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

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.