Vitamin C and ICU, sepsis, COVID-19

by Harri Hemilä
Department of Public Health
University of Helsinki, Finland
harri.hemila@helsinki.fi
https://www.mv.helsinki.fi/home/hemila
May 26, 2023



  1. Meta-analyses
  2. Re-analyses of studies on vitamin C and critical illness
  3. Short commentaries
  4. Comments on flawed analyses and editorials on vitamin C and critical illness



Meta-analyses

Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: a meta-regression analysis
 Hemilä H, Chalker E.
J Intensive Care 2020
https://doi.org/10.1186/s40560-020-0432-y
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7006137

Vitamin C can shorten the length of stay in the ICU: a meta-analysis.
Hemilä H, Chalker E.
Nutrients 2019
https://doi.org/10.3390/nu11040708
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521194
https://www.ncbi.nlm.nih.gov/pubmed/30934660


Re-analyses of studies on vitamin C and critical illness


Reanalysis of the LOVIT trial
Abrupt termination of vitamin C from ICU patients may increase mortality: secondary analysis of the LOVIT trial.
Hemilä H, Chalker E.
Eur J Clin Nutr. 2022
https://doi.org/10.1038/s41430-022-01254-8
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10115628

Reanalysis of the CITRIS-ALI trial
Reanalysis of the effect of vitamin C on mortality in the CITRIS-ALI trial: important findings dismissed in the trial report.
Hemilä H, Chalker E.
Front Med (Lausanne). 2020
https://doi.org/10.3389/fmed.2020.590853
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7575729

Reanalysis of the COVID A to Z trial
Vitamin C may increase the recovery rate of outpatient cases of SARS-CoV-2 infection by 70%: reanalysis of the COVID A to Z randomized clinical trial.
Hemilä H, Carr A, Chalker E.
Front Immunol. 2021
https://doi.org/10.3389/fimmu.2021.674681
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8141621

Analyses of COVID-19 and sepsis trials and discussion of biased editorials in JAMA about vitamin C and sepsis
Bias against vitamin C in mainstream medicine: examples from trials of vitamin C for infections.
Hemilä H, Chalker E.
Life (Basel). 2022
https://doi.org/10.3390/life12010062
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8779885

Flaws in a Mendelian randomization study on vitamin C and COVID-19
Assessment of vitamin C effects on pneumonia and COVID-19 using Mendelian randomization: analysis may be misleading.
Hemilä H, Chalker E.
Eur J Clin Nutr. 2022
https://doi.org/10.1038/s41430-022-01091-9
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8853427

Spectacular reduction in the mortality of acutely injured patients by the administration of vitamins C and E and selenium.
Hemilä H.
JPEN J Parenter Enteral Nutr. 2009
https://doi.org/10.1177/0148607108328520
https://helda.helsinki.fi/handle/10138/16985
https://www.mv.helsinki.fi/home/hemila//h/2009_L_JPEN.pdf

Reanalysis of a rat study on vitamin C effect on endotoxin toxicity
The protective effect of vitamins a and C on endotoxin-induced oxidative renal tissue damage in rats.
Hemilä H.
Tohoku J Exp Med. 2006
https://doi.org/10.1620/tjem.208.99

Short commentaries

Vitamin C and COVID-19.
Hemilä H, de Man AME.
Front Med (Lausanne). 2021
https://doi.org/10.3389/fmed.2020.559811
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7848027

Vitamin C as a Possible Therapy for COVID-19.
Hemilä H, Chalker E.
Infect Chemother. 2020
https://doi.org/10.3947/ic.2020.52.2.222
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7335649


Vitamin C and SARS coronavirus.
Hemilä H.
J Antimicrob Chemother. 2003  
https://doi.org/10.1093/jac/dkh002
https://helda.helsinki.fi/handle/10138/225886


Comments on flawed analyses and editorials on vitamin C and critical illness


Misleading findings in Dresen's review on vitamin C for critical illness
https://pubpeer.com/publications/2C4D925EB3E88C3305E7DED31D2F53#1
Comments on:
Dresen E, Lee ZY, Hill A, Notz Q, Patel JJ, Stoppe C.
History of scurvy and use of vitamin C in critical illness: A narrative review.
Nutr Clin Pract.2023;38(1):46-54.
https://pubmed.ncbi.nlm.nih.gov/36156315

Benefit of OTC formula against COVID-19 is explained by selection bias.
Hemilä H.
J Evid Based Integr Med. 2021
https://doi.org/10.1177/2515690x211058417
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8591635
Comments on:
Margolin L, Luchins J, Margolin D, Margolin M, Lefkowitz S.
20-week study of clinical outcomes of over-the-counter COVID-19 prophylaxis and treatment.
J Evid Based Integr Med. 2021;26:2515690X211026193.
https://pubmed.ncbi.nlm.nih.gov/34225463

Vitamin C and zinc lozenges for COVID-19?
Hemilä H, Chalker E.
J Am Pharm Assoc. 2021
https://doi.org/10.1016/j.japh.2021.05.018
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8163692
Comments on:
Marwitz KK.
The pharmacist's active role in combating COVID-19 medication misinformation.
J Am Pharm Assoc (2003). 2021;61(2):e71-e74.
https://pubmed.ncbi.nlm.nih.gov/33199166

Misleading editorial on the COVID A to Z trial
Pubpeer
https://pubpeer.com/publications/7C275B4F3B2A74D33320D4D9C37AA3#1
Comments on:
Michos ED, Cainzos-Achirica M.
Supplements for the treatment of mild COVID-19 challenging health beliefs with science from A to Z.
JAMA Netw Open. 2021;4(2):e210431.
https://pubmed.ncbi.nlm.nih.gov/33576814
see also: https://doi.org/10.3390/life12010062

Flaws in the meta-analysis on mortality in septic patients treated with vitamin C by Scholz et al. (2021)
Pubpeer
https://pubpeer.com/publications/B48864E0668536925C58F70070746D#1
Scholz SS, Borgstedt R, Ebeling N, Menzel LC, Jansen G, Rehberg S.
Mortality in septic patients treated with vitamin C: a systematic meta-analysis.
Crit Care. 2021;25(1):17.
https://pubmed.ncbi.nlm.nih.gov/33407793

Commentary: The long history of vitamin C: from prevention of the common cold to potential aid in the treatment of COVID-19.
Hemilä H, Chalker E.
Front Immunol. 2021
https://doi.org/10.3389/fimmu.2021.659001
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8047412
Comments on:
Cerullo G, Negro M, Parimbelli M, Pecoraro M, Perna S, Liguori G, Rondanelli M, Cena H, D'Antona G.
The long history of vitamin C: from prevention of the common cold to potential aid in the treatment of COVID-19.
Front Immunol. 2020;11:574029.
https://pubmed.ncbi.nlm.nih.gov/33193359

Commentary: Vitamin C supplementation for prevention and treatment of pneumonia.
Hemilä H, Chalker E.
Front Med (Lausanne). 2021;7:595988.
https://doi.org/10.3389/fmed.2020.595988
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7854566
Comments on:
Padhani ZA, Moazzam Z, Ashraf A, Bilal H, Salam RA, Das JK, Bhutta ZA.
Vitamin C supplementation for prevention and treatment of pneumonia.
Cochrane Database Syst Rev. 2020;4(4):CD013134.
https://pubmed.ncbi.nlm.nih.gov/32337708

Misleading editorial on vitamin C in JAMA
Hemilä H
Pubpeer 2020
https://pubpeer.com/publications/07DCB1F79D50182367BF913CC69004#1
Comments on:
Kalil AC.
Lack of benefit of high-dose vitamin C, thiamine, and hydrocortisone combination for patients with sepsis.
JAMA. 2020;323(5):419-420.
https://pubmed.ncbi.nlm.nih.gov/31950983
see also: https://doi.org/10.3390/life12010062

Biased editorial on vitamin C in JAMA
Pubpeer
https://pubpeer.com/publications/6C1E79E2B8EA7E2DEED9B46C2B717C#1
Comments on:
Brant EB, Angus DC.
Is high-dose vitamin C beneficial for patients with sepsis?
JAMA. 2019;322(13):1257-1258.
https://pubmed.ncbi.nlm.nih.gov/31573621
see also: https://doi.org/10.3390/life12010062

Statistical problems in a meta-analysis on vitamin C and critically ill patients
Pubpeer
https://pubpeer.com/publications/31E6DF677EC5A16CFBD1908ADACD15#1
Comments on:
Putzu A, Daems AM, Lopez-Delgado JC, Giordano VF, Landoni G.
The effect of vitamin C on clinical outcome in critically ill patients: a systematic review with meta-analysis of randomized controlled trials.
Crit Care Med. 2019;47(6):774-783.
https://pubmed.ncbi.nlm.nih.gov/30839358

Misleading meta-analysis on vitamin C and critically ill patients
Pubpeer
https://pubpeer.com/publications/D661E94CBDF6C6A9C04B8ACCD32DFC#1
Comments on:
Langlois PL, Manzanares W, Adhikari NKJ, Lamontagne F, Stoppe C, Hill A, Heyland DK.
Vitamin C administration to the critically ill: a systematic review and meta-analysis.
JPEN J Parenter Enteral Nutr. 2019;43(3):335-346.
https://pubmed.ncbi.nlm.nih.gov/30452091

Misleading meta-analysis on vitamin C for sepsis patients
Pubpeer
https://pubpeer.com/publications/2D26F22CEA264D1B84910D89AD26D7#1
Comments on:
Li J.
Evidence is stronger than you think: a meta-analysis of vitamin C use in patients with sepsis.
Crit Care. 2018;22(1):258.
https://pubmed.ncbi.nlm.nih.gov/30305111