Vitamin C and cardiac disorders

by Harri Hemilä

Department of Public Health
University of Helsinki, Finland
harri.hemila@helsinki.fi
https://www.mv.helsinki.fi/home/hemila
Jan 31, 2025

Meta-analyses and re-analyses
Flaws in the analyses on vitamin C and cardiac disorders by other authors
Flawed controlled trials on vitamin C and cardiovascular diseases
Flawed Mendelian randomization studies on vitamin C and cardiovascular diseases

Meta-analyses and re-analyses

Hemilä H, de Man AME.
Vitamin C deficiency can lead to pulmonary hypertension: a systematic review of case reports.
BMC Pulm Med. 2024
https://doi.org/10.1186/s12890-024-02941-x
https://pmc.ncbi.nlm.nih.gov/articles/PMC10949735

Rozemeijer S, Hemilä H, van Baaren M, de Man AME.
Vitamin C may reduce troponin and CKMB levels after PCI and CABG: a meta-analysis.
BMC Cardiovasc Disord. 2023
https://doi.org/10.1186/s12872-023-03459-6

https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10512653

Hemilä H, Chalker E, de Man AME.
Vitamin C may improve left ventricular ejection fraction: a meta-analysis.
Front Cardiovasc Med. 2022
https://doi.org/10.3389/fcvm.2022.789729
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8913583

Hemilä H, Suonsyrjä T.
Vitamin C for preventing atrial fibrillation in high risk patients: a systematic review and meta-analysis.
BMC Cardiovascular Disorders 2017
https://doi.org/10.1186/s12872-017-0478-5
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286679

Hemilä H.
Publication bias in meta-analysis of ascorbic acid for postoperative atrial fibrillation.
American Journal for Health System Pharmacy 2017;74(6):372-373.
https://doi.org/10.2146/ajhp160999
https://www.mv.helsinki.fi/home/hemila/H/2017_L_AJHP.pdf

Flaws in the analyses on vitamin C and cardiac disorders by other authors

These meta-analyses have some shortcomings but the shortcomings do no invalidate the conclusion that there is strong evidence that vitamin C has effects on AF. Thereby these meta-analyses are consistent with the conclusions of the meta-analysis by Hemilä and Suonsyrjä (2017), that vitamin C has effects on cardiac disorders in some conexts.

Flaws in the inclusion of trials and in referring to earlier meta-analyses
Pubpeer
https://pubpeer.com/publications/3C3BC7155720D6313E0A0EB6091A7B

Comments on:

Khan SA et al. (2020)

Vitamin C for cardiac protection during percutaneous coronary intervention: a systematic review of randomized controlled trials.

Nutrients. 2020

https://pubmed.ncbi.nlm.nih.gov/32718091

Vitamin C for cardiac surgery patients: several errors in a published meta-analysis. Comment on “Effects of vitamin C on organ function in cardiac surgery patients: a systematic review and meta-analysis.. Nutrients 2019, 11, 2103”.
Hemilä H, Chalker E.
Nutrients 2020
https://doi.org/10.3390/nu12020586
See the Supplementary file for more details:
https://www.mdpi.com/2072-6643/12/2/586/s1

Comments on:

Hill et al. (2019)

Effects of vitamin C on organ function in cardiac surgery patients: a systematic review and meta-analysis.

Nutrients 2019

https://pubmed.ncbi.nlm.nih.gov/31487905

Misleading review on vitamin C and cardiac patients
Pubpeer
https://pubpeer.com/publications/DEBED5D9F498A0C940E18841C25C75

Comments on:

Hill A et al. (2018)

Vitamin C to improve organ dysfunction in cardiac surgery patients-review and pragmatic approach.

Nutrients 2018

https://www.mdpi.com/2072-6643/10/8/974

Random-Effects Assumption in Meta-analyses.
Hemilä H.
JAMA. 2019
https://doi.org/10.1001/jama.2019.5439
https://www.ncbi.nlm.nih.gov/pubmed/31265091

Comments on:

Shi R et al. (2018)

Sole and combined vitamin C supplementation can prevent postoperative atrial fibrillation after cardiac surgery: A systematic review and meta-analysis of randomized controlled trials.

Clin Cardiol. 2018

https://www.ncbi.nlm.nih.gov/pubmed/29603289

Errors in a meta-analysis on vitamin C and post-operative atrial fibrillation.
Hemilä H.
Int J Surg. 2019
https://doi.org/10.1016/j.ijsu.2019.01.025
https://www.ncbi.nlm.nih.gov/pubmed/30831247

Comments on:

Hu et al. (2017)

Efficacy and safety of vitamin C for atrial fibrillation after cardiac surgery: A meta-analysis with trial sequential analysis of randomized controlled trials.

Int J Surg. 2017

https://www.ncbi.nlm.nih.gov/pubmed/27956113

Publication bias in meta-analysis of ascorbic acid for postoperative atrial fibrillation
Hemilä H
Am J Health Syst Pharm. 2017
https://doi.org/10.2146/ajhp160999

Comments on:

Baker and Coleman (2016)

Meta-analysis of ascorbic acid for prevention of postoperative atrial fibrillation after cardiac surgery.

Am J Health Syst Pharm. 2016

https://www.ncbi.nlm.nih.gov/pubmed/27806938

Flawed controlled trials on vitamin C and cardiovascular diseases

Hemilä H.
Gültekin (2021) paper has a substantial number of identical data with the 20-year earlier Demirag (2001) paper
Pubpeer 2022 Feb
https://pubpeer.com/publications/8150B66EC0289FA4BF7C9ADB1C48A9

Comments on:

Gültekin Y, Güzel A, Karakaya A, Beşoğul Y.

Combined effects of the implementation of magnesium and ascorbic acid on myocardial ischemia-reperfusion in open heart surgery.

Anatolian Current Medical Journal. 2021;3(4):319-26.

https://doi.org/10.38053/acmj.982137

Hemilä H.
Statistical problems in the vitamin C trial with PCI patients by Shafaei-Bajestani et al. (2019)
Pubpeer 2022 Feb
https://pubpeer.com/publications/1B59AD863839D55215841C1124C2D3

Comments on:

Shafaei-Bajestani N, Talasaz AH, Salarifar M, Pourhosseini H, Sadri F, Jalali A.

Potential role of vitamin C intracoronary administration in preventing cardiac injury after primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction.

J Res Pharm Pract. 2019;8(2):75-82.

https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6636420

https://pubmed.ncbi.nlm.nih.gov/31367642

Hemilä H.
Statistical problems in the vitamin C trial with CABG patients by Moludi et al. (2020)
Pubpeer 2022 Feb
https://pubpeer.com/publications/2E9E504061A7DC2AF6B2692D8632F1

Comments on:

Moludi J, Alizadeh M, Chehri G, Jafari-Vayghyan H, Foroumandi E, Maleki V, Ebrahimi B, Sadeghpour A, Alizadehasi A, Tabaee AS.

The effect of vitamin C supplementation on cardiac enzymes after coronary artery bypass graft: a double-blind randomized control trial.

Current Nutrition & Food Science. 2020;16(5):833-8.

https://doi.org/10.2174/1573401315666190712213051

Flawed Mendelian randomization studies on vitamin C and cardiovascular diseases

Hemilä H, Chalker E.
Vitamin C and the risk of atrial fibrillation: Mendelian randomization study may be misleading.
Clin Nutr. 2022
https://doi.org/10.1016/j.clnu.2022.04.029

Comments on:

Chen L, Sun X, Wang Z, Lu Y, Chen M, He Y, Xu H, Zheng L.

The impact of plasma vitamin C levels on the risk of cardiovascular diseases and Alzheimer's disease: A Mendelian randomization study.

Clin Nutr. 2021;40(10):5327-5334.

https://pubmed.ncbi.nlm.nih.gov/34537655

Hemilä H, Chalker E.
Vitamin C and the risk of cardiovascular diseases: Mendelian randomization study may be misleading.
Eur J Prev Cardiol. 2022
https://doi.org/10.1093/eurjpc/zwac067

Comments on:

Yuan S, Zheng JS, Mason AM, Burgess S, Larsson SC.

Genetically predicted circulating vitamin C in relation to cardiovascular disease.

Eur J Prev Cardiol. 2022;28(16):1829-1837.

https://pubmed.ncbi.nlm.nih.gov/34057996