conspectus of researchon copper metabolism and requirements

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2034 KARL E. MASON vegetarian type of diet, differences in cop per content of soil and/or water, contami nation through common use of tinned-cop per cooking utensils, or some combination of these factors can provide an explanation is speculative. The estimated minimal re quirement of 2.0 mg is based upon statisti cal analyses of the balance data ( 154). The data of De ( 154) clearly support observa tions of others (100, 451, 452) that as di etary copper intake increases there is an increase in the amount retained, up to an intake of about 8 mg/day. It should also be noted that in the diets used by Butler and Daniel (84) a mineral and baking powder mix was added, providing at two meals a total of 2.37 mg of copper per day, thus explaining the high levels of intake and output. However, there is no valid basis for their concluding statement that "a copper allowance of 4.5 to 5.0 mg is needed to cover the requirements of all healthy young women, depending on cli matic conditions." The study of Kyer and Bethel (431) is the only known report on copper require ments of the pregnant woman. In view of a 2- to 3-fold increase in serum ceruloplasmin during gestation, presumably attained through calls upon storage depots of the liver and other organs and tissues, an in crease in daily intake of copper to replace this tissue depletion would be anticipated. In this study a healthy young woman was maintained during the last 3 months of her pregnancy and for 2 weeks after delivery on a uniform diet providing a daily intake of about 2.2 mg of copper. At this level of intake she was able to meet normal needs for pregnancy and early lactation. Balance studies carried out during the past 14 years, represented by the last eight listed in table 3, indicate that levels less than 2 mg and sometimes not greatly in excess of 1 mg may maintain positive cop per balance. Such conclusions are in gen eral accord with information provided by parenteral nutrition studies, as discussed in the following section. Nevertheless, it is important to bear in mind that at these low levels of intake there is, as yet, no means of determining to what extent body mechanisms of copper homeostasis may in volve decreases of copper stored in the liver and other tissues of the body. Total parenteral nutrition. The advent of total parenteral nutrition (hyperalimentation) and its application to problems of post-surgical nutrition and gastrointestinal disorders has added greatly to knowledge of copper utilization and requirements. A number of observations which have par ticular relevance to adult human require ments for copper warrant consideration at this point. Shils et al. (712) report the case of an adult male, with bowel resected from the third part of the duodenum to the ascend ing colon, who was maintained in good nutritional status solely on parenteral feed ing for many months. The basic parenteral fluid was essentially devoid of copper, but was supplemented with various trace ele ments which included 0.40 mg copper/day. Bergstrom et al. (45) describe a 43-year old woman suffering from epilepsy and cerebral damage due to CO^. intoxication from a fire, who was maintained for 7 months and 13 days on total parenteral nutrition, with an estimated daily intake of 0.10 mg/day of copper. Perhaps more impressive is similar treat ment of a 36-year old woman during a 10month period in a hospital following resec tion of her intestinal tract between the duodenum and descending colon (790). During her hospitalization she gained 34 pounds. Subsequently, after mastering the technique of administering her parenteral fluids at home, she was able to carry out her household duties effectively. Through out the postoperative period her parenteral solution provided 0.018 mg/day of copper. The only other source of copper, the 100 mg of protein hydrolysate, might have provided about 0.075 mg/day and ac counted for a total intake of 0.093 mg/day. Essentially the same experience, with em ployment of a similar parenteral fluid sup plemented with 0.06 mg/day is reported by Langer et al. (441) in the management of two women, 21 and 34 years of age, fol lowing extensive intestinal resection. These two reports (441, 790) appear to indicate that the minimal daily intravenous require ment for adult man may well be less than the proposed additions of 0.3 to 0.4 mg/day Downloaded from jn.nutrition.org by guest on February 27, 2013
COPPER METABOLISM AND REQUIREMENTS OF MAN 2035 to solutions used for total patenterai nutri tion for prolonged periods (177, 711, 712, 864). To these, of course, must be added the amount contributed by the casein hydrolysate or other protein components of the infÃºsate. These vary considerably in their copper content. Somewhat contrary to these estimates is the report of Mc- Kenzie et al. (511) that in seven adult patients in a surgical intensive care unit a parenteral infÃºsate providing 0.09 to 0.8 mg of copper resulted in a negative bal ance in all cases. Some useful information has also come from studies concerned with copper levels required to compensate for states of cop per deficiency resulting from an inade quacy in parenteral fluids. An excellent example is the study of Vilter et al. (808). In a 56-year old woman with malabsorption and severe systemic sclerosis of the intestine, maintained on total parenteral nutrition for 2.5 months, they observed typical manifestations of copper deficiency. For 4 months she had shown leucopenia, neutropenia and a hypocellular bone mar row, considered typical manifestations of copper deficiency. Serum copper was very low (0.02 fig/ml ) and serum ceruloplasmin was not demonstrable. Intravenous admin istration of 1 mg/day for 7 days resulted in an excellent response, still evident 90 days later. Hence 7 mg of copper sulfate dis tributed over 90 days, equivalent to 0.077 mg of copper per day, represented more than minimal requirements for this woman. Here again, a reasonable estimate of cop per acquired via the protein hydrolysate component might increase the uptake to approximately 0.1 mg/day. Dunlap et al. ( 177) describe a state of copper deficiency in a 45-year old woman and a 12-year old girl receiving long-term parenteral nutrition following extensive bowel surgery. The older subject, after almost total dependence on parenteral feeding for about 17 months, developed anemia and neutropenia which responded rapidly to oral copper sulfate (5 mg CuSO4 or 1.25 mg elemental copper) daily, which was continued for 45 days. With discon tinuation of copper-therapy for about one month, deficiency symptoms were again apparent and responded well to 1.6 mg copper sulfate (0.4 mg/day) given intra venously. After 2 weeks the daily dose was increased to 1 mg copper for 5 weeks. Sub sequently, she was on a parenteral dose of 0.4 mg copper daily and showed no evi dence of recurrence of hÃ©matologieabnor malities. The younger subject, who had been dependent entirely on parenteral nutrition for only 4 months, showed neutro penia (but no anemia) which also re sponded to oral copper therapy. The fact that oral copper was effectively absorbed by both subjects, in whom the duodenum had been anastomosed to the transverse colon, provides additional evidence that the stomach and duodenum play a major role in the absorption of copper in man. Of special interest are the data derived from studies on the older subject clearly indicating that a daily parenteral intake of 0.4 mg of elemental copper effected a rapid recovery from a deficiency state. The observations of Vilter et al. ( 808 ), also carried out on a single adult woman, are in close agreement with those of Dunlap et al. (177). One conclusion that may be justified from these two studies is that the "uncom plicated" minimal intravenous requirement of copper for man may well be less than 0.4 mg per day. By "uncomplicated" is meant under situations where ingested copper is not being subjected to the in fluence of many other components of the diet (other trace elements which compete for binding sites, dietary fiber, phytates, etc.) or may otherwise interfere with maxi mal absorption. Assuming a 40 to 60% ab sorption of oral copper, this would repre sent an oral intake of approximately 1 mg/ day. Two recent examples of the inadequacy of parenteral infusÃ¢tescommonly in use in hospitals can be cited. Weekly serum cop per determinations on eight adult patients receiving total parenteral nutrition for 3 to 13 weeks revealed a progressive decrease of serum copper and three patients showed severe hypocupremia. The infÃºsate had no detectable copper. All responded rapidly to oral copper feeding (217). Another study (726) describes a progressive decline in plasma copper (and also zinc) in 13 sub jects with active gastrointestinal disorders Downloaded from jn.nutrition.org by guest on February 27, 2013
Page 1 and 2:
A CONSPECTUS OF RESEARCH ON COPPER
Page 3 and 4:
INTRODUCTION The discovery of coppe
Page 5 and 6: COPPER METABOLISM AND REQUIREMENTS
Page 53 and 54: s &5Â°.S0 0lÃ¬Â»"oPH o^â€
Page 55: Ã®1co 1stW Â»aÂ«a3 COPPER MET
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