Flawed vitamin C and Common Cold papers

by Harri Hemilš


Department of Public Health
University of Helsinki, Finland
harri.hemila@helsinki.fi
http://www.mv.helsinki.fi/home/hemila
Feb 18, 2020


  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. Recent citations of the Chalmers review and the Karlowski trial
  4. Comments on other biased texts on vitamin C and the common cold


Problems with influential reviews on vitamin C and the common cold

In 1975 Thomas Chalmers wrote a review in which he concluded that vitamin C is not effective against the common cold.
http://dx.doi.org/10.1016/0002-9343(75)90127-8
http://www.mv.helsinki.fi/home/hemila/reviews/Chalmers_1975_ch.pdf

The Chalmers review has been extensively cited in journal articles and textbooks, see:
http://www.mv.helsinki.fi/home/hemila/Chalmers1975CitedBy.htm
See a short description of Thomas Chalmers:
http://en.wikipedia.org/wiki/Thomas_C._Chalmers

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
http://dx.doi.org/10.1080/07315724.1995.10718483
http://hdl.handle.net/10138/42358  Links to references are added
http://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
http://hdl.handle.net/10138/20335
http://www.mv.helsinki.fi/home/hemila/reviews/chalmers

Who was Thomas Chalmers:
    http://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
    http://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
    http://annals.org/aim/fullarticle/709574/tributes-thomas-chalmers
    http://annals.org/aim/fullarticle/709576/tributes-thomas-chalmers
    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
    http://journals.sagepub.com/doi/full/10.1177/0141076815586354
    http://journals.sagepub.com/doi/abs/10.1177/0141076815606279





In 1975 Michael Dykes and Paul Meier wrote a review which similarly concluded that vitamin C is not effective to colds.
http://www.mv.helsinki.fi/home/hemila/reviews/Dykes_1975_ch.pdf
That review has also been extensively cited in journal articles and textbooks.
See a short description of Paul Meier:
http://en.wikipedia.org/wiki/Paul_Meier_(statistician)

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
http://dx.doi.org/10.1016/S0899-9007(96)00223-7
https://helda.helsinki.fi/handle/10138/225877
http://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
http://hdl.handle.net/10138/20335
http://www.mv.helsinki.fi/home/hemila/reviews/dykes

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



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.
http://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
http://dx.doi.org/10.1016/S0899-9007(96)00223-7
https://helda.helsinki.fi/handle/10138/225877
http://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
http://hdl.handle.net/10138/20335
http://www.mv.helsinki.fi/home/hemila/reviews/truswell


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.
http://www.mv.helsinki.fi/home/hemila/CC/Karlowski_1975_ch.pdf

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]
http://dx.doi.org/10.1016/0895-4356(96)00189-8
https://helda.helsinki.fi/handle/10250/8082
http://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
http://dx.doi.org/10.1016/0895-4356(96)00191-6
https://helda.helsinki.fi/handle/10138/225873
http://www.mv.helsinki.fi/home/hemila/H/1996_L_JCE.pdf
http://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
http://dx.doi.org/10.1002/sim.2347
https://helda.helsinki.fi/handle/10138/228098
http://www.mv.helsinki.fi/home/hemila/H11.pdf
http://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
http://hdl.handle.net/10138/20335
http://www.mv.helsinki.fi/home/hemila/karlowski


Recent citations of the Chalmers review and the Karlowski trial

In 2010, the Chalmers review was cited in PLOS MEDICINE as an example of "important systematic reviews"
See comment:
Hemilš H. Vitamin C and the common cold: early systematic reviews and the justification for new trials.
PLoS Med 2010 [e-letter 27 October 2010]
http://dx.doi.org/10.1371/journal.pmed.1000326  (see Comments section)
http://www.plosmedicine.org/annotation/listThread.action?root=22149

In 2010, the CONSORT group cited the Karlowski trial as an example of the importance of blinding
See comment:
Hemilš H. Citation bias in the CONSORT comments on blinding.
BMJ [e-Letter 18 May 2010]
http://dx.doi.org/10.1136/bmj.c869 (see Responses section)
http://www.bmj.com/rapid-response/2011/11/02/citation-bias-consort-comments-blinding

In 2009, a paper in JACI claimed that vitamin C is ineffective against colds, and the statement was based on on the Karlowski trial
See comment:
Hemilš H. Vitamin C for the common cold should not be rejected on the basis of old and erroneous articles.
JACI 2009;124:859
http://dx.doi.org/10.1016/j.jaci.2009.06.015
http://www.mv.helsinki.fi/home/hemila/H31.pdf

In 2009, a paper in J Thrombosis and Haemostasis cited the Karlowski trial as an evidence of the placebo effect
Hemilš H. Assessment of the importance of double-blinding should be based on systematic reviews: rebuttal.
J Thrombosis Haemostasis 2008;6:1247-1248
http://dx.doi.org/10.1111/j.1538-7836.2008.03006.x
http://hdl.handle.net/10138/25297 Links to references are added

In 2007 and 2008, two papers in AJE cited the Karlowski trial as evidence of the placebo effect
See comment:
Hemilš H. The author replies. Am J Epidemiol 2008;167:501-502
http:/dx.doi.org/10.1093/aje/kwm374
http://aje.oxfordjournals.org/content/167/4/501.full
http://www.mv.helsinki.fi/home/hemila/H20.pdf
(Reply to: http://dx.doi.org/10.1093/aje/kwm372 )
Hemilš H. RE: “Bias in clinical intervention research”.
Am J Epidemiol 2007;165:1219
http://dx.doi.org/10.1093/aje/kwm081
http://www.ncbi.nlm.nih.gov/pubmed/17426041

In 2006, a paper in Statistics in Medicine cited the Karlowski trial as an evidence of the placebo effect
See comment:
Hemilš H. Analysis of clinical data with breached blindness.
Stat Med 2006;25:1434-1437
http://dx.doi.org/10.1002/sim.2347
https://helda.helsinki.fi/handle/10138/228098
http://www.mv.helsinki.fi/home/hemila/H11.pdf
http://www.mv.helsinki.fi/home/hemila/H/2006_L_SIM.pdf

In 2005, a review in CID cited both the Chalmers review and the Karlowski trial as a justification to claim that vitamin C is ineffective against colds
See comment:
Hemilš H. Echinacea, vitamin C, the common cold, and blinding.
CID 2005;41:762-763
http://dx.doi.org/10.1086/432629


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

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://rdcu.be/bMXpF 

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

 

Hemilš H. Problems with statements by experts.
In: Do vitamins C and E affect respiratory infections? Thesis 2006 pp. 63-66
http://hdl.handle.net/10138/20335
http://www.mv.helsinki.fi/home/hemila/experts


Hemilš H. Vitamin C and illness.
Skeptical Inquirer 1995;19(Nr.4;July/August):62
https://helda.helsinki.fi/handle/10138/225885
http://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
http://dx.doi.org/10.1097/00017285-199403000-00008
https://helda.helsinki.fi/handle/10138/225884
http://www.mv.helsinki.fi/home/hemila/H/HH_1994L.pdf