Skip to main content
SpringerLink
Log in

Zinc Supplementation or Regulation of its Homeostasis: Advantages and Threats

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

To accomplish its multifunctional biological roles, zinc requires precise homeostatic mechanisms. There are efficient mechanisms that regulate zinc absorption from the alimentary tract and its excretion by the kidney depending on the organism demands. The regulatory mechanisms of cellular zinc inflow, distribution, and zinc outflow are so efficient that symptoms of zinc deficiency are rare, and symptoms connected with its massive accumulation are even more rare. The efficiency of homeostatic mechanisms that prevent zinc deficiency or excessive zinc accumulation in the organism is genetically conditioned. It seems that an essential element of zinc homeostasis is the efficiency of zinc transmembrane exchange mechanisms. Intracellular free zinc concentration is higher than in extracellular space. Physiologically, the active outflow of zinc ions from the cell depends on the increase of its concentration in extracellular space. The ion pumps activity depends on the efficiency by which the cell manages energy. Considering the fact that zinc deficiency accelerates apoptosis and that excessive zinc accumulation inside cells results in a toxic effect that forces its death brings about several questions: Is intensification and acceleration of changes in zinc metabolism with age meaningful? Is there a real zinc deficiency occurring with age or in connection with the aforementioned pathological processes, or is it just a case of tissue and cell redistribution? When discussing factors that influence zinc homeostasis, can we consider zinc supplementation or regulation of zinc balance in the area of its redistribution? To clarify these aspects, an essential element will also be the clear understanding of the nomenclature used to describe changes in zinc balance. Zinc homeostasis can be different in different age groups and depends on sex, thus zinc dyshomeostasisrefers to changes in its metabolism that deviate from the normal rates for a particular age group and sex. This concept is very ample and implies that zinc deficiency may result from a low-zinc diet, poor absorption, excessive loss of zinc, zinc redistribution in intra- and extracellular compartments, or a combination of these factors that is inadequate for the given age and sex group. Such factor or factors need to be considered for preventing particular homeostasis disorders (or dyshomeostasis). Regulation of zinc metabolism by influencing reversal of redistribution processes ought to be the main point of pharmacologic and nonpharmacologic actions to reestablish zinc homeostasis. Supplementation and chelation are of marginal importance and can be used to correct long-term dietary zinc deficiency or zinc poisoning or in some cases in therapeutic interventions. In view of its biological importance, the problem posed by the influence of zinc metabolism requires further investigation. To date, one cannot consider, for example, routine zinc supplementation in old age, because changes of metabolism with age are not necessarily a cause of zinc deficiency. Supplementation is warranted only in cases in which deficiency has been established unambiguously. An essential element is to prevent sudden changes in zinc metabolism, which lead to dyshomeostasis in the terms defined here. The primary prophylaxes, regular physical activity, efficient treatment of chronic diseases, are all elements of such prevention.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Vallee BL, Falchuk KH (1993) The biochemical basis of zinc physiology. Physiol Rev 73:79–94

    PubMed  CAS  Google Scholar 

  2. Kokot F, Tatoń J (1991) Zaburzenia przemiany materii w Chorobach Wewnêtrznych pod red. F. Kokota, PZWL Warszawa 670

  3. Holtmeier HJ, Kuhn M, Rummel K (1976) Zink ein lebenswichtiges Mineral, Wissenschaftliche Verlagsgeselschaft MbH. Stuttgart 13

  4. Turner AJ, Brown CD, Carson JA, Barens K (2000) The neprilysin family in health and disease. Adv Exp Med Biol 477:229–240

    Article  PubMed  CAS  Google Scholar 

  5. Lopez-Ongil S, Senchak V, Saura M, Zaragoza C, Ames M, Ballerman BJ, Rodriguez-Puyol M, Rodroguez-Puyol D, Lowenstein CJ (2000) Superoxide regulation of endothelin converting enzyme. J Biol Chem 275:26423–26429

    Article  PubMed  CAS  Google Scholar 

  6. Cousins RJ (1986) Toward a molecular understanding of zinc metabolism. Clin Physiol Biochem 4:20–30

    PubMed  CAS  Google Scholar 

  7. Csermely P, Somogyi J (1989) Zinc as a possible mediator of signal transduction in T lymphocytes. Acta Physiol Hung 74:195–197

    PubMed  CAS  Google Scholar 

  8. Avery RA, Bettger WJ (1992) Zinc deficiency alters the protein composition of the membrane skeleton but not the extractability or oligomeric form of spectrin in rat erythrocyte membranes. J Nutr 122:428–434

    PubMed  CAS  Google Scholar 

  9. Bettger WJ, O’Dell BL (1981) A critical physiological role of zinc in the structure and function of biomembranes. Life Sci 28:1425–1438

    Article  PubMed  CAS  Google Scholar 

  10. Carvalho A (1972) Binding and release of cations by sarcoplasmic reticulum before and after removal of lipids. Eur J Biochem 27:491–502

    Article  PubMed  CAS  Google Scholar 

  11. Dorup I, Clausen T (1991). Effects of magnesium and zinc deficiencies on growth and protein synthesis in skeletal muscle and the heart. Br J Nutr 66:493–504

    Article  PubMed  CAS  Google Scholar 

  12. Driscoll ER, Bettger WJ (1992) Zinc deficiency in the rat alters the lipid composition of the erythrocyte membrane Triton shell. Lipids 27:972–977

    Article  PubMed  CAS  Google Scholar 

  13. Evans RM (1988) The steroid and thyroid hormone receptor superfamily. Science 240:889–895

    Article  PubMed  CAS  Google Scholar 

  14. Harrison NL, Radke HK, Tamkun MM, Lovinger DM (1993) Modulation of gating of cloned rat and human K+ channels by micromolar Zn+2. Mol Pharmacol 43:482–486

    PubMed  CAS  Google Scholar 

  15. Maccara IG (1985) Oncogenesis, ions and phospholipids. Am J Physiol 248:C3–C11

    Google Scholar 

  16. Csermely P, Sandor P, Radics L, Somogyi J (1989) Zinc forms complexes with higher kinetical stability than calcium, 5-F-BAPTA as a good example. Biochem Biophys Res Commun 165:838–844

    Article  PubMed  CAS  Google Scholar 

  17. Lowe NM, Green A, Rhodes JM, Lombard M, Jalan R, Jackson MJ (1993) Studies of human zinc kinetics using the stable isotope 70Zn. Clin Sci 84:113–117

    PubMed  CAS  Google Scholar 

  18. Girchev R, Tzachev K (1988) Metabolism and homeostasis of zinc and copper. Acta Physiol Pol 39(Suppl 32):103–118

    PubMed  CAS  Google Scholar 

  19. King JC, Shames DM, Woodhouse LR (2000) Zinc homeostasis in humans. J Nutr 130:1360S–1366S

    PubMed  CAS  Google Scholar 

  20. Darlu P, Lalouel JM, Henrotte JG, Rao DC (1983) A genetic study of red blood zinc concentration in man. Hum Hered 33:311–318

    PubMed  CAS  Google Scholar 

  21. Henrotte JG, Santarromana M, Pia M (1987) Genetic factors regulating zinc concentrations in mics spleen and liver: relationship with the H-2 complex. Immunogenetics 25:408–410

    Article  PubMed  CAS  Google Scholar 

  22. Henrotte JG, Santarromana M, Franck G, Bourdon R (1990) Blood and tissue zinc levels in spontaneously hypertensive rats. J Am Coll Nutr 9:340–344

    PubMed  CAS  Google Scholar 

  23. Henrotte JG, Santarromana M, Franck G, Guicheney P, Boulu R, Bourdon R (1992) High cardiac zinc levels in spontaneously hypertensive rats. J Hypertens 10:553–559

    Article  PubMed  CAS  Google Scholar 

  24. Olholm-Larsen P (1979) Serum zinc levels in heterozygous carriers of the gene for acrodermatitis enteropathica. Hum Genet 46:65–74

    Article  PubMed  CAS  Google Scholar 

  25. Smith JC, Zeller JA, Brown ED, Ong SC (1976) Elevated Plasma zinc: a heritable anomaly. Science 193:496–498

    Article  PubMed  CAS  Google Scholar 

  26. McMaster D, McCrum E, Patterson CC, Kerr MM, O’Reilly D, Evans AE, Love AH (1992) Serum copper and zinc in random samples of the population of Northen Ireland. Am J Clin Nutr 56:440–446

    PubMed  CAS  Google Scholar 

  27. Simons TJB (1991) Intracellular free zinc and zinc buffering in human red blood cells. J Membr Biol 123:63–71

    Article  PubMed  CAS  Google Scholar 

  28. Simson TJB (1991) Calcium-dependent zinc efflux in human red blood cells. J Membr Biol 123:73–80

    Article  Google Scholar 

  29. Bobilya DJ, Briske-Anderson M, Reeves PG (1992) Zinc transport into endothelial cell is a facilitated process. J Cell Physiol 151:1–7

    Article  PubMed  CAS  Google Scholar 

  30. Raffaniello RD, Shih-Yu L, Teichberg S, Wapnir RA (1992) Distinct mechanisms of zinc uptake at the apical and basolateral membranes of caco-2 cells. J Cell Physiol 152:356–361

    Article  PubMed  CAS  Google Scholar 

  31. Tacnet F, Lauthier F, Ripoche P (1993) Mechanisms of zinc transport into pig small intestine brush-border membrane vesicles. J Physiol 465:57–72

    PubMed  CAS  Google Scholar 

  32. Gracia CE, Kdcoyne CM, Cardillo C, Cannon RO 3, Quyyumi AA, Panza JA (1995) Effect of copper-zinc superoxide dismutase on endothelium-dependent vasodilation in patients with essential hypertension. Hypertension 26:863–868

    Google Scholar 

  33. Sato M, Yanagisawa H, Nojima Y, Tamura J, Wada O (2002) Zn deficiency aggravates hypertension in spontaneously hypertensive rats: possible role of Cu/Zn-superoxide dismutase. Clin Exp Hypertens 24:355–370

    Article  PubMed  CAS  Google Scholar 

  34. Cebeci SA, Kocaturk PA, Kavas GO (2002) Hypertension: does impaired endothelium-dependent relaxation affect superoxide scavenging? Biol Trace Elem Res 90:239–249

    Article  PubMed  CAS  Google Scholar 

  35. Sato M, Kurihara N, Moridaira K, Sakamoto H, Tamura J, Wada O, Yanagisawa H (2003) Dietary Zn deficiency does not influence systemic blood pressure and vascular nitric oxide signaling in normotensive rats. Biol Trace Elem Res 91:157–172

    Article  PubMed  CAS  Google Scholar 

  36. Yanagisawa H, Sato M, Nodera M, Wada O (2004). Excessive zinc intake elevates systemic blood pressure levels in normotensive rats—potential role of superoxide-induced oxidative stress. J Hypertens 22:543–550

    Article  PubMed  CAS  Google Scholar 

  37. Davydenko NV, Smirnova IP, Kvasha EA, Gorbas EAIM, Koblianskaia AV (1995) Interrelatioship between dietary intake of minerals and prevalence of hypertension. Vopr Pitan 6:17–19

    PubMed  Google Scholar 

  38. Davydenko NV, Smirnova IP, Kvasha EA, Gorbas EAIM (1995) The relationship between the copper and zinc intake with food and the prevalence of ischaemic heart disease and its risk factors. Lik Sprava 5-6:73–77

    PubMed  Google Scholar 

  39. Anonymous (1985) Megadose zinc intakes impairs immune responses. Nutr Rev 43:141–143

    Google Scholar 

  40. Chandra RK (1984) Excessive intake of zinc impairs immune response. JAMA 252:1443–1445

    Article  PubMed  CAS  Google Scholar 

  41. Ripa S, Ripa R (1994) Zinc and atherosclerosis. Minerva Med 85:647–654

    PubMed  CAS  Google Scholar 

  42. Ripa S, Ripa R (1994) Zinc and arterial pressure. Minerva Med 85:455–459

    PubMed  CAS  Google Scholar 

  43. Singh RB, Niaz MA, Rastogi SS, Bajaj S, Gaoli Z, Shoumin Z (1998) Current zinc intake and diabetes and coronary artery disease and factors associated with insulin resistance in rural and urban populations of North India. J Am Coll Nutr 17:564–570

    PubMed  CAS  Google Scholar 

  44. Chiplonkar SA, Agte VV, Tarwadi KV, Paknikar KM, Diwate UP (2004) Micronutrient deficiencies as predisposing factors for hypertension in lacto-vegetarian Indian adults. J Am Coll Nutr 23:239–247

    PubMed  CAS  Google Scholar 

  45. Schutte AE, Van Rooyen JM, Huisman HW, Kruger HS, Malan NT, De Didder JH (2003) Dietary risk markers that contribute to the aetiology of hypertension in black South African children: the THUSA BANA study. J Hum Hypertens 17:29–35

    Article  PubMed  CAS  Google Scholar 

  46. Fodor JG, Rusted IE (1987) Electrolyte profiles in a hypertensive population: The Newfoundland Study. Clin Invest Med 10:586–591

    PubMed  CAS  Google Scholar 

  47. Hajjar I, Kotchen T (2003) Regional variations of blood pressure in the United States are associated with regional variation in dietary intakes: the NHANES-II data. J Nutr 133:211–214

    PubMed  CAS  Google Scholar 

  48. Lindeman RD, Clark ML, Colmore JP (1971) Influence of age and sex on plasma and red-cell zinc concentration. J Gerontol 26:358–363

    Google Scholar 

  49. Wastney ME, Ahmed S, Henkin RI (1992) Changes in regulation of human zinc metabolism with age. Am J Physiol 263(5 Pt 2):R1162–R1168

    PubMed  CAS  Google Scholar 

  50. Donahue AN, Aschner M, Lash LH, Syversen T, Sonntag WE (2006) Growth hormone administration to aged animals reduces disulfide glutathione levels in hippocampus. Mech Ageing Dev 127:57–63

    Article  PubMed  CAS  Google Scholar 

  51. Hodkinson CF, Kelly M, Coudray C, Gilmore WS, Hannigan BM, O’Connor JM, Strain JJ, Wallace JM (2005) Zinc status and age-related changes in peripheral blood leucocyte subpopupations in healthy men and women aged 55–70 y: the ZENITH study. Eur J Clin Nutr 59(Suppl 2):S63–S67

    Article  PubMed  CAS  Google Scholar 

  52. Ravaglia G, Forti P, Maioli F, Bastagli L, Facchini A, Mariani E, Savarino L, Sassi S, Cucinotta D, Lenaz G (2000) Effect of micronutrient on natural killer cell immune function in healthy free-living subjects aged ≥90 y. Am J Clin Nutr 71:590–598

    PubMed  CAS  Google Scholar 

  53. Mocchegiani E, Malavolta M, Marcellini F, Pawelec G (2006) Zinc, oxidative stress, genetic background and immunosenescence: implications for healthy ageing. Immunity and Ageing 3:6

    Article  PubMed  Google Scholar 

  54. Mocchegiani E, Costarelli L, Giacconi R, Cipriano C, Muti E, Rink L, Malavolta M (2006) Zinc homeostasis in aging: two elusive faces of the same metal. Rejuvenation Res 9:351–354

    Article  PubMed  CAS  Google Scholar 

  55. Tubek S (2005) The zinc content in lymphocytes and the activity of zinc ions efflux from lymphocytes in primary arterial hypertension. Biol Trace Elem Res 107:89–99

    Article  PubMed  CAS  Google Scholar 

  56. Sprietsma JE (1999) Modern diets and diseases: NO-zinc balance. Under Th1, zinc and nitrogen monoxide (NO) collectively protect against viruses, AIDS, autoimmunity, diabetes, allergies, asthma, infectious diseases, atherosclerosis and cancer. Med Hypotheses 53:6–16

    Article  PubMed  CAS  Google Scholar 

  57. Chandra RK (1981) Immune response in overnutrition. Cancer Res 41:3795–3796

    PubMed  CAS  Google Scholar 

  58. Takakura M (1998) Analysis of zinc concentrations in leucocytes and its application to patients with non-insulin-dependent diabetes mellitus. Hokkaido Igaku Zasshi 73:571–580

    PubMed  CAS  Google Scholar 

  59. Treves S, Trentini PL, Ascanelli M, Bucci G, Di Vrigilio F (1994) Apoptosis is dependent on intracellular zinc and independent of intracellular calcium in lymphocytes. Exp Cell Res 211:339–343

    Article  PubMed  CAS  Google Scholar 

  60. Malaiyandi LM, Honick AS, Rintoul GL, Wang QJ, Reynolds IJ (2005) Zn2+ inhibits mitochondrial movement in neurons by phosphatidylinositol 3-kinase activation. J Neurosci 25:9507–9514

    Article  PubMed  CAS  Google Scholar 

  61. Capasso M, Jeng JM, Malavolta M, Mocchegiani E, Sensi SL (2005) Zinc dyshomeostasis: a key modulator of neuronal injury. J Alzheimers Dis 8:93–108

    PubMed  CAS  Google Scholar 

  62. Kromhout D, Wibowo AA, Herber i wsp RF (1985) Trace metals and coronary heart disease risk indicators in 152 elderly men (The Zutphen Study). Am J Epidemiol 122:378–385

    PubMed  CAS  Google Scholar 

  63. Ripa S, Ripa R (1995) Zinc and immune function. Minerva Med 86:315–318

    PubMed  CAS  Google Scholar 

  64. Przybylski J (1991) The role of arterial chemoreceptors and tissue oxygen supply in primary arterial hypertension pathogenesis, based upon investigations carried out on animal model (SAH). Qualifying thesis. Medical University of Warsaw, Warsaw, pp 24–42, 85–167 (in Polish).

  65. Ishikawa Y, Kudo H, Kagawa Y, Sakamoto S (2005) Increased plasma of zinc in obese adult females on a weight-loss program based on a hypocaloric balanced diet in vivo 19:1035–1037

  66. Simon SF, Taylor CG (2001) Dietary zinc supplementation attenuates hyperglycemia in db/db mice. Exp Biol Med (Maywood) 226:43–51

    CAS  Google Scholar 

  67. Raz I, Karsai D, Katz M (1989) The influence of zinc supplementation on glucose homeostasis in NIDDM. Diabetes Res 11:73–79

    PubMed  CAS  Google Scholar 

  68. Schoner W, Scheiner-Bobis G (2005) Endogenous cardiac glycosides: hormones using the sodium pump as signal transducer. Semin Nephrol 25:343–351

    Article  PubMed  CAS  Google Scholar 

  69. Schoner W, Bauer N, Muller-Ehmsen J, Kramer U, Hambarchian N, Schwinger R, Moeller H, Kost H, Weitkamp C, Schweitzer T, Kirch U, Neu H, Grunbaum EG (2003) Ouabain as a mammalian hormone. Ann NY Acad Sci 986:678–684

    Article  PubMed  CAS  Google Scholar 

  70. Tubek S (2001) Increased absorption of zinc from alimentary tract in the primary arterial hypertension. Biol Trace Elem Res 83:31–38

    Article  PubMed  CAS  Google Scholar 

  71. Henderson LM, Brewer GJ, Dressman JB, Swidan SZ, DuRoss DJ, Adair CH, Barnett JL, Berardi RR (1996) Use of zinc tolerance test and 24-hour urinary zinc content to assess oral zinc absorption. J Am Coll Nutr 15:79–83

    PubMed  CAS  Google Scholar 

  72. Neve J, Hanocq M, Peretz A, Abi Khalil F, Pelen F, Famaey JP, Fontaine J (1991) Pharmacokinetic study of orally administered zinc in humans: evidence for an enteral recirculation. Eur J Drug Metab Pharmacokinet 16:315–323

    Article  PubMed  CAS  Google Scholar 

  73. Balesaria S, Hogstrand Ch (2006) Identification, cloning and characterization of a plasma membrane zinc efflux transporter, TrZnT-1, from fugu pufferfish (Takifugu rubripes). Biochem J 394:485–493

    Article  PubMed  CAS  Google Scholar 

  74. Agte VV, Chiplonkar SA, Tarwadi KV (2005) Factors influencing zinc status of apparently healthy Indians. J Am Coll Nutr 24:334–341

    PubMed  CAS  Google Scholar 

  75. Vivoli G, Bergomi M, Rovesti S et al (1995) Zinc, copper and zinc- or copper-dependent enzymes in human hypertension. Biol Trace Elem Res 49:97–106

    Article  PubMed  CAS  Google Scholar 

  76. Kok J, Van der Schoot C, Veldhuizen M, Wolterbeek HT (1993) The uptake of zinc by erythrocytes under near-physiological conditions. Biol Trace Elem Res 38:13–26

    PubMed  Google Scholar 

  77. Tubek S (2006) Selected zinc metabolism parameters in relation to insulin, renin–angiotensin–aldosterone system and blood pressure in healthy subjects—gender differences. Biol Trace Elem Res 114:65–72

    Article  PubMed  CAS  Google Scholar 

  78. Tetef ML, Synold TW, Chow W, Leong L, Margolin K, Morgan R, Raschko J, Shibata S, Somlo G, Yen Y, Groshen S, Johnson K, Lenz HJ, Gandara D, Doroshow JH (2001) Phase I trial of 96-hour continuous infusion of dexrazoxane in patients with advanced malignancies. Clin Cancer Res 7:1569–1576

    PubMed  CAS  Google Scholar 

  79. Cuajungco MP, Lees GJ (1997) Zinc metabolism in the brain: relevance to human neurodegenerative disorders. Neurobiol Dis 4:137–169

    Article  PubMed  CAS  Google Scholar 

  80. Yoo MH, Lee JY, Lee SE, Koh JY, Yoon YH (2004) Protection by pyruvate of rat retinal cells against zinc toxicity in vitro, and pressure-induced ischemia in vivo. Invest Ophthalmol Vis Sci 45:1523–1530

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Physical Education and Physiotherapy, Institute of Technology, Opole, Prószkowska Street 76, 45-758, Opole, Poland

    Sławomir Tubek

Authors
  1. Sławomir Tubek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sławomir Tubek.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tubek, S. Zinc Supplementation or Regulation of its Homeostasis: Advantages and Threats. Biol Trace Elem Res 119, 1–9 (2007). https://doi.org/10.1007/s12011-007-0043-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-007-0043-7

Keywords

Search

Navigation