Meta-analyses on vitamin C and the common cold: from Linus Pauling and Thomas Chalmers to the Cochrane Collaboration

by Harri Hemilä

This text is based on page 28 of Hemilä (2006)
This document has up to date links to documents that are available via the net.
Harri Hemilä
Department of Public Health
University of Helsinki, Helsinki, Finland


This file:

Version May 29, 2012

.. Since then I never pay any attention to anything by ‘experts.’
I calculate everything myself.
I’ll never make that mistake again, reading the experts’ opinions.
Of course, you only live one life, and you make all your mistakes,
and learn what not to do, and that’s the end of you.
       Richard Feynman, 1985
       "Surely You're Joking, Mr. Feynman"

Have no respect whatsoever for authority;
forget who said it and instead look at what he starts with, where he ends up,
and ask yourself, "is it reasonable?"
       Richard Feynman, 1988
       "What Do You Care What Other People Think?"

I wish to propose for the reader’s favourable consideration a doctrine which may, I fear, appear wildly paradoxical and subversive. The doctrine in question is this: that it is undesirable to believe a proposition when there is no ground whatever for supposing it true, I must, of course, admit that if such an opinion became common it would completely transform our social life and our political system; since both are at present faultless, this must weight against it. I am also aware (what is more serious) that it would tend to diminish the incomes of clairvoyants, bookmakers, bishops and others who live on the irrational hopes of those who have done nothing to deserve good fortune here or hereafter.
      Bertrand Russell, 1928
      Sceptical Essays

When an old and distinguished person speaks to you, listen to him carefully - and with respect but do not believe him. Never put your trust in anything but your own intellect. Your elder, no matter whether he has grey hair or has lost his hair, no matter whether he is a Nobel Laureate, may be wrong. The world progresses, year by year, century by century, as the members of the younger generation find out what was wrong among the things that their elders said. So you must always be skeptical - always think for yourself.
    There are, of course, exceptional circumstances: when you are taking an examination, it is smart to answer the questions not by saying what you think is right, but rather what you think the professor thinks is right.

    Linus Pauling, 1955
    Advice to Students

In the 1970s, three meta-analyses on vitamin C and the common cold were published (Pauling 1971a, 1971b; Chalmers 1975). In fact, these three papers were among the first few meta-analyses carried out in medicine. However, the conclusions of these three meta-analyses diverged substantially.

Linus Pauling (1971a; see separate Background and Comments on the meta-analyses) combined the P-values derived from 4 placebo-controlled trials by the Fisher method, concluding that there was strong evidence that vitamin C decreased the ‘incidence of colds’ (P = 0.0014), and the ‘integrated morbidity’ due to colds (P = 0.000022). In a second meta-analysis, Pauling (1971b) focused on ‘days of illness per person’ in the best two trials (Cowan et al. 1942; Ritzel 1961; Table 3 in Background). Combining the P-values by the Fisher method led him to conclude that "The null hypothesis of equal effectiveness of ascorbic acid and placebo is rejected at the level P less than 0.001."

Thomas Chalmers (1975; see Comments) carried out a meta-analysis of 8 placebo-controlled trials, calculating the unweighted average of the treatment effect. According to his calculation, colds in vitamin C groups were 0.11 ± 0.24 (SE) days shorter, and the incidence of colds in vitamin C groups was 0.09 ± 0.06 (SE) episodes less per year, neither of which is a statistically or clinically significant difference. This meta-analysis of vitamin C and the common cold was Thomas Chalmers’ second, his first being published in the 1960s (Grace et al. 1966).

In the late 1980s, a fourth meta-analysis by Jos Kleinen on vitamin C and the common cold was published, but neither combined P-values nor pooled estimates were calculated (Kleijnen et al. 1989 see Comments).

In the 1990s, a series of meta-analyses which focused on various different questions related to the possible effects of vitamin C on the common cold was published (Hemilä 1992a, 1994a1996a, 1996b, 1997a, 1997b, 1999a). Since all 21 trials with regular ≥1 g/day doses had found that vitamin C was better than placebo when measuring the severity or duration of colds, the sign-test was used to calculate the probability that all 21 trials would find vitamin C to be better than placebo (P = 2exp(-21) = 0.0000005; Fig. 3 in Hemilä 2006; Hemilä 1994a). A Cochrane Review on vitamin C and the common cold also appeared in the late 1990s (Douglas et al. 1998 see comments in Hemilä 2006).

Because meta-analysis has been extensively used as a method of analyzing the potential effect of vitamin C on the common cold, the opportunities provided by this method as well as some of its limitations are considered in detail elsewhere (see p. 28-35 Hemilä (2006)).

In addtition to the meta-analyses, an influential review on vitamin C and the common cold was published in JAMA in 1975 (Dykes and Meier 1975 see Comments). The second author was Paul Meier, who is an eminent statistician.

Vitamin C and common cold meta-analyses and reviews are discussed on separate pages:

Pauling's meta-analyses (1971a,b)

Chalmers' meta-analysis (1975)

Kleijnen's meta-analysis (1989)

The Cochrane Collaboration meta-analysis (1998) see Hemilä (2006)

The Dykes and Meier review (1975)

Truswell's mini-review (1986)

A separate page discusses various problems of meta-analysis


Chalmers TC (1975) Effects of ascorbic acid on the common cold: an evaluation of the evidence. Am J Med 58:532-6

Cowan DW, Diehl HS, Baker AB (1942) Vitamins for the prevention of colds. JAMA 120:1268-71 CH BM

Douglas RM, Chalker EB, Treacy B (1998) Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev (2000);(2):CD000980

Dykes MHM, Meier P (1975) Ascorbic acid and the common cold: evaluation of its efficacy and toxicity. JAMA 231:1073-9   CH 

Grace ND, Muench H, Chalmers TC (1966) The present status of shunts for portal hypertension in cirrhosis. Gastroenterology 50:684-91

Hemilä H (1992a) Vitamin C and the common cold. Br J Nutr 67:3-16   Manu with links to Refs  CH

Hemilä H (1994a) Does vitamin C alleviate the symptoms of the common cold? a review of current evidence. Scand J Infect Dis 26:1-6    Manu with links to Refs

Hemilä H (1996a) Vitamin C supplementation and common cold symptoms: problems with inaccurate reviews. Nutrition 12:804-9  Manu with links to Refs  CH

Hemilä H (1996b) Vitamin C and common cold incidence: a review of studies with subjects under heavy physical stress. Int J Sports Med 17:379-83   CH   Manu with links to Refs

Hemilä H (1997a) Vitamin C and infectious diseases. In: Vitamin C in Health and Disease [Packer L, Fuchs J, eds]. NY: Marcel Dekker. pp 471-503

Hemilä H (1997b) Vitamin C supplementation and the common cold - was Linus Pauling right or wrong? Int J Vitam Nutr Res 67:329-35    other link

Hemilä H (1999a) Vitamin C supplementation and common cold symptoms: factors affecting the magnitude of the benefit. Med Hypotheses 52:171-8    CH

Hemilä H (2006) Do vitamins C and E affect respiratory infections? [Dissertation]. University of Helsinki, Finland   Hemilä 2006

Kleijnen J, Riet G, Knipschild PG (1989) Vitamine C en verkoudheid; overzicht van een megadosis literatuur [in Dutch]. Ned Tijdschr Geneeskd 133;1532-5
English translation: Vitamin C and the common cold; a review of the megadose literature. In: Food Supplements and Their Efficacy. pp 21-8. Thesis for University of Limburg (1991); Netherlands; ISBN 90 900 4581 3

Pauling L (1971a) The significance of the evidence about ascorbic acid and the common cold. Proc Natl Acad Sci USA 68:2678-81  PMC

Pauling L (1971b) Ascorbic acid and the common cold. Am J Clin Nutr 24:1294-9   NLM

Ritzel G (1961) Kritische Beurteilung des Vitamins C als Prophylacticum und Therapeuticum der Erkältungskrankheiten [in German; Critical analysis of the role of vitamin C in the treatment of the common cold]. Helv Med Acta 28:63-8 TRANSLATION    Ritzel 1961 in German ch  

Truswell AS (1986) Ascorbic acid [letter]. N Engl J Med 315:709 

© 2006-2010 Harri Hemilä. This text is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.  

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