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
harri.hemila@helsinki.fi
.. 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,
1994a, 1996a,
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:
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 TRANSLATIONRitzel
1961
in
German ch