Skip to main content

Advertisement

SpringerLink
Log in

The effect of zinc supplementation on blood pressure: a systematic review and dose–response meta-analysis of randomized-controlled trials

  • Review
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

A Correction to this article was published on 20 March 2020

This article has been updated

Abstract

Purpose

Despite previous investigations on the effects of zinc supplementation on blood pressure, inconsistent findings are available in this regard. Therefore, we conducted a systematic review and meta-analysis of randomized clinical trials on the effects of zinc supplementation on blood pressure (BP) in adults.

Methods

Relevant studies published up to September 2019 were searched through PubMed/Medline, Scopus, ISI Web of Science, and Google Scholar using suitable keywords. All randomized clinical trials (RCTs) that examined the effect of oral zinc supplementation on systolic blood pressure (SBP) or diastolic blood pressure (DBP) in adults were included.

Results

Overall, nine trials were included in our study. Zinc supplementation significantly reduced SBP compared to the control [weighted mean differences (WMD) − 1.49 mmHg; 95% CI − 2.85 to − 0.13; P = 0.03]. However, zinc supplementation had no significant effects on DBP (WMD − 0.88 mmHg; 95% CI − 2.04 to 0.29; P = 0.14). Nonlinear analysis failed to indicate a significant influence of supplementation dosage or duration on both SBP and DBP. Sensitivity analysis showed that no individual study had a significant impact on our final results. In addition, we found no evidence for the presence of small-study effects among studies for both SBP and DBP.

Conclusion

We found a significant reduction in SBP following zinc supplementation. However, zinc supplementation had no significant effect on DBP. In addition, no nonlinear association was found between supplementation dosage and duration with changes in both SBP and DBP. Further RCTs using different dosages of zinc in various durations are required to confirm our conclusion.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Change history

  • 20 March 2020

    The original version of this article unfortunately contained a mistake. The family name of “Israel Júnior Borges do Nascimento” was incorrect.

References

  1. Pagidipati NJ, Gaziano TA (2013) Estimating deaths from cardiovascular disease: a review of global methodologies of mortality measurement. Circulation 127(6):749–756

    Article  PubMed  PubMed Central  Google Scholar 

  2. Forouzanfar MH, Liu P, Roth GA, Ng M, Biryukov S, Marczak L, Alexander L, Estep K, Abate KH, Akinyemiju TF (2017) Global burden of hypertension and systolic blood pressure of at least 110 to 115 mm Hg, 1990–2015. JAMA 317(2):165–182

    Article  PubMed  Google Scholar 

  3. Chan M (2013) A global brief on hypertension. World Health Organization, Geneva

    Google Scholar 

  4. Lawes CM, Hoorn SV, Rodgers A (2008) Global burden of blood-pressure-related disease, 2001. Lancet 371(9623):1513–1518

    Article  PubMed  Google Scholar 

  5. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, De Ferranti S, Després J-P, Fullerton HJ (2016) Executive summary: heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation 133(4):447–454

    Article  PubMed  Google Scholar 

  6. Townsend N, Wickramasinghe K, Bhatnagar P, Smolina K, Nichols M, Leal J, Luengo-Fernandez R, Rayner M (2012) Coronary heart disease statistics. A conpendium of health statistics. University of Oxford, Oxford

    Google Scholar 

  7. Savica V, Bellinghieri G, Kopple JD (2010) The effect of nutrition on blood pressure. Annu Rev Nutr 30:365–401

    Article  CAS  PubMed  Google Scholar 

  8. Appel LJ (2017) The effects of dietary factors on blood pressure. Cardiol Clin 35(2):197–212

    Article  PubMed  Google Scholar 

  9. Mousavi SM, Karimi E, Hajishafiee M, Milajerdi A, Amini MR, Esmaillzadeh A (2019) Anti-hypertensive effects of cinnamon supplementation in adults: a systematic review and dose-response meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr. https://doi.org/10.1080/10408398.2019.1678012

    Article  PubMed  Google Scholar 

  10. Vallee BL, Auld DS (1990) Zinc coordination, function, and structure of zinc enzymes and other proteins. Biochemistry 29(24):5647–5659

    Article  CAS  PubMed  Google Scholar 

  11. Chasapis CT, Loutsidou AC, Spiliopoulou CA, Stefanidou ME (2012) Zinc and human health: an update. Arch Toxicol 86(4):521–534

    Article  CAS  PubMed  Google Scholar 

  12. Wang X, Wu W, Zheng W, Fang X, Chen L, Rink L, Min J, Wang F (2019) Zinc supplementation improves glycemic control for diabetes prevention and management: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. https://doi.org/10.1093/ajcn/nqz041

    Article  PubMed  PubMed Central  Google Scholar 

  13. Mousavi SM, Djafarian K, Mojtahed A, Varkaneh HK, Shab-Bidar S (2018) The effect of zinc supplementation on plasma C-reactive protein concentrations: a systematic review and meta-analysis of randomized controlled trials. Eur J Pharmacol 834:10–16. https://doi.org/10.1016/j.ejphar.2018.07.019

    Article  CAS  PubMed  Google Scholar 

  14. Ranasinghe P, Wathurapatha WS, Ishara MH, Jayawardana R, Galappatthy P, Katulanda P, Constantine GR (2015) Effects of zinc supplementation on serum lipids: a systematic review and meta-analysis. Nutr Metab 12:26. https://doi.org/10.1186/s12986-015-0023-4

    Article  CAS  Google Scholar 

  15. Cortese-Krott MM, Kulakov L, Opländer C, Kolb-Bachofen V, Kröncke K-D, Suschek CV (2014) Zinc regulates iNOS-derived nitric oxide formation in endothelial cells. Redox Biol 2:945–954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Nevarez-Lopez SC, Simental-Mendia LE, Guerrero-Romero F, Burciaga-Nava JA (2019) Zinc deficiency is an independent risk factor for prehypertension in healthy subjects. Int J Vitam Nutr Res Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung Journal international de vitaminologie et de nutrition. https://doi.org/10.1024/0300-9831/a000593

    Article  PubMed  Google Scholar 

  17. Cozzolino M, Delcanale P, Montali C, Tognolini M, Giorgio C, Corrado M, Cavanna L, Bianchini P, Diaspro A, Abbruzzetti S, Viappiani C (2019) Enhanced photosensitizing properties of protein bound curcumin. Life Sci 233:116710. https://doi.org/10.1016/j.lfs.2019.116710

    Article  CAS  PubMed  Google Scholar 

  18. Kim J (2013) Dietary zinc intake is inversely associated with systolic blood pressure in young obese women. Nutr Res Pract 7(5):380–384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Feyh A, Bracero L, Lakhani HV, Santhanam P, Shapiro JI, Khitan Z, Sodhi K (2016) Role of dietary components in modulating hypertension. J Clin Exp Cardiol 7(4):1–15

    Article  Google Scholar 

  20. Ranasinghe P, Wathurapatha WS, Galappatthy P, Katulanda P, Jayawardena R, Constantine GR (2018) Zinc supplementation in prediabetes: a randomized double-blind placebo-controlled clinical trial. J Diabetes 10(5):386–397

    Article  CAS  PubMed  Google Scholar 

  21. Naghizadeh S, Kheirouri S, Ojaghi H, Kaffash AJ (2018) Zinc supplementation attenuate diabetic indices in patients with diabetic retinopathy. Prog Nutr 20(2-S):263–269

    CAS  Google Scholar 

  22. Seet RC, Lee C-YJ, Lim EC, Quek AM, Huang H, Huang SH, Looi WF, Long LH, Halliwell B (2011) Oral zinc supplementation does not improve oxidative stress or vascular function in patients with type 2 diabetes with normal zinc levels. Atherosclerosis 219(1):231–239

    Article  CAS  PubMed  Google Scholar 

  23. Kim J, Lee S (2012) Effect of zinc supplementation on insulin resistance and metabolic risk factors in obese Korean women. Nutr Res Pract 6(3):221–225

    Article  PubMed  PubMed Central  Google Scholar 

  24. Suliburska J, Skrypnik K, Szulińska M, Kupsz J, Bogdański P (2018) Effect of hypotensive therapy combined with modified diet or zinc supplementation on biochemical parameters and mineral status in hypertensive patients. J Trace Elem Med Biol 47:140–148

    Article  CAS  PubMed  Google Scholar 

  25. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(4):264–269

    Article  PubMed  Google Scholar 

  26. Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savović J, Schulz KF, Weeks L, Sterne JA (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928

    Article  PubMed  PubMed Central  Google Scholar 

  27. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    Article  CAS  PubMed  Google Scholar 

  28. Borenstein M, Hedges LV, Higgins JP, Rothstein HR (2011) Introduction to meta-analysis. Wiley, Hoboken

    Google Scholar 

  29. Hozo SP, Djulbegovic B, Hozo I (2005) Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 5(1):13

    Article  PubMed  PubMed Central  Google Scholar 

  30. Furuya-Kanamori L, Barendregt JJ, Doi SA (2018) A new improved graphical and quantitative method for detecting bias in meta-analysis. Int J Evid Based Healthc 16(4):195–203

    Article  PubMed  Google Scholar 

  31. Afkhami-Ardekani M, Karimi M, Mohammadi SM, Nourani F (2008) Effect of zinc sulfate supplementation on lipid and glucose in type 2 diabetic patients. Pak J Nutr 7(4):550–553

    Article  CAS  Google Scholar 

  32. Parham M, Amini M, Aminorroaya A, Heidarian E (2008) Effect of zinc supplementation on microalbuminuria in patients with type 2 diabetes: a double blind, randomized, placebo-controlled, cross-over trial. Rev Diabetic Stud 5(2):102

    Article  PubMed  PubMed Central  Google Scholar 

  33. Sadeghi SM, Sadeghi F, Akhlaghi M (2019) Effect of zinc supplementation on weight and food intake in patients under hemodialysis. Int J Nutr Sci 4(2):72

    Google Scholar 

  34. Tabrizi FPF, Alipoor B, Ostadrahimi A, Sadagiani MM (2011) Effect of zinc supplementation on inflammatory markers in women with polycystic ovary syndrome. Shiraz E Med J 12(1):30–38

    Google Scholar 

  35. Carpenter WE, Lam D, Toney GM, Weintraub NL, Qin Z (2013) Zinc, copper, and blood pressure: human population studies. Med Sci Monit 19:1–8. https://doi.org/10.12659/msm.883708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Roohani N, Hurrell R, Kelishadi R, Schulin R (2013) Zinc and its importance for human health: an integrative review. J Res Med Sci 18(2):144–157

    PubMed  PubMed Central  Google Scholar 

  37. Canatan H, Bakan I, Akbulut M, Halifeoglu I, Cikim G, Baydas G, Kilic N (2004) Relationship among levels of leptin and zinc, copper, and zinc/copper ratio in plasma of patients with essential hypertension and healthy normotensive subjects. Biol Trace Elem Res 100(2):117–123. https://doi.org/10.1385/BTER:100:2:117

    Article  CAS  PubMed  Google Scholar 

  38. Bergomi M, Rovesti S, Vinceti M, Vivoli R, Caselgrandi E, Vivoli G (1997) Zinc and copper status and blood pressure. J Trace Elem Med Biol 11(3):166–169. https://doi.org/10.1016/S0946-672X(97)80047-8

    Article  CAS  PubMed  Google Scholar 

  39. 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(5):355–370

    Article  CAS  PubMed  Google Scholar 

  40. Sato M, Kurihara N, Moridaira K, Sakamoto H, Ji T, 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(2):157–171

    Article  CAS  PubMed  Google Scholar 

  41. Kunutsor SK, Laukkanen JA (2016) Serum zinc concentrations and incident hypertension: new findings from a population-based cohort study. J Hypertens 34(6):1055–1061

    Article  CAS  PubMed  Google Scholar 

  42. Forstermann U, Sessa WC (2012) Nitric oxide synthases: regulation and function. Eur Heart J 33(7):829–837. https://doi.org/10.1093/eurheartj/ehr304

    Article  CAS  PubMed  Google Scholar 

  43. Hermann M, Flammer A, Luscher TF (2006) Nitric oxide in hypertension. J Clin Hypertens (Greenwich) 8(12 Suppl 4):17–29

    Article  CAS  Google Scholar 

  44. Yang WW, Krukoff TL (2000) Nitric oxide regulates body temperature, neuronal activation and interleukin-1 beta gene expression in the hypothalamic paraventricular nucleus in response to immune stress. Neuropharmacology 39(11):2075–2089. https://doi.org/10.1016/s0028-3908(00)00054-x

    Article  CAS  PubMed  Google Scholar 

  45. Riordan JF (2003) Angiotensin-I-converting enzyme and its relatives. Genome Biol 4(8):225. https://doi.org/10.1186/gb-2003-4-8-225

    Article  PubMed  PubMed Central  Google Scholar 

  46. Tanonaka K, Marunouchi T (2016) Angiotensin-converting enzyme 2. Nihon yakurigaku zasshi Folia pharmacologica Japonica 147(2):120–121. https://doi.org/10.1254/fpj.147.120

    Article  CAS  PubMed  Google Scholar 

  47. Dobzhansky T, Epling C (1948) The suppression of crossing over in inversion heterozygotes of Drosophila pseudoobscura. Proc Natl Acad Sci USA 34(4):137–141. https://doi.org/10.1073/pnas.34.4.137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Miloradovic Z, Ivanov M, Mihailovic-Stanojevic N, Grujic Milanovic J, Jovovic D, Vajic UJ, Markovic-Lipkovski J (2014) Acute superoxide radical scavenging reduces blood pressure but does not influence kidney function in hypertensive rats with postischemic kidney injury. Biomed Res Int 2014:512619. https://doi.org/10.1155/2014/512619

    Article  PubMed  PubMed Central  Google Scholar 

  49. Feng D, Ma B, Nazary-Vannani A, Kord-Varkaneh H, Fatahie S, Papageorgiou M, Poursoleiman F, Bd IJ, Li H, Ham D, Wang D (2019) The effects of green coffee been extract supplementation on lipid profile in humans: a systematic review and meta-analysis of randomized controlled trials. Nutr Metab Cardiovasc Dis. https://doi.org/10.1016/j.numecd.2019.10.002

    Article  PubMed  Google Scholar 

  50. Filippini T, Violi F, D'Amico R, Vinceti M (2017) The effect of potassium supplementation on blood pressure in hypertensive subjects: a systematic review and meta-analysis. Int J Cardiol 230:127–135. https://doi.org/10.1016/j.ijcard.2016.12.048

    Article  PubMed  Google Scholar 

  51. Chopra S, Baby C, Jacob JJ (2011) Neuro-endocrine regulation of blood pressure. Indian J Endocrinol Metab 15(Suppl 4):S281–288. https://doi.org/10.4103/2230-8210.86860

    Article  PubMed  PubMed Central  Google Scholar 

  52. National Institute of Health (2019) Zinc. National Institute of Health, Bethesda

    Google Scholar 

  53. Yanagisawa H (2008) Zinc deficiency and clinical practice—validity of zinc preparations. Yakugaku Zasshi 128(3):333–339. https://doi.org/10.1248/yakushi.128.333

    Article  CAS  PubMed  Google Scholar 

  54. Penttila O, Hurme H, Neuvonen PJ (1975) Effect of zinc sulphate on the absorption of tetracycline and doxycycline in man. Eur J Clin Pharmacol 9(2–3):131–134. https://doi.org/10.1007/bf00614009

    Article  CAS  PubMed  Google Scholar 

  55. Lomaestro BM, Bailie GR (1995) Absorption interactions with fluoroquinolones. 1995 Update. Drug Saf 12(5):314–333. https://doi.org/10.2165/00002018-199512050-00004

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

None.

Author information

Authors and Affiliations

  1. Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, P.O. Box 14155-6117, Tehran, Iran

    Seyed Mohammad Mousavi, Manije Darooghegi Mofrad, Alireza Milajerdi & Ahmad Esmaillzadeh

  2. Students’ Scientific Research Center (SSRC), Tehran University of Medical Sciences (TUMS), Tehran, Iran

    Seyed Mohammad Mousavi

  3. University Hospital and School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Israel Júnior Borges do Nascimento

  4. Department of Nutrition and Integrative Physiology, College of Health, University of Utah, Salt Lake City, USA

    Tahereh Mokhtari

  5. Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular, Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Ahmad Esmaillzadeh

  6. Food Security Research Center, Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran

    Ahmad Esmaillzadeh

Authors
  1. Seyed Mohammad Mousavi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Manije Darooghegi Mofrad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Israel Júnior Borges do Nascimento
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alireza Milajerdi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tahereh Mokhtari
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ahmad Esmaillzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SMM and AE conceived the study. TM and AM carried out the literature search and screening articles. MDM and HKV performed data extraction and quality assessment, independently. SMM, JR, and TM analyzed and interpreted data and wrote the manuscript. AE supervised the study. The final version of manuscript has been read and approved by all authors.

Corresponding author

Correspondence to Ahmad Esmaillzadeh.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Additional information

The original version of this article was revised: The family name of “Israel Júnior Borges do Nascimento” was incorrect.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mousavi, S.M., Mofrad, M.D., do Nascimento, I.J.B. et al. The effect of zinc supplementation on blood pressure: a systematic review and dose–response meta-analysis of randomized-controlled trials. Eur J Nutr 59, 1815–1827 (2020). https://doi.org/10.1007/s00394-020-02204-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-020-02204-5

Keywords

Search

Navigation