Vitamin C for preventing and treating pneumonia

Cochrane review (2013):

https://hdl.handle.net/10138/225862
https://www.researchgate.net/publication/6549713
https://doi.org/10.1002/14651858.cd005532.pub3

Summary of the findings and a discussion of implications:
J R Soc Med 2007 JRSM 2007 in PMC

A 2025 review on vitamin C for pneumonia:
https://pubmed.ncbi.nlm.nih.gov/39803741

Harri Hemilä
Department of Public Health,
University of Helsinki, Helsinki, Finland
harri.hemila@helsinki.fi

Home: https://www.mv.helsinki.fi/home/hemila
Papers on pneumonia and other severe infections:
https://www.mv.helsinki.fi/home/hemila/vitc_pneumonia.htm
Jan 31, 2025

The 2013 version is available at the links above.

In 2016 we updated the review, and the updated review is available here:
https://www.mv.helsinki.fi/home/hemila/CP/CochranePneumonia_2016.pdf

Cochrane Collaboration rejected the above 2016 update for reasons that are not related to the scientific validity of the review.
In June 2016 we responded to reviewer comments:
https://www.mv.helsinki.fi/home/hemila/CP/ARI_June2016_pneu_responses.pdf

Our responses to the comments of
Mark Jones from the Cochrane Acute Respiratory Infections (ARI) group,
are available here:
https://www.mv.helsinki.fi/home/hemila/CP/MarkJones_pneu_responses.pdf

None of the Mark Jones' comments pointed out any genuine scientific problems in our 2016 update.
Many of his comments reveal that he did not read our 2016 update carefully, see yourself.

The rejection decision in February 2017 by Chris Del Mar did not point out any specific scientific reasons for the rejection:
https://www.mv.helsinki.fi/home/hemila/CP/ChrisDelMar_2017_pneu_comments.pdf

None of the above comments pointed out any genuine scientific problems in our 2016 update, read the comments and responses yourself.

##########

A new Cochrane review on vitamin C and pneumonia was published in 2020.

The review had numerous severe flaws, see:

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 Apr 27;4(4):CD013134.

Flaws described in:
https://doi.org/10.3389/fmed.2020.595988
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7854566

References available via web:

Included trials
Excluded trials
Other references cited in the Cochrane Review
Misleading and erroneous studies on vitamin C and pneumonia or sepsis

Included trials

Glazebrook 1942

https://doi.org/10.1017/s0022172400012596
https://pmc.ncbi.nlm.nih.gov/articles/PMC2199803

Pauling's analysis:
https://scarc.library.oregonstate.edu/coll/pauling/rnb/31/31-103.html
https://scarc.library.oregonstate.edu/coll/pauling/rnb/33/33-034.html
https://scarc.library.oregonstate.edu/coll/pauling/rnb/33/33-035.html

Hunt 1994
https://doi.org/10.5281/zenodo.6406235
https://pubmed.ncbi.nlm.nih.gov/7814237

Kimbarowski 1967
https://doi.org/10.5281/zenodo.7116182
https://pubmed.ncbi.nlm.nih.gov/5614915

Mochalkin 1970
https://doi.org/10.5281/zenodo.7097483
https://pubmed.ncbi.nlm.nih.gov/5515787

Mochalkin 1974 (same data)
https://doi.org/10.5281/zenodo.7097562
https://pubmed.ncbi.nlm.nih.gov/4444248

Mochalkin 1975 (same data)
https://doi.org/10.5281/zenodo.7097591
https://pubmed.ncbi.nlm.nih.gov/1210310

Pitt 1979
https://www.academia.edu/78271637
https://doi.org/10.1001/jama.1979.03290350028016
https://www.ncbi.nlm.nih.gov/pubmed/368370
https://www.mv.helsinki.fi/home/hemila/CC/Pitt_1979_ch.pdf
https://www.mv.helsinki.fi/home/hemila/CC/Pitt_1979_bm.pdf

Tanaka 2000
https://doi.org/10.1001/archsurg.135.3.326
https://pubmed.ncbi.nlm.nih.gov/10722036
A copy available

Excluded trials

Cook 2007
https://doi.org/10.1001/archinte.167.15.1610
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc2034519

Dahlberg 1944
https://doi.org/10.1111/j.0954-6820.1944.tb05420.x
https://www.mv.helsinki.fi/home/hemila/CC/Dahlberg_1944_ch.pdf
https://www.mv.helsinki.fi/home/hemila/CC/Dahlberg_1944_bm.pdf

Hunt 1984
https://www.mv.helsinki.fi/home/hemila/CP/Hunt_1984_ch.pdf
https://www.mv.helsinki.fi/home/hemila/CP/Hunt_1984_bm.pdf
https://www.ncbi.nlm.nih.gov/pubmed/6376396

Kahn 2011
https://doi.org/10.1097/BCR.0b013e318204b336
https://www.ncbi.nlm.nih.gov/pubmed/21131846

Mahalanabis 2006a
https://doi.org/10.1038/sj.ejcn.1602368

Mahalanabis 2006b
https://www.mv.helsinki.fi/home/hemila/CP/Mahalanabis_2006_bm.pdf

Nathens 2002
https://doi.org/10.1097/00000658-200212000-00014
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1422648
https://www.ncbi.nlm.nih.gov/pubmed/12454520

Pico Sirvent 2013 Poster.pdf
Sirvent 2013 Poster.pdf

Scheunert 1949
https://zenodo.org/doi/10.5281/zenodo.10932392

Sesso 2008
https://doi.org/10.1001/jama.2008.600
file://www.ncbi.nlm.nih.gov/pmc/articles/PMC2586922

Wahed 2008
https://www.mv.helsinki.fi/home/hemila/CP/Wahed_2008_bm.pdf
https://pubmed.ncbi.nlm.nih.gov/18946457

Other references cited in the Cochrane Review (2013)

Akaike 2001 PubMed
Albaum 1996 doi Albaum 1996 PubMed

Anderson 1972
https://pmc.ncbi.nlm.nih.gov/articles/PMC1940935
Correction 1 (1973).
https://pmc.ncbi.nlm.nih.gov/articles/PMC1941144
Correction 2.
https://pmc.ncbi.nlm.nih.gov/articles/PMC1941189

Ashor 2014 doi
Ashton 1999 doi Ashton 1999 PubMed

Baik 2000 doi
Bakaev 2004 PubMed Bakaev 2004 fulltext
Beisel 1982 doi

Bhoite 2011
https://www.researchgate.net/publication/268359705
https://www.academia.edu/87062455

Bissell 1980 PubMed
Bjordahl 2012 PubMed
Bloomfield 1999 doi

Bohnholzer 1937 Doi
see also:
Gunzel 1937_Doi

Briggs 1984 Ref List
Bruno 2006 PubMed
Buffinton 1992 doi Buffinton 1992 PubMed

Carpenter KJ. The History of Scurvy and Vitamin C. Cambridge University Press: Cambridge, UK, 1986.
https://www.cambridge.org/fi/academic/subjects/history/history-medicine/history-scurvy-and-vitamin-c
https://archive.org/details/historyofscurvyv0000carp
https://archive.org/details/historyofscurvyv0000carp_l0m0

Cathcart 1981 doi Cathcart 1981 PubMed paper available via links
Cemek 2006 PubMed
Chakrabarti 1955 doi Chakrabarti 1955 bm Chakrabarti 1955 PubMed

Dalton 1962
https://doi.org/10.5281/zenodo.14494491
https://pubmed.ncbi.nlm.nih.gov/13883259

Dehghani 2014 PubMed
Dirlewanger 2002 doi Dirlewanger 2002 PubMed
Doherty 1991 doi

Elwood 1976 doi Elwood 1976 PMC
Galley 1996 Doi Galley 1996 PubMed
Gander 1936 Doi
Goetzl 1974 PubMed
Goodwin 1998 doi Goodwin 1998 PubMed
Hathcock 2005 AJCN

Hemilä 1984
https://doi.org/10.1016/0014-5793(84)81232-6

Hemilä 1992
https://hdl.handle.net/10138/223363
https://doi.org/10.1079/bjn19920004

Hemilä 1996
https://www.researchgate.net/publication/14347859
https://hdl.handle.net/10138/225881
https://doi.org/10.1055/s-2007-972864

Hemilä 1996a
https://hdl.handle.net/10138/225872
https://www.researchgate.net/publication/14378347
https://doi.org/10.1016/0895-4356(96)00189-8
Discussion in:
https://doi.org/10.1016/0895-4356(96)00190-4
https://hdl.handle.net/10138/225873
https://www.researchgate.net/publication/28363121
https://doi.org/10.1016/0895-4356(96)00191-6

Hemilä 1996b
https://hdl.handle.net/10138/225877
https://www.researchgate.net/publication/14233989
https://doi.org/10.1016/s0899-9007(96)00223-7

Hemilä 1997
https://www.researchgate.net/publication/13914252
https://hdl.handle.net/10138/225875
https://doi.org/10.1097/00006454-199709000-00003

Hemlä 1997a
https://www.mv.helsinki.fi/home/hemila/H/HH_1997_MDek.pdf

Hemilä 1997b
https://hdl.handle.net/10138/223362
https://www.researchgate.net/publication/14153016
https://doi.org/10.1017/s0007114500002889
Discussion in:
https://doi.org/10.5281/zenodo.14610440
https://www.researchgate.net/publication/28369859
https://doi.org/10.1079/BJN19970201

Hemilä 1999
https://hdl.handle.net/10138/223761
https://www.researchgate.net/publication/12959141
https://doi.org/10.1054/mehy.1997.0639

Hemilä 2004a
https://hdl.handle.net/10138/225867
https://www.researchgate.net/publication/8123995
https://doi.org/10.7205/milmed.169.11.920

Hemilä 2004b
https://doi.org/10.1378/chest.125.2.557

Hemilä 2006
https://hdl.handle.net/10138/20335
https://doi.org/10.5281/zenodo.6395595

Hemilä 2007a
https://doi.org/10.1177/014107680710001109
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2099400

Hemilä 2009a
https://doi.org/10.1093/aje/kwn413
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661323

Hemilä 2011a
https://doi.org/10.2147/CLEP.S16114
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046185

Hemilä 2013a
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078152
https://hdl.handle.net/10138/225864
https://doi.org/10.1002/14651858.CD000980.pub4
https://www.mv.helsinki.fi/home/hemila/CC [Links to the References of the review]

Hemilä 2013b
https://hdl.handle.net/10138/225863
https://doi.org/10.1002/14651858.cd006665.pub3
https://www.mv.helsinki.fi/home/hemila/CT/2013_Coch_Tetanus_CD006665.pdf

Hemilä 2013c
https://doi.org/10.1186/1710-1492-9-46
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018579

Hemilä 2014
https://doi.org/10.1186/1710-1492-10-58
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4363347

Hess AF. Scurvy: Past and Present. Philadelphia PA: Lippincott; 1920.
https://www.gutenberg.org/ebooks/40505
https://digital.library.cornell.edu/catalog/chla2903792
https://archive.org/search?query=creator%3A%22Hess+Alfred+Fabian%22
See also:
Hemilä H. The symptoms of vitamin C deficiency. 1. Observations and descriptions by Hess, Lind, Trotter and Blane. Zenodo. 2024.
https://doi.org/10.5281/zenodo.10685194

Hess 1932

https://doi.org/10.5281/zenodo.14609616 [NEJM: sections on vitamin C]

https://doi.org/10.1056/NEJM1932101320715
see also:

https://doi.org/10.5281/zenodo.14609694 [JAMA: sections on vitamin C]

https://doi.org/10.1001/jama.1932.02730430005002

Higgins 2003 doi     Higgins 2003

Hochwald 1937 Doi
Holley 2011 PubMed
Hopstaken 2004 doi Hopstaken 2004 PubMed
Hrobjartsson 2010 doi
Hughes 1988 Doi

Ioannidis 2007 doi    Ioannidis 2007 PubMed

IOM 2000, p.95
https://doi.org/10.17226/9810

https://www.ncbi.nlm.nih.gov/books/NBK225483

https://www.ncbi.nlm.nih.gov/books/NBK225480

https://nap.nationalacademies.org/read/9810/chapter/7

https://pubmed.ncbi.nlm.nih.gov/25077263

Jones 1982
https://www.academia.edu/602454 Jones 1982 ch

Juraschek 2012 doi      Juraschek 2012 PubMed

Karlowski 1975 doi Karlowski 1975 PubMed
Kiekara 1996 doi Kiekara 1996 PubMed
Kinsman 1971 doi
Klenner 1948 Doi   paper available via links
Klenner 1951 Doi   paper available via links

Lau 2006 doi       Lau 2006 PubMed
Levine 1999 doi Levine 1999 PubMed
Li 2006 doi       Li 2006 PubMed

Louhiala 2014
https://hdl.handle.net/10138/228056

https://www.researchgate.net/publication/262026733

https://doi.org/10.1111/fct.12110

Luberoff 1978
https://doi.org/10.5281/zenodo.14673568

Lydersen 2009 doi     Lydersen 2009 PubMed

Mandal 2011 doi       Mandal 2011 PubMed
Manning 2013 doi        Manning 2013 PMC    Manning 2013 PubMed
Manzella 1979 doi    Manzella 1979 PubMed
May 2013 doi                     May 2013 PMC May 2013 PubMed
Melbye 1992 doi    Melbye 1992 PubMed
Merchant 2004 doi
Mizgerd 2006 doi
Mosdol 2008 doi          Mosdol 2008 PubMed
Musher 2007 doi                     Musher 2007 PubMed
Musher 2014 doi
Nualart 2003 doi    Nualart 2003 PubMed

Packer 1979 doi
Padayatty 2004 doi
Padayatty 2010 doi Padayatty 2010 PubMed
Papoulidis 2011 doi   Papoulidis 2011 PubMed

Paynter 2010 doi    Paynter 2010 PubMed
Pazzaglia 1983 doi Pazzaglia 1983_PubMed Pazzaglia 1983 ch

Powers 2008 doi    Powers 2008 PMC    Powers 2008 PubMed
Prina 2015 doi

Rayment 2003 doi       Rayment 2003 PubMed
Raynaud-Simon 2010 doi    Raynaud-Simon 2010 PubMed
Rice 2000 doi    Rice 2000 PubMed
Rivers 1987 doi    Rivers 1987 PubMed

Robertson 1932
https://doi.org/10.5281/zenodo.14496927
https://doi.org/10.1097/00005792-193405000-00001

Other old reviews on vitamin C and infections:
https://doi.org/10.5281/zenodo.14497214 https://doi.org/10.1152/physrev.1934.14.3.309

https://doi.org/10.5281/zenodo.14527877

Ruuskanen 2011 doi    Ruuskanen 2011 PubMed

Sabin 1939 doi    Sabin 1939 PMC
Schleicher 2009 doi    Schleicher 2009 PubMed
Siegel 1975 doi

Slotkin 1944_doi

https://www.mv.helsinki.fi/home/hemila/CP/Slotkin_1944.pdf

https://www.seanet.com/%7Ealexs/ascorbate/194x/slotkin-ge_j_urol_1944-v52-p566.html
https://www.whale.to/v/c/slotkin.html

Sterne 2011 doi   Sterne 2011 PubMed
Swingler 1998 doi
Syrjälä 1998 doi
Terrin 2005 doi
Thomas 1978 PMC

Walker 2013 doi     Walker 2013 PubMed
Wang 1997 doi     Wang 1997 PubMed
Wang 2012 doi    Wang 2012 PubMed
Wang 2013 doi    Wang 2013 PubMed
Webb 2007 doi

WHO 1999b doi     WHO 1999b fulltext
Young 1994 doi Young 1994 PubMed
Zhang 2011 doi Zhang_2011 PubMed

Misleading and erroneous studies on vitamin C and pneumonia or sepsis

Reintam Blaser A, et al.
Intravenous vitamin C therapy in adult patients with sepsis: A rapid practice guideline.
Acta Anaesthesiol Scand. 2023

See comments in:
https://doi.org/10.3389/fmed.2024.1450091
https://pmc.ncbi.nlm.nih.gov/articles/PMC11446763

LOVIT-COVID Investigators.
Intravenous vitamin C for patients hospitalized with COVID-19: two harmonized randomized clinical trials.
JAMA. 2023
See comments in:
https://doi.org/10.3389/fmed.2024.1391346
https://pmc.ncbi.nlm.nih.gov/articles/PMC11151746

Lamontagne F, et al.; LOVIT Investigators and the Canadian Critical Care Trials Group.
Intravenous vitamin C in adults with sepsis in the intensive care unit.
N Engl J Med. 2022

See comments in:
https://doi.org/10.1038/s41430-022-01254-8
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10115628

Hui LL, Nelson EAS, Lin SL, Zhao JV.
The role of vitamin C in pneumonia and COVID-19 infection in adults with European ancestry: a Mendelian randomisation study.
Eur J Clin Nutr. 2022

See comments in:
https://doi.org/10.1038/s41430-022-01091-9
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8853427

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

See comments in:
https://doi.org/10.3389/fmed.2020.595988
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7854566

Li R, Guo C, Li Y, Liang X, Yang L, Huang W.
Therapeutic target and molecular mechanism of vitamin C-treated pneumonia: a systematic study of network pharmacology.

Food Funct. 2020

See comments in:
https://doi.org/10.1039/d0fo02189j
https://pubmed.ncbi.nlm.nih.gov/33449981

Fowler AA 3rd, et al.
Effect of vitamin C infusion on organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and severe acute respiratory failure: the CITRIS-ALI randomized clinical trial.
JAMA. 2019

See comments in:
https://doi.org/10.3389/fmed.2020.590853
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7575729

Williams PT.
Dose-response relationship between exercise and respiratory disease mortality.
Med Sci Sports Exerc. 2014

See comments in:
https://doi.org/10.1249/mss.0000000000000544