Abstract
Heart failure (HF) is a prevalent syndrome resulting in a high mortality rate. HF may be associated with zinc deficiency through a reduction in dietary intake, decreased absorption due to gastrointestinal edema, impaired motility or intestinal zinc losses. Diseases concomitant with HF such as diabetes mellitus (DM) and hypertension may enhance zinc deficiency. Medications given for HF may affect zinc metabolism in different ways. It was shown that thiazides may cause zincuria and a decrease in tissue zinc concentration. There is conflicting evidence about furosemide, even though patients with chronic furosemide treatment showed low tissue zinc levels in autopsies. Treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) resulted in zincuria and zinc deficiency, but this outcome was not consistent in all studies. Beta-blockers did not alter plasma zinc concentration. Matrix metalloproteinases (MMPs) and ACE are zinc-containing enzymes, which play a role in the process of remodeling in HF. It was shown that ACE inhibitors may inhibit the activity of different MMPs. The exact interrelationship between HF, zinc-containing enzymes, zinc deficiency and the clinical manifestation of HF has to be investigated.
Similar content being viewed by others
References
Weigand E. Absorption of trace elements: Zinc. Int J Vitam Nutr Res Suppl 1983;25:67–81.
Sandstrom B. Bioavailability of zinc. Eur J Clin Nutr 1997; Suppl 1:S17–S19.
King JC, Cousins RJ. Zinc. In: Shils ME, Shike M, Ross CA, Caballero B, Cousins RJ, editors Modern Nutrition in Health and Disease, 10th edn. Philadelphia: Lippincott Williams & Wilkins 2005. p. 271–85.
King JC. Assessment of techniques for determining human zinc requirements. J Am Diet Assoc 1986;86:1523–8.
Walsh CT, Sandstead HH, Prasad AS, Newberne PM, Fraker PJ. Zinc: Health effects and research priorities for the 1990s. Environ Health Perspect 1994;102 Suppl 2:5–46.
Cousins RJ. Zinc. In: Ziegler E, Filer LJ, editors. Present Knowledge in Nutrition. Washington, DC: ILSI Press, 1996:293–306.
Prasad AS. Zinc deficiency. BMJ 2003;326:409–10.
Atlihan F, Soylemezoglu T, Gokce A, Guvendik G, Satici O. Zinc and copper in congestive heart failure. Turk J Pediatr 1990;32:33–8.
Oster O. Trace element concentrations (Cu, Zn, Fe) in sera from patients with dilated cardiomyopathy. Clin Chim Acta 1993;214: 209–18.
Topuzoglu G, Erbay AR, Karul AB, Yensel N. Concentrations of copper, zinc, and magnesium in sera from patients with idiopathic dilated cardiomyopathy. Biol Trace Elem Res 2003;95:11–17.
Havranek E, Bumbalova A, Riecanska E, Riecansky I, Schreinerova Z, Belakova M, et al. Blood levels of Fe, Zn, Br and Rb determined by radionuclide x-ray fluorescence analysis in patients with dilated cardiomyopathy. Bratisl Lek Listy 1994;95:15–20.
Chou HT, Yang HL, Tsou SS, Ho RK, Pai PY, Hsu HB. Status of trace elements in patients with idiopathic dilated cardiomyopathy in central Taiwan. Zhonghua Yi Xue Za Zhi (Taipei) 1998;61: 193–8.
Golik A, Cohen N, Ramot Y, Maor J, Moses R, Weissgarten J, et al. Type II diabetes mellitus, congestive heart failure, and zinc metabolism. Biol Trace Elem Res 1993;39:171–5.
Gorelik O, Almoznino-Sarafian D, Feder I, Wachsman O, Alon I, Litvinjuk V, et al. Dietary intake of various nutrients in older patients with congestive heart failure. Cardiology 2003;99: 177–81.
Witte KK, Nikitin NP, Parker AC, von Haehling S, Volk HD, Anker SD, et al. The effect of micronutrient supplementation on quality-of-life and left ventricular function in elderly patients with chronic heart failure. Eur Heart J 2005;26:2238–44.
Reyes AJ, Olhaberry JV, Leary WP, Lockett CJ, van der Byl K. Urianry zinc excretion, diuretics, zinc deficiency and some side-effects of diuretics. S Afr Med J 1983;64:936–41.
Reyes AJ, Leary WP, Lockett CJ, Alcocer L. Diuretics and zinc. S Afr Med J 1982;62:373–5.
Leary WP, Reyes AJ, Wynne RD, K van der Byl. Renal excretory actions of furosemide, of hydrochlorothiazide and of the vasodilator flosequinan in healthy subjects. J Int Med Res 1990;18: 120–41.
Leary WP, Reyes AJ, van der Byl K. Effects of an acebutolol-hydrochlorothiazide combination on urinary solute excretion in healthy adults. S Afr Med J 1986;69:98–100.
Wester PO. Urinary zinc excretion during treatment with different diuretics. Acta Med Scand 1980;208:209–12.
Golik A, Averbukh Z, Cohn M, Maor J, Berman S, Shaked U, et al. Effect of diuretics on captopril-induced urinary zinc excretion. Eur J Clin Pharmacol 1990;38:359–161.
Kirchgessner M, Motz C, Roth HP. Influence of dietary amiloride supplement on the zinc status of growing rats with marginal zinc supply. Res Exp Med (Berl) 1995;195:237–42.
Verho M, Bossaller W, Heinen B. Serum trace-element levels in piretanide-treated hypertensives: a double-blind trial against hydrochlorothiazide plus amiloride. Int J Clin Pharmacol Res 1987;7:5–11.
Golik A, Modai D, Weissgarten J, Cohen N, Averbukh Z, Sigler E, et al. Hydrochlorothiazide-amiloride causes excessive urinary zinc excretion. Clin Pharmacol Ther 1987;42:42–4.
Wester PO. Tissue zinc at autopsy-relation to medication with diuretics. Acta Med Scand 1980;208:269–71.
Mountokalakis T, Dourakis S, Karatzas N, Maravelias C, Koutselinis A. Zinc deficiency in mild hypertensive patients treated with diuretics. J Hypertens Suppl 2:S571–2.
Berne X, Carias D, Cioccia AM, Gonzalez E, Hevia P. Effect of the diuretic furosemide on urinary essential nutrient loss and on body stores in growing rats. Arch Latinoam Nutr 2005;55: 154–60.
Cohen N, Golik A, Dishi V, Zaidenstein R, Weissgarten J, Averbukh Z, et al. Effect of furosemide oral solution versus furosemide tablets on diuresis and electrolytes in patients with moderate congestive heart failure. Miner Electrolyte Metab 1996;22:248–52.
Cohen N, Alon I, Almoznino-Sarafian D, Zaidenstein R, Weissgarten J, Gorelik O, et al. Metabolic and clinical effect of oral magnesium supplementation in furosemide-treated patients with severe congestive heart failure. Clin Cardiol 2000;23:433–6.
Allain P, Leblondel G, Granry JC. The effects of captopril and enalapril on tissue levels of various elements in spontaneously hypertensive rats. Fundam Clin Pharmacol 1989;3:329–35.
Zumkley H, Bertram HP, Vetter H, Zidek W, Losse H. Zinc metabolism during captopril treatment. Horm Metab Res 1985;17:256–8.
Abu-Hamdan DK, Desai H, Sondheimer J, Felicetta J, Mahajan S, McDonald F. Taste acuity and zinc metabolism in captopril-treated hypertensive male patients. Am J Hypertens 1988;1:303S–8S.
O’Connor DT, Strause L, Saltman P, Parmer RJ, Cervenka J. Serum zinc is unaffected by effective captopril treatment of hypertension. J Clin Hypertens 1987;3:405–8.
Golik A, Modai D, Averbukh Z, Sheffy M, Shamis A, Cohen N, et al. Zinc metabolism in patients treated with captopril versus enalapril. Metabolism 1990;39:665–7.
Rubio-Luengo MA, Maldonado-Martin A, Gil-Extremera B, Gonzalez-Gomez L, Luna del Castillo JD. Variations in magnesium and zinc in hypertensive patients receiving different treatments. Am J Hypertens 1995;8:689–95.
Golik A, Zaidenstein R, Dishi V, Blatt A, Cohen N, Cotter G, et al. Effects of captopril and enalapril on zinc metabolism in hypertensive patients. J Am Coll Nutr 1998;17:75–8.
Baykal Y, Yilmaz MI, Celik T, Gok F, Rehber H, Akay C, et al. Effects of antihypertensive agents, alpha receptor blockers, beta blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and calcium channel blockers, on oxidative stress. J Hypertens 2003;21:1207–11.
Koren-Michowitz M, Dishy V, Zaidenstein R, Yona O, Berman S, Weissgarten J, et al. The effect of losartan and losartan/hydrochlorothiazide fixed-combination on magnesium, zinc, and nitric oxide metabolism in hypertensive patients: a prospective open-label study. Am J Hypertens 2005;18:358–63.
Reinhardt D, Sigusch HH, Hensse J, Tyagi SC, Korfer R, Figulla HR. Cardiac remodelling in end stage heart failure: upregulation of matrix metalloproteinase (MMP) irrespective of the underlying disease, and evidence for a direct inhibitory effect of ACE inhibitors on MMP. Heart 2002;88:525–30.
Zumkley H, Bertram HP, Vetter H, Zidek W, Wessels F. Zinc concentrations in plasma and erythrocytes in digitalized patients. Klin Wochenschr 1981;59:1345–7.
Wester PO. The urinary excretion of trace elements before and during treatment with hydralazine. Acta Med Scand 1975;197: 307–9.
Peters JM, Lonnerdal B, Keen CL. Effect of the antihypertensive drug hydralazine on mineral metabolism in the rat. Toxicol Lett 1988;41:193–202.
Ghayour-Mobarhan M, Lamb DJ, Taylor A, Vaidya N, Livingstone C, Wang T, et al. Effect of statin therapy on serum trace element status in dyslipidaemic subjects. J Trace Elem Med Biol 2005;19:61–7.
Leonhardt W, Kurktschiev T, Meissner D, Lattke P, Abletshauser C, Weidinger G, et al. Effects of fluvastatin therapy on lipids, antioxidants, oxidation of low density lipoproteins and trace metals. Eur J Clin Pharmacol 1997;53:65–9.
Hidalgo J, Giralt M, Garvey JS, Armario A. Effect of morphine administration on rat liver metallothionein and zinc metabolism. J Pharmacol Exp Ther 1991;259:274–8.
Lo HS, Chiang HC, Lin AM, Chiang HY, Chu YC, Kao LS. Synergistic effects of dopamine and Zn2+ on the induction of PC12 cell death and dopamine depletion in the striatum: possible implication in the pathogenesis of Parkinson’s disease. Neurobiol Dis 2004;17:54–61.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cohen, N., Golik, A. Zinc balance and medications commonly used in the management of heart failure. Heart Fail Rev 11, 19–24 (2006). https://doi.org/10.1007/s10741-006-9189-1
Issue Date:
DOI: https://doi.org/10.1007/s10741-006-9189-1