conspectus of researchon copper metabolism and requirements

2028 KARL E. MASON
quirements of 0.077 to 0.11 mg/kg body
weight for growing pigs (772). In later
studies on 21 similar infants 4 to 19 months
of age ( 128), daily supplements of greater
than 0.15 mg/kg proved quite adequate
to correct for neutropenia, considered to be
the earliest manifestation and most sensi
tive indicator of adequacy of treatment
of copper deficiency in man. Subsequently,
oral supplements of 2.5 mg/day were
usually employed as a routine measure to
assure much more than estimated require
ments (276).
On the basis of his personal experiences,
Cordano (124, 125) recommends that
manufactured formulas for premature in
fants be supplemented with copper such
as to provide 0.09 mg/100 kcal, rather than
the 0.06 mg/100 kcal recommended by the
Committee on Nutrition of the American
Academy of Pediatrics (19) which, since
then, has recognized this need. This pro
vides approximately 0.1 mg/kg/day, and
is somewhat less than the supplement of
0.1 to 0.5 mg/day proposed by Ashkenazi
et al. (25) for prematures subsisting on
milk only. In such considerations there has
been recognized a need to make provision
for such commonplace factors as intestinal
interactions between copper and iron in
iron-fortified formulas (700), régurgita
tion, prolonged diarrhea and infections. On
the basis of the evidence presented, it
seems that the daily requirement of cop
per for young and reasonably healthy in
fants may be met by daily intakes of 0.05
to 0.1 mg/kg/day.
Total parenteral nutrition. The develop
ment of a procedure for providing "total
Sarenteral nutrition" by means of an injsate
of nutrients introduced via an in
dwelling catheter inserted into a large cen
tral vein by Dudrick et al. (176 )and Wilmore
et al. (852, 853) ushered in a new
era in therapeutic nutrition. Its original
application in conjunction with surgical
treatment of catastrophic gastrointestinal
anomalies of infants has since been widely
extended to the management of a variety
of gastrointestinal disorders, burns, infec
tions and other situations in which subjects
are unable to meet nutritional needs by the
oral route. By appropriate modifications,
this procedure has been effectively ex
tended from its hospital applications to
the prolonged maintenance of subjects in
the home environment (66, 304, 385, 441,
711, 724). Total parenteral nutrition, espe
cially when prolonged in infants and
adults, has provided much new and help
ful information concerning copper require
ments of man.
However, problems arise in the interpre
tation of the results. One must first assume
that copper introduced parenterally sub
stitutes for that portion of orally ingested
copper absorbed by the intestinal tract and
transported to the liver and to the systemic
vascular system. While, as discussed pre
viously (p. 1991), it is generally accepted
that roughly 40 to 60% of ingested copper
is absorbed, wide individual variations
exist, due to differences in gastrointestinal
functions, nature of the diet, derangements
of metabolism and states of stress.
It is noteworthy that in their classic
studies with infants, Dudrick et al. (175,
176) and Wilmore et al. (853) took care
to provide in their parenteral fluids both
vitamins and minerals. The latter included
zinc, copper, manganese, cobalt and iodine.
Copper was provided at a level of 0.22
mg/kg body weight. This represents a
rather generous supply when compared to
estimated requirements of 0.05 to 0.10 mg/
kg/day. In any case, failure to follow these
guidelines resulted in occurrence of sev
eral cases of copper deficiency in infants
(25, 394, 463) and in adults (177, 808).
Although traces of copper are present in
fibrin and casein hydrolysates and in crys
talline amino acid mixtures commonly used
in parenteral solutions, direct analyses (57,
317, 342, 590) demonstrate their variability
and inadequacy to meet nutritional needs
for copper. The proposed use of plasma
transfusions given twice weekly (209 ) does
not compensate for this (704). What is
said of copper is also true of zinc (57, 342,
590 ). Investigators now add trace elements
to the basic hyperalimentation formulae
(174, 214, 367, 382, 383, 709, 710, 712,
724) providing copper in approximately
the amount (0.22 mg/kg body weight)
originally proposed by Wilmore et al.
(853). Essentially the same supplement is
recommended by Ricour et al. (639),
Wretling (864) and by Karpel and Peden
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