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
Oct 19, 2023


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



Meta-analyses and re-analyses



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

An early version of the above text was prepared for a Cochrane review
Hemilä H, Suonsyrjä T.
Vitamin C for treating atrial fibrillation
https://www.mv.helsinki.fi/home/hemila/H/2015_vitC_AF_draft.pdf
That version was rejected with a statement:
"Reason for withdrawal from publication: The CRG withdrew this protocol as the current author team is unable to progress to the final stage of the review. The editors consider this title as low priority for the current portfolio of the Heart Group and therefore this title is not open to a new author team."
https://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011471.pub2/abstract
Thus, our Cochrane review draft found a 45% decrease (95% CI 33% - 56%) in post-operative AF in 8 non-US studies (Analysis 1.2, page 57 of the draft), yet such a finding has low priority in Cochrane Collaboration.
The actual reasons for rejection were not described, see the final reviewer comments and our responses:
https://www.mv.helsinki.fi/home/hemila/H/vitC_AF_1308_reviewer_comments.pdf
See the protocol on which the review was based:
https://www.mv.helsinki.fi/home/hemila/H/HH_2015_CochAF_Protocol.pdf

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://www.mdpi.com/2072-6643/12/2/586/htm
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 rypass graft: a double-blind bandomized 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