conspectus of researchon copper metabolism and requirements

INTRODUCTION
The discovery of copper, following that
of gold and silver, goes back to the post
glacial epoch in southwestern Asia, espe
cially the semi-arid regions of Central
Anatolia and Iran, during the period 6000
to 3000 B.C. (834). The later Bronze Age
(3000-1000 B.C.) takes its name from the
use during this period of bronze, an alloy
of copper and tin. The word copper is de
rived from the Latin cuprum, a corrup
tion of cyprium, named after the island of
Cyprus which was an important source of
copper about 3000 B.C. Thus, aside from
gold and silver, which were employed
chiefly for ornamental purposes, copper
represents the first metal to be used by
mankind for more practical purposes. The
alloys of copper and tin (bronze), copper
and zinc (brass), and of copper, zinc and
nickel (nickel silver or German silver),
have had a tremendous impact upon
human development over many past
centuries.
Beginning about the time of Hippocrates
(400 B.C.) copper compounds were com
monly prescribed in the treatment of men
tal, pulmonary and other diseases. During
the 19th century many different copper
compounds came into use in the unsuc
cessful treatment of a wide variety of
human diseases (447). Copper amulets
were also in vogue. Not until about 150
years ago was copper recognizd as a nor
mal constituent of blood. And as early as
1900, Abderhalden (1) recorded that ani
mals kept on a whole milk diet developed
an anemia that could not be prevented by
additions of inorganic iron, and recog
nized the fact that some other mysterious
substance, probably organic, was wanting.
But the thought that copper should ever
be considered an important component of
the diet for either animals or man was
quite remote until the second decade of
this century, following closely on the heels
of the discovery of vitamins A, B, C, D
and E. At this time there appeared the
reports of Hart et al. (311, 312) and Waddell
et al. (812) corroborating the obser
vations of Abderhalden and indicating that
1981
either extracts or the ash of dried cabbage,
corn meal and chlorophyll, all essentially
iron-free, definitely favored assimilation
and utilization of iron in hemoglobin build
ing in rabbits fed a whole milk diet. Also,
at about this same time, McHargue (507)
recorded results of studies on rats fed puri
fied diets deficient in copper, zinc and/or
manganese in which he employed impro
vised glass-lined cages. This represents the
first known use of cages of this type. Mc
Hargue concluded that manganese in par
ticular, and possibly copper and zinc, have
important functions in animal metabolism.
There followed the classic studies of
Hart, Steenbock, Waddell and Elvehjem
(313) demonstrating that rats fed ex
clusively on milk developed an anemia
which was responsive to iron only after the
addition of copper; also, that the same
relationships prevailed in chicks fed diets
of milk and rice ( 187). Later came evi
dence from experimental studies with pigs
( 188) that whereas impure organic salts of
iron cured nutritional anemia, the pure
salts failed to do so unless supplemented
with small amounts of copper. Recognition
of the clinical importance of these early
observations was first given by Mills (520,
521) and Josephs (389) who reported that
copper supplements accelerated hemo
globin synthesis in hypochromic anemia of
infants treated with iron salts. Although
several investigators were not in agree
ment (274, 275, 476), others confirmed
these findings (186, 399, 455, 799) and ex
tended them to hypochromic microcytic
anemia of adults (521). The early history
and later developments are detailed in
several reviews (99, 540, 693). During this
same period appeared Tompsett's report
( 785 ) of the first copper balance study car
ried out on 17 human subjects, indicating
that the normal daily intake appeared to
vary from 2.0 to 2.5 mg/day. In the same
Received for publication October 16, 1978.
1 Requests for reprints should be directed to Nutri
tion Institute. Science and Education Administration,
Building 307. Room 217, USDA. Beltsville. Maryland
20705.
- Deceased December S. 1978.
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