Yadrick, Ken-
ney, and Winterfeldt, 1989), and hypochromic micro-
cytic anemia, leukopenia, osteopenia (Graham, 1971),
myeloneuropathy (Hedera
et al
., 2003; Rowin and
Lewis, 2005), heart arrhythmias (Kopp, Klevay, and
Feliksik, 1983; Klevay
et al
., 1984; Reiser
et al
., 1985),
increased LDL cholesterol and/or decreased HDL cho-
lesterol (Klevay
et al
., 1984; Reiser
et al
., 1987; Hooper
et al
., 1980), low plasma Cu concentration, low plasma
ceruloplasmin activity, low erythrocyte superoxide dis-
mutase (ESOD) activity (Milne, 1998), low erythrocyte
glutathione peroxidase (EGPx), low platelet Cu, low
cytochrome
c
oxidase (CCO) activity, and increased
activity of clotting factors V and VIII (Milne and
Nielsen, 1996). Experience suggested to one observer
that the most sensitive indicators of Cu status are
platelet cytochrome
c
oxidase activity and Cu concen-
tration, erythrocyte SOD and glutathione peroxidase,
and activity of clotting factors V and VIII (Milne and
Nielsen, 1996). Some of these are noted in Table 3. In
addition, fi ndings in Table 3 suggest a Zn/Cu molar
ratio >18 over an extended period of time increases the
risk of Cu defi ciency. It is notable that available data do
not identify a threshold for an adverse effect by Zn.
Because chemically similar metals compete for bind-
ing ligands (Hill and Matrone, 1970; Allaway
et al
.,
8.7 Toxicity
8.7.1 Dietary and Supplement Intakes
Intakes of Zn and Cu should be proportionate
( Sandstead 1995). The copper requirement seems
directly related to Zn intake (Table 7). In contrast,
when protein intake is increased, the Cu requirement
is decreased. The data in Table 7 were derived from
balance studies carried out at the USDA Grand Forks
Human Nutrition Research Center (Sandstead, 1982).
The data were analyzed by multiple stepwise regres-
sion analysis of potential predictors, including Cu
balance, diet Zn, diet nitrogen (N), diet Ca, and diet
phosphorus (P). Copper balance, diet Zn, and diet N
had a signifi cant infl uence (
n
= 161;
R
2
= 0.59,
P
< 0.0001).
It is notable that addition of the ~ 0.34 mg of Cu, lost
daily in sweat under moderate conditions (Jacob
et al
.,
1981) to the fi ndings in Table 7, increases the total Cu
requirement to levels substantially >0.90 mg recom-
mended for adults in the 2001 Dietary Reference Intake
(Committee on Micronutrients, 2001).
TABLE 7 Copper Requirement (mg/day) of Adult Men Fed Mixed Diets of Common
Foods Providing Four Levels of Protein and Zinc (Sandstead, 1982)
a,b
Protein, g
40
60
80
100
5 mg Zn
1.0 (0.73-1.28)
c
[6.7-3.8]
d
0.95 (0.67-1.23) [7.3-3.9]
0.89 (0.61-1.17) [7.9-4.2]
0.83 (0.55-1.11) [8.9-4.4]
10 mg Zn
1.26 (0.98-1.54) [9.9-6.3]
1.20 (0.92-1.48) [10.6-6.6]
1.14 (0.86-1.42) [11.3-6.9]
1.08 (0.80-1.36) [12.2-7.2]
15 mg Zn
1.50 (1.22-1.78) [12.0-8.2]
1.45 (1.17-1.67) [12.5-8.8]
1.39 (1.11-1.67) [13.2-8.8]
1.33 (1.05-1.61) [13.9-9.1]
20 mg Zn
1.76 (1.48-2.04) [13.2-9.6]
1.70 (1.42-1.98) [13.7-9.8]
1.64 (1.36-1.92) [14.3-10.2]
1.58 (1.30-1.86) [15.0-10.5]
a
Cu intake = 0.87 + 0.49 (Cu balance) + 0.05 (Zn intake) − 0.02 (N intake).
Intake = Requirement when balance is in equilibrium.
b
For total requirement add 0.34 mg to account for daily surface loss of Cu under moderate environmental conditions (Jacob
et al
., 1981).
c
95% confi dence interval.
d
Zn = Cu molar ratio.
