Flawed vitamin C and Common Cold papers

by Harri Hemilš


Department of Public Health
University of Helsinki, Finland
harri.hemila@helsinki.fi
https://www.mv.helsinki.fi/home/hemila
Oct 28, 2022


  1. Problems with influential reviews on vitamin C and the common cold
  2. Problems with the most influential vitamin C and common cold trial by Karlowski et al (1975)
  3. Comments on other biased texts on vitamin C and the common cold



Problems with influential reviews on vitamin C and the common cold


Hemilš H, Chalker E.
Bias against vitamin C in mainstream medicine: examples from trials of vitamin C for infections.
Life (Basel). 2022
https://doi.org/10.3390/life12010062
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8779885


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In 1975 Thomas Chalmers wrote a review in which he concluded that vitamin C is not effective against the common cold.

https://pubmed.ncbi.nlm.nih.gov/1092164/
https://doi.org/10.1016/0002-9343(75)90127-8
https://www.mv.helsinki.fi/home/hemila/reviews/Chalmers_1975_ch.pdf

The Chalmers review has been extensively cited in journal articles and textbooks, see Table 3 in:
https://doi.org/10.3390/life12010062
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8779885


In 1995 the Chalmers review was shown to be seriously flawed. It has errors in data extraction and calculations:
Hemilš H, Herman ZS. Vitamin C and the common cold: a retrospective analysis of Chalmers’ review.
J Am Coll Nutr 1995;14:116-123
https://doi.org/10.1080/07315724.1995.10718483
https://hdl.handle.net/10138/42358 
https://www.mv.helsinki.fi/home/hemila/H/HH_1995.pdf

See also:
Hemilš H. Chalmers' meta-analysis (1975)
In: Do vitamins C and E affect respiratory infections? Thesis 2006 pp. 36-38
https://hdl.handle.net/10138/20335
https://doi.org/10.5281/zenodo.6395595

Who was Thomas Chalmers:
    https://www.nytimes.com/1995/12/29/nyregion/dr-thomas-c-chalmers-a-president-of-mt-sinai-dies-at-78.html
    https://en.wikipedia.org/wiki/Thomas_C._Chalmers
    https://www.jameslindlibrary.org/articles/thomas-c-chalmers-1917-1995
    https://circulatingnow.nlm.nih.gov/2014/12/18/thomas-c-chalmers-clinical-research-pragmatist
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2878827    David Sackett describes in this paper that Thomas Chalmers' 1955 clinical trial report changed his career and led to the emergence of the EBM movement
    https://doi.org/10.1136/bmj.g371  According to Richard Smith and Drummond Rennie, Thomas Chalmers was one of the "three individuals from an earlier generation [who] were particularly important in inspiring" the EBM movement
    https://doi.org/10.7326/0003-4819-124-7-199604010-00022
    https://doi.org/10.7326/0003-4819-124-7-199604010-00023
    https://doi.org/10.7326/0003-4819-124-7-199604010-00024
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1335248
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1335469
    https://doi.org/10.1016/S0140-6736(96)90369-4
    https://doi.org/10.1001/jama.1996.03540080078041
    https://doi.org/10.1016/S0197-2456(96)90026-4
    https://doi.org/10.1016/S0197-2456(97)82189-7
    https://doi.org/10.1177/0141076815586354
    https://doi.org/10.1177/0141076815606279



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In 1975 Michael Dykes and Paul Meier wrote a review which similarly concluded that vitamin C is not effective to colds.
https://pubmed.ncbi.nlm.nih.gov/1089817/
https://doi.org/10.1001/jama.1975.03240220051025
https://www.mv.helsinki.fi/home/hemila/reviews/Dykes_1975_ch.pdf


The Dykes-Meier review has been extensively cited in journal articles and textbooks, see Table 3 in:
https://doi.org/10.3390/life12010062
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8779885


See a short description of Paul Meier:
https://en.wikipedia.org/wiki/Paul_Meier_(statistician)
https://doi.org/10.1191%2F1740774504cn011xx
https://doi.org/10.1016%2FS0140-6736(11)61438-4
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477951/


In 1996 the Dykes & Meier review was shown to be flawed
:
Hemilš H. Vitamin C supplementation and common cold symptoms: problems with inaccurate reviews.
Nutrition 1996;12:804-809
https://doi.org/10.1016/S0899-9007(96)00223-7
https://helda.helsinki.fi/handle/10138/225877
https://www.mv.helsinki.fi/home/hemila/H/HH_1996_NUT.pdf

See also:
Hemilš H. The Dykes and Meier review (1975)
In: Do vitamins C and E affect respiratory infections? Thesis 2006 pp. 42-45
https://hdl.handle.net/10138/20335
https://doi.org/10.5281/zenodo.6395595

See also:
Linus Pauling's criticism of the Dykes and Meier (1975) review:
Pauling L (1976b) Ascorbic acid and the common cold: evaluation of its efficacy and toxicity. Part I. Medical Tribune 17(12):18-9
Pauling L (1976c) Ascorbic acid and the common cold. Part II. Medical Tribune 17(13):37-8


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In 1986 A Steward Truswell reviewed the studies on vitamin C and the common cold in a minireview in NEJM.
Although the text was short, the journal with great prestige and wide circulation makes the statements important.
https://www.mv.helsinki.fi/home/hemila/reviews/Truswell_1986_ch.pdf

In 1996, Truswell's minireview was shown to be flawed:
Hemilš H. Vitamin C supplementation and common cold symptoms: problems with inaccurate reviews.
Nutrition 1996;12:804-809
https://doi.org/10.1016/S0899-9007(96)00223-7
https://helda.helsinki.fi/handle/10138/225877
https://www.mv.helsinki.fi/home/hemila/H/HH_1996_NUT.pdf

See also:
Hemilš H. Truswell's mini-review (1986)
In: Do vitamins C and E affect respiratory infections? Thesis 2006 pp. 45
https://hdl.handle.net/10138/20335
https://doi.org/10.5281/zenodo.6395595


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Problems with the most influential vitamin C and common cold trial by Karlowski et al (1975)

In 1975 Thomas Karlowski and Thomas Chalmers et al. published an RCT on vitamin C and the common cold in which they concluded that “the effects demonstrated might be explained equally well by a break in the double blind” and the trial has been extensively cited as evidence that vitamin C is useless for colds.
https://pubmed.ncbi.nlm.nih.gov/163386/
https://doi.org/10.1001/jama.1975.03240220018013
https://www.mv.helsinki.fi/home/hemila/CC/Karlowski_1975_ch.pdf

The Karlowski-Chalmers trial has been extensively cited in journal articles and textbooks, see Table 2 in:
https://doi.org/10.3390/life12010062
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8779885


In 1996, the Karlowski trial was shown to be erroneously analyzed:
Hemilš H. Vitamin C, the placebo effect, and the common cold: a case study of how preconceptions influence the analysis of results.
J Clin Epidemiol 1996;49:1079-1084 [Discussion in: 1996;49:1085-1087, see below]
https://doi.org/10.1016/0895-4356(96)00189-8
https://helda.helsinki.fi/handle/10250/8082
https://www.mv.helsinki.fi/home/hemila/H/HH_1996_JCE.pdf

Hemilš H. Response to the dissent by Thomas Chalmers.
J Clin Epidemiol 1996;49:1087
https://doi.org/10.1016/0895-4356(96)00191-6
https://helda.helsinki.fi/handle/10138/225873
https://www.mv.helsinki.fi/home/hemila/H/1996_L_JCE.pdf
https://www.mv.helsinki.fi/home/hemila/H/HH_1996_JCE2.pdf

Further statistical issues of the Karlowski trial:
Hemilš H. Analysis of clinical data with breached blindness.
Stat Med 2006;25:1434-1437
https://doi.org/10.1002/sim.2347
https://helda.helsinki.fi/handle/10138/228098
https://www.mv.helsinki.fi/home/hemila/H/2006_L_SIM.pdf

See also:
Hemilš H. The most influential trial on vitamin C and the common cold; The conclusions of the Karlowski et al trial (1975)
In: Do vitamins C and E affect respiratory infections? Thesis 2006 pp. 21-27, 59-60
https://hdl.handle.net/10138/20335
https://doi.org/10.5281/zenodo.6395595



Comments on other biased texts on vitamin C and the common cold

Hemilš H. Problems with statements by experts.
In: Do vitamins C and E affect respiratory infections? Thesis 2006 pp. 63-66
https://hdl.handle.net/10138/20335
https://doi.org/10.5281/zenodo.6395595

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.
Hemilš 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

Hemilš H. Flaws in the vitamin C and common cold meta-analysis by Ran et al. (2020). Pubpeer 2021
https://pubpeer.com/publications/A8A31D990B9983EED502D199D2F4F5#1
Comments on the meta-analysis:
https://doi.org/10.1155/2020/8573742
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7569434/

Hemilš H. Shortcomings in the vitamin C and common cold meta-analysis by Ran et al. (2018) Pubpeer 2021
https://pubpeer.com/publications/077EAB95E9141BE6A455C30F0A688E#1
Comments on the meta-analysis:
https://doi.org/10.1155/2018/1837634
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6057395/


This was retracted:
https://doi.org/10.1155/2023/9848057
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10110384

"due to a fundamental error identified in the calculations underlying the conclusions,
as raised by readers of the article, Dr. Colby Vorland and Dr. Andrew Brown of the Indiana University School of Public Health-Bloomington,
and Dr. Harri Hemilš of the University of Helsinki, summarized on PubPeer: https://pubpeer.com/publications/077EAB95E9141BE6A455C30F0A688E.



Hemilš H, Chalker E. Meta-analysis on vitamin C and the common cold in children may be misleading. Eur J Clin Pharmacol. 2019
https://doi.org/10.1007/s00228-019-02733-x
https://www.mv.helsinki.fi/home/hemila/H/Vorilhon_2019_Problems.pdf
https://www.mv.helsinki.fi/home/hemila/H/Vorilhon_2019_Problems_Supplement.pdf
https://doi.org/10.5281/zenodo.6395643


This is comment on:
Vorilhon P, et al. Efficacy of vitamin C for the prevention and treatment of upper respiratory tract infection. A meta-analysis in children. Eur J Clin Pharmacol. 2019
https://doi.org/10.1007/s00228-018-2601-7

 
Further severe problems in the Vorilhon meta-analysis are describe in this document:
https://helda.helsinki.fi/handle/10138/333365
https://doi.org/10.5281/zenodo.6395731

Because of the severe flaws, the Vorilhon meta-analysis was retracted in 2021
https://pubmed.ncbi.nlm.nih.gov/33988724/
https://doi.org/10.1007/s00228-021-03150-9

Hemilš H, Chalker E. Commentary: The Long History of Vitamin C: From Prevention of the Common Cold to Potential Aid in the Treatment of COVID-19. Front Immunol. 2021

https://pubmed.ncbi.nlm.nih.gov/33868305/
https://doi.org/10.3389/fimmu.2021.659001

Hemilš H. Vitamin C in Clinical Therapeutics. Clin Ther. 2017

https://pubmed.ncbi.nlm.nih.gov/28863879/
https://doi.org/10.1016/j.clinthera.2017.08.005

Hemilš H. The effect of vitamin C on the common cold. J Pharm Pract. 2011

https://pubmed.ncbi.nlm.nih.gov/21712220/
https://doi.org/10.1177/0897190010392376

Hemilš H. Randomised trials on vitamin C. Br J Nutr. 2011

https://pubmed.ncbi.nlm.nih.gov/20979683/
https://doi.org/10.1017/s000711451000351x

Hemilš H. Vitamin C for the common cold should not be rejected on the basis of old and erroneous articles. J Allergy Clin Immunol. 2009

https://pubmed.ncbi.nlm.nih.gov/19660806/
https://doi.org/10.1016/j.jaci.2009.06.015

Hemilš H. The role of vitamin C in the treatment of the common cold. Am Fam Physician. 2007

https://pubmed.ncbi.nlm.nih.gov/17992770/
https://www.aafp.org/link_out?pmid=17992770
https://www.aafp.org/afp/2007/1015/p1111a.html
https://www.mv.helsinki.fi/home/hemila/H/2007_L_AFP_2p.pdf

Hemilš H. Vitamin C and exercise-induced immunodepression. Eur J Clin Nutr. 2007

https://pubmed.ncbi.nlm.nih.gov/17426740/
https://doi.org/10.1038/sj.ejcn.1602751

Hemilš H. Small trials focusing on surrogate end points may be uninformative. Eur J Appl Physiol. 2007
https://pubmed.ncbi.nlm.nih.gov/17219167/
https://doi.org/10.1007/s00421-006-0387-2


Hemilš H. The effect of nutrition on exercise-induced immunodepression. Nutr Rev. 2006

https://pubmed.ncbi.nlm.nih.gov/17063930/
https://doi.org/10.1111/j.1753-4887.2006.tb00179.x

Hemilš H. Echinacea, vitamin C, the common cold, and blinding. Clin Infect Dis. 2005

https://pubmed.ncbi.nlm.nih.gov/16080106/
https://doi.org/10.1086/432629


Hemilš H. Vitamin C and illness.
Skeptical Inquirer 1995;19(Nr.4;July/August):62
https://helda.helsinki.fi/handle/10138/225885
https://www.mv.helsinki.fi/home/hemila/H/HH_1995L.pdf

Hemilš H. The good and harm of vitamin C.
Nutrition Today 1994;29(Nr.2;April):49-50
https://doi.org/10.1097/00017285-199403000-00008
https://helda.helsinki.fi/handle/10138/225884
https://www.mv.helsinki.fi/home/hemila/H/HH_1994L.pdf