Skip to main content
Top
Published in: BMC Cardiovascular Disorders 1/2017

Open Access 01-12-2017 | Research article

Vitamin C for preventing atrial fibrillation in high risk patients: a systematic review and meta-analysis

Authors: Harri Hemilä, Timo Suonsyrjä

Published in: BMC Cardiovascular Disorders | Issue 1/2017

Login to get access

Abstract

Background

Atrial fibrillation (AF), a common arrhythmia contributing substantially to cardiac morbidity, is associated with oxidative stress and, being an antioxidant, vitamin C might influence it.

Methods

We searched the Cochrane CENTRAL Register, MEDLINE, and Scopus databases for randomised trials on vitamin C that measured AF as an outcome in high risk patients. The two authors independently assessed the trials for inclusion, assessed the risk of bias, and extracted data. We pooled selected trials using the Mantel-Haenszel method for the risk ratio (RR) and the inverse variance weighting for the effects on continuous outcomes.

Results

We identified 15 trials about preventing AF in high-risk patients, with 2050 subjects. Fourteen trials examined post-operative AF (POAF) in cardiac surgery patients and one examined the recurrence of AF in cardioversion patients. Five trials were carried out in the USA, five in Iran, three in Greece, one in Slovenia and one in Russia.
There was significant heterogeneity in the effect of vitamin C in preventing AF. In 5 trials carried out in the USA, vitamin C did not prevent POAF with RR = 1.04 (95% CI: 0.86–1.27). In nine POAF trials conducted outside of the USA, vitamin C decreased its incidence with RR = 0.56 (95% CI: 0.47–0.67). In the single cardioversion trial carried out in Greece, vitamin C decreased the risk of AF recurrence by RR = 0.13 (95% CI: 0.02–0.92).
In the non-US cardiac surgery trials, vitamin C decreased the length of hospital stay by 12.6% (95% CI 8.4–16.8%) and intensive care unit (ICU) stay by 8.0% (95% CI 3.0–13.0%). The US trials found no effect on hospital stay and ICU stay. No adverse effects from vitamin C were reported in the 15 trials.

Conclusions

Our meta-analysis indicates that vitamin C may prevent post-operative atrial fibrillation in some countries outside of the USA, and it may also shorten the duration of hospital stay and ICU stay of cardiac surgery patients. Vitamin C is an essential nutrient that is safe and inexpensive. Further research is needed to determine the optimal dosage protocol and to identify the patient groups that benefit the most.
Appendix
Available only for authorised users
Literature
2.
go back to reference Hogue Jr CW, Creswell LL, Gutterman DD, Fleisher LA. American College of Chest Physicians. Epidemiology, mechanisms, and risks: American College of Chest Physicians guidelines for the prevention and management of postoperative atrial fibrillation after cardiac surgery. Chest. 2005;128(2 Suppl):9S–16S.CrossRefPubMed Hogue Jr CW, Creswell LL, Gutterman DD, Fleisher LA. American College of Chest Physicians. Epidemiology, mechanisms, and risks: American College of Chest Physicians guidelines for the prevention and management of postoperative atrial fibrillation after cardiac surgery. Chest. 2005;128(2 Suppl):9S–16S.CrossRefPubMed
3.
go back to reference Carnes CA, Chung MK, Nakayama T, Nakayama H, Baliga RS, Piao S, et al. Ascorbate attenuates atrial pacing-induced peroxynitrite formation and electrical remodeling and decreases the incidence of postoperative atrial fibrillation. Circ Res. 2001;89:E32–8.CrossRefPubMed Carnes CA, Chung MK, Nakayama T, Nakayama H, Baliga RS, Piao S, et al. Ascorbate attenuates atrial pacing-induced peroxynitrite formation and electrical remodeling and decreases the incidence of postoperative atrial fibrillation. Circ Res. 2001;89:E32–8.CrossRefPubMed
4.
go back to reference Violi F, Pastori D, Pignatelli P, Loffredo L. Antioxidants for prevention of atrial fibrillation: a potentially useful future therapeutic approach? A review of the literature and meta-analysis. Europace. 2014;16:1107–16.CrossRefPubMed Violi F, Pastori D, Pignatelli P, Loffredo L. Antioxidants for prevention of atrial fibrillation: a potentially useful future therapeutic approach? A review of the literature and meta-analysis. Europace. 2014;16:1107–16.CrossRefPubMed
5.
go back to reference Morita N, Sovari AA, Xie Y, Fishbein MC, Mandel WJ, Garfinkel A, et al. Increased susceptibility of aged hearts to ventricular fibrillation during oxidative stress. Am J Physiol Heart Circ Physiol. 2009;297:H1594–605.CrossRefPubMedPubMedCentral Morita N, Sovari AA, Xie Y, Fishbein MC, Mandel WJ, Garfinkel A, et al. Increased susceptibility of aged hearts to ventricular fibrillation during oxidative stress. Am J Physiol Heart Circ Physiol. 2009;297:H1594–605.CrossRefPubMedPubMedCentral
6.
go back to reference Van Wagoner DR. Oxidative stress and inflammation in atrial fibrillation: role in pathogenesis and potential as a therapeutic target. J Cardiovasc Pharmacol. 2008;52:306–13.CrossRefPubMed Van Wagoner DR. Oxidative stress and inflammation in atrial fibrillation: role in pathogenesis and potential as a therapeutic target. J Cardiovasc Pharmacol. 2008;52:306–13.CrossRefPubMed
7.
go back to reference Ballmer PE, Reinhart WH, Jordan P, Buhler E, Moser UK, Gey KF. Depletion of plasma vitamin C but not of vitamin E in response to cardiac operations [correction in 1995;110:1972]. J Thor Cardiovasc Surg. 1994;108:311–20. Ballmer PE, Reinhart WH, Jordan P, Buhler E, Moser UK, Gey KF. Depletion of plasma vitamin C but not of vitamin E in response to cardiac operations [correction in 1995;110:1972]. J Thor Cardiovasc Surg. 1994;108:311–20.
8.
go back to reference Lassnigg A, Punz A, Barker R, Keznickl P, Manhart N, Roth E, Hiesmayr M. Influence of intravenous vitamin E supplementation in cardiac surgery on oxidative stress: a double-blinded, randomized, controlled study. Br J Anaesthesia. 2003;90:148–54.CrossRef Lassnigg A, Punz A, Barker R, Keznickl P, Manhart N, Roth E, Hiesmayr M. Influence of intravenous vitamin E supplementation in cardiac surgery on oxidative stress: a double-blinded, randomized, controlled study. Br J Anaesthesia. 2003;90:148–54.CrossRef
9.
go back to reference Rodemeister S, Duquesne M, Adolph M, Nohr D, Biesalski HK, Unertl K. Massive and long-lasting decrease in vitamin C plasma levels as a consequence of extracorporeal circulation. Nutrition. 2014;30:673–8.CrossRefPubMed Rodemeister S, Duquesne M, Adolph M, Nohr D, Biesalski HK, Unertl K. Massive and long-lasting decrease in vitamin C plasma levels as a consequence of extracorporeal circulation. Nutrition. 2014;30:673–8.CrossRefPubMed
10.
go back to reference Basili S, Tanzilli G, Mangieri E, Raparelli V, Di Santo S, Pignatelli P, et al. Intravenous ascorbic acid infusion improves myocardial perfusion grade during elective percutaneous coronary intervention: relationship with oxidative stress markers. JACC Cardiovasc Interv. 2010;3:221–9.CrossRefPubMed Basili S, Tanzilli G, Mangieri E, Raparelli V, Di Santo S, Pignatelli P, et al. Intravenous ascorbic acid infusion improves myocardial perfusion grade during elective percutaneous coronary intervention: relationship with oxidative stress markers. JACC Cardiovasc Interv. 2010;3:221–9.CrossRefPubMed
11.
go back to reference Oktar GL, Sinci V, Kalaycioglu S, Soncul H, Gökgöz L, Halit V, Ersöz A. Biochemical and hemodynamic effects of ascorbic acid and alpha-tocopherol in coronary artery surgery. Scand J Clin Lab Investig. 2001;61:621–9.CrossRef Oktar GL, Sinci V, Kalaycioglu S, Soncul H, Gökgöz L, Halit V, Ersöz A. Biochemical and hemodynamic effects of ascorbic acid and alpha-tocopherol in coronary artery surgery. Scand J Clin Lab Investig. 2001;61:621–9.CrossRef
12.
go back to reference Wang ZJ, Hu WK, Liu YY, Shi DM, Cheng WJ, Guo YH, et al. The effect of intravenous vitamin C infusion on periprocedural myocardial injury for patients undergoing elective percutaneous coronary intervention. Can J Cardiol. 2014;30:96–101.CrossRefPubMed Wang ZJ, Hu WK, Liu YY, Shi DM, Cheng WJ, Guo YH, et al. The effect of intravenous vitamin C infusion on periprocedural myocardial injury for patients undergoing elective percutaneous coronary intervention. Can J Cardiol. 2014;30:96–101.CrossRefPubMed
13.
go back to reference Ashor AW, Lara J, Mathers JC, Siervo M. Effect of vitamin C on endothelial function in health and disease: a systematic review and meta-analysis of randomised controlled trials. Atherosclerosis. 2012;235:9–20.CrossRef Ashor AW, Lara J, Mathers JC, Siervo M. Effect of vitamin C on endothelial function in health and disease: a systematic review and meta-analysis of randomised controlled trials. Atherosclerosis. 2012;235:9–20.CrossRef
14.
go back to reference Juraschek SP, Guallar E, Appel LJ, Miller 3rd ER. Effects of vitamin C supplementation on blood pressure: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2012;95:1079–88.CrossRefPubMedPubMedCentral Juraschek SP, Guallar E, Appel LJ, Miller 3rd ER. Effects of vitamin C supplementation on blood pressure: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2012;95:1079–88.CrossRefPubMedPubMedCentral
15.
go back to reference Sadat U, Usman A, Gillard JH, Boyle JR. Does ascorbic acid protect against contrast-induced acute kidney injury in patients undergoing coronary angiography: a systematic review with meta-analysis of randomized, controlled trials. J Am Coll Cardiol. 2013;62:2167–75.CrossRefPubMed Sadat U, Usman A, Gillard JH, Boyle JR. Does ascorbic acid protect against contrast-induced acute kidney injury in patients undergoing coronary angiography: a systematic review with meta-analysis of randomized, controlled trials. J Am Coll Cardiol. 2013;62:2167–75.CrossRefPubMed
16.
go back to reference Levine M, Rumsey SC, Daruwala R, Park JB, Wang Y. Criteria and recommendations for vitamin C intake. JAMA. 1999;281:1415–23.CrossRefPubMed Levine M, Rumsey SC, Daruwala R, Park JB, Wang Y. Criteria and recommendations for vitamin C intake. JAMA. 1999;281:1415–23.CrossRefPubMed
17.
go back to reference Institute of Medicine. Vitamin C. In: Dietary reference intakes for vitamin C, vitamin E, selenium and carotenoids. Washington DC: National Academy Press; 2000. p. 95–185. Institute of Medicine. Vitamin C. In: Dietary reference intakes for vitamin C, vitamin E, selenium and carotenoids. Washington DC: National Academy Press; 2000. p. 95–185.
18.
go back to reference Bjordahl PM, Helmer SD, Gosnell DJ, Wemmer GE, O'Hara WW, Milfeld DJ. Perioperative supplementation with ascorbic acid does not prevent atrial fibrillation in coronary artery bypass graft patients. Am J Surg. 2012;204:862–7.CrossRefPubMed Bjordahl PM, Helmer SD, Gosnell DJ, Wemmer GE, O'Hara WW, Milfeld DJ. Perioperative supplementation with ascorbic acid does not prevent atrial fibrillation in coronary artery bypass graft patients. Am J Surg. 2012;204:862–7.CrossRefPubMed
19.
go back to reference Dehghani MR, Madjidi N, Rahmani A, Asgari B, Rezaei Y. Effect of oral vitamin C on atrial fibrillation development after isolated coronary artery bypass grafting surgery: A prospective randomized clinical trial. Cardiol J. 2014;21:492–9.CrossRefPubMed Dehghani MR, Madjidi N, Rahmani A, Asgari B, Rezaei Y. Effect of oral vitamin C on atrial fibrillation development after isolated coronary artery bypass grafting surgery: A prospective randomized clinical trial. Cardiol J. 2014;21:492–9.CrossRefPubMed
20.
go back to reference Eslami M, Badkoubeh RS, Mousavi M, Radmehr H, Salehi M, Tavakoli N, et al. Oral ascorbic acid in combination with beta-blockers is more effective than beta-blockers alone in the prevention of atrial fibrillation after coronary artery bypass grafting. Tex Heart Inst J. 2007;34:268–74.PubMedPubMedCentral Eslami M, Badkoubeh RS, Mousavi M, Radmehr H, Salehi M, Tavakoli N, et al. Oral ascorbic acid in combination with beta-blockers is more effective than beta-blockers alone in the prevention of atrial fibrillation after coronary artery bypass grafting. Tex Heart Inst J. 2007;34:268–74.PubMedPubMedCentral
21.
go back to reference Papoulidis P, Ananiadou O, Chalvatzoulis E, Ampatzidou F, Koutsogiannidis C, Karaiskos T, et al. The role of ascorbic acid in the prevention of atrial fibrillation after elective on-pump myocardial revascularization surgery: A single-center experience - a pilot study. Interact Cardiovasc Thorac Surg. 2011;12:121–4.CrossRefPubMed Papoulidis P, Ananiadou O, Chalvatzoulis E, Ampatzidou F, Koutsogiannidis C, Karaiskos T, et al. The role of ascorbic acid in the prevention of atrial fibrillation after elective on-pump myocardial revascularization surgery: A single-center experience - a pilot study. Interact Cardiovasc Thorac Surg. 2011;12:121–4.CrossRefPubMed
22.
go back to reference Polymeropoulos E. Vitamin C for prophylaxis of post-operative atrial fibrillation in on-pump cardiac surgery procedures, ClinicalTrials.gov NCT01107730. 2015. Polymeropoulos E. Vitamin C for prophylaxis of post-operative atrial fibrillation in on-pump cardiac surgery procedures, ClinicalTrials.gov NCT01107730. 2015.
23.
go back to reference Antonic M, Lipovec R, Gregorcic F, Juric P, Kosir G. Perioperative ascorbic acid supplementation does not reduce the incidence of postoperative atrial fibrillation in on-pump coronary artery bypass graft patients. J Cardiol. 2017;69:98–102. doi:10.1016/j.jjcc.2016.01.010. Antonic M, Lipovec R, Gregorcic F, Juric P, Kosir G. Perioperative ascorbic acid supplementation does not reduce the incidence of postoperative atrial fibrillation in on-pump coronary artery bypass graft patients. J Cardiol. 2017;69:98–102. doi:10.​1016/​j.​jjcc.​2016.​01.​010.
24.
25.
go back to reference Samadikhah J, Golzari SEJ, Sabermarouf B, Karimzadeh I, Tizro P, Khanli HM, et al. Efficacy of combination therapy of statin and vitamin C in comparison with statin in the prevention of post-CABG atrial fibrillation. Adv Pharm Bull. 2014;4:97–100.PubMed Samadikhah J, Golzari SEJ, Sabermarouf B, Karimzadeh I, Tizro P, Khanli HM, et al. Efficacy of combination therapy of statin and vitamin C in comparison with statin in the prevention of post-CABG atrial fibrillation. Adv Pharm Bull. 2014;4:97–100.PubMed
28.
go back to reference Colby JA, Chen WT, Baker WL, Coleman CI, Reinhart K, Kluger J, et al. Effect of ascorbic acid on inflammatory markers after cardiothoracic surgery. Am J Health-Syst Pharm. 2011;68:1632–9.CrossRefPubMed Colby JA, Chen WT, Baker WL, Coleman CI, Reinhart K, Kluger J, et al. Effect of ascorbic acid on inflammatory markers after cardiothoracic surgery. Am J Health-Syst Pharm. 2011;68:1632–9.CrossRefPubMed
29.
go back to reference Healy RM, Day D, Van Gorder C. Ascorbic acid utilization for atrial-fibrillation prophylaxis post coronary-artery-bypass graft and valve replacement surgeries: An interim analysis of a prospective, randomized study [Abstract 285]. Pharmacotherapy. 2010;30:445e–6e. Healy RM, Day D, Van Gorder C. Ascorbic acid utilization for atrial-fibrillation prophylaxis post coronary-artery-bypass graft and valve replacement surgeries: An interim analysis of a prospective, randomized study [Abstract 285]. Pharmacotherapy. 2010;30:445e–6e.
30.
go back to reference Donovan PC, Kramer RS. Prophylaxis to Reduce Postoperative Atrial Fibrillation in Cardiac Surgery, ClinicalTrials.gov NCT00953212. 2012. Donovan PC, Kramer RS. Prophylaxis to Reduce Postoperative Atrial Fibrillation in Cardiac Surgery, ClinicalTrials.gov NCT00953212. 2012.
31.
go back to reference Sadeghpour A, Alizadehasl A, Kyavar M, Sadeghi T, Moludi J, Gholizadeh F, Totonchi Z, Ghadrdoost B. Impact of vitamin C supplementation on post-cardiac surgery ICU and hospital length of stay. Anesth Pain Med. 2015;5:e25337.PubMedPubMedCentral Sadeghpour A, Alizadehasl A, Kyavar M, Sadeghi T, Moludi J, Gholizadeh F, Totonchi Z, Ghadrdoost B. Impact of vitamin C supplementation on post-cardiac surgery ICU and hospital length of stay. Anesth Pain Med. 2015;5:e25337.PubMedPubMedCentral
32.
go back to reference Korantzopoulos P, Kolettis TM, Kountouris E, Dimitroula V, Karanikis P, Pappa E, et al. Oral vitamin C administration reduces early recurrence rates after electrical cardioversion of persistent atrial fibrillation and attenuates associated inflammation. Int J Cardiology. 2005;102:321–6.CrossRef Korantzopoulos P, Kolettis TM, Kountouris E, Dimitroula V, Karanikis P, Pappa E, et al. Oral vitamin C administration reduces early recurrence rates after electrical cardioversion of persistent atrial fibrillation and attenuates associated inflammation. Int J Cardiology. 2005;102:321–6.CrossRef
34.
go back to reference Lydersen S, Fagerland MW, Laake P. Recommended tests for association in 2×2 tables. Stat Med. 2009;28:1159–75.CrossRefPubMed Lydersen S, Fagerland MW, Laake P. Recommended tests for association in 2×2 tables. Stat Med. 2009;28:1159–75.CrossRefPubMed
36.
go back to reference Panagiotou OA, Contopoulos-Ioannidis DG, Ioannidis JP. Comparative effect sizes in randomised trials from less developed and more developed countries: meta-epidemiological assessment. BMJ. 2013;346:f707.CrossRefPubMedPubMedCentral Panagiotou OA, Contopoulos-Ioannidis DG, Ioannidis JP. Comparative effect sizes in randomised trials from less developed and more developed countries: meta-epidemiological assessment. BMJ. 2013;346:f707.CrossRefPubMedPubMedCentral
37.
go back to reference Padayatty SJ, Sun H, Wang Y, Riordan HD, Hewitt SM, Katz A, et al. Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med. 2004;140:533–7.CrossRefPubMed Padayatty SJ, Sun H, Wang Y, Riordan HD, Hewitt SM, Katz A, et al. Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med. 2004;140:533–7.CrossRefPubMed
38.
go back to reference Levy D, Kannel WB. Postoperative atrial fibrillation and mortality: do the risks merit changes in clinical practice? J Am Coll Cardiol. 2004;43:749–51.CrossRefPubMed Levy D, Kannel WB. Postoperative atrial fibrillation and mortality: do the risks merit changes in clinical practice? J Am Coll Cardiol. 2004;43:749–51.CrossRefPubMed
39.
go back to reference Hrobjartsson A, Gotzsche PC. Placebo interventions for all clinical conditions. Cochrane Database Syst Rev. 2010;1:CD003974. Hrobjartsson A, Gotzsche PC. Placebo interventions for all clinical conditions. Cochrane Database Syst Rev. 2010;1:CD003974.
40.
go back to reference Tanaka H, Matsuda T, Miyagantani Y, Yukioka T, Matsuda H, Shimazaki S. Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: a randomized, prospective study. Arch Surg. 2000;135:326–31.CrossRefPubMed Tanaka H, Matsuda T, Miyagantani Y, Yukioka T, Matsuda H, Shimazaki S. Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: a randomized, prospective study. Arch Surg. 2000;135:326–31.CrossRefPubMed
Metadata
Title
Vitamin C for preventing atrial fibrillation in high risk patients: a systematic review and meta-analysis
Authors
Harri Hemilä
Timo Suonsyrjä
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2017
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-017-0478-5

Other articles of this Issue 1/2017

BMC Cardiovascular Disorders 1/2017 Go to the issue