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Effects of perioperative vitamin E and zinc co-supplementation on systemic inflammation and length of stay following coronary artery bypass graft surgery: a randomized controlled trial

European Journal of Clinical Nutrition volume 78, pages 120–127 (2024)Cite this article

Subjects

Abstract

Objectives

Coronary artery bypass graft (CABG) surgery has been reported to be associated with lower postoperative plasma antioxidant and zinc levels. We hypothesized that perioperative supplementation of vitamin E and zinc might improve short-term postoperative outcomes.

Methods

In this placebo-controlled double-blind, randomized study, patients undergoing CABG performed with cardiopulmonary bypass were recruited. The intervention group received zinc and vitamin E supplementation (1200 IU vitamin E and 120 mg elemental zinc) the day before surgery, followed by postoperative daily supplementation of 30 mg zinc and 200 IU vitamin E from the 2nd day after surgery to 3 weeks. The control group received placebos. Length of stay (LOS) in the intensive care unit and hospital, sequential organ failure assessment score on 3rd day after surgery, and plasma inflammatory markers on days 3 and 21 post-surgery were evaluated.

Results

Seventy-eight patients completed the study (40 in the intervention group and 38 in the placebo group). The hospital LOS was significantly shorter (p < 0.05) in the intervention group. Postoperative changes in plasma albumin levels were not different between the two groups. The plasma zinc level was higher (p < 0.0001), but plasma C-reactive protein (p = 0.01), pentraxin 3 (p < 0.0001), interferon γ (p < 0.05), malondialdehyde (p < 0.05), and aspartate aminotransferase (p < 0.01) were lower in the intervention group compared to the placebo group.

Conclusions

Perioperative vitamin E and zinc supplementation significantly reduced hospital LOS and the inflammatory response in CABG surgery patients. In these patients, the optimal combination and dose of micronutrients need further study but could include zinc and vitamin E.

Clinical trial registry

This trial was registered at ClinicalTrials.gov website (NCT05402826).

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Figure 1
Fig. 2: Plasma levels of biomarkers in the two groups before and after the surgery.

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Data availability

The data of this study are available from the corresponding author upon reasonable request.

References

  1. Jongman RM, Zijlstra JG, Kok WF, van Harten AE, Mariani MA, Moser J, et al. Off-pump CABG surgery reduces systemic inflammation compared with on-pump surgery but does not change systemic endothelial responses: a prospective randomized study. Shock. 2014;42:121–8. https://doi.org/10.1097/shk.0000000000000190

    Article  CAS  PubMed  Google Scholar 

  2. Murphy GJ, Angelini GD. Side effects of cardiopulmonary bypass: what is the reality? J Card Surg. 2004;19:481–8. https://doi.org/10.1111/j.0886-0440.2004.04101.x

    Article  CAS  PubMed  Google Scholar 

  3. Milei J, Forcada P, Fraga CG, Grana DR, Iannelli G, Chiariello M, et al. Relationship between oxidative stress, lipid peroxidation, and ultrastructural damage in patients with coronary artery disease undergoing cardioplegic arrest/reperfusion. Cardiovasc Res. 2007;73:710–9. https://doi.org/10.1016/j.cardiores.2006.12.007

    Article  CAS  PubMed  Google Scholar 

  4. Christen S, Finckh B, Lykkesfeldt J, Gessler P, Frese-Schaper M, Nielsen P, et al. Oxidative stress precedes peak systemic inflammatory response in pediatric patients undergoing cardiopulmonary bypass operation. Free Radic Biol Med. 2005;38:1323–32. https://doi.org/10.1016/j.freeradbiomed.2005.01.016

    Article  CAS  PubMed  Google Scholar 

  5. Pang Y, Li Y, Zhang Y, Wang H, Lang J, Han L, et al. Effects of inflammation and oxidative stress on postoperative delirium in cardiac surgery. Front Cardiovasc Med. 2022;9:1049600. https://doi.org/10.3389/fcvm.2022.1049600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Zakkar M, Guida G, Suleiman MS, Angelini GD. Cardiopulmonary bypass and oxidative stress. Oxid Med Cell Longev. 2015;2015:189863. https://doi.org/10.1155/2015/189863

    Article  PubMed  PubMed Central  Google Scholar 

  7. Jouybar R, Kabgani H, Kamalipour H, Shahbazi S, Allahyary E, Rasouli M, et al. The perioperative effect of ascorbic acid on inflammatory response in coronary artery bypass graft surgery; a randomized controlled trial coronary artery bypass graft surgery. Int Cardiovasc Res J. 2017;6:1.

    Google Scholar 

  8. Ali- Hasan- Al- Saegh S, Mirhosseini SJ, Tahernejad M, Mahdavi P, Shahidzadeh A, Karimi-Bondarabadi AA, et al. Impact of antioxidant supplementations on cardio-renal protection in cardiac surgery: an updated and comprehensive meta-analysis and systematic review. Cardiovasc Ther. 2016;34:360–70. https://doi.org/10.1111/1755-5922.12207

    Article  CAS  PubMed  Google Scholar 

  9. Lassnigg A, Punz A, Barker R, Keznickl P, Manhart N, Roth E, et al. Influence of intravenous vitamin E supplementation in cardiac surgery on oxidative stress: a double-blinded, randomized, controlled study. Br J Anaesth. 2003;90:148–54. https://doi.org/10.1093/bja/aeg042

    Article  CAS  PubMed  Google Scholar 

  10. Axford-Gately RA, Wilson GJ. Myocardial infarct size reduction by single high dose or repeated low dose vitamin E supplementation in rabbits. Can J Cardiol. 1993;9:94–8.

    CAS  PubMed  Google Scholar 

  11. Jaxa-Chamiec T, Bednarz B, Drozdowska D, Gessek J, Gniot J, Janik K, et al. Antioxidant effects of combined vitamins C and E in acute myocardial infarction. The randomized, double-blind, placebo controlled, multicenter pilot Myocardial Infarction and VITamins (MIVIT) trial. Kardiol Pol. 2005;62:344–50.

    PubMed  Google Scholar 

  12. Hou HT, Xue LG, Zhou JY, Wang SF, Yang Q, He GW. Alteration of plasma trace elements magnesium, copper, zinc, iron and calcium during and after coronary artery bypass grafting surgery. J Trace Elem Med Biol. 2020;62:126612 https://doi.org/10.1016/j.jtemb.2020.126612

    Article  CAS  PubMed  Google Scholar 

  13. Shenkin A, Berger MM. Micronutrients: a low blood concentration is not equivalent to deficiency. Clin Nutr. 2022;41:2562–4. https://doi.org/10.1016/j.clnu.2022.09.015

    Article  PubMed  Google Scholar 

  14. Powell SR. The antioxidant properties of zinc. J Nutr. 2000;130:1447s–54s. https://doi.org/10.1093/jn/130.5.1447S

    Article  CAS  PubMed  Google Scholar 

  15. Karagulova G, Yue Y, Moreyra A, Boutjdir M, Korichneva I. Protective role of intracellular zinc in myocardial ischemia/reperfusion is associated with preservation of protein kinase C isoforms. J Pharmacol Exp Ther. 2007;321:517–25.

    Article  CAS  PubMed  Google Scholar 

  16. Boehme AK, Hays AN, Kicielinski KP, Arora K, Kapoor N, Lyerly MJ, et al. Systemic inflammatory response syndrome and outcomes in intracerebral hemorrhage. Neurocrit Care. 2016;25:133–40. https://doi.org/10.1007/s12028-016-0255-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Aguilar Diaz De Leon J, Borges CR. Evaluation of oxidative stress in biological samples using the thiobarbituric acid reactive substances assay. J Vis Exp. 2020. https://doi.org/10.3791/61122

  18. Nouri-Majalan N, Ardakani EF, Forouzannia K, Moshtaghian H. Effects of allopurinol and vitamin E on renal function in patients with cardiac coronary artery bypass grafts. Vasc Health Risk Manag. 2009;5:489.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Duncan A, Talwar D, McMillan DC, Stefanowicz F, O’Reilly DS. Quantitative data on the magnitude of the systemic inflammatory response and its effect on micronutrient status based on plasma measurements. Am J Clin Nutr. 2012;95:64–71. https://doi.org/10.3945/ajcn.111.023812

    Article  CAS  PubMed  Google Scholar 

  20. Berger MM, Soguel L, Shenkin A, Revelly JP, Pinget C, Baines M, et al. Influence of early antioxidant supplements on clinical evolution and organ function in critically ill cardiac surgery, major trauma, and subarachnoid hemorrhage patients. Crit Care. 2008;12:R101 https://doi.org/10.1186/cc6981

    Article  PubMed  PubMed Central  Google Scholar 

  21. Santos HO, Teixeira FJ, Schoenfeld BJ. Dietary vs. pharmacological doses of zinc: a clinical review. Clin Nutr. 2020;39:1345–53. https://doi.org/10.1016/j.clnu.2019.06.024

    Article  CAS  PubMed  Google Scholar 

  22. Ai AL, Hall D, Bolling SF. Interleukin-6 and hospital length of stay after open-heart surgery. Biol Psichiatr Psichofarmakol. 2012;14:79–82.

    PubMed  PubMed Central  Google Scholar 

  23. Nouri-Majalan N, Ardakani EF, Forouzannia K, Moshtaghian H. Effects of allopurinol and vitamin E on renal function in patients with cardiac coronary artery bypass grafts. Vasc Health Risk Manag. 2009;5:489–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Nathens AB, Neff MJ, Jurkovich GJ, Klotz P, Farver K, Ruzinski JT, et al. Randomized, prospective trial of antioxidant supplementation in critically ill surgical patients. Ann Surg. 2002;236:814.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Dey S, Kashav R, Kohli JK, Magoon R, ItiShri, Walian A, et al. Systemic immune-inflammation index predicts poor outcome after elective off-pump CABG: a retrospective, single-center study. J Cardiothorac Vasc Anesth. 2021;35:2397–404. https://doi.org/10.1053/j.jvca.2020.09.092

    Article  CAS  PubMed  Google Scholar 

  26. Bastrup-Birk S, Skjoedt MO, Munthe-Fog L, Strom JJ, Ma YJ, Garred P. Pentraxin-3 serum levels are associated with disease severity and mortality in patients with systemic inflammatory response syndrome. PLoS One. 2013;8:e73119 https://doi.org/10.1371/journal.pone.0073119

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  27. Holubcova Z, Kunes P, Mandak J, Kolackova M, Andrys C, Krejsek J, et al. Could pentraxin 3 be a new diagnostic marker for excessive inflammatory response in cardiac surgery? Thorac Cardiovasc Surg. 2014;62:670–6. https://doi.org/10.1055/s-0034-1384668

    Article  PubMed  Google Scholar 

  28. Gunes T, Bozok S, Kestelli M, Yurekli I, Ilhan G, Ozpak B, et al. α-tocopherol and ascorbic acid in early postoperative period of cardiopulmonary bypass. J Cardiovasc Med (Hagerstown). 2012;13:691–9. https://doi.org/10.2459/JCM.0b013e328356a2dc

    Article  CAS  PubMed  Google Scholar 

  29. Mertens K, Lowes D, Webster N, Talib J, Hall L, Davies MJ, et al. Low zinc and selenium concentrations in sepsis are associated with oxidative damage and inflammation. BJA: Br J Anaesth. 2015;114(6):990–9.

    Article  CAS  PubMed  Google Scholar 

  30. Schoenborn JR, Wilson CB. Regulation of interferon-gamma during innate and adaptive immune responses. Adv Immunol. 2007;96:41–101. https://doi.org/10.1016/s0065-2776(07)96002-2

    Article  CAS  PubMed  Google Scholar 

  31. Franke A, Lante W, Fackeldey V, Becker HP, Thode C, Kuhlmann WD, et al. Proinflammatory and antiinflammatory cytokines after cardiac operation: different cellular sources at different times. Ann Thorac Surg. 2002;74:363–70. https://doi.org/10.1016/s0003-4975(02)03658-5

    Article  PubMed  Google Scholar 

  32. Franke A, Lante W, Markewitz A, Weinhold C. In vitro restoration of post-operatively decreased IFN-gamma levels after cardiac surgery and its effect on pro- and anti-inflammatory mediators. J Surg Res. 2006;136:266–72. https://doi.org/10.1016/j.jss.2006.06.036

    Article  CAS  PubMed  Google Scholar 

  33. Busch CJ, Binder CJ. Malondialdehyde epitopes as mediators of sterile inflammation. Biochim Biophys Acta Mol Cell Biol Lipids. 2017;1862:398–406. https://doi.org/10.1016/j.bbalip.2016.06.016

    Article  CAS  PubMed  Google Scholar 

  34. Canbaz S, Duran E, Ege T, Sunar H, Cikirikcioglu M, Acipayam M. The effects of intracoronary administration of vitamin E on myocardial ischemia-reperfusion injury during coronary artery surgery. Thorac Cardiovasc Surg. 2003;51:57–61. https://doi.org/10.1055/s-2003-38983

    Article  CAS  PubMed  Google Scholar 

  35. van Boxtel AG, Bramer S, Soliman Hamad MA, van Straten AH. Perioperative serum aspartate aminotransferase level as a predictor of survival after coronary artery bypass grafting. Ann Thorac Surg. 2012;94:1492–8. https://doi.org/10.1016/j.athoracsur.2012.05.098

    Article  PubMed  Google Scholar 

  36. Gultekin Y, Bolat A, Hatice K, Tekeli Kunt A. Does aspartate aminotransferase to alanine aminotransferase ratio predict acute kidney injury after cardiac surgery? Heart Surg Forum. 2021;24:E506–e11. https://doi.org/10.1532/hsf.3849

    Article  PubMed  Google Scholar 

  37. Sato K, Gosho M, Yamamoto T, Kobayashi Y, Ishii N, Ohashi T, et al. Vitamin E has a beneficial effect on nonalcoholic fatty liver disease: a meta-analysis of randomized controlled trials. Nutrition. 2015;31:923–30. https://doi.org/10.1016/j.nut.2014.11.018

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank the staff of the Cardiac Intensive Care Unit of Shafa Hospital.

Funding

This work was supported by a research grant from Shahid Beheshti University of Medical Sciences.

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Authors and Affiliations

  1. Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, No. 7, Hafezi St., Farahzadi Blvd., Qods Town, Tehran, Iran

    Elham Makiabadi & Javad Nasrollahzadeh

  2. Department of Surgery, School of Medicine, Shafa Hospital, Kerman University of Medical Sciences, Kerman, Iran

    Reza Nakhaeizadeh

  3. Department of Cardiac Intensive Care Unit, School of Medicine, Shafa Hospital, Kerman University of Medical Sciences, Kerman, Iran

    Mohammad Soleimani

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Contributions

The research was conceived by JN, designed by JN, EM, and RN; conducted by EM and RN, and MS; data were analyzed by JN; the paper was written by EM and JN. All authors approved the final version of the manuscript.

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Correspondence to Javad Nasrollahzadeh.

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Makiabadi, E., Nakhaeizadeh, R., Soleimani, M. et al. Effects of perioperative vitamin E and zinc co-supplementation on systemic inflammation and length of stay following coronary artery bypass graft surgery: a randomized controlled trial. Eur J Clin Nutr 78, 120–127 (2024). https://doi.org/10.1038/s41430-023-01356-x

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