Vitamin C and the Common Cold -papers

by Harri Hemilä

Department of Public Health
University of Helsinki, Finland
harri.hemila@helsinki.fi
https://www.mv.helsinki.fi/home/hemila
Nov 8, 2022

The impact of Linus Pauling in the initiation of the series of
controlled trials in the 1970s: see a brief summary with links at:
https://www.mv.helsinki.fi/home/hemila/pauling

For the problems in flawed meta-analyses and reviews
on vitamin C and the common cold, see summaries at:
https://www.mv.helsinki.fi/home/hemila/flawed_vitC_colds.htm

The papers on the common cold are divided in categories and if the same paper falls into several categories, it is listed in each of them

Cochrane Review on vitamin C and the common cold

Other reviews on vitamin C and the common cold

Summary of vitamin C, vitamin E, zinc lozenge studies on the common cold:
Hemilä H.
Vitamins and minerals [book chapter].
In: "Common cold " (Eccles R, Weber O, eds.) Birkhauser Verlag, 2009:275-307
   Abstract and references:
https://www.mv.helsinki.fi/home/hemila/birkhauser
   Available at:
https://doi.org/10.1007/978-3-7643-9912-2_13
https://doi.org/10.1007/978-3-7643-9912-2
https://www.amazon.com/Common-Birkh%C3%A4user-Advances-Infectious-Diseases/dp/3764398949
https://www.barnesandnoble.com/w/common-cold-ronald-eccles/1136783297
    A manuscript version:
https://helda.helsinki.fi/handle/10138/228060

Douglas RM, Hemilä H. Vitamin C for preventing and treating the common cold.
PLoS Med 2005;2:e168
https://doi.org/10.1371/journal.pmed.0020168
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc1160577/

Hemilä H. Vitamin C, respiratory infections, and the immune system.
Trends Immunol 2003;24:579-580
https://doi.org/10.1016/j.it.2003.09.004
https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7129436/

Hemilä H, Douglas RM. Vitamin C and acute respiratory infections.
Int J TB Lung Disease 1999;3:756-761
https://www.ingentaconnect.com/content/iuatld/ijtld/1999/00000003/00000009/art00004
https://www.mv.helsinki.fi/home/hemila/H/HH_1999_IJTLD.pdf

Vitamin C and the incidence of colds

Although there is strong evidence that vitamin C does not decrease the averge incidence of colds in the general community, there is strong evidence that some sub-populations benefit of vitamin C, so that colds are prevented in them:
Hemilä H. Prophylactic benefit of vitamin C in large trials (Table 20).
In: Do vitamins C and E affect respiratory infections? Thesis 2006 pp. 44
https://hdl.handle.net/10138/20335
https://doi.org/10.5281/zenodo.6395595

Strong evidence that in some conditions males and females differ:
Hemilä H. Vitamin C and sex differences in respiratory tract infections.
Respir Med 2008;102:625-626
https://doi.org/10.1016/j.rmed.2007.12.011
https://helda.helsinki.fi/handle/10250/8280
https://www.mv.helsinki.fi/home/hemila/H/2008_L_RespMed.pdf

Effects of vitamin C on military personnel may be explained by heavy physical stress and crowding of people:
Hemilä H. Vitamin C supplementation and respiratory infections: a systematic review. Mil Med 2004;169:920-925
https://doi.org/10.7205/MILMED.169.11.920
https://www.mv.helsinki.fi/home/hemila/H/HH_2004.pdf

Dietary vitamin C had no correlation with common cold incidence in middle-aged male smokers
Hemilä H, Kaprio J, Albanes D, Heinonen OP, Virtamo J.
Vitamin C, vitamin E and beta-carotene in relation to common cold incidence in male smokers. Epidemiology 2002;13:32-37
https://doi.org/10.1097/00001648-200201000-00006
https://www.jstor.org/pss/3703244
https://hdl.handle.net/10138/18059

Studies with males in the UK found decrease in common cold incidence; the explanation may be low dietary vitamin C intake when the trials were carried out:
Hemilä H. Vitamin C intake and susceptibility to the common cold.
Br J Nutr 1997;77:59-72 [Discussion in: 1997;78:857-866, see below]
https://doi.org/10.1017/S0007114500002889
https://helda.helsinki.fi/handle/10138/13886
https://www.mv.helsinki.fi/home/hemila/H/HH_1997_BJN.pdf
    Discussion:
    Hemilä H. Vitamin C intake and susceptibility to the common cold – Reply.
Br J Nutr 1997;78:861-866
    https://doi.org/10.1079/BJN19970201
    https://helda.helsinki.fi/handle/10138/223364
    https://www.mv.helsinki.fi/home/hemila/H/HH_1997_BJN2.pdf

Another presentation of the UK study findings:
Hemilä H. Prophylactic effect of vitamin C on recurrent colds in the UK trials (Table 22).
In: Do vitamins C and E affect respiratory infections? Thesis 2006 pp. 46-47
https://hdl.handle.net/10138/20335
https://doi.org/10.5281/zenodo.6395595

The first meta-analysis on the effect of vitamin C on people under heavy short-term physical stress which was based on 3 RCTs
Hemilä H. Vitamin C and common cold incidence: a review of studies with subjects under heavy physical stress.
Int J Sports Med 1996;17:379-383
https://doi.org/10.1055/s-2007-972864
https://helda.helsinki.fi/handle/10138/225881
https://www.mv.helsinki.fi/home/hemila/H/HH_1996_IJSM.pdf

>=1 g/day of vitamin C does not prevent colds:
Hemilä H. Does vitamin C alleviate the symptoms of the common cold? A review of current evidence.
Scand J Infect Dis 1994;26:1-6
https://doi.org/10.3109/00365549409008582
https://helda.helsinki.fi/handle/10138/228102
https://www.mv.helsinki.fi/home/hemila/H/HH_1994.pdf

>=1 g/day of vitamin C does not prevent colds:
Hemilä H. Vitamin C and the common cold.
Br J Nutr 1992;67:3-16
https://doi.org/10.1079/BJN19920004
https://www.mv.helsinki.fi/home/hemila/H/HH_1992.pdf

Vitamin C and common cold duration and severity

Vitamin C halved the duration of colds in male adolescent swimmers but not in female adolescent swimmers:
Constantini NW, Dubnov-Raz G, Eyal BB, Berry EM, Cohen AH, Hemilä H.
The effect of vitamin C on upper respiratory infections in adolescent swimmers: a randomized trial.
Eur J Pediatrics 2011;170:59-63
https://doi.org/10.1007/s00431-010-1270-z
https://helda.helsinki.fi/handle/10138/228085
https://www.mv.helsinki.fi/home/hemila/H/HH_2011_EurJPediatr.pdf

Effects of vitamin C on military personnel may be explained by heavy physical stress or/and crowding of people:
Hemilä H. Vitamin C supplementation and respiratory infections: a systematic review.
Mil Med 2004;169:920-925
https://doi.org/10.7205/MILMED.169.11.920
https://www.mv.helsinki.fi/home/hemila/H/HH_2004.pdf

On average the benefit of vitamin C has been greater in adults than in children, and with a dose of >=2 g/day compared with 1 g/day.
Hemilä H. Vitamin C supplementation and common cold symptoms: factors affecting the magnitude of the benefit.
Med Hypotheses 1999;52:171-178
https://doi.org/10.1054/mehy.1997.0639
https://helda.helsinki.fi/handle/10138/223761
https://www.mv.helsinki.fi/home/hemila/H/HH_1999_MH.pdf

>=1 g/day of vitamin C shortens and alleviates colds:
Hemilä H. Does vitamin C alleviate the symptoms of the common cold? A review of current evidence.
Scand J Infect Dis 1994;26:1-6
https://doi.org/10.3109/00365549409008582
https://helda.helsinki.fi/handle/10138/228102
https://www.mv.helsinki.fi/home/hemila/H/HH_1994.pdf

>=1 g/day of vitamin C shortens and alleviates colds:
Hemilä H. Vitamin C and the common cold. Br J Nutr 1992;67:3-16
https://doi.org/10.1079/BJN19920004
https://www.mv.helsinki.fi/home/hemila/H/HH_1992.pdf

Vitamin C and complications of the common cold: exacerbation of asthma

Hemilä H. Vitamin C and common cold-induced asthma: a systematic review and statistical analysis.
Allergy, Asthma Clin Immunol 2013;9:46
https://doi.org/10.1186/1710-1492-9-46
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018579

Linus Pauling and the common cold

Hemilä H. Vitamin C and the common cold; Meta-analysis; Pauling's meta-analyses (1971a,b);
In: Do vitamins C and E affect respiratory infections? Thesis 2006 pp. 11-13, 28, 35-36
https://hdl.handle.net/10138/20335
https://doi.org/10.5281/zenodo.6395595
https://www.mv.helsinki.fi/home/hemila/pauling

Hemilä H. Vitamin C supplementation and the common cold - was Linus Pauling right or wrong?
Int J Vitam Nutr Res 1997;67:329-335
https://doi.org/10.5281/zenodo.6406111
https://helda.helsinki.fi/handle/10250/7980
https://www.mv.helsinki.fi/home/hemila/H/HH_1997_IJVNR.pdf
https://www.ncbi.nlm.nih.gov/pubmed/9350474

Letters and commentaries

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/

Hemilä H
Statistical problems in the vitamin C and common cold trial with South Korean army recruits. BMJ Military 2020
https://militaryhealth.bmj.com/content/168/2/117.responses

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 Pharmacy Practice 2011;24:241-242
https://doi.org/10.1177/0897190010392376
https://helda.helsinki.fi/handle/10138/228058

Hemilä H. Randomised trials on vitamin C.
Br J Nutr 2011;105:485-487
https://doi.org/10.1017/S000711451000351X
https://www.ncbi.nlm.nih.gov/pubmed/20979683

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