Vitamin C for preventing and treating pneumonia

Cochrane review  doi:10.1002/14651858.CD005532.pub3 

https://helda.helsinki.fi/handle/10138/225862

by Harri Hemilä and Pekka Louhiala (2013)

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


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 youself.

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.


References available via web:

Contents

  1. Included trials 
  2. Excluded trials  
  3. Other references cited in the Cochrane Review
  4. Misleading and erroneous studies on vitamin C and pneumonia or sepsis
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 serious infections:
https://www.mv.helsinki.fi/home/hemila/vitc_pneumonia.htm
 April 5, 2024

Included trials 

Glazebrook 1942_PMC 
     Comment in BMJ 1942 June by the authors
     Comment in BMJ 1942 commentary
     Comment in BMJ 1942 Nov by the authors
     Comment in BMJ 1944 Nov by the authors  
     Description of the study backgound via an earlier paper in J Hyg (1941)

       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 ch_ZENODO   Hunt 1994 ch    Hunt 1994 bm   Hunt 1994 PubMed

Kimbarowski 1967 translation_ZENODO     Kimbarowski 1967 PubMed
    Kimbarowski 1967 German ch     Kimbarowski 1967 German bm

Mochalkin 1970 translation ZENODO           Mochalkin 1970 PubMed
       Mochalkin 1970 Russian ch   Mochalkin 1970 Russian bm

       Mochalkin 1974 translation ZENODO (same data as in 1970)    
       Mochalkin 1974 (OCR characters in Russian)        Mochalkin 1974 bm       Mochalkin 1974 PubMed

       Mochalkin 1975 translation ZENODO (republication of 1970 with 2 vitC groups combined)    
       Mochalkin 1975 (OCR characters in Russian)
       Mochalkin 1975 (OCR characters in Russian)          Mochalkin 1975 bm       Mochalkin 1975 PubMed

Pitt 1979 doi     Pitt 1979 PubMed    Pitt 1979 ch     Pitt 1979 bm
https://www.academia.edu/78271637

Tanaka 2000 Doi   Tanaka 2000 PubMed
A copy available


Excluded trials  

Cook 2007 doi   Cook 2007 PMC   Cook 2007 PubMed

Dahlberg 1944 doi    Dahlberg 1944 ch   Dahlberg 1944 bm 

Hunt 1984 ch       Hunt 1984 bm    Hunt 1984 PubMed

Kahn 2011 doi    Kahn 2011 PubMed

Mahalanabis 2006a doi 

Mahalanabis 2006b bm 

Nathens 2002 PMC    Nathens 2002 PubMed    Nathens 2002 doi

 Pico Sirvent 2013 Poster.pdf
 Sirvent 2013 Poster.pdf

Scheunert 1949 

Sesso 2008 doi    Sesso 2008 PMC    Sesso 2008 PubMed
  
Wahed 2008 bm


Other references cited in the Cochrane Review


Akaike 2001 PubMed
Albaum 1996 doi     Albaum 1996 PubMed 
Anderson 1973 PMC   Anderson 1972 PMC    Anderson 1972 and 1973 ch
Ashor 2014 doi
Ashton 1999 doi    Ashton 1999 PubMed

Baik 2000 doi
Bakaev 2004 PubMed     Bakaev 2004 fulltext
Beisel 1982 doi
Bhoite 2011
Bissell 1980 PubMed
Bjordahl 2012 PubMed
Bloomfield 1999 doi
Bohnholzer 1937 translation ZENODO    Bohnholzer 1937 ch    Bohnholzer 1937 bm
    see also:      Gunzel 1937
Briggs 1984 Ref List
Bruno 2006 PubMed
Buffinton 1992 doi   Buffinton 1992 PubMed   
Carpenter 1986 Cambridge    
Cathcart 1981 doi   Cathcart 1981 PubMed  paper available via links 
Cemek 2006 PubMed
Chakrabarti 1955 doi    Chakrabarti 1955 bm   Chakrabarti 1955 PubMed

Dalton 1962 ch    Dalton 1962    Dalton 1962 bm   Dalton 1962 PubMed    
Dehghani 2014 PubMed
Dirlewanger 2002 doi    Dirlewanger 2002 PubMed  
Doherty 1991 doi

Elwood 1976 doi    Elwood 1976 PMC  Elwood 1976 JECH    Elwood 1976 ch (54 KB)  
Gaffey 1996 Doi    Galley 1996 PubMed    
Gander 1936 translation ZENODO      Gander 1936 bm
Goetzl 1974 PubMed
Goodwin 1998 doi       Goodwin 1998 PubMed
Hathcock 2005 AJCN 

Hemilä 1984 doi
Hemilä 1992 doi        Hemilä 1992            Hemilä 1992 hdl         Hemilä 1992 PubMed
Hemilä 1996 doi        Hemilä 1996            Hemilä 1996 hdl         Hemilä 1996 PubMed
Hemilä 1996a doi      Hemilä 1996a          Hemilä 1996a hdl        Hemilä 1996a PubMed
   Discussion:  Chalmers 1996                   Hemilä 1996 hdl          Hemilä 1996        Hemilä 1996 
Hemilä 1996b doi     Hemila 1996b          Hemilä 1996b hdl        Hemilä 1996b PubMed
Hemilä 1997 doi                                       Hemilä 1997 hdl        Hemilä 1997
Hemilä 1997a  
Hemilä 1997b doi     Hemilä 1997b         Hemilä 1997b PubMed    Discussion   Discussion
Hemilä 1999 doi                                    Hemilä 1999 hdl          Hemilä 1999 PubMed

Hemilä 2004a doi
Hemilä 2004b doi
Hemilä 2006                Hemilä 2006    
Hemilä 2007a doi        Hemilä 2007a PMC
Hemilä 2009a doi        Hemilä 2009a PMC
Hemilä 2011a doi        Hemilä 2011a PMC

Hemilä 2013a doi  https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078152/  
Hemilä 2013a web page links references

Hemilä 2013b doi      
Hemilä 2013c doi      Hemilä 2013c PMC
Hemilä 2014 doi        Hemilä 2014 PMC

Hess 1920 (search book author = Hess)   Hess 1920 pages 88 and 99


https://www.gutenberg.org/ebooks/40505
https://www.gutenberg.org/files/40505/40505-h/40505-h.htm
https://digital.library.cornell.edu/catalog/chla2903792
https://archive.org/details/cu31924073869996
https://archive.org/details/b29823778
https://archive.org/details/scurvypastpresen00hess
https://archive.org/details/scurvypastpresen00hessiala
https://archive.org/details/scurvypastpresen00hessuoft
https://archive.org/details/39002086348019.med.yale.edu
https://archive.org/details/scurvypastandpr00hessgoog
https://archive.org/details/nutritionfoundat0000hess
https://openlibrary.org/books/OL6631267M



Hess 1932 NEJM doi  Hess 1932 ch   Hess 1932 bm
     also: Hess 1932 JAMA doi 
Higgins 2003 doi     Higgins 2003 

Hochwald 1937 translation_ZENODO      Hochwald 1937 bm
Holley 2011 PubMed
Hopstaken 2004 doi  Hopstaken 2004 PubMed   
Hrobjartsson 2010 doi
Hughes 1988 Zenodo  

Ioannidis 2007 doi       Ioannidis 2007 PubMed
 IOM 2000 p. 95 
Jones 1982 https://www.academia.edu/602454   Jones 1982 ch             Jones 1982 bm
Juraschek 2012 doi      Juraschek 2012 PubMed

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

Lau 2006 doi             Lau 2006 PubMed
Levine 1999 doi         Levine 1999 PubMed
Li 2006 doi           Li 2006 PubMed
Louhiala 2014 doi      Louhiala 2014 hdl
Luberoff 1978 ch       Luberoff 1978 bm
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    Pazzaglia 1983 bm

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  
Robertsson 1934 doi          Robertsson 1934 ch    Robertsson 1934 bm
      Other old reviews on vitamin C and infections:
      Perla 1937 pt I             Perla 1937 pt II
      Clausen_1934_doi       Clausen 1934
Ruuskanen 2011 doi          Ruuskanen 2011 PubMed   

Sabin 1939 doi                        Sabin 1939 PMC
Schleicher 2009 doi                Schleicher 2009 PubMed
Siegel 1975 doi
Slotkin 1944_doi    Slotkin 1944      Slotkin 1944     Slotkin 1944    
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

LOVIT-COVID Investigators.
Intravenous Vitamin C for Patients Hospitalized With COVID-19: Two Harmonized Randomized Clinical Trials. JAMA. 2023 Nov 14;330(18):1745-1759.

See comments in:
https://pubpeer.com/publications/38194670B815AEE6450D922AA405E2#2

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 Jun 23;386(25):2387-2398.

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 Apr;76(4):588-591.

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 Apr 27;4(4):CD013134.

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 May 1;11(5):4765-4772.

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 Oct 1;322(13):1261-1270.

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 Apr;46(4):711-7.

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


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