conspectus of researchon copper metabolism and requirements

COPPER METABOLISM AND REQUIREMENTS OF MAN 2025
What has been outlined in this con
spectus, up to this point, has been an
assessment of past and current knowledge
regarding the role that copper may play in
the metabolism of man, with occasional
reference to ancillary information gained
from observations on laboratory and farm
animals. Attention has been called to the
distribution of copper in the body; the
vast array of cuproproteins and evidence
as to their roles in maintaining functional
and morphological integrity of specific tis
sues and organs; the absorption, transport
and excretion of copper; its omnipresence
in foods; its important roles in prenatal
and postnatal life, and; the nature of states
induced by naturally occurring, experimen
tally induced and congenitally determined
copper deficiency. It is hoped that this
digest of knowledge will provide an ade
quate basis for considerations of the mini
mal copper requirements of man.
In considering human requirements for
copper there are many factors whose in
fluence is exceedingly difficult to evaluate
because of limited knowledge available. A
few examples may be cited. That portion of
dietary copper which is actually absorbed
probably varies considerably, depending
upon its chemical state in the foods con
sumed and the influence of other dietary
components. Best estimates indicate an
absorption of 40 to 60% of the oral intake
(p. 1991). In addition to the unabsorbed
copper and biliary copper components of
the feces, inadequate consideration has
been given to contributions provided by
secretions of the salivary glands, gastric
and intestinal mucosa and pancreas, and
by dehiscence of epithelial cells of intesti
nal villi. At least, the extent of reabsorption
of copper released via these various
pathways has not been clearly determined.
Despite frequent statements in the litera
ture that some of the copper in bile may
be reabsorbed, there exists other evidence
that this copper is so firmly bound to pro
teins that it is not reabsorbed by the gall
bladder or intestinal mucosa in any signifi
cant amounts (266).
Balance studies are limited by the pre
cision with which intake and output can
be measured. For an element such as cop
per which has a slow rate of turnover, a
variable degree of intestinal absorption,
strong homeostatic mechanisms and an
almost exclusive output via the feces, in
terpretations of balance studies becomes
very difficult. The sporadic nature of defe
cation and rather wide individual variation
make balance studies of 7 to 14 days neces
sary for obtaining valid data. Replacement
of carmine by polyethylene glycol 4000, as
a fecal marker, should shorten this time
period (848).
Biological availability is also an impor
tant but largely unknown factor. Little is
known about the chemical nature of cop
per in foods, the extent to which it may
react with chelating substances such as
dietary fiber, or how its absorption may be
influenced by the protein-binding poten
tialities of other trace elements such as zinc
and molybdenum. To these factors must
be added the inflence of acute and chronic
infections, use of antimicrobial agents, dys
function of the gastrointestinal tract and
other stress states. Usually, in well con
ducted copper balance studies on man,
healthy subjects are selected and as many
as possible of the above mentioned in
fluences are eliminated. The discussion to
follow will focus on accumulated evidence
from balance studies and from experiences
with total parenteral nutrition as to what
may represent the minimal requirements
of man for copper during infancy, child
hood and adulthood.
Infants
Specific requirements of healthy human
infants for copper have been difficult to
determine with any degree of accuracy.
To provide a picture of the problem, it
seems appropriate to review current infor
mation with respect to: 1) milk as a source
of copper for the premature and full-term
infant; 2) copper balance studies on in
fants; 3) naturally occurring states of cop
per deficiency; and 4) studies on infants
largely or totally dependent upon total
parenteral nutrition (hyperalimentation )
for extended periods of time.
Milk as a source of copper. It has long
been recognized that the copper content
of human milk is two to three times higher
than that of cow's milk, and that the con
tent of human colostrum is two to three
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