Flawed vitamin C and Common Cold papers
by Harri Hemilä
- Problems with influential reviews on
vitamin C and the common cold
- Problems
with the most influential
vitamin C and common cold trial by Karlowski et al (1975)
- Comments
on other biased texts on vitamin C
and the common cold
Problems with influential
reviews on
vitamin C and the common cold
Hemilä 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
##########################################
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:
Hemilä 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:
Hemilä 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
##########################################
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:
Hemilä 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:
Hemilä 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
##########################################
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:
Hemilä 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:
Hemilä 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
######################################
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:
Hemilä 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
Hemilä 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:
Hemilä 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:
Hemilä 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
Hemilä 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.
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/pmc8853427Hemilä 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/
Hemilä 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 Hemilä of the University of Helsinki,
summarized on PubPeer: https://pubpeer.com/publications/077EAB95E9141BE6A455C30F0A688E.
Hemilä 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
Hemilä 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
Hemilä 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
Hemilä 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
Hemilä H. Randomised trials on vitamin C. Br J Nutr. 2011
https://pubmed.ncbi.nlm.nih.gov/20979683/
https://doi.org/10.1017/s000711451000351x
Hemilä 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
Hemilä 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
Hemilä 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
Hemilä 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
Hemilä 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
Hemilä 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
Hemilä 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
Hemilä 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