Supplemental Readings and References
899
of zinc through sweating, and geophagia (the practice of
eating earth and clay, which bind zinc and other metals).
All showed clinical improvement following oral supple-
mentation with zinc.
The jejunum is the principal absorptive region, although
zinc absorption occurs through out the small intestine. Up-
take occurs both by an active transport process, the activity
of which varies inversely with zinc status, and by a pas-
sive process. The increase in serum zinc following a single
oral or parenteral bolus of zinc decreases absorption within
about
6
hours. In contrast, with slow intravenous infusion,
significant decrease in zinc absorption may not occur for
4 days. Intestinal metallothionein is induced by and binds
zinc. It increases by about
6
hours following a bolus of
zinc and may block absorption by sequestering the metal
in the mucosal cells. The evidence is largely circumstan-
tial. Uptake by the liver is by an active process.
Fecal zinc is derived from unabsorbed dietary zinc and
zinc in desquamated epithelial cells and gastrointestinal
secretions. Active intestinal secretion of zinc decreases in
zinc-depleted animals and may be a regulated step in zinc
homeostasis.
Excretion of zinc in urine (0.3-0
. 6
mg/d) is indepen-
dent of dietary intake. It is increased in renal disease, in
alcoholic cirrhosis, in hepatic porphyria, following major
operations, in severely burned patients, and in response to
treatment with ethylenediaminetetraacetic acid.
The
normal
concentration
of
zinc
in
sweat
is
1.15 /xg/mL, decreasing to about 0.6 /xg/mL in zinc defi-
ciency. In tropical climates, zinc loss from this source may
reach 4 mg/d. Menstrual zinc loss is about 15 /xg/d.
The zinc content of human milk is highest in colostrum.
The average zinc concentration in human milk is approx-
imately 1.5 /xg/mL. Fresh cow’s milk averages 4 /xg/mL,
but human milk is a better source of zinc for infant nu-
trition because of lower bioavailability of zinc in cow’s
milk.
Zinc is relatively nontoxic but, if present in the diet at
high concentration and in readily available form, it can
interfere with the absorption of calcium, copper, iron, and
cadmium and can produce anemia. These elements, in turn,
can decrease zinc absorption if present in sufficient quan-
tities. Use of zinc salt lozenges has been claimed to reduce
the duration of the common cold. However, many random-
ized, double-bind, placebo-controlled trials have failed to
show any beneficial effects of zinc lozenges in reducing
the duration of upper respiratory tract viral infections.
Acrodermatitis enteropathica
(AE) is an autosomal
recessive disorder characterized by defective absorption
of zinc, thickened, ulcerated skin on the extremities and
around body orifices, alopecia, diarrhea, growth failure,
and abnormalities in immune function. The concentration
of zinc in serum and hair is reduced. AE, and a similar
disease of cattle known as adema disease or lethal trait
A-46, respond to large amounts of oral zinc. Malabsorp-
tion of zinc occurs in both the human and animal diseases.
Human milk seems to alleviate AE, presumably because
it provides zinc in a form that can be readily absorbed.
Supplemental Readings and References
J. S. Adams and G. Lee: Gains in bone mineral density with resolution of
vitamin D intoxication.
A n n a ls o f In te rn a l M ed ic in e
127, 203 (1997).
D. G. Barceloux: Manganese.
C lin ica l T oxicology
37, 293 91999).
D. G. Barceloux: Zinc.
C lin ica l T o xico lo g y
37, 279 (1999).
D. Beshgetoor and M. Hambidge: Clinical conditions altering copper
metabolism in humans.
C lin ica l N u tritio n
67, 1017S (1998).
M. J. Bingham, T-J. Ong, K. H. Summer, et al.: Physiologic function of the
Wilson disease gene product, ATP7B.
C lin ica l N u tritio n
67,982S (1998).
A. L. Boskey: Biomineralization: conflicts, challenges, and opportunities.
J o u rn a l o f C ellu la r B io ch em istry S u p p lem en ts
30, 83 (1998).
F. Bronner: Calcium absorption—a paradigm for mineral absorption.
Jo u r-
n a l o f N u tritio n
128,917 (1998).
F. Bronner and D. Pansu: Nutritional aspects of calcium absorption.
J o u rn a l
o f N u tritio n
129, 9 (1999).
D. A. Bushinsky and R. D. Monk: Calcium.
L a n c e t
352, 306 (1998).
S. Chan, B. Gerson, and S. Subramaniam: The role of copper molybdenum,
selenium, and zinc in nutrition and health.
T oxicology
18, 673 (1998).
T. W. Clarkson: Mercury—an element of mystery.
N ew E n g la n d Jo u rn a l o f
M e d icin e
323, 1137 (1990).
A. Cordano: Clinical manifestations of nutritional copper deficiency in in-
fants and children.
C lin ica l N u tritio n
67, 1012S (1998).
H. F. DeLuca and C. Zierold: Mechanisms and functions of vitamin D.
N u tritio n R eview s
56, S4 (1998).
J. S. Duthie, H. P. Solanki, M. Knshnamurthy, et al.: Milk-alkali syn-
drome with metastatic calcification.
A m e rica n J o u rn a l o f M ed icin e
99,
102 (1995).
R. Eastell: Treatment of postmenopausal osteoporosis.
N ew E n g la n d J o u rn a l
o f M ed ic in e
338, 736 (1998).
K. E. Ensrud, D. M. Black, L. Palermo, et al.: Treatment with alendronate
prevents fractures in women at highest risk.
A rch ives o f In te rn a l M ed icin e
157, 2617(1997).
E. Evron, S. Goland, J. von der Walde, et al.: Idiopathic calcitriol-induced
hypercalcemia.
A rch ives o f In te rn a l M ed ic in e
157, 2142 (1997).
D. Feldman: Vitamin D, parathyroid hormone, and calcium: a complex reg-
ulatory network.
A m e rica n J o u rn a l o f M ed icin e
107, 637 (1999).
P. Gamero, W. J. Shih, E. Gineyts, et al.: Comparison of new biochemical
markers of bone turnover late postmenopausal osteoporotic women in
response to alendronate treatment.
J o u rn a l o f C lin ica l E n d o crin o lo g y a n d
M eta b o lism
79,1693 (1994).
F. H. Gloneux, N. J. Bishop, H. Plotkin, et ah: Cyclic administration
of pamidronate in children with severe osteogenesis imperfecta.
N ew
E n g la n d J o u rn a l o f M ed icin e
339, 986 (1998).
G. A. Greendale, N. P. Lee, and E. R. Arriola: The Menopause.
L a n c e t
353,
571 (1999).
J. Guardiola, X. Xiol, R. Sallie, et al.: Influence of the vitamin D receptor
gene polymorphism on bone loss in men after liver transplantation.
A n n a ls
o f In te rn a l M ed ic in e
131, 752 (1999).
J. G. Hall: A bone is not a bone is not a bone.
J o u rn a l o f P ed ia trics
133, 5
(1998).
J. R. Hansford and L. M. Mulligan: Multiple endocrine neoplasia type 2 and
RET: from neoplasia to neurogenesis.
J o u rn a l o f M ed ic a l G en etics
37,
817(2000).
