Abstract
Pharmacological doses of zinc can adversely affect body copper status. The resulting copper deficiency can impact directly upon cholesterol metabolism and a suboptimal copper status has been observed to influence markers of hemostasis (specifically fibrinogen and the copper-containing coagulation factors V and VIII). The aim of this investigation was to examine the effect of a low level of zinc supplementation, to include dietary intake, at the United States tolerable upper intake level of 40 mg/d upon indicators of lipid metabolism, hemostasis, and copper. Thirty-eight subjects were recruited onto a double-blind placebo-controlled intervention trial and randomly selected to one of two groups. Group 1 took zinc supplements (30 mg/d) for 14 wk followed by copper supplements (3 mg/d) for 8 wk (to counteract adverse effects, if any, of zinc supplementation). A second group took placebo supplements for the full duration of the trial. Estimated dietary zinc intake approximated 10 mg/d. The effect of supplement was analyzed by repeated-measures analysis of variance (anova). Results indicate that no effect of zinc supplementation on putative indices of copper status, lipoprotein metabolism, and markers of hemostasis. These results indicate that short-term low-level zinc supplementation (total intake 40 mg/d) is not detrimental to health.
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A. S. Prasad, G. J. Brewer, E. R. Schoomaker, et al., Hypocupraemia induced by zinc therapy in adults, J. Am. Med. Assoc. 240, 2166–2168 (1978).
K. G. Porter, D. McMaster, M. E. Elmes, et al., Anaemia and low serum copper during zinc therapy, Lancet 2, 774 (1977).
H. N. Hoffman II, R. L. Phyliky, and C. R. Fleming, Zinc-induced copper deficiency, Gastroenterology 94, 508–512 (1988).
W. K. Patterson, B. A. Winkelmann, and Perry MC, Zinc-induced copper deficiency: megamineral sideroblastic anemia, Ann. Intern. Med. 103, 385–386 (1985).
L. M. Klevay, Elements of ischemic heart disease, Perspect. Biol. Med. 20, 186–192 (1977).
D. M. Mederios, Hypertension in the Wistar-Kyoto rat as a result of post-weaning copper restriction, Nutr. Res. 7, 231–235 (1987).
S. Reiser, A. Powel, C. Y. Yang, et al., Effect of copper intake on blood cholesterol and its lipoprotein distribution in men, Nutr. Rep. Int. 36, 641–649 (1987).
L. M. Klevay, W. K. Cranfield, S. K. Gallagher, et al., Decreased glucose tolerance in 2 men during experimental copper depletion, Nutr. Rep. Int. 33, 371–382 (1986).
M. R. Black, D. M. Medeiros, E. Brunett, et al., Zinc supplements and serum lipids in young adult white males, Am. J. Clin. Nutr. 47, 970–975 (1988).
P. L. Hooper, L. Visconti, P. J. Garry, et al., Zinc lowers high density lipoprotein-cholesterol levels, J. Am. Med. Assoc. 224, 1960–1961 (1980).
J. C. Godfrey, B. Conant-Sloane, D. S. Smith, et al., Zinc gluconate and the common cold: a controlled clinical trial, J. Intern. Med. Res. 20, 234–246 (1992).
S. B. Mossad, M. L. Macknin, S. V. Medendorp, et al., Zinc gluconate lozenges for treating the common cold in children: a randomised, double-blinded, placebo-controlled trial, Ann. Intern. Med. 125, 81–88 (1996).
J. Duchateau, G. Delepesse, R. Vrijens, et al., Beneficial effects of oral zinc supplementation on the immune response of old people, Am. J. Med. 70, 1001–1004 (1981).
Institute of Medicine, Food and Nutrition Board, Dietary Reference Intakes: Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium and Zinc, National Academy Press. Washington DC (2001).
H. H. Sandstead and S. Smith Jr, Deliberations and evaluations of approaches, end-points and paradigms for determining zinc dietary recommendations, J. Nutr. 126, 2410s–2418s (1996).
H. H. Sandstead, Requirements and toxicity of essential trace elements illustrated by zinc and copper, Am. J. Clin. Nutr. 61, 621s–624s (1995).
D. B. Milne, C. D. Davis, and F. H. Nielsen, Low dietary zinc alters indices of copper function and status in post-menopausal women, Am. J. Clin. Nutr. 17, 701–708 (2001).
S. Samman and D. C. K. Roberts, The effect of zinc supplements on lipoproteins and copper status, Atherosclerosis 70, 247–252 (1988).
J. H. Freeland-Graves, B. J. Friedman, W. H. Han, et al., Effect of zinc supplementation on plasma high-density lipoprotein cholesterol and zinc, Am. J. Clin. Nutr. 35, 988–992 (1982).
S. M. Lynch and L. M. Klevay, Effects of dietary Cu deficiency on plasma coagulation factor activities in male and female mice, J. Nutr. Biochem. 3, 387–391 (1992).
J. J. Mann, C. M. Lawler, G. A. Vehar, et al., Coagulation factor V contains Cu ion, J. Biol. Chem. 259, 12,949–12,951 (1984).
N. Bihoreau, S. Pin, A. de Kersabiec, et al., Cu-atom identification in active site and inactive forms of plasma-derived factor VIII and recombinant factor VIII-II, Eur. J. Biochem. 220, 41–48 (1994).
W. R. Church, R. L. Jernigan, J. Toole, et al., Coagulation factors V and VIII and ceruloplasmin constitute a family of structurally related proteins, Proc. Natl. Acad. Sci. USA 81, 6934–6937 (1984).
S. M. Lynch and L. M. Klevay, Effect of dietary Cu deficiency on plasma fibrinolytic activity in male and female mice, Nutr. Res. 13, 913–922 (1993).
H. Crawley, Food Portion Sizes, 3rd ed., Her Majesty’s Stationary Office, London (1992).
R. J. Henry, N. Chiamori, J. L. Jacobs, et al., Determination of ceruloplasmin oxidase in serum, Proc. Soc. Exp. Biol. Med. 104, 620–624 (1960).
J. Calvin and C. P. Price CP, Measurement of alpha 1 antichymotrypsin by immunoturbidity, Ann. Clin. Biochem. 23, 296–299 (1986).
D. G. Jones and N. F. Suttle, Some effects of copper deficiency on leukocyte function in cattle and sheep, Res. Vet. Sci. 31, 151–156 (1981).
Department of Health, Dietary Reference Values for Food Energy and Nutrients for the United Kingdom, Her Majesty’s Stationary Office, London (1991).
L. M. Gatto and S. Samman, The effect of zinc supplementation on plasma lipids and low-density lipoprotein oxidation in males, Free Radical Biol. Med. 19, 517–521 (1995).
P. R. Gordon and B. L. O’Dell, Short-term zinc deficiency and hemostasis in the rat, Proc. Soc. Exp. Biol. Med. 163, 240–244 (1980).
P. R. Gordon and B. L. O’Dell, Zinc deficiency and impaired platelet aggregation in guinea pigs, J. Nutr. 113, 239–245 (1983).
P. R. Gordon, C. W. Woodruff, H. L. Anderson, et al., Effect of acute zinc deprivation on plasma zinc and platelet aggregation in adult males, Am. J. Clin. Nutr. 35, 113–118 (1982).
G. Marx and A. Eldor, The procoagulant effect of zinc on fibrin clot formation, Am. J. Hematol. 19, 151–159 (1985).
D. R. Van Campen and P. V. Scaife, Zinc interference with copper absorption in rats, J. Nutr. 91, 473–476 (1967).
L. M. Klevay, Hypercholesterolemia in rats produced by an increase in the ratio of zinc to copper ingested, Am. J. Clin. Nutr. 26, 1060–1068 (1973).
L. M. Klevay, W. G. Pond, and D. M. Medeiros, Decreased high density lipoprotein cholesterol and apoprotein A-I in plasma and ultrastructural pathology in cardiac muscle of young pigs fed a diet high in zinc, Nutr. Res. 8, 1227–1239 (1994).
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Bonham, M., O’Connor, J.M., McAnena, L.B. et al. Zinc supplementation has no effect on lipoprotein metabolism, hemostasis, and putative indices of copper status in healthy men. Biol Trace Elem Res 93, 75–86 (2003). https://doi.org/10.1385/BTER:93:1-3:75
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DOI: https://doi.org/10.1385/BTER:93:1-3:75