Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Communication
  • Published:

A moderately high intake compared to a low intake of zinc depresses magnesium balance and alters indices of bone turnover in postmenopausal women

Abstract

Objective: To determine whether moderately high or low intakes of zinc adversely affect the copper status of postmenopausal women to result in unfavorable changes in calcium and magnesium metabolism and other indicators of bone turnover.

Design: After a 10-day equilibration period in which the diet provided 31.5 μmol (2 mg) Cu and 137.7 μmol (9 mg) Zn/8.4 MJ (2000 kcal), the subjects were randomly divided into two groups, with one group fed the basal diet supplemented to provide15.7 μmol (1 mg) Cu/8.4 MJ, and the other group fed the same diet supplemented to provide 47.2 μmol (3 mg) Cu/8.4 MJ. After equilibration, both groups were fed the basal diet with no zinc supplemented (provided 45.9 μmol [3 mg] Zn/8.4 MJ) for 90 days; this was followed by another 10-day equilibration period before the basal diet was supplemented with zinc to provide 811 μmol (53 mg)/8.4 MJ for 90 days.

Setting: The metabolic unit of the Grand Forks Human Nutrition Research Center, Grand Forks, ND, USA.

Subjects: A total of 28 postmenopausal women recruited by advertisement throughout the United States of America. Among them, 25 women (64.9+6.7 y) completed the study; 21 as designed.

Results: The moderately high intake compared to the low intake of zinc increased the excretion of magnesium in the feces and urine, which resulted in a decreased magnesium balance. In the women fed low dietary copper, plasma osteocalcin was higher during the low-zinc than high-zinc dietary period. The urinary excretion of N-telopeptides was increased and the serum calcitonin concentration was decreased by high dietary zinc regardless of dietary copper.

Conclusions: A moderately high intake of zinc (811 μmol/day; 53 mg/day) did not induce changes in copper metabolism that resulted in unfavorable changes in bone or mineral metabolism. However, low dietary zinc (45.9 μmol/day; 3 mg/day) apparently resulted in undesirable changes in circulating calcitonin and osteocalcin. As a moderately high intake of zinc decreased magnesium balance, further study of the possibility that a high intake of zinc is a health concern for individuals consuming less than the recommended amounts of magnesium is warranted.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  • Aggett PJ, Crofton RW, Khin C, Gvozdanovic S & Gvozdanovic D (1983): The mutual inhibitory effects on their bioavailability of inorganic zinc and iron. In Zinc Deficiency in Human Subjects, eds AS Prasad, A Cadvar, GJ Brewer & PJ Aggett, pp 117–124. New York: Alan R, Liss.

    Google Scholar 

  • Analytical Methods Committee (1990): Methods of destruction of organic matter. Analyst 85, 642–656.

  • Bauer DC (2001): Biochemical markers of bone turnover: the study of osteoporotic fracture. In Bone Markers: Biochemical and Clinical Perspectives (Proc Meeting 2000), ed. R Eastell, pp 219–223. London: Martin Dunitz.

    Google Scholar 

  • Brewer GJ (2000): Raulin Award Lecture: Wilson's disease therapy with zinc and tetrathiomolybdate. J. Trace Elem. Exp. Med. 13, 51–61.

    Article  CAS  Google Scholar 

  • Christenson RH (1997): Biochemical markers of bone metabolism: an overview. Clin. Biochem. 30, 573–593.

    Article  CAS  Google Scholar 

  • Danks DM (1988): Copper deficiency in humans. Ann. Rev. Nutr. 8, 235–257.

    Article  CAS  Google Scholar 

  • Davis CD, Milne DB & Nielsen FH (2000): Changes in dietary zinc and copper affect zinc-status indicators of postmenopausal women, notably extracellular superoxide dismutase and amyloid precursor proteins. Am. J. Clin. Nutr. 71, 781–788.

    Article  CAS  Google Scholar 

  • Dimai HP, Hall SL, Stilt-Coffing B & Farley JR (1998): Skeletal response to dietary zinc in adult female mice. Calcif. Tissue Int. 62, 309–315.

    Article  CAS  Google Scholar 

  • Donangelo CM, Woodhouse LR, King SM, Viteri FE & King JC (2002): Supplemental zinc lowers measures of iron status in young women with low iron reserves. J. Nutr. 132, 1860–1864.

    Article  CAS  Google Scholar 

  • Eaton-Evans J, McIlrath EM, Jackson WE, McCartney H & Strain JJ (1996): Copper supplementation and the maintenance of bone mineral density in middle-aged women. J. Trace Elem. Exp. Med. 9, 87–94.

    Article  CAS  Google Scholar 

  • Fischer PWF, Giroux A & L’Abbe MR (1984): Effect of zinc supplementation on copper status in adult man. Am. J. Clin. Nutr. 40, 743–746.

    Article  CAS  Google Scholar 

  • Food and Nutrition Board (1989): Recommended Dietary Allowances, 10th edition. Washington, DC: National Academy Press.

  • Food and Nutrition Board (1997): Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press.

  • Food and Nutrition Board (2001): Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press.

  • Fox MRS, Tao S-H, Fry Jr BE & Lee YH (1988): Production of Mg deficiency anemia by Zn and phytate in young Japanese quail. In Trace Elements in Man and Animals, Vol 6, eds LS Hurley, CL Keen, B Lonnerdal & RB Rucker, pp 575–576. New York: Plenum Press.

    Chapter  Google Scholar 

  • Harris JA & Benedict FG (1919): A Biometric Study of Basal Metabolism in Men. Carnegie Publication No. 279. Philadelphia: JB Lippincott.

    Google Scholar 

  • Hurley LS (1981): Teratogenic aspects of manganese, zinc, and copper nutrition. Physiol. Rev. 61, 249–295.

    Article  CAS  Google Scholar 

  • Kenny MA & McCoy H (1997): Adding zinc reduces bone strength of rats fed a low-calcium diet. Biol. Trace Elem. Res. 58, 35–41.

    Article  Google Scholar 

  • Leonhard MS (1999): Do forestomach epithelia exhibit a Mg2+/2H+-exchanger? Magnesium Res. 12, 99–108.

    Google Scholar 

  • McCarroll NA (1993): Bone disorders (osteoporosis). Anal. Chem. 65, 388R–395R.

    Article  CAS  Google Scholar 

  • McCoy H, Kenney MA & Williams L (1992): Low magnesium diet depresses HDL cholesterol in rats. FASEB J. 6, A1666.

    Google Scholar 

  • Milne DB, Davis CD & Nielsen FH (2001): Low dietary zinc alters indices of copper function and status in postmenopausal women. Nutrition 17, 701–708.

    Article  CAS  Google Scholar 

  • Peretz A, Bergmann P, Papadopoulos T, Siderova V & Neve J (2000): Effect of zinc supplementation on biological parameters of bone turnover in healthy men. In Trace Elements in Man and Animals, Vol. 10, eds AM Roussel, RA Anderson & AE Favier, pp 1009–1012. New York: Kluwer Academic/Plenum Publishers.

    Google Scholar 

  • Sandstead HH (1995): Requirements and toxicity of essential trace elements, illustrated by zinc and copper. Am. J. Clin. Nutr. 61 (Suppl), 621S–624S.

    Article  CAS  Google Scholar 

  • Saris N-EL, Krestinina OV, Azarashvili TS, Odinokova IV, Tyynela J & Evtodienko YuV (2001): Regulation of ATP synthase by Ca2+ and Mg2+-dependent phosphorylation of subunit c. In Advances in Magnesium Research. Nutrition and Health, eds Y Rayssiguier, A Mazur & J Durlach, pp 101–106. Eastleigh, England: John Libbey.

    Google Scholar 

  • Shaul O, Hilgemann DW, Almeida-Engler J, Van Montagu M, Inze D & Galili G (1999): Cloning and characterization of a novel Mg2+/H+ exchanger. EMBO J. 18, 3973–3980.

    Article  CAS  Google Scholar 

  • Sims RL, Mullen LM & Milne DB (1990): Application of inductively coupled plasma emission spectroscopy to multielement analysis of foodstuffs used in metabolic studies. J. Food Compos. Anal. 3, 27–37.

    Article  CAS  Google Scholar 

  • Song MK, Adham NF & Ament ME (1986): Levels and distribution of zinc, copper, magnesium, and calcium in rats fed different levels of dietary zinc. Biol. Trace Elem. Res. 11, 75–88.

    Article  CAS  Google Scholar 

  • Spencer H, Rubio N, Kramer L, Norris C & Osis D (1987): Effect of zinc supplements on the intestinal absorption of calcium. J. Am. Coll. Nutr. 6, 47–51.

    Article  CAS  Google Scholar 

  • Starcher BC, Hill CH & Madaras JG (1980): Effect of zinc deficiency on bone collagenase and collagen turnover. J. Nutr. 110, 2095–2102.

    Article  CAS  Google Scholar 

  • Strain JJ (1998): Copper and postmenopausal osteoporosis. In Copper and Zinc in Inflammatory and Degenerative Diseases, eds KD Rainsford, R Milanino, JRJ Sorenson & GP Velo, pp 173–178. Lancaster: Kluwer Academic Publishers.

    Chapter  Google Scholar 

  • Strause L, Saltman P, Smith KT, Bracker M & Andon MB (1994): Spinal bone loss in postmenopausal women supplemented with calcium and trace minerals. J. Nutr. 124, 1060–1064.

    Article  CAS  Google Scholar 

  • Tanimoto H, Lau K-HW, Nishimoto SK, Wergedal JE & Baylink DJ (1991): Evaluation of the usefulness of serum phosphatases and osteocalcin as serum markers in a calcium depletion-repletion rat model. Calcif. Tissue Int. 48, 101–110.

    Article  CAS  Google Scholar 

  • Tiegs RD, Body JJ, Wahner HW, Barta J, Riggs BL & Heath III H (1985): Calcitonin secretion in postmenopausal osteoporosis. N. Engl. J. Med. 312, 1097–1100.

    Article  CAS  Google Scholar 

  • Uauy R, Olivares M & Gonzalez M (1998): Essentiality of copper in humans. Am. J. Clin. Nutr. 67 (Suppl), 952S–959S.

    Article  CAS  Google Scholar 

  • Uehara M, Chiba H, Fujii A, Matsuzaki H, Masuyama R & Suzuki K (2001): Induction of phospholipid hydroperoxides in relation to change of tissue mineral distribution caused by magnesium-deficiency in rats. In Advances in Magnesium Research. Nutrition and Health, eds Y Rayssiguier, A Mazur & J Durlach, pp 291–296. Eastleigh, England: John Libbey.

    Google Scholar 

  • Walsh CT, Sandstead HH, Prasad AS, Newberne PM & Fraker PJ (1994): Zinc: health effects and research priorities for the 1990s. Environ. Health Perspect. 102 (Suppl. 2), 5–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yadrick MK, Kenny MA & Winterfeldt EA (1989): Iron, copper, and zinc status: response to supplementation with zinc or zinc and iron in adult females. Am. J. Clin. Nutr. 49, 145–150.

    Article  CAS  Google Scholar 

  • Yamaguchi M (1998): Role of zinc in bone formation and bone resorption. J. Trace Elem. Exp. Med. 11, 119–135.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr Craig Boreiko and the International Lead Zinc Research Organization for financial support, LuAnn Johnson for statistical support, and Mary Rydell for manuscript preparation and handling. We also thank the members of the Grand Forks Human Nutrition Research Center clinical staff whose special talents and skills made this study possible: Leslie Klevay (medical supervision), James Penland (psychological supervision), Henry Lukaski (exercise physiology), Bonita Hoverson and staff (dietary), Sandra Gallagher and staff (clinical chemistry and metabolic unit), and Terrence Shuler and staff (mineral analysis).

Author information

Authors and Affiliations

Authors

Contributions

The US Department of Agriculture, Agricultural Research Service, Northern Plains Area, is an equal opportunity/affirmative action employer, and all agency services are available without discrimination. Mention of a trademark or proprietary product does not constitute a guarantee or warranty by the US Department of Agriculture and does not imply its approval to the exclusion of other products that also might be suitable. This study was supported in part by the International Lead Zinc Organization. Portions of these data were presented at the VIth Conference of the International Society for Trace Element Research In Humans, Quebec City, Quebec, Canada, and published in abstract form (J. Trace Elem. Exp. Med. 14, 286–287, 2001).

Contributors: The study was designed and supervised by DBM and FHN. The paper was written by FHN.

Guarantor: FH Nielsen.

Corresponding author

Correspondence to F H Nielsen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nielsen, F., Milne, D. A moderately high intake compared to a low intake of zinc depresses magnesium balance and alters indices of bone turnover in postmenopausal women. Eur J Clin Nutr 58, 703–710 (2004). https://doi.org/10.1038/sj.ejcn.1601867

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ejcn.1601867

Keywords

This article is cited by

Search

Quick links