Department of
Public Health
University of Helsinki,
Finland
harri.hemila@helsinki.fi
https://www.mv.helsinki.fi/home/hemila
Jan
31, 2025
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
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://www.researchgate.net/publication/15407891
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
https://www.researchgate.net/publication/35656439
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://helda.helsinki.fi/handle/10138/225877
https://www.researchgate.net/publication/14233989
https://doi.org/10.1016/S0899-9007(96)00223-7
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
https://www.researchgate.net/publication/35656439
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
https://doi.org/10.5281/zenodo.11546757
Pauling
L (1976c) Ascorbic
acid and the common cold. Part II.
Medical
Tribune 17(13):37-8
https://doi.org/10.5281/zenodo.11547088
##########################################
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
https://doi.org/10.1056/NEJM198609113151113
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://helda.helsinki.fi/handle/10138/225877
https://www.researchgate.net/publication/14233989
https://doi.org/10.1016/S0899-9007(96)00223-7
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
######################################
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://helda.helsinki.fi/handle/10250/8082
https://www.researchgate.net/publication/14378347
https://doi.org/10.1016/0895-4356(96)00189-8
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://hdl.handle.net/10138/225873
https://www.researchgate.net/publication/28363121
https://doi.org/10.1016/0895-4356(96)00191-6
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
https://www.researchgate.net/publication/35656439
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
https://www.researchgate.net/publication/35656439
Hemilä H. Errors in a
meta-analysis on vitamin C and COVID-19. PubPeer
2025.
https://pubpeer.com/publications/DE4E4A151A55A52A0ACD7F5ACC7C98#1
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/pmc8853427
Hemilä
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://hdl.handle.net/10138/318103
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
https://www.mv.helsinki.fi/home/hemila/H/2005_L_CID.pdf
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://hdl.handle.net/10138/228957
https://www.researchgate.net/publication/319419633
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://hdl.handle.net/10138/228058
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. Evidence-based
medicine and the role of antioxidants in physically stressed people.
Nutr
Rev. 2009;67(1):61-3.
https://hdl.handle.net/10138/228068
https://www.researchgate.net/publication/23790555
https://doi.org/10.1111/j.1753-4887.2008.00134.x
https://www.mv.helsinki.fi/home/hemila/H/2009_L_NutRev.pdf
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/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://www.researchgate.net/publication/51390866
https://doi.org/10.1038/sj.ejcn.1602751
https://www.mv.helsinki.fi/home/hemila/H/2007_L_EJCN.pdf
Hemilä
H. Small
trials focusing on surrogate end points may be uninformative.
Eur
J Appl Physiol. 2007
https://hdl.handle.net/10138/228092
https://www.researchgate.net/publication/6582824
https://pubmed.ncbi.nlm.nih.gov/17219167/
https://doi.org/10.1007/s00421-006-0387-2
https://www.mv.helsinki.fi/home/hemila/H/2007_L_EJAP.pdf
Hemilä
H. The effect of nutrition on exercise-induced immunodepression.
Nutr Rev. 2006
https://hdl.handle.net/10138/228097
https://www.researchgate.net/publication/237288826
https://pubmed.ncbi.nlm.nih.gov/17063930/
https://doi.org/10.1111/j.1753-4887.2006.tb00179.x
https://www.mv.helsinki.fi/home/hemila/H/2006_L_NutRev.pdf
Hemilä H. Echinacea,
vitamin C, the common cold, and blinding.
Clin
Infect Dis. 2005
https://hdl.handle.net/10138/253841
https://www.researchgate.net/publication/7680103
https://pubmed.ncbi.nlm.nih.gov/16080106/
https://doi.org/10.1086/432629
https://www.mv.helsinki.fi/home/hemila/H/2005_L_CID.pdf
Hemilä
H. Vitamin
C and illness.
Skeptical
Inquirer
1995;19(Nr.4;July/August):62
https://hdl.handle.net/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://hdl.handle.net/10138/225884
https://doi.org/10.1097/00017285-199403000-00008
https://www.mv.helsinki.fi/home/hemila/H/HH_1994L.pdf