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(Journal of Nutrition. 1999;129:2278-2279.)
© 1999 The American Society for Nutritional Sciences

Article

Cupric Oxide Should Not Be Used As a Copper Supplement for Either Animals or Humans

David H. Baker

Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana, IL 61801


   INTRODUCTION
TOP
 INTRODUCTION
REFERENCES
 
Animal studies have shown conclusively that the copper (Cu) in analytical-grade cupric oxide (CuO) is unavailable for absorption from the gut (Aoyagi and Baker 1993Citation , Baker et al. 1991Citation , Cromwell et al. 1989Citation , Ledoux et al. 1991Citation ). In fact, the bioavailability of Cu in CuO relative to that in CuSO4 · 5H2O is not significantly different from zero (Aoyagi and Baker 1993Citation ). This finding was important in animal nutrition because before 1990, CuO was the primary source of Cu used in trace-mineral premixes for swine, poultry and companion animals. It was popular because among the Cu sources available in feed-grade form, CuO (80% Cu) was high in Cu and therefore occupied less "space" in trace-mineral premixes.

Cupric oxide continues to be the principal source of Cu used in vitamin-mineral supplements for humans. Because these supplements are provided as tablets, CuO with its high concentration of Cu, occupies less space in the tablet than would CuSO4 · 5H2O (25% Cu), yet it seems gratuitous that this form of Cu is still being used when the animal studies have shown so conclusively that the Cu in CuO is very poorly utilized. In a recent survey of pharmacies, supermarkets and supplement stores, I found only a few (among many) vitamin-mineral products that contained Cu in a form other than CuO. Interestingly, a similar survey of mineral-fortified food products revealed that almost all that contained added Cu used CuSO4 · 5H2O as the source of Cu. Virtually all infant formulas and enteral products contain supplemental Cu, and most of these products use CuSO4 · 5H2O. Among common Cu sources used as supplements, CuSO4 · 5H2O is somewhat unusual in that it is readily soluble in water (cupric chloride and cupric acetate are the other common Cu sources that are water soluble). As shown in TableCitation 1, solubility of Cu salts in either water or acid is not a reliable measure of bioavailability. Cuprous oxide, for example, is very insoluble in both water and acid, but the Cu in this compound is as bioavailable as that in CuSO4 · 5H2O.


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  		Table 1. Solubility characteristics and relative bioavailability of copper sources based on chick bioassays

 
Cupric oxide is no longer used as a Cu supplement in animal nutrition, but it continues to be used in vitamin-mineral supplements (tablets) for humans. Teenagers and adults consuming energy-restricted diets often rely on supplements to ensure that vitamin and mineral requirements are being met. It seems possible that such individuals may be Cu deficient, because the CuO in the tablet they are taking is not providing bioavailable Cu. A diet recall survey of 400 rural women in Illinois conducted by Reber et al. (1990)Citation showed that 90% of their sample of women who consumed fewer then 7.53 MJ/d were ingesting <1.5 mg Cu/d, the lower limit of a safe and adequate Cu intake as suggested by the Food and Nutrition Board of the National Academy of Sciences (NRC 1989Citation ). Klevay and Medeiros (1996)Citation and Klevay (1998)Citation reported that 61% of the diets in Canada, Belgium, the U.K. and the U.S. provide <1.5 mg Cu/d, and almost one third provide <1 mg Cu/d. Low Cu intakes have been implicated in ischemic heart disease and osteoporosis; control of blood pressure, cholesterol and glucose metabolism also require adequate intakes of Cu (Klevay, 1998Citation ).

Unfortunately, reliable noninvasive procedures to assess Cu status in humans are not available. For this reason, there is no RDA for Cu, only a suggested adequate intake level of 1.5–3.0 mg/d for adults (NRC 1989Citation ). It is well established that high zinc, ascorbic acid and cysteine intakes reduce Cu absorption (Aoyagi and Baker 1994Citation , Baker and Czarnecki-Maulden 1987Citation , Di Silvestro and Harris 1981Citation , Hill and Starcher 1965Citation , Magee and Matrone 1962Citation , Milne and Omaye 1980Citation , Murthy et al. 1974Citation , Van Campen and Gross, 1968Citation , Van Campen and Scaife 1967Citation , Van Den Berg and Beynen 1992Citation ). A scenario could be suggested in which a segment of the population was restricting energy intake and also consuming megadoses of ascorbic acid and zinc together with a vitamin-mineral supplement containing CuO. It seems likely that such individuals would be Cu deficient.

Manufacturers of vitamin-mineral supplements should discontinue use of CuO as a source of Cu. Other Cu compounds are available that provide utilizable forms of Cu. Among these, Cu2O (88% Cu), CuCl (64.2% Cu), CuCO3 · Cu(OH)2, known as alkaline Cu carbonate (57% Cu), CuCl2 (47.3% Cu), cupric acetate (35.0% Cu) and CuSO4 · 5H2O (25.5% Cu) would be good choices. Clearly, chemical, physical and organoleptic properties of Cu salts must be considered. The resulting pill or tablet may be larger, but at least it will furnish Cu in a form that can be utilized.

Manuscript received July 19, 1999. Initial review completed August 6, 1999. Revision accepted August 23, 1999.


   REFERENCES
TOP
 INTRODUCTION
 REFERENCES
 

1. Aoyagi S., Baker D. H. Bioavailability of copper in analytical-grade and feed-grade inorganic copper sources when fed to provide copper at levels below the chicks requirement. Poult. Sci. 1993;72:1075-1083[Medline]

2. Aoyagi S., Baker D. H. Copper-amino acid complexes are partially protected against inhibitory effects of L-cysteine and L-ascorbate. J. Nutr. 1994;124:388-395

3. Baker D. H., Ammerman C. B. Copper bioavailability. Ammerman C. B. Baker D. H. Lewis A.J. eds. Bioavailability of Nutrients for Animals: Amino Acids, Minerals, and Vitamins 1995:127-156 Academic Press San Diego, CA.

4. Baker D. H., Aoyagi S. Trace mineral update for poultry: copper, zinc and manganese utilization. Proceedings of the Arkansas Nutrition Conference 1993:127-135 Fayetteville AR.

5. Baker D. H., Czarnecki-Maulden G. L. Pharmacologic role of cysteine in ameliorating or exacerbating mineral toxicities. J. Nutr. 1987;117:1003-1010

6. Baker D. H., Odle J., Funk M. A., Wieland T. M. Bioavailability of copper in cupric oxide, cuprous oxide and in a copper-lysine complex. Poult. Sci. 1991;70:177-179[Medline]

7. Cromwell G. L., Stahly T. S., Monegue H. J. Effects of source and level of copper on performance and liver copper stores in weanling pigs. J. Anim. Sci. 1989;67:2996-3002

8. Di Silvestro R. A., Harris E. D. A postabsorptive effect of L-ascorbic acid on copper metabolism in chicks. J. Nutr. 1981;111:1964-1968

9. Hill C. H., Starcher B. Effect of reducing agents on copper deficiency in the chick. J. Nutr. 1965;85:271-274[Medline]

10. Klevay L. M. Lack of a recommended dietary allowance for copper may be hazardous to your health. J. Am. Coll. Nutr. 1998;17:322-326[Abstract/Free Full Text]

11. Klevay L. M., Medeiros D. M. Deliberations and evaluations of the approaches, endpoints and paradigms for dietary recommendations about copper. J. Nutr. 1996;126:2419S-2426S

12. Ledoux D. R., Henry P. R., Ammerman C. B., Rao P. V., Miles R. D. Estimation of the relative bioavailability of inorganic copper sources for chicks using tissue uptake of copper. J. Anim. Sci. 1991;69:215-222[Abstract]

13. Magee A. C., Matrone G. Studies on growth, copper metabolism and iron metabolism of rats fed high levels of zinc. J. Nutr. 1962;72:233-242

14. Milne D. B., Omaye S. T. Effects of vitamin C on copper and iron metabolism in the guinea pig. Int. J. Vitam. Nutr. Res. 1980;50:301-308[Medline]

15. Murthy L., Klevay L. M., Petering H. G. Interrelationships of zinc and copper nutriture in the rat. J. Nutr. 1974;104:1458-1465

16. National Research Council Recommended Dietary Allowances 10th ed. 1989 National Academy Press Washington, DC.

17. Reber, R. J., Pankau, J. W. & Misner, J. E. (1990) Nutritional intakes of middle-aged women. University of Illinois Extension Publication no. 10, pp. 1–13. Urbana, IL.

18. Van Campen D., Gross E. Influence of ascorbic acid on the absorption of copper by rats. J. Nutr. 1968;95:617-622

19. Van Campen D. R., Scaife P. U. Zinc interference with copper absorption in rats. J. Nutr. 1967;91:473-476

20. Van Den Berg G. J., Beynen A. C. Influence of ascorbic acid supplementation on copper metabolism in rats. Br. J. Nutr. 1992;68:701-715[Medline]




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